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Found 54 results

  1. EDDIEKIRK

    Diabetes

    Diabetes Diabetes is a condition wherein the body either produces inadequate amounts of insulin or fails to utilize available insulin properly. An estimated 1 million Americans suffer from Type 1 diabetes, which develops in childhood. Another 15 million suffer from Type 2 diabetes, also known as adult onset diabetes, which develops later in life. Symptoms generally include an imbalance of blood sugar levels and a high level of sugar excreted through the urine. Initial studies showed that cannabis has no effect on blood sugar levels. A recent test-tube study showed that very high doses of synthetic THC might aggravate diabetes, but that same research also indicates that continued use of cannabis creates a tolerance to the potential aggravation. [ii] No human studies have found that cannabis or synthetic cannabinoids contribute to symptoms of diabetes. At the same time, no human studies have been undertaken to prove or disprove the reports of long-term diabetics who claim that cannabis use causes an immediate lowering of abnormally high blood sugar levels. [iii] Some diabetics also claim that cannabis helps stabilize blood sugar levels and maintain mental stability, or correct mood swings caused by fluctuating blood sugar levels. [iv] Separating the apparent blood sugar response from the anti-anorexic properties of cannabis is currently a matter for further investigation. Diabetics are frequently instructed to refrain from alcohol use because of its high caloric content. Cannabis may provide a psychologically valuable alternative to alcohol in stress reduction, a major factor in managing the potentially life threatening symptoms of diabetes. Hence, cannabis may function in several ways to reduce and stabilize blood sugar levels for patients suffering from diabetes. However, regardless of mounting anecdotal evidence in medical practice, including medical testimony before a district court in California, [v] no scientific papers have been published on the effectiveness of cannabis in treating diabetes. While cannabis has been used as a replacement for insulin, diabetics are strongly advised to continue their physician’s prescribed treatment plan. Maugh, “Inhaled formed of insulin passes first test.” Los Angeles Times/Seattle Times, June 17, 1998 [ii] Hollister, “Health aspects of marijuana.” Pharmacological Review, Vol. 38, No. 1, 1986 [iii] Grinspoon, “Anecdotal surveys on diabetes.” The Forbidden Medicine Website, http://www.rxmarijuana.com [iv] Diabetic reports from Seattle and from the Sonoma Alliance for Medical Marijuana, 1998 [v] “Pot garden’s size brought case to court.” Sonoma Union Democrat (California), March 19, 1998 Drinking Chamomile Tea May Help Fight Complications Of Diabetes ScienceDaily (Sep. 16, 2008) — Drinking chamomile tea daily with meals may help prevent the complications of diabetes, which include loss of vision, nerve damage, and kidney damage, researchers in Japan and the United Kingdom are reporting. -------------------------------------------------------------------------------- The findings could lead to the development of a new chamomile-based drug for type 2 diabetes, which is at epidemic levels in this country and spreading worldwide, they note. Their study appears in the Sept. 10 issue of the ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication. In the new study, Atsushi Kato and colleagues point out that chamomile, also known as manzanilla, has been used for years as a medicinal cure-all to treat a variety of medical problems including stress, colds, and menstrual cramps. Scientists recently proposed that the herbal tea might also be beneficial for fighting diabetes, but the theory hasn't been scientifically tested until now. To find out, the researchers fed chamomile extract to a group of diabetic rats for 21 days and compared the results to a group of control animals on a normal diet. The chamomile-supplemented animals showed a significant decrease in blood glucose levels compared with the controls, they say. The extract also showed significant inhibition of both ALR2 enzymes and sorbitol, whose elevated levels are associated with increased diabetic complications, the scientists say. source: http://www.sciencedaily.com/releases/2008/...80915164519.htm Non-Psychoactive Cannabinoid Reduces Incidence Of Diabetes, Study Says Non-Psychoactive Cannabinoid Reduces Incidence Of Diabetes, Study Says - NORML Marijuana Compound May Help Stop Diabetic Retinopathy Marijuana Compound May Help Stop Diabetic Retinopathy Anticoagulant Effects of a Cannabis Extract in an Obese Rat Model Anticoagulant effects of a Cannabis extract in an obese rat model. Neuroprotective and Blood-Retinal Barrier-Preserving Effects of Cannabidiol Neuroprotective and Blood-Retinal Barrier-Preserving Effects of Cannabidiol in Experimental Diabetes -- El-Remessy et al. 168 (1): 235 -- American Journal of Pathology The Cannabinergic System as a Target for Anti-inflammatory Therapies http://www.ingentaconnect.com/conten...00013/art00008 Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes Unbound MEDLINE | Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats. Journal article Cannabidiol reduces the development of diabetes in an animal study IACM-Bulletin Getting Eye On Cannabinoids Getting Eye On Cannabinoids: The Hempire - [cannabis, britain] Marijuana compound could prevent eye damage in diabetics Marijuana compound could prevent eye damage in diabetics: The Hempire - [cannabis, hemp] The synthetic cannabinoid HU-210 attenuates neural damage in diabetic mice Diabetes | Evolutionism | Dr. Bob Melamede Cannabidiol arrests onset of autoimmune diabetes in NOD mice CSA: Cannabis Research - Diabetes Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes Unbound MEDLINE | Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes. Journal article Beneficial effects of a Cannabis sativa extract on diabetes induced neuropathy and oxidative stress. Unbound MEDLINE | Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress. Journal article Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress. Unbound MEDLINE | Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress. Journal article Happy reading!
  2. Hey there, Friends! Thought I might start trying to compile a more current list of high CBD strains for patents who are looking to grow or want to know what to look for before they go strain shopping. Cannatonic and Harlequin are fairly well-known, but I am certain there must be others. The lists I have found on the Net are fairly old. The CBD.org site is the best I've fond, but it's a bit clunky and doesn't seem to be updated regularly. I imagine that some of you are tied into what's going on in the world of MMJ breeding and could provide better and/or more up to date info. The more details you can provide about a strain, the better the list will be. Thanks so much for sharing your knowledge.
  3. From the album: EDDIEKIRK

    Potential Therapeutic Uses of medical Cannabis

    © Eddie Kirk

  4. THIS IS THE HIDDEN PICTURE OF THE ZIPPO LIGHTER BRING US THIS LINK AND YOU WIN THE LIGHTER SHOWN AS WELL AS FREE SHIPPING/ (must be a private member to claim prize) Contest won 2-2-2014 by soulreaper Why you should injest cannabis if you have MS, arthritis, epilepsy,spinal cord injury, stroke etc. A doctor told me that those who have immune system disorders (ie. lupus, rheumatoid arthritis) or any disease that affects the brain (neurons) like ALS, alzheimers, parkinsons, epilepsy, etc. should be injesting cannabis...either with tincture, capsules, medibles, edibles etc. Cannabis works over 4 times stronger when injested. You can just juice mature leaves, or cook the leaf/bud mix in with alcohol or fat because it's alcohol/fat soluable. I can't stand the taste, so I prefer capsules! Having said you need to be injesting.....you have to be VERY careful not to overdose. It is not an experience you ever want to repeat. If you are new to injesting, ask those who have had experience with it. Injest only with experienced friends. Some panic and go to the er where they can't do anything for you an experienced person could do. Which is to lie down, try to drink and eat or go to sleep(if you're lucky)!! So what I've learned is to take a drop (if it's tinc you prefer) before bedtime and see how it hits you. If you don't notice it, do 2 drops the next night. Ditto until you find the dose for you. I've had patients that could only take a drop for the first week. Now they are up to a teaspoon 4 times a day! Another thing I learned from the medical marijuana conference is that if you take hemp milk or hemp protein powder or hemp nuts...anything hemp along with your cannabis, they help boost the effects of cannabis. Never seen the stuff you ask!! I've seen it at Fred Meyers, new seasons & whole foods (aka whole paycheck)! Sorry if this is redundant! Happy, safe, effective medicating!
  5. Cannabinoids for Fibromyalgia Syndrome FibroAction has got an article discussing a recent journal article from Fibromyalgia Syndrome (Fibro) expert, Dr Roland Staud MD, and EB Koo, an undergraduate student at the University of Florida, discussing whether cannabinoids are a new treatment option for Fibromyalgia Syndrome. This is in light of the study by Skrabek et al, who carried out what was apparently the first randomized, controlled trial to assess the benefit of nabilone, a synthetic cannabinoid, on pain reduction and quality of life improvement in patients with Fibro. FibroAction is a new organisation, basd in the UK, which aims to make accurate, up-to-date information about Fibromyalgia Syndrome (Fibro) readily available, as well as raise awareness of the condition. My link Cannabinoids for Fibromyalgia Syndrome An article has been e-published ahead of print in the journal Nature Clinical Practice. Rheumatology by Fibromyalgia Syndrome expert, Dr Roland Staud MD, and EB Koo, an undergraduate student at the University of Florida, discussing whether cannabinoids are a new treatment option for Fibromyalgia Syndrome. [1] Dr Staud, author of 'Fibromyalgia for Dummies', is Professor of Medicine at the College of Medicine and Director of the Center for Musculoskeletal Pain Research at the University of Florida. The article discusses cannabinoids as a treatment option for Fibromyalgia Syndrome in light of the study by Skrabek et al, discussed in an article in the February issue of the Journal of Pain. [2] Skrabek et al carried out what was apparently the first randomized, controlled trial to assess the benefit of nabilone, a synthetic cannabinoid, on pain reduction and quality of life improvement in patients with Fibromyalgia Syndrome. [2] The randomized, double-blind, placebo-controlled trial was carried out on 40 patients with Fibromyalgia Syndrome. The primary outcome measure, visual analog scale (VAS) for pain, and the secondary outcome measures, number of tender points, the average tender point pain threshold, and the Fibromyalgia Impact Questionnaire (FIQ), were evaluated at 2 and 4 weeks into the trial and then again after a 4-week washout period. [2] Skrabek et al's trial found that there were significant decreases in the VAS (-2.04, P < .02), FIQ (-12.07, P < .02), and anxiety (-1.67, P < .02) in the nabilone treated group at 4 weeks, and that after the 4-week wash-out period, all benefits were lost, with the nabilone treated group returning to their baseline levels of pain and quality of life. There were no significant improvements in the placebo group. The treatment group experienced more side effects per person at 2 and 4 weeks (1.58, P < .02 and 1.54, P < .05), respectively, and although nabilone was not associated with serious adverse effects, some patients did experience drowsiness, dry mouth, vertigo and ataxia. [2] Skrabek et al said that: "Nabilone appears to be a beneficial, well-tolerated treatment option for fibromyalgia patients, with significant benefits in pain relief and functional improvement. ... As nabilone improved symptoms and was well-tolerated, it may be a useful adjunct for pain management in fibromyalgia." Nabilone, a synthetic cannabinoid, is used to treat chemotherapy-induced nausea and vomiting in patients who do not respond well to other anti-emetics. However, it has also been studied for use in treating cancer pain and neuropathic pain. Cannabinoids are chemicals that are structurally similar to cannabis or THC (the main psychoactive substance found in cannabis), or that bind to cannabinoid receptors. References: Staud R, Koo EB. Are cannabinoids a new treatment option for pain in patients with fibromyalgia? Nat Clin Pract Rheumatol. 2008 Jun 3. [Epub ahead of print]. Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008 Feb;9(2):164-73. Epub 2007 Nov 5. Fibromyalgia and Alternative Treatments From acupuncture to chiropractic, from massage to meditation, alternative treatments are in great demand. That's especially true for people with pain-related illnesses such as fibromyalgia. Alternative medicine, including herbal therapy and homeopathy, is a form of "drug-free" doctoring that views the mind and body as a fully integrated system. For people with fibromyalgia, some alternative treatments work well. That's because holistic therapies influence your total being. In that way, they may allow you to reduce your medications and increase your normal activities. Study findings show that standard acupuncture may be effective in treating some people with fibromyalgia. Both biofeedback and electroacupuncture have also been used for relief of fibromyalgia symptoms. However, before you try alternative treatments, talk with your doctor. Check to see what limitations might apply to you. Working with your doctor, you can find an acceptable way to blend conventional medicine with alternative treatments or natural remedies. When you do, you may be able to increase restful sleep and reduce your fibromyalgia pain. Can acupuncture treat fibromyalgia? With acupuncture, a practitioner inserts one or more dry needles into the skin and underlying tissues at specific points. Gently twisting or otherwise manipulating the needles causes a measurable release of endorphins into the bloodstream. Endorphins are the body's natural opioids. In addition, according to acupuncture practitioners, energy blocks are removed. Removing them is said to restore the flow of energy along the meridians, which are specific energy channels. Studies show that acupuncture may alter brain chemistry. It appears to do this by changing the release of neurotransmitters. These neurotransmitters stimulate or inhibit nerve impulses in the brain that relay information about external stimuli and sensations such as pain. In this way, the patient's pain tolerance is increased. One acupuncture treatment in some patients may last weeks to help alleviate chronic pain. What is electroacupuncture? Electroacupuncture is another way of stimulating the acupuncture points. It uses a needle hooked up to small wires connected to very slight electrical currents. Heat - moxibustion -- and massage - acupressure -- can also be used during this electroacupuncture process. Laser acupuncture is yet another offshoot of this alternative therapy. It may occasionally be effective for the treatment of carpal tunnel syndrome. While it uses the same points, there are no needles involved. There are precautions to take if you want to try acupuncture. First, make sure you find a licensed acupuncturist who has a lot of experience. Also, make sure the acupuncturist uses only disposable needles. There are multiple styles of acupuncture. The style used depends on where the practitioner studied. For instance, Chinese acupuncture depends on larger bore needles and the practitioner may be more aggressive with moving them. Japanese acupuncture uses thinner bore needles with a relatively gentle approach. You'll need to find the style that suits your fibromyalgia needs. My link Marijuana Ingredient May Cut Fibromyalgia Pain Preliminary Study Shows Less Pain, Better Quality of Life in Fibromyalgia Patients Taking Nabilone By Miranda Hitti WebMD Health NewsReviewed by Brunilda Nazario, MDFeb. 19, 2008 -- Nabilone, a pain drug based on marijuana's active ingredient, may ease fibromyalgia pain. So say Canadian researchers, based on a preliminary, short-term study. The study included 40 fibromyalgia patients. First, they did three things: Rate the intensity of their fibromyalgia pain. The rating scale ranged from 0 (no pain) to 10 (the worst pain imaginable). Their average rating was about 6. Rate their quality of life. The rating scale ranged from 0 to 100, with higher scores indicating worse quality of life. Their average rating was 66. Get a check of their tender points -- parts of the body that are often sensitive in fibromyalgia patients. The researchers then split the patients into two groups. For a month, one group of patients took nabilone daily. The other group took a placebo pill. The patients didn't know which pill they were taking. After a month of nabilone treatment, fibromyalgia pain was less intense and quality of life had improved. No such changes were seen with the placebo. Nabilone treatment didn't affect the patients' number of tender points. And it didn't cure fibromyalgia pain -- when patients stopped taking nabilone, their fibromyalgia pain returned to its former intensity. Nabilone was well tolerated, but side effects were more commonly reported in the nabilone group. Those side effects -- which included drowsiness, dry mouth, vertigo, and movement problems -- were "generally mild," write the researchers. Longer studies are needed to track the long-term effects, note the University of Manitoba's Ryan Quinlan Skrabek, MD, and colleagues. Their study appears in the February edition of The Journal of Pain. source: http://www.webmd.com/fibromyalgia/news/200...?src=RSS_PUBLIC Pot Drug May Cut Fibromyalgia Pain Preliminary Study Shows Less Pain, Better Quality of Life in Fibromyalgia Patients Taking Nabilone By Miranda Hitti WebMD Health News Reviewed By Brunilda Nazario, MD Feb. 19, 2008 -- Nabilone, a pain drug based on marijuana's active ingredient, may ease fibromyalgia pain. So say Canadian researchers, based on a preliminary, short-term study. The study included 40 fibromyalgia patients. First, they did three things: Rate the intensity of their fibromyalgia pain. The rating scale ranged from 0 (no pain) to 10 (the worst pain imaginable). Their average rating was about 6. Rate their quality of life. The rating scale ranged from 0 to 100, with higher scores indicating worse quality of life. Their average rating was 66. Get a check of their tender points -- parts of the body that are often sensitive in fibromyalgia patients. The researchers then split the patients into two groups. For a month, one group of patients took nabilone daily. The other group took a placebo pill. The patients didn't know which pill they were taking. After a month of nabilone treatment, fibromyalgia pain was less intense and quality of life had improved. No such changes were seen with the placebo. Nabilone treatment didn't affect the patients' number of tender points. And it didn't cure fibromyalgia pain -- when patients stopped taking nabilone, their fibromyalgia pain returned to its former intensity. Nabilone was well tolerated, but side effects were more commonly reported in the nabilone group. Those side effects -- which included drowsiness, dry mouth, vertigo, and movement problems -- were "generally mild," write the researchers. Longer studies are needed to track the long-term effects, note the University of Manitoba's Ryan Quinlan Skrabek, MD, and colleagues. Their study appears in the February edition of The Journal of Pain. SOURCES: Skrabek, R. The Journal of Pain, February 2008; vol 9: pp 164-173. © 2008 WebMD Inc. All rights reserved. source: http://www.rxlist.co...rticlekey=87306 Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Russo EB. Source GW Pharmaceuticals, 2235 Wylie Avenue, Missoula, MT 59802, USA. erusso@montanadsl.net Abstract OBJECTIVES: This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis. METHODS: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources. RESULTS: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging. CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines. Republished from Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):31-9. Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology. The disease is characterized by widespread musculoskeletal pain, fatigue and multiple tender points in the neck, spine, shoulders and hips. An estimated 3 to 6 million Americans are afflicted by fibromyalgia, which is often poorly controlled by standard pain medications. Fibromyalgia patients frequently self-report using cannabis therapeutically to treat symptoms of the disease,[1-2] and physicians – in instances where it is legal for them do so – often recommend the use of cannabis to treat musculoskeletal disorders.[3-4] To date however, there are few clinical trials assessing the use of cannabinoids to treat the disease. Previous clinical and preclinical trials have shown that both naturally occurring and endogenous cannabinoids hold analgesic qualities,[9-12] particularly in the treatment of pain resistant to conventional pain therapies. (Please see the 'Chronic Pain' section of this book for further details.) As a result, some experts have suggested that cannabinoids are potentially applicable for the treatment of chronic pain conditions such as fibromyalgia,[13] and have theorized that the disease may be associated with an underlying clinical deficiency of the endocannabinoid system.[14] REFERENCES [1] Swift et al. 2005. Survey of Australians using cannabis for medical purposes. Harm Reduction Journal 4: 2-18. [2] Ware et al. 2005. The medicinal use of cannabis in the UK: results of a nationwide survey. International Journal of Clinical Practice 59: 291-295. [3] Dale Gieringer. 2001. Medical use of cannabis: experience in California. In: Grotenhermen and Russo (Eds). Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York: Haworth Press: 153-170. [4] Gorter et al. 2005. Medical use of cannabis in the Netherlands. Neurology 64: 917-919. [5] Schley et al. 2006. Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief. Current Medical Research and Opinion 22: 1269-1276. [6] Skrabek et al. 2008. Nabilone for the treatment of pain in fibromyalgia. The Journal of Pain 9: 164-173. <a href="http://norml.org/library/item/fibromyalgia#b7">[7] Ware et al. 2010. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesthesia and Analgesia 110: 604-610. [8] Fiz et al. 2011. Cannabis use in patients with fibromyalgia: Effect on symptoms relief and health-related quality of life. PLoS One 6. [9] Burns and Ineck. 2006. Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain. The Annals of Pharmacotherapy 40: 251-260. [10] David Secko. 2005. Analgesia through endogenous cannabinoids. CMAJ 173. [11] Wallace et al. 2007. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology 107:785-96. [12] Cox et al. 2007. Synergy between delta9-tetrahydrocannabinol and morphine in the arthritic rat. European Journal of Pharmacology 567: 125-130. [13] Lynch and Campbell. 2011. op. cit. [14] Ethan Russo. 2004. Clinical endocannabinoid deficiency (CECD): Can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuroendocrinology Letters 25: 31-39. My link
  6. A preliminary controlled study to determine whether whole plant cannabis extracts can improve ... Investigating abnormal protein is already promi- nent in neuroscientific research for neurodegenerative conditions (eg CJD, and Huntington's disease) PDF download Nabilone Could Treat Chorea and Irritability in Huntington’s Disease Adrienne Curtis, B.A., B.Sc. and Hugh Rickards, M.D., M.R.C.Psych., Department of Psychiatry, University of Birmingham, Birmingham, United Kingdom SIR: Huntington’s disease causes chorea and psychiatric abnormalities. Psychiatric symptoms were found in one study in 51 out of 52 patients.1 Dysphoria, agitation, irritability, apathy, and anxiety were found in above 50% of the patients sampled. Many sources postulate that cannabinoids could have a beneficial effect on the symptoms of Huntington’s disease, especially on choreatic movements.2–4 As well as providing possible symptomatic relief in Huntington’s disease, there is also some evidence5 that cannabinoids might have a neuroprotective effect which could delay the onset of symptoms by delaying or preventing the death of striatal neurons. This neuroprotective effect has also been postulated by other sources.6–8 To date there are only two reports on the use of cannabinoids in Huntington’s disease in the literature. Cannabidiol, a nonpsychotropic cannabinoid, had no effect on chorea severity in 15 patients.9 In one single patient, single dose, uncontrolled open clinical trial using nabilone, 1.5mg, the chorea increased significantly.10 We present a case of a female patient with irritability, which improved after the introduction of cannabis. This improvement was maintained by treatment with nabilone. Case Report The patient was a 43-year-old female who died in December 2003. She developed symptoms of Huntington’s disease at the age of 24 and her husband gave up paid employment to care for her in 1990 when she was 30 years old. In 1995, he reported difficulties in caring for his wife. These difficulties were related to personality changes due to her illness. She increasingly resisted help from professionals, especially care assistants, and refused any suggestion of short-term respite care. She became disinhibited and frequently undressed herself and walked around naked inside and occasionally outside the house. She exhibited a number of dangerous behaviors, such as leaving taps running and fires burning, and leaving burning cigarettes around. Her husband became concerned about the effect that the care for his chronically ill wife was having on his son, who was born in 1984. The patient went into residential care in 1996. The patient’s husband visited two or three times every week and he always took his wife out for a trip. These trips were difficult because of the patient’s refusal to be strapped into the car or her wheelchair, which sometimes resulted in falls caused by violent choreic movements when he was unable to physically hold her in the chair because he was using his hands for some other purpose. In 2001, he began to give his wife cannabis to smoke when he took her out on these regular trips. When he returned his wife to the nursing home after these visits the staff were aware of a significant difference in the patient. The cannabis appeared to improve her mood and she was calmer and more relaxed. Prior to the introduction of cannabis she was extremely impatient and would get angry if required to wait even a few minutes for a cigarette. After taking cannabis, she was able to wait a while without screaming and throwing things. The patient also willingly accepted the use of a car seat belt and wheelchair harness. In December 2001, the local general practitioner prescribed a regimen of nabilone, a synthetic 9-keto cannabinoid, which the patient began taking, 1mg each day. The husband and the nursing home staff both reported improvements in behavior and reduction of chorea coinciding with the introduction of cannabis and maintained by daily taking nabilone. Comment This report has many limitations. It is a single case report and no measurements were taken at the time of the introduction of cannabis and nabilone. The information was obtained by interviewing the husband and staff from the care home in 2005. The symptoms of Huntington’s disease do change over time and the movements are different in the later stages of the disease. However both the husband and the staff are sure that the introduction of cannabis was beneficial and greatly improved the patient’s quality of life in her last years. There is need for further trials to establish the therapeutic use of cannabinoids in the symptomatic treatment of Huntington’s disease. ACKNOWLEDGMENTS The first author receives an unrestricted educational grant from Cambridge Laboratories, which holds the European marketing rights for nabilone. REFERENCES 1. Paulsen JS, Ready RE, Hamilton JM, et al: Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry 2001; 71:310–314[Abstract/Free Full Text] 2. Consroe P: Brain cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol Dis 1998; 5:534–551[CrossRef][Medline] 3. Craufurd D, Thompson JC, Snowden JS: Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol 2001; 14:219–226[Medline] 4. Goutopoulos A, Makriyannis A: From cannabis to cannabinergics: new therapeutic opportunities. Pharmacol Therapeutics 2002; 95:103–117[CrossRef][Medline] 5. Aiken CT, Tobin AJ, Schweitzer ES: A cell-based screen for drugs to treat Huntington’s disease. Neurobiol Dis 2004; 16:546–555[CrossRef][Medline] 6. Baker D, Pryce G: The therapeutic potential of cannabis in multiple sclerosis. Expert Opin Investig Drugs 2003; 12:561–567[CrossRef][Medline] 7. Croxford JL, Miller SD: Towards cannabis and cannabinoid treatment of multiple sclerosis. Drugs Today 2004; 40:663–676[CrossRef][Medline] 8. Russo E: Future of cannabis and cannabinoids in therapeutics. J Cannabis Therapeutics 2003; 3:163–174 9. Consroe P, Laguna J, Allender J, et al: Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 1991; 40:701–708[CrossRef][Medline] 10. Muller-Vahl KR, Schneider U, Emrich HMl: Nabilone increases choreatic movements in Huntington’s disease. Mov Disord 1999; 14:1038–1040[CrossRef][Medline] My link Longitudinal Evaluation of Neuropsychiatric Symptoms in Huntington's Disease Jennifer C. Thompson, Ph.D., Jenny Harris, B.Sc., Andrea C. Sollom, M.A., Cheryl L. Stopford, Ph.D., Elizabeth Howard, MBChB, Julie S. Snowden, Ph.D., David Craufurd, M.Sc. The Journal of Neuropsychiatry and Clinical Neurosciences, Jan 2012; 24 (1); 53-60. doi: 10.1176/appi.neuropsych.11030057 /Images/icons/at05_pdf.png PDF EFFECTS OF CANNABIDIOL IN HUNTINGTON'S DISEASE Neurology 36 (Suppl 1) April 1986 p. 342 Reuven Sandyk, Paul Consroe, Lawrence Z. Stern, and Stuart R. Snider, Tucson, AZ Cannabidiol (CBD) is a major nonpsychoactive cannabinoid of marijuana. Based on reports indicating possible efficacy of CBD in dystonic movements (Neurology 1984; 34 [suppl 1]: 147 and 1985; 35 [suppl 1]: 201), we tried CBD in three patients with Huntington's disease (HD). The patients;, aged 30 to 56, had HD of 7 to 12 years' duration. Their condition has been slowly progressive and unresponsive to prior therapy with neuroleptics. Orally administered CBD was initiated at 300 mg/d and increased 1 week later to 600 mg/d for the next 3 weeks. Mild improvement ( 5 to 15%) in the choreic movements was documented using the tongueprotrusion test (Neurology [Minneap} 1972; 22: 929-33) and a chorea severity evaluation scale (Br J Clin Pharmacol 1981; 11: 129-51) after the first week. Further improvement (20 to 40%) was noticed after the second week of CBD, and this remained stable for the following 2 weeks. Except for transient, mild hypotension, no side effects were recorded, and laboratory tests were normal. Withdrawal of CBD after 48 hours resulted in return of choreic movements to the pre-CBD state. (Supported in part by NINCDS grant #NS15441) source: http://www.druglibrary.org/ Huntington’s disease (HD) is a neurodegenerative autosomal dominant disorder that usually presents in the midlife and is ultimately fatal. The genetic defect affects the IT15 gene located in the short arm of chromosome 4 and that encodes a protein called huntingtin (The Huntington’s Disease Collaborative Group, 1993). The mutation consists of an enlarged repeat of CAG triplets in the 5' coding region, that result in an abnormal polyglutamine tract in the amino-terminal portion of this protein (reviewed by Cattaneo et al., 2005). Normal gene contains between 6 and 35 repeats. Incomplete penetrance was seen for repeats between 36 and 39, whereas the pathology develops with a number of repeats higher than 40 (Landes and Bates, 2004). Mutated huntingtin becomes toxic preferentially for striatal medium-spiny neurons that project to the globus pallidus and the substantia nigra. This produces a progressive degeneration of the striatum that results in a biphasic pattern of motor abnormalities that evolves from an early hyperkinetic phase (choreic movements) to a late akinetic and more disabling phase (reviewed by Walker, 2007). The disease also presents cortical degeneration which originates cognitive dysfuntion and psychiatric symptoms, which are more evident at advanced phases. Despite the fact that the mutated gene responsible for HD has been already identified, the precise molecular and cellular mechanisms underlying striatal degeneration are still unknown and, consequently, the therapeutic outcome for HD patients is still too poor. Several types of compounds are presently under clinical evaluation, including minocycline, coenzyme Q10, unsaturated fatty acids and inhibitors of histone deacetylases (reviewed by Stack and Ferrante, 2007), and a great promise has been concentrated with the case of cannabinoid-based compounds, which have been reported to alleviate motor abnormalities and/or to serve as potential neuroprotective molecules (reviewed by Sagredo et al., 2007). Cannabinoid-based compounds are a large series of compounds able to target different elements of the so-called cannabinoid system, an intercellular signaling system active in the brain and also in the periphery (reviewed by Mackie and Stella, 2006). This includes selective agonists or antagonists for the CB1 or CB2 receptors, and also for other related receptor types (e.g. TRPV1 receptors), non-selective agonists, and inhibitors of the endocannabinoid generation or inactivation (reviewed by Fowler, 2007). Some of these compounds have been recently examined in animal or cellular models of HD and, although the matter is still far to be completely elucidated, some results have provided promising expectatives for a clinical evaluation in patients (reviewed by Sagredo et al., 2007). Thus, several studies have demonstrated that the loss of CB1 receptor-mediated signaling observed in the basal ganglia of HD patients and animal models (Maccarrone et al., 2007) is a very early event that takes place before the appearance of major neuropathological signs and functional abnormalities, and that it is susceptible of pharmacological correction (Sagredo et al., 2007). In parallel to this progressive decrease experienced by CB1 receptors during the course of this disease, CB2 receptors, whose presence in the healthy striatum is relatively modest, are, however, markedly up-regulated in reactive microglial cells in response to the striatal damage, thus representing a novel target to reduce the toxic influence of these cells on neuronal homeostasis (Fernández-Ruiz et al., 2007). These two observations have served as a basis to explore, at the preclinical level, the potential of both cannabinoid receptor types, and also of other elements of this signaling system in HD. For example, CB1 receptor agonists and inhibitors of the endocannabinoid inactivation have been examined for their possible antihyperkinetic effect, presumably exerted through acutely recovering the neurochemical deficits typical of first grades of this disorder (reviewed by Lastres-Becker et al., 2003). This potential, however, seems to be restricted to certain cannabinoids that combine the capability to enhance the cannabinoid signaling and also to activate TRPV1 receptors (reviewed by Fernández-Ruiz and González, 2005). In addition, cannabinoid agonists can also serve as neuroprotective agents in HD being capable to delay the progression of the striatal degeneration in different experimental models of this disease (reviewed by Sagredo et al., 2007). The neuroprotective effect of cannabinoids would be exerted through three key mechanisms: (i) their capability to normalize glutamate homeostasis, an effect mediated by CB1 receptors, that would allow to reduce excitotoxic events that occur in this pathology (reviewed by Sagredo et al., 2007); (ii) the antioxidant potential of certain cannabinoids, that would be exerted through cannabinoid receptor-independent mechanisms and that would allow to reduce the oxidative injury that also takes place in HD (reviewed by Sagredo et al., 2007); and (iii) their activity at the CB2 receptors to control the microglial influence on neuronal survival, thus reducing the local inflammatory events that are associated with the striatal degeneration (reviewed by Fernández-Ruiz et al., 2007). My link What is Huntington's Disease? http://www.youtube.com/watch?v=4HgFUvVyHYQ Huntington's disease could be helped through new developments in Scotland involving the medicinal properties of cannabis. The team of experts at the University of Aberdeen discovered that a naturally-occurring molecule in marijuana - cannabidiol - does not provide the high associated with tetrahydrocannabinol (THC) and as such could be used as an "acceptable drug treatment". It is believed that many strains of production cannabis are aimed at ramping up the THC content at the expense of cannabidiol, meaning that smoking marijuana could, if anything, exacerbate the problems associated with Huntington's disease and multiple sclerosis. Dr Bettina Platt, commenting on the findings, said: "We are hoping that our findings can instruct the development of cannabidiol-based treatments for disorders related to mitochondrial dysfunction such as Parkinson's disease or Huntington's disease." Earlier this month, the NHS reported findings from research in the US published in journal Cancer which linked testicular cancer to the use of cannabis by young males. My link Chemical in Cannabis Helps Cells Grow Last Updated (Friday, 01 May 2009 14:56) Written by InfoWeb The fact that cannabis is forbidden in most countries is only a recent event. In the past, starting centuries ago, people always smoked pot for various reasons, including leisure, resting purposes, going into trance, or for medicinal use. In Western societies, it has been mostly forbidden, even though not all of its effects have been fully understood up to this point. This is evidenced by the fact that only recently have researchers managed to identify a substance in cannabis that actually promotes cell growth and helps our bodies function properly. Out of the 60+ active substances that can be found in the average cannabis or marijuana strain, science has only been able to analyze and assess the threat levels of just a few until now. Yet, there are strict laws in place in every country that forbid the use of the plant, even though you can, for instance, buy flamethrowers in the US, as they pose no danger to anyone. A team of researchers from the University of Aberdeen describes the roles and functions of cannabidiol, a molecule that is naturally synthesized in the cannabis plant, publishing its finds in the Journal of Neuroscience. It appears that this substance, also known as CBD, has great potential to relieve pain, even though it's not the substance that gives pot its “high” label. Even though physicians have known for quite a long time that the compound can make pains felt by multiple sclerosis patients more bearable, they have never focused on harnessing this power to do good. Now, UA School of Medical Sciences researcher Dr Bettina Platt, has found out that CBD doesn't actually act on the peripheral nervous system, like other drugs do, but on the brain cells, or neurons themselves, influencing the activity of mitochondria, which are a sort of mini power plants for the cells. Understandably, influencing such an important cellular component into producing more energy is not a bad thing, yet the plant remains illegal because some believe that the other components may indeed be dangerous. However, no one takes the time to actually check them one by one. “We are hoping that our findings can instruct the development of cannabidiol based treatments for disorders related to mitochondrial dysfunction such as Parkinson's disease or Huntington's disease. There are different strains of cannabis out there and many no longer contain cannabidiol. In fact, these have been deliberately bred out to enhance the THC content,” Platt says, while drawing attention to the fact that smoking cannabis will not necessarily cure these conditions. In turn, she advocates the extraction of CBD from plants for scientific reasons. It could then be used to synthesize various drugs, which, with some luck, could offer much-needed pain relief for people suffering from some of the worse medical conditions known to man. source: GOOGLE WIKIPEDIA
  7. Study: Cannabinoid Reduces Breast Cancer Cell Aggression Saturday, November 24 2007 @ 12:31 AM EST Edited by: Michael Hess Cannabidiol may be helpful in reducing the aggressiveness of breast cancer cells BBSNews 2007-11-24 -- (IACM) In a mouse model of metastatic breast cancer the natural non- psychotropic cannabinoid cannabidiol (CBD) reduced the aggressiveness of breast cancer cells. CBD inhibited a protein called Id-1. Id proteins play an important role in tumour cell biology. The researchers of the California Pacific Medical Center Research Institute concluded that "CBD represents the first nontoxic exogenous agent that can significantly decrease Id- 1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness." The authors stressed that they were not suggesting patients smoke cannabis. They added that it would be highly unlikely that effective concentrations of CBD could be reached by smoking cannabis. Lead researcher Dr. Sean McAllister said: "Right now we have a limited range of options in treating aggressive forms of cancer. Those treatments, such as chemotherapy, can be effective but they can also be extremely toxic and difficult for patients. This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects." (Sources: BBC News of 19 November 2007; McAllister SD, Christian RT, Horowitz MP, Garcia A, Desprez PY. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Mol Cancer Ther 2007;6(11):2921-7.) source: http://bbsnews.net/a...071124003153693 The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation Luciano De Petrocellis*,†, Dominique Melck*,‡, Antonella Palmisano§, Tiziana Bisogno‡, Chiara Laezza¶, Maurizio Bifulco¶, and Vincenzo Di Marzo‡,‖ +Author Affiliations †Istituto di Cibernetica and ‡Istituto per la Chimica di Molecole di Interesse Biologico (affiliated with the National Institute for the Chemistry of Biological Systems, Consiglio Nazionale delle Ricerche), Consiglio Nazionale delle Ricerche, Via Toiano 6, 80072 Arco Felice, Naples, Italy; § Istituto di Ricerche sull’Adattamento dei Bovini e dei Bufali all’Ambiente del Mezzogiorno, Consiglio Nazionale delle Ricerche, Ponticelli, 80147 Naples, Italy; and ¶Centro di Studio der l’Endocrinologia e l’Oncologia Sperimentale, Consiglio Nazionale Delle Richerche and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli ‘Federico II,’ 80131 Naples, Italy Communicated by Rita Levi-Montalcini, Institute of Neurobiology, Consiglio Nazionale delle Ricerche, Rome, Italy (received for review March 6, 1998) Abstract Anandamide was the first brain metabolite shown to act as a ligand of “central” CB1 cannabinoid receptors. Here we report that the endogenous cannabinoid potently and selectively inhibits the proliferation of human breast cancer cells in vitro. Anandamide dose-dependently inhibited the proliferation of MCF-7 and EFM-19 cells with IC50 values between 0.5 and 1.5 μM and 83–92% maximal inhibition at 5–10 μM. The proliferation of several other nonmammary tumoral cell lines was not affected by 10 μM anandamide. The anti-proliferative effect of anandamide was not due to toxicity or to apoptosis of cells but was accompanied by a reduction of cells in the S phase of the cell cycle. A stable analogue of anandamide ®-methanandamide, another endogenous cannabinoid, 2-arachidonoylglycerol, and the synthetic cannabinoid HU-210 also inhibited EFM-19 cell proliferation, whereas arachidonic acid was much less effective. These cannabimimetic substances displaced the binding of the selective cannabinoid agonist [3H]CP 55,940 to EFM-19 membranes with an order of potency identical to that observed for the inhibition of EFM-19 cell proliferation. Moreover, anandamide cytostatic effect was inhibited by the selective CB1 receptor antagonist SR 141716A. Cell proliferation was arrested by a prolactin mAb and enhanced by exogenous human prolactin, whose mitogenic action was reverted by very low (0.1–0.5 μM) doses of anandamide. Anandamide suppressed the levels of the long form of the prolactin receptor in both EFM-19 and MCF-7 cells, as well as a typical prolactin-induced response, i.e., the expression of the breast cancer cell susceptibility gene brca1. These data suggest that anandamide blocks human breast cancer cell proliferation through CB1-like receptor-mediated inhibition of endogenous prolactin action at the level of prolactin receptor. source: http://www.pnas.org/...4/8375.abstract Suppression of Nerve Growth Factor Trk Receptors and Prolactin Receptors by Endocannabinoids Leads to Inhibition of Human Breast and Prostate Cancer Cell Proliferation1 Dominique Melck, Luciano De Petrocellis, Pierangelo Orlando, Tiziana Bisogno, Chiara Laezza, Maurizio Bifulco and Vincenzo Di Marzo Istituto per la Chimica di Molecole di Interesse Biologico (D.M., T.B., V.D.M.), Istituto di Cibernetica (L.D.P.), and Istituto di Biochimica delle Proteine ed Enzimologia (P.O.), Consiglio Nazionale delle Ricerche, 80072 Arco Felice (NA); and Centro di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II (C.L., M.B.), 80131 Naples, Italy Address all correspondence and requests for reprints to: Dr. Vincenzo Di Marzo, Istituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, 80072 Arco Felice (NA), Italy. E-mail: vdm@trinc.icmib.na.cnr.it. Anandamide and 2-arachidonoylglycerol (2-AG), two endogenous ligands of the CB1 and CB2 cannabinoid receptor subtypes, inhibit the proliferation of PRL-responsive human breast cancer cells (HBCCs) through down-regulation of the long form of the PRL receptor (PRLr). Here we report that 1) anandamide and 2-AG inhibit the nerve growth factor (NGF)-induced proliferation of HBCCs through suppression of the levels of NGF Trk receptors; 2) inhibition of PRLr levels results in inhibition of the proliferation of other PRL-responsive cells, the prostate cancer DU-145 cell line; and 3) CB1-like cannabinoid receptors are expressed in HBCCs and DU-145 cells and mediate the inhibition of cell proliferation and Trk/PRLr expression. ß-NGF-induced HBCC proliferation was potently inhibited (IC50 = 50–600 nM) by the synthetic cannabinoid HU-210, 2-AG, anandamide, and its metabolically stable analogs, but not by the anandamide congener, palmitoylethanolamide, or the selective agonist of CB2 cannabinoid receptors, BML-190. The effect of anandamide was blocked by the CB1 receptor antagonist, SR141716A, but not by the CB2 receptor antagonist, SR144528. Anandamide and HU-210 exerted a strong inhibition of the levels of NGF Trk receptors as detected by Western immunoblotting; this effect was reversed by SR141716A. When induced by exogenous PRL, the proliferation of prostate DU-145 cells was potently inhibited (IC50 = 100–300 nM) by anandamide, 2-AG, and HU-210. Anandamide also down-regulated the levels of PRLr in DU-145 cells. SR141716A attenuated these two effects of anandamide. HBCCs and DU-145 cells were shown to contain 1) transcripts for CB1 and, to a lesser extent, CB2 cannabinoid receptors, 2) specific binding sites for [3H]SR141716A that could be displaced by anandamide, and 3) a CB1 receptor-immunoreactive protein. These findings suggest that endogenous cannabinoids and CB1 receptor agonists are potential negative effectors of PRL- and NGF-induced biological responses, at least in some cancer cells. source: http://endo.endojour...tract/141/1/118 CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma Alessia Ligresti, Aniello Schiano Moriello, Katarzyna Starowicz, Isabel Matias, Simona Pisanti, Luciano De Petrocellis, Chiara Laezza, Giuseppe Portella, Maurizio Bifulco, and Vincenzo Di Marzo Endocannabinoid Research Group, Istituto di Chimica Biomolecolare (A.L., A.S.M., K.S., I.M., V.D.M.), and Istituto di Cibernetica (A.S.M., L.D.P.), Consiglio Nazionale delle Ricerche Pozzuoli, Italy; Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano", Università di Napoli "Federico II", Napoli, Italy (S.P., C.L., G.P., M.B.); and Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Fisciano, Italy (S.P., M.B.) 9-Tetrahydrocannabinol (THC) exhibits antitumor effects on various cancer cell types, but its use in chemotherapy is limited by its psychotropic activity. We investigated the antitumor activities of other plant cannabinoids, i.e., cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid, and assessed whether there is any advantage in using Cannabis extracts (enriched in either cannabidiol or THC) over pure cannabinoids. Results obtained in a panel of tumor cell lines clearly indicate that, of the five natural compounds tested, cannabidiol is the most potent inhibitor of cancer cell growth (IC50 between 6.0 and 10.6 µM), with significantly lower potency in noncancer cells. The cannabidiol-rich extract was equipotent to cannabidiol, whereas cannabigerol and cannabichromene followed in the rank of potency. Both cannabidiol and the cannabidiol-rich extract inhibited the growth of xenograft tumors obtained by s.c. injection into athymic mice of human MDA-MB-231 breast carcinoma or rat v-K-ras-transformed thyroid epithelial cells and reduced lung metastases deriving from intrapaw injection of MDA-MB-231 cells. Judging from several experiments on its possible cellular and molecular mechanisms of action, we propose that cannabidiol lacks a unique mode of action in the cell lines investigated. At least for MDA-MB-231 cells, however, our experiments indicate that cannabidiol effect is due to its capability of inducing apoptosis via: direct or indirect activation of cannabinoid CB2 and vanilloid transient receptor potential vanilloid type-1 receptors and cannabinoid/vanilloid receptor-independent elevation of intracellular Ca2+ and reactive oxygen species. Our data support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer source: http://jpet.aspetjou...ract/318/3/1375 9-Tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells through Cdc2 Regulation María M. Caffarel1, David Sarrió2, José Palacios2, Manuel Guzmán1 and Cristina Sánchez1 1 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University and 2 Breast and Gynecological Cancer Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain Requests for reprints: Cristina Sánchez, Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain. Phone: 34-913944668; Fax: 34-913944672; E-mail: csg@bbm1.ucm.es. It has been proposed that cannabinoids are involved in the control of cell fate. Thus, these compounds can modulate proliferation, differentiation, and survival in different manners depending on the cell type and its physiopathologic context. However, little is known about the effect of cannabinoids on the cell cycle, the main process controlling cell fate. Here, we show that 9-tetrahydrocannabinol (THC), through activation of CB2 cannabinoid receptors, reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis. In particular, THC arrests cells in G2-M via down-regulation of Cdc2, as suggested by the decreased sensitivity to THC acquired by Cdc2-overexpressing cells. Of interest, the proliferation pattern of normal human mammary epithelial cells was much less affected by THC. We also analyzed by real-time quantitative PCR the expression of CB1 and CB2 cannabinoid receptors in a series of human breast tumor and nontumor samples. We found a correlation between CB2 expression and histologic grade of the tumors. There was also an association between CB2 expression and other markers of prognostic and predictive value, such as estrogen receptor, progesterone receptor, and ERBB2/HER-2 oncogene. Importantly, no significant CB2 expression was detected in nontumor breast tissue. Taken together, these data might set the bases for a cannabinoid therapy for the management of breast cancer.(Cancer Res 2006; 66(13): 6615-21) source: http://cancerres.aac...ract/66/13/6615 Science: A combination of THC and prochlorperazine effective in reducing nausea and vomiting in women following breast surgery Researchers of the University of Arkansas and the Central Arkansas Veterans Hospital System investigated the effects of 5 mg oral THC and 25 mg rectal prochlorperazine on the rate of nausea and vomiting in women following breast surgery under general anaesthesia. The rate of nausea decreased from 59 per cent to 15 per cent and the rate of vomiting from 29 per cent to 3 per cent compared to non-treated patients. A retrospective review of 242 eligible patients, who underwent surgery between July 2001 and March 2003 was performed. 127 patients received surgery before September 2002 and did not receive a prophylaxis. 115 patients received surgery after September 2002 and were treated before surgery with oral THC (dronabinol) and rectal prochlorperazine. Data were collected from hospital records. Researchers concluded that post-operative nausea and vomiting (PONV) is a "significant problem in breast surgical patients. Preoperative treatment with dronabinol and prochlorperazine significantly reduced the number and severity of episodes of PONV." source: http://www.cannabis-...el.php?id=219#1 Science: Cannabidiol inhibits tumour growth in leukaemia and breast cancer in animal studies Italian researchers investigated the anti-tumour effects of five natural cannabinoids of the cannabis plant (cannabidiol, cannabigerol, cannabichromene, cannabidiol-acid and THC-acid) in breast cancer. Cannabidiol (CBD) was the most potent cannabinoid in inhibiting the growth of human breast cancer cells that had been injected under the skin of mice. CBD also reduced lung metastases deriving from human breast cancer cells that had been injected into the paws of the animals. Researchers found that the anti-tumour effects of CBD were caused by induction of apoptosis (programmed cell death). They concluded that their data "support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer." These observations are supported by investigations of US scientists who found out that exposure of leukaemia cells to CBD led to a reduction in cell viability and induction of apoptosis. In living animals CBD caused a reduction in number of leukaemia cells. The scientists noted that CBD "may be a novel and highly selective treatment for leukemia." source: http://www.cannabis-...el.php?id=220#2 Science: A combination of THC and prochlorperazine effective in reducing nausea and vomiting in women following breast surgery Researchers of the University of Arkansas and the Central Arkansas Veterans Hospital System investigated the effects of 5 mg oral THC and 25 mg rectal prochlorperazine on the rate of nausea and vomiting in women following breast surgery under general anaesthesia. The rate of nausea decreased from 59 per cent to 15 per cent and the rate of vomiting from 29 per cent to 3 per cent compared to non-treated patients. A retrospective review of 242 eligible patients, who underwent surgery between July 2001 and March 2003 was performed. 127 patients received surgery before September 2002 and did not receive a prophylaxis. 115 patients received surgery after September 2002 and were treated before surgery with oral THC (dronabinol) and rectal prochlorperazine. Data were collected from hospital records. Researchers concluded that post-operative nausea and vomiting (PONV) is a "significant problem in breast surgical patients. Preoperative treatment with dronabinol and prochlorperazine significantly reduced the number and severity of episodes of PONV." source: http://www.cannabis-...el.php?id=219#1 “Medical Marijuana” Takes On New Meaning for Metastatic Breast Cancer If you have breast cancer, you may have considered the use of “medical marijuana” at some point during your chemo treatment. Smoking marijuana has provided some women with relief from the nausea and vomiting that can accompany chemo, relief that the range of normal side effect drugs weren’t able to give. Some states permit the legal use of medical marijuana; most don’t. Nevertheless, most women who want to try marijuana seem to be able to get it. Personally, I didn’t experience any severe problems with nausea. But I was astounded at the number of people who, prior to treatment, offered to get me a supply if I thought I needed it! Now, doctors at the California Pacific Medical Center Research Institute in San Francisco have released a study, in the current issue of Molecular Cancer Therapeutics, that may in the future open the door to a much more critical use of marijuana: stopping the spread of metastatic breast cancer. It seems that a compound found in cannabis (the scientific name for marijuana), CBD, has been shown (in the lab) to stop the human gene Id-1 from directing cancer cells to multiply and spread. California Pacific Senior researcher Pierre-Yves Desprez, in an interview with HealthDay News, noted that the Id-1 genes “are very bad. They push the cells to behave like embryonic cells and grow. They go crazy, they proliferate, they migrate. We need to be able to turn them off." Desprez and fellow researcher Sean D. McAllister joined forces just two years ago. Desprez had been studying the Id-1 gene for 12 years; McAllister was a cannabis expert, but not involved in cancer research. Together they found that Id-1 is the “orchestra conductor” that directs breast cancer cells to grow and spread. And that CBD inhibits Id-1; it turns it off, puts it to sleep, pick your metaphor. Bottom line, it neutralizes it. And the cancer stops spreading. Both researchers pointed out that CBD is non-toxic and non-psychoactive. In other words, patients wouldn’t get high taking it. And its non-toxicity is an important attribute; Desprez and McAllister predict that, to be effective, patients might have to take CBD for several years. They also cautioned that smoking marijuana isn’t going to cure metastatic breast cancer; the level of CBD necessary to inhibit Id-1 simply can’t be obtained that way. While studies are still very much in the preliminary stages, it’s interesting to think that a plant that has been used medicinally for nearly 5,000 years may in the future be a key element in controlling cancer. As recently as 1937 (when it was outlawed in the U.S.), marijuana (“cannabis sativa”) was being touted as an analgesic, anti-emetic, narcotic, and sedative. Parke-Davis, once America’s oldest and largest drug manufacturer (and now a division of drug giant Pfizer), offered “Fluid Extract Cannabis” via catalogs. Until the invention of aspirin in the mid-1800s, cannabis was the civilized world’s main pain reliever. Now it’s illegal. Here’s hoping that someday soon cannabis returns, this time as a successful treatment for metastatic breast cancer. source: http://www.healthcen...6/takes-cancer/ Marijuana Compound May Stop Breast Cancer From Spreading, Study Says A compound found in cannabis may stop breast cancer from spreading throughout the body, according to a new study by scientists at California Pacific Medical Center Research Institute. The researchers are hopeful that the compound called CBD, which is found in cannabis sativa, could be a non-toxic alternative to chemotherapy. "Right now we have a limited range of options in treating aggressive forms of cancer," said lead researcher Dr. Sean D. McAllister, a cancer researcher at CPMCRI, in a news release. "Those treatments, such as chemotherapy, can be effective but they can also be extremely toxic and difficult for patients. This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects." The researchers tested CBD to inhibit the activity of a gene called Id-1, which is believed to be responsible for the aggressive spread of cancer cells throughout the body, away from the original tumor site. "We know that Id-1 is a key regulator of the spread of breast cancer," said Dr. Pierre-Yves Desprez, a cancer researcher at CPMCRI and the senior author of the study, in a news release. "We also know that Id-1 has also been found at higher levels in other forms of cancer. So what is exciting about this study is that if CBD can inhibit Id-1 in breast cancer cells, then it may also prove effective at stopping the spread of cancer cells in other forms of the disease, such as colon and brain or prostate cancer." Comparing it with another ingredient isolated from marijuana called THC, which is used in some medical treatments, the researchers said CBD does not have any psychoactive properties, so using it would not violate any state or federal laws. However, the researchers stressed that they are not suggesting that breast cancer patients smoke marijuana. They say it is highly unlikely that effective concentrations of CBD could be reached by smoking pot. The study is published in the latest issue of the journal Molecular Cancer Therapeutics. source: http://www.foxnews.c...,312132,00.html Sean D. McAllister, PhD Introduction Our research team is studying the potential of the endocannabinoid system to control cell fate with the goal of developing therapeutic interventions for aggressive cancers. This newly discovered biological system can be regulated by many different classes of cannabinoid compounds that work through specific cellular receptors. The cloned cannabinoid receptors have been termed cannabinoid 1 (CB1) and (CB2). ∆9-tetrahydrocannabinol (THC), a mixed CB1 and CB2 receptor agonist, is the primary active constituent of Cannabis sativa and is currently being used in a clinical trial for the treatment of aggressive recurrent glioblastoma multiforme (GBM). Cannabinoids are also being used in clinical trials for purposes unrelated to their direct anticancer activity. The compounds have been reported to be well tolerated during chronic oral and systemic administration. In addition to Δ9-THC, cannabidiol (CBD), cannabinol (CBN) and cannabigerol (CBG) are also present in reasonable quantities in Cannabis. CBN has low affinity for CB1 and CB2 receptors, whereas the non-psychotropic cannabinoids, CBD and CBG, have negligible affinity for the cloned receptors. We have determined that these additional cannabinoids are also effective and inhibiting aggressive cancers. Importantly, we have discovered in vitro that a synergistic increase in the antiproliferative and apoptotic activity of cannabinoids can be produced by combining specific ratios of CB1 and CB2 receptors agonists with non-psychotropic cannabinoids. We are currently determining the molecular mechanism that may explain the synergistic increase in anticancer activity that is observed with the combination treatments. We are also studying whether this combination strategy will lead to greater antitumor activity in vivo. In addition to the combination therapy project, we are working in collaboration with Dr. Pierre Desprez to develop novel inhibitors of Id-1 using cannabinoid compounds. Id-1 is a helix-loop-helix protein that acts as an inhibitor of basic helix-loop-helix transcription factors that control cell differentiation, development and carcinogenesis. Past research of Id-1 expression in normal and cancerous breast cells, as well as in mouse mammary glands and in human breast cancer biopsies, demonstrated that increased Id-1 expression was associated with a proliferative and invasive phenotype. Specifically, it was found that Id-1 was constitutively expressed at a high level in aggressive breast cancer cells and human biopsies, and that aggressiveness was reverted in vitro and in vivo when Id-1 expression was targeted using antisense technology. Importantly, we have recently discovered that CBD, a nontoxic cannabinoid that lacks psychoactivity, can inhibit Id-1 gene expression in metastatic breast cancer cells and consequently their aggressive phenotype. The down-regulation of expression was the result of the inhibition of the endogenous Id-1 promoter and corresponding mRNA and protein levels. CBD and compounds based off of its structure can therefore potentially be used as therapeutic agents. CBD also inhibits breast cancer metastasis in vivo. Based off of our recent findings, we are currently involved in 1) developing novel CBD analogs for the treat of aggressive breast cancers 2) discovering the detailed mechanisms through which cannabinoid compounds regulate Id-1 expression. source: http://www.cpmc.org/...ience/sean.html McAllister SD, Christian RT, Horowitz MP, Garcia A, Desprez PY. California Pacific Medical Center, Research Institute, 475 Brannan Street, San Francisco, CA 94107, USA. mcallis@cpmcri.org Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness. source: http://www.ncbi.nlm....Pubmed_RVDocSum N. California Researchers Testing Whether Marijuana Chemical Can Slow Cancer Growth, With Funding by Susan G. Komen for the Cure® Largest Breast Cancer Organization Investing $60 Million to Research Despite Down Economy SAN FRANCISCO, April 9 /PRNewswire-USNewswire/ -- Testing whether a powerful ingredient in marijuana can help slow the growth of aggressive breast cancer cells is just one of six Bay Area breast cancer studies being funded this year by Susan G. Komen for the Cure®, the global leader in the breast cancer movement announced today. The projects are part of a $60 million portfolio of 2009 research grants that Komen for the Cure is investing with scientists worldwide to find the cures for breast cancer. "Breast cancer doesn't care about the economy, and with more than 1.3 million new cases of breast cancer expected this year, the need for new research is more urgent than ever," said Hala Moddelmog, Komen's CEO and president. In the Bay Area this year, Komen's $1.8 million in grants will go to the University of California at San Francisco, Stanford University School of Medicine and California Pacific Medical Center. The UCSF study will try to improve bilingual communication and education between Latinas and their health care providers. One Stanford grant, if successful, could reverse some of the debilitating neurological and cognitive side effects of brain metastases, halt the progression of disease and possibly reduce mortality. And CPMC researchers will test whether cannabidiol - an ingredient in marijuana - can inhibit the aggressive growth of some breast cancers. "Komen's infusion of millions of dollars into research projects means that promising research that is designed to treat and ultimately eradicate breast cancer will continue," said Eric Winer, M.D., Komen's chief scientific advisor. During the past 27 years, Komen has invested $400 million to fund research globally, starting with Komen's first grant in 1982 for $28,000. A decade later, the annual total had grown to 21 grants worth $590,000 and 10 years after that, Komen distributed $21 million in research funds. This year, Komen is providing researchers worldwide with $60 million. In the last three years alone, Komen has invested nearly $237 million for breast cancer research. In 2008, Komen created Promise Grants - a new category of multi-year, multi-million dollar grants designed to discover and deliver cures for breast cancer more quickly. Here is a list of local institutions, the researchers and the projects Komen is funding this year, pending agreements: University of California at San Francisco *Celia Kaplan, $450,185, Breast Cancer Risk Reduction in Primary Care Clinics: A Bilingual Intervention for Women and Physicians Stanford University School of Medicine *Irene Wapnir, $600,000, From Bench to Bedside: Treatment of Breast Cancer Brain Metastasis with 131I and Radiosensitizers *Roeland Nusse, $180,000, 'Wnt signaling in human breast cancer stem cells. *Michael Clarke, $180,000, Functions of microRNAs in metastatic tumor initiating cells of human breast cancer *Howard Chang, $180,000, Noncoding RNA, Polycomb and Breast Cancer Progression California Pacific Medical Center *Sean McAlister, $593,713, Inhibition of Breast Cancer Cell Aggressiveness by Cannabidiol About Susan G. Komen for the Cure® Nancy G. Brinker promised her dying sister, Susan G. Komen, she would do everything in her power to end breast cancer forever. In 1982, that promise became Susan G. Komen for the Cure and launched the global breast cancer movement. Today, Komen for the Cure is the world's largest grassroots network of breast cancer survivors and activists fighting to save lives, empower people, ensure quality care for all and energize science to find the cures. Thanks to events like the Komen Race for the Cure®, we have invested more than $1.3 billion to fulfill our promise, becoming the largest source of nonprofit funds dedicated to the fight against breast cancer in the world. For more information about Susan G. Komen for the Cure, breast health or breast cancer, visit www.komen.org or call 1-877 GO KOMEN. SOURCE Susan G. Komen for the Cure source: http://news.prnewswi...C...3872&EDATE= Cannabis compound 'halts cancer' The CBD compound found in cannabis is non-toxicA compound found in cannabis may stop breast cancer spreading throughout the body, US scientists believe.The California Pacific Medical Center Research Institute team are hopeful that cannabidiol or CBD could be a non-toxic alternative to chemotherapy. Unlike cannabis, CBD does not have any psychoactive properties so its use would not violate laws, Molecular Cancer Therapeutics reports. The authors stressed that they were not suggesting patients smoke marijuana. They added that it would be highly unlikely that effective concentrations of CBD could be reached by smoking cannabis. This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects <br clear="all"> Lead researcher Dr Sean McAllister CBD works by blocking the activity of a gene called Id-1 which is believed to be responsible for the aggressive spread of cancer cells away from the original tumour site - a process called metastasis. Past work has shown CBD can block aggressive human brain cancers. The latest work found CBD appeared to have a similar effect on breast cancer cells in the lab. Future hope Lead researcher Dr Sean McAllister said: "Right now we have a limited range of options in treating aggressive forms of cancer. "Those treatments, such as chemotherapy, can be effective but they can also be extremely toxic and difficult for patients. "This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects." Dr Joanna Owens of Cancer Research UK said: "This research is at a very early stage. "The findings will need to be followed up with clinical trials in humans to see if the CBD is safe, and whether the beneficial effects can be replicated. "Several cancer drugs based on plant chemicals are already used widely, such as vincristine - which is derived from a type of flower called Madagascar Periwinkle and is used to treat breast and lung cancer. It will be interesting to see whether CBD will join them." Maria Leadbeater of Breast Cancer Care said: "Many people experience side-effects while having chemotherapy, such as nausea and an increased risk of infection, which can take both a physical and emotional toll. "Any drug that has fewer side-effects will, of course, be of great interest." But she added: "It is clear that much more research needs to be carried out." Caution content may be shocking! WHAT IS BREAST CANCER? Breast cancer itself is a malignant tumor than can form in one or both breasts, and usually develops in the milk-producing ducts of the breast, known as the the lobules. According to the website www.Cancer.org: Breast cancer is the most common cancer among women in the United States, other than skin cancer. It is the second leading cause of cancer death in women, after lung cancer. The chance of a woman having invasive breast cancer some time during her life is a little less 1 in 8. The chance of dying from breast cancer is about 1 in 35. Now Breast Cancer isn't only found in women, it can also occur in men, although not as common, but just as deadly. The most recent statistics for 2011 from the American Cancer Society estimate as follows: About 230,480 new cases of invasive breast cancer in women About 57,650 new cases of carcinoma in situ (CIS) will be found (CIS is non-invasive and is the earliest form of breast cancer). About 39,520 deaths from breast cancer (women) HOW CAN YOU PREVENT IT? THE GENETIC FACTORSBecause there is a higher chance of cancer in women with a family history, women should consult a medical professional who is specifically trained in risk assessment in order to help you decide the best methods for early detection. In Western countries, up to 10% of breast cancer is attributed to genetic predisposition. It can be transmitted through either the mother or father, with the possibility of either parent transmitting the abnormality without ever developing it -- as in, they're simply carriers. However, an excess of ovarian, colon, prostatic, and other cancers are inherited in the same abnormal mutation as breast cancer, so if any of these are present in family members, it is recommended that you take precautions. Most breast cancers are due to genetic mutations, with women who get the disease at an early age predisposed to the development of breast cancer. Mentioned on www.MindFully.org: WHERE IN THE WORLD IS CANCER?
  8. CANCER- PANCREATIC/ and use of Cannabis Molecule That Facilitates Cancer Spread In Both Cells And Their Surroundings Found ScienceDaily (Jan. 21, 2008) — The discovery that a molecule drives local tumor growth, as well as its ability to flourish and spread, opens a new window for understanding and treating cancer by taking aim at both cancer cells and their surrounding environment. A Dartmouth Medical School team led by Dr. Murray Korc found that a member of a common molecular family plays a role in the progress of a particularly resilient and aggressive pancreatic cancer, and that its influence is not restricted to that cancer. The work builds on studies by Korc, professor and chair of medicine at DMS, and colleagues at University of California, Irvine on glypican molecules, which interact with many growth factors implicated in cancer. A receptor called glypican-1 (GPC1) is abnormally abundant in pancreatic ductal adenocarcinoma, the most common and deadliest form of pancreatic cancer, often diagnosed after it has spread or metastasized. Human pancreatic cells deprived of their own GPC1 had reduced growth in culture, as well as when they were transplanted into immunocompromised mice (known as athymic for the lack of a thymus gland) that don't reject human cancer cells, the researchers demonstrated. "Tumors grow more slowly and are smaller. Interestingly, they also have less angiogenesis (blood vessel growth) and less metastasis," said Korc, also a professor pharmacology and toxicology and member of the Norris Cotton Cancer Center. Since GPC1 is common in many tissues, the researchers wanted to determine its role in the host environment, or how it functions in a patient. Knocking out the gene for GPC1 in mice, they created an athymic mouse population that lacked GPC1; then they introduced cancer cells. Host mice devoid of GPC1 had smaller pancreatic tumors that were less angiogenic and less metastatic when exposed to tumor cell lines with normal levels of GPC1. The metastatic potential of mouse melanoma (skin cancer) cells injected into mice with no GPC1 was also greatly decreased, the researchers found. "We've shown that GPC1 in the cancer cells and in the host—that is, the patient—is important not only for tumor growth, but for tumor angiogenesis and metastasis, Korc said. "This raises the possibility for therapeutic manipulations that will target GPC1 in both cancer cells and in patients to slow tumor growth and to prevent metastasis." Zeroing in on mechanisms that allow metastasis to occur more efficiently -namely, presence of GPC1—in either the cancer cells or the host, offers new options against cancer. The approach seems promising because, added Korc, "Host-cancer interactions are becoming significant as clinicians and cancer researchers realize that the environment around cancer cells is just as important as the cancer cells themselves." This research was reported in the January Journal of Clinical Investigation. Co-authors on the research are Takuma Aikawa, Chery A. Whipple, Jason Gunn, Alison Young, of DMS, and Martha E. Lopez and Arthur D. Lander of UC Irvine. Adapted from materials provided by Dartmouth Medical School. source: http://www.scienceda...80117180113.htm Pancreatic cancer has one of the highest morbidity rates due mainly to the fact that early detection is rare. The symptom profile of most patients is not very distinct. I would encourage folks who have ANY issues with digestion or elimination to get it thoroughly checked A.S.A.P. This is one you don't want to mess with. Regardless of the type of treatment, early detection is the key to survival. Experimental Therapeutics, Molecular Targets, and Chemical Biology Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes Arkaitz Carracedo1, Meritxell Gironella2, Mar Lorente1, Stephane Garcia2, Manuel Guzmán1, Guillermo Velasco1 and Juan L. Iovanna2 1 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain and 2 U624 Institut National de la Sante et de la Recherche Medicale, Marseille, France Requests for reprints: Guillermo Velasco, Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, c/ José Antonio Novais s/n, 28040 Madrid, Spain. Phone: 34-91-394-4668; Fax: 34-91-394-4672; E-mail: gvd@bbm1.ucm.es. Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue. Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, ( increased ceramide levels, and © up-regulated mRNA levels of the stress protein p8. These effects were prevented by blockade of the CB2 cannabinoid receptor or by pharmacologic inhibition of ceramide synthesis de novo. Knockdown experiments using selective small interfering RNAs showed the involvement of p8 via its downstream endoplasmic reticulum stress–related targets activating transcription factor 4 (ATF-4) and TRB3 in 9-tetrahydrocannabinol–induced apoptosis. Cannabinoids also reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue. In conclusion, results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress–related genes ATF-4 and TRB3. These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer. (Cancer Res 2006; 66(13): 6748-55) Source: http://cancerres.aac...ract/66/13/6748 Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say by Paul Armentano, NORML, Cancer Research July 1st, 2006 Madrid, Spain: Compounds in cannabis inhibit cancer cell growth in human breast cancer cell lines and in pancreatic tumor cell lines, according to a pair of preclinical trials published in the July issue of the journal of the American Association for Cancer Research. In one trial, investigators at Complutense University in Spain and the Institut National de la Sante et de la Recherche Medicale (INSERM) in France assessed the anti-cancer activity of cannabinoids in pancreatic cancer cell lines and in animals. Cannabinoid administration selectively increased apoptosis (programmed cell death) in pancreatic tumor cells while ignoring healthy cells, researchers found. In addition, "cannabinoid treatment inhibited the spreading of pancreatic tumor cells ... and reduced the growth of tumor cells" in animals. "These findings may contribute to ... a new therapeutic approach for the treatment of pancreatic cancer," authors concluded. In the second trial, investigators at Spain's Complutense University reported that THC administration "reduces human breast cancer cell proliferation [in vitro] by blocking the progression of the cell cycle and by inducing apoptosis." Authors concluded that their findings "may set the bases for a cannabinoid therapy for the management of breast cancer." Previous preclinical data published in May in the Journal of Pharmacological and Experimental Therapeutics reported that non-psychoactive cannabinoids, particularly cannabidiol (CBD), dramatically halt the spread of breast cancer cells and recommended their use in cancer therapy. Separate trials have also shown cannabinoids to reduce the size and halt the spread of glioma (brain tumor) cells in animals and humans in a dose dependent manner. Additional preclinical studies have demonstrated cannabinoids to inhibit cancer cell growth and selectively trigger malignant cell death in skin cancer cells, leukemic cells, lung cancer cells, and prostate carcinoma cells, among other cancerous cell lines. source: http://safeaccessnow...cle.php?id=3563 Molecule That Facilitates Cancer Spread In Both Cells And Their Surroundings Found ScienceDaily (Jan. 21, 2008) — The discovery that a molecule drives local tumor growth, as well as its ability to flourish and spread, opens a new window for understanding and treating cancer by taking aim at both cancer cells and their surrounding environment. A Dartmouth Medical School team led by Dr. Murray Korc found that a member of a common molecular family plays a role in the progress of a particularly resilient and aggressive pancreatic cancer, and that its influence is not restricted to that cancer. The work builds on studies by Korc, professor and chair of medicine at DMS, and colleagues at University of California, Irvine on glypican molecules, which interact with many growth factors implicated in cancer. A receptor called glypican-1 (GPC1) is abnormally abundant in pancreatic ductal adenocarcinoma, the most common and deadliest form of pancreatic cancer, often diagnosed after it has spread or metastasized. Human pancreatic cells deprived of their own GPC1 had reduced growth in culture, as well as when they were transplanted into immunocompromised mice (known as athymic for the lack of a thymus gland) that don't reject human cancer cells, the researchers demonstrated. "Tumors grow more slowly and are smaller. Interestingly, they also have less angiogenesis (blood vessel growth) and less metastasis," said Korc, also a professor pharmacology and toxicology and member of the Norris Cotton Cancer Center. Since GPC1 is common in many tissues, the researchers wanted to determine its role in the host environment, or how it functions in a patient. Knocking out the gene for GPC1 in mice, they created an athymic mouse population that lacked GPC1; then they introduced cancer cells. Host mice devoid of GPC1 had smaller pancreatic tumors that were less angiogenic and less metastatic when exposed to tumor cell lines with normal levels of GPC1. The metastatic potential of mouse melanoma (skin cancer) cells injected into mice with no GPC1 was also greatly decreased, the researchers found. "We've shown that GPC1 in the cancer cells and in the host—that is, the patient—is important not only for tumor growth, but for tumor angiogenesis and metastasis, Korc said. "This raises the possibility for therapeutic manipulations that will target GPC1 in both cancer cells and in patients to slow tumor growth and to prevent metastasis." Zeroing in on mechanisms that allow metastasis to occur more efficiently -namely, presence of GPC1—in either the cancer cells or the host, offers new options against cancer. The approach seems promising because, added Korc, "Host-cancer interactions are becoming significant as clinicians and cancer researchers realize that the environment around cancer cells is just as important as the cancer cells themselves." This research was reported in the January Journal of Clinical Investigation. Co-authors on the research are Takuma Aikawa, Chery A. Whipple, Jason Gunn, Alison Young, of DMS, and Martha E. Lopez and Arthur D. Lander of UC Irvine. Adapted from materials provided by Dartmouth Medical School. source: http://www.scienceda...80117180113.htm Q. I would like you to know about medical marijuana for cancer. In her late 30s, my wife was diagnosed with pancreatic cancer, stage 4a. It was a 6 cm tumor that had grown around the hepatic artery and portal vein. At first I thought marijuana was just for nausea caused by her chemo, but then I found a study in the journal Cancer Research (July 1, 2006). It showed that cannabinoids specifically fight pancreatic tumor cells. I changed her diet and started her on a regimen and she is now cancer free. The regimen is being studied at the University of Wisconsin. I hope others can benefit from medical marijuana. A. For years, marijuana research was suspected of being a way to rationalize people getting high. But as a recent article in Science News points out, scientists are now starting to take it seriously (June 19, 2010). The article you cite demonstrates that compounds from marijuana make pancreatic tumor cells commit suicide. Other cancer researchers have followed up with studies on its effectiveness against a range of tumors in test tubes, including breast, colon, glioblastoma brain tumors and lymphoma, a blood cancer. None are yet in clinical trials, but this will be an interesting field to watch. We are delighted your wife got such a good response for such a difficult-to-treat cancer.
  9. Cachexia is often seen in end-stage cancer, and in that context is called "cancer cachexia." In patients with congestive heart failure, there is also a cachectic syndrome. Also, a cachexia co-morbidity is seen in patients that have any of the range of illnesses classified as "COPD" (chronic obstructive pulmonary disease), particularly emphysema. Some severe cases of schizophrenia can present this condition where it is named vesanic cachexia (from vesania, a Latin term for insanity).[citation needed] It also can be observed in such parasitic diseases as african trypanosomiasis (Sleeping sickness).[citation needed] In each of these settings there is full-body wasting, which hits the skeletal muscle especially hard, resulting in muscle atrophy and great muscle loss. However, when presenting comorbidly with malabsorbtion syndrome, (as seen, for example, in Crohn's Disease or Celiac Disease) simply consuming more food is not sufficient to reverse wasting and the malabsorbtion must be treated before the patient will be able to stabilize body mass.[5] Cachexia not only worsens survival for people with cancer, but it interferes with quality of life. People with cachexia are less able to tolerate treatments, such as chemotherapy, and often have more side effects. For those who have surgery, postoperative complications are more common. Cachexia also worsens cancer fatigue, one of the most annoying symptoms of cancer. Mechanism The exact mechanism in which these diseases cause cachexia is poorly understood, but there is probably a role for inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which is also nicknamed cachexin (also spelled cachectin) for this reason, Interferon gamma (IFNγ), and Interleukin 6 (IL-6), as well as the tumor-secreted proteolysis inducing factor (PIF). Related malnutrition syndromes are kwashiorkor and marasmus, although these do not always have an underlying causative illness; they are most often symptomatic of severe malnutrition. Those suffering from the eating disorder anorexia nervosa appear to have high plasma levels of ghrelin. Ghrelin levels are also high in patients who have cancer-induced cachexia.[6] Treatment Currently, there are no widely accepted drugs to treat cachexia and there are no FDA-approved drugs to treat cancer cachexia. Cachexia may be treated by steroids such as corticosteroids or drugs that mimic progesterone, which increase appetite, may reverse weight loss, but have no evidence of reversing muscle loss.[7] Medical marijuana has been allowed for the treatment of cachexia in some US states such as Nevada, Michigan, Washington, Oregon, California, Colorado, New Mexico, and Arizona.[7][8] Evaluation There are several ways that cachexia can be evaluated. Some of these measures include: Body mass index (BMI) -- Body mass index describes not only relative body weight, but can give more information about a healthy weight. BMI is calculated using a formula of height and weight. Lean muscle mass -- Measuring body composition can help determine the ratio of lean muscle mass to body fat. Tests used to do this may include skin folds and bioimpedance. Food intake diaries -- Keeping a food diary is an important activity when looking to prevent or cope with cachexia. At the same time, it's important to keep in mind that the malnutrition of cachexia can occur even with an adequate intake of calories. Blood tests -- Some lab tests that are useful in evaluating cachexia include white blood cell counts (WBC), serum albumin, transferin levels, uric acid, and inflammatory markers, such as C-reactive protein (CRP). Omega-3 fatty acids A 2007 systematic review of n-3 fatty acids and cachexia found seventeen studies, eight of which were high-quality. It concluded that there was evidence that oral n-3 fatty acid supplements benefit cancer patients, improving appetite, weight and quality of life.[9] A 2009 trial found that a supplement of eicosapentaenoic acid helped cancer patients retain muscle mass.[10] source Medical Marijuana and Cachexia Watch this video http://www.youtube.com/watch?v=har8I0Lqsd4 What Is Cachexia? Cachexia is any general reduction in vitality and strength of body and mind resulting from a debilitating chronic disease. Medical Marijuana and Cachexia Cachexia is a wasting syndrome that causes weakness and a loss of weight, fat, and muscle, which affects patients with advanced cancer, AIDS, and some other major chronic progressive diseases. Cachexia and anorexia, or a lack of appetite, often occur together. Currently, there is no widely accepted drug to treat cachexia. Patients are often treated with steroids and/or nutritional supplements that provide easy-to-absorb nutrients. A 2009 trial found that a supplement of eicosapentaenoic acid helped cancer patients retain muscle mass. Scientists are also studying how human growth hormone treatments can help wasting syndrome patients. However, it is extremely expensive and could cost over $40,000 per year to use. In order to manage cachexia, patients must reduce nausea and vomiting in order to increase food intake. And according to scientific and anecdotal evidence, using medical marijuana is a safe, effective way to do so. The National Cancer Institute is in the process of evaluating the effects of THC for treatment-related and cancer-related anorexia and cachexia. Many marijuana states include cachexia on their list of qualifying conditions. Additionally, marijuana side effects are typically mild and are classified as "low risk," with euphoric mood changes among the most frequent side effects. If you or someone you know is looking to find relief from cachexia, MarijuanaDoctors.com can help. We can connect you with hundreds of quality marijuana doctors across the country in all legal marijuana states. Book an appointment today and let us help improve your quality of life! Source Cannabinoids and Cachexia [Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients]. Nauck F, Klaschik E. Loss of appetite and cachexia are frequent symptoms in palliative care patients. However, therapeutic regimens often prove ineffective, and the quality of life of many patients is significantly impaired by these symptoms. Causes and pathophysiology of anorexia and cachexia are complex and must be identified and treated. Symptomatic pharmacological therapy aims at metabolic, neuroendocrinological and catabolic changes. Prokinetic drugs, corticosteroids and gestagenes are used for symptomatic therapy. Recently, the use of cannabinoids for treatment of loss of appetite and cachexia has become the focus of interest. In cancer patients, cannabinoids proved more effective than placebo but less than gestagenes. Compared to placebo, higher efficacy of cannabinoids could be demonstrated in patients with AIDS as well as in patients with Morbus Alzheimer. However, side effects, such as dizziness, tiredness and daze led to discontinuation of the cannabinoid therapy in some patients. Cancer cachexia and cannabinoids. Gorter RW. Anorexia and cachexia are diagnosed in more than two-thirds of all cancer patients with advanced disease, and are independent risk factors for morbidity and mortality. Anorexia, nausea and vomiting often are described as more significant inhibiting factors for quality of life of cancer patients than even intense pain. In 1986, delta-9-tetrahydrocannabinol (THC), the main effective constituent of cannabis, was licensed as an anti-emetic drug in cancer patients receiving chemotherapy. In addition, in clinical studies THC has shown significant stimulation of appetite and increase of body weight in HIV-positive and cancer patients. The appetite-stimulating effect of cannabis itself has also been well documented in many anecdotal cases. There are strong indications that cannabis is better tolerated than THC alone, because cannabis contains several additional cannabinoids, like cannabidiol (CBD), which antagonize the psychotropic actions of THC, but do not inhibit the appetite-stimulating effect. Therefore, we intend to compare the therapeutic effects of whole-plant extracts of cannabis to those of THC (dronabinol) alone in controlled studies. Abstract and key points • Cannabinoids are components isolated from Cannabis sativa and Cannabis indica plants (hemp). • The antiemetic efficacy of cannabis in chemotherapy-induced nausea/vomiting has been established in a systematic review. • The use of cannabinoids for anorexia-cachexia-syndrome in advanced cancer is not supported by the evidence from randomised controlled trials. • Several randomised controlled trials indicate a mild analgesic effect of cannabinoids in cancer patients. • Dose-limitating central nervous and cardiovascular adverse effects have frequently been observed in clinical studies. Cannabinoids are components isolated from Cannabis sativa and Cannabis indica plants (hemp). This summary deals with cannabinoid products for medical use. Medical cannabinoids are claimed to alleviate nausea and vomiting in chemo-/radiotherapy and in palliative care. They are also recommended for the treatment of anorexia and cachexia in patients with advanced cancer and for the control of chronic tumor pain. The pharmacokinetics of cannabinoids have been intensively investigated and cannabinoid effects in humans have been linked to their agonist activity at two cannabinoid receptors. The antiemetic efficacy of cannabinoids in chemotherapy-induced nausea/vomiting has been established in a systematic review. If cannabinoids can offer improvements over modern antiemetic medication, especially serotonin antagonists, in preventing acute or delayed chemotherapy induced nausea and vomiting is still unclear. Only anecdotal evidence is available to support the use of medical cannabinoids against radiotherapy-related nausea and nausea in palliative care patients. The use of cannabinoids for anorexia-cachexia-syndrome in advanced cancer is not supported by the evidence from randomised controlled trials. Several randomised controlled trials also indicate a mild analgesic effect of cannabinoids in cancer patients. Insufficient evidence is available to support the introduction of cannabinoids into widespread clinical use as analgesics. The main limitation of cannabinoids is seen in the high frequency of serious adverse effects on the central nervous system and the cardiovascular system. Known absolute and relative contraindications and pharmacological interactions should be carefully considered. Medical cannabinoids are subject to country-specific prohibitory legislation. Considering the availability of well-investigated and established medications for chemotherapy-induced nausea and chronic pain, a first-line use of medical cannabinoids is not recommended. Medical cannabinoids might be beneficial in individual cases as adjuncts to other antiemetic or analgesic medication when standard treatment fails in symptom control. Potential hazards and toxicities should be considered. Case notes "It affected everything I did," says Addario, who is alive and well nine years later in San Carlos, Calif. "I literally could not get up and down the stairs." There is a name for what Addario experienced: cachexia. It is the muscle wasting and weight loss that are so often cancer's sidekick. Doctors and patients have long assumed cachexia is an integral part of cancer, and it's rarely discussed. "Ninety percent of oncologists completely ignore the cachexia because there's no known therapy," says Alfred Goldberg, a professor of cell biology who studies protein and muscle breakdown at Harvard Medical School in Boston. But that could soon change as two potential cachexia treatments are now in Phase 3 clinical trials. If studies continue to go well, the drugs could become available for lung cancer patients within the next two to three years. The main goal of both medications is to give people more muscle strength as they fight cancer. But they may do even more, scientists hope. "It's not clear that if you treat cachexia you will prolong life," says Dr. Egidio Del Fabbro, a palliative care physician at the University of Texas M.D. Anderson Cancer Center in Houston, but "we suspect it will." Del Fabbro is not involved with either of the companies developing the drugs,GTx Inc. of Memphis, Tenn., and Helsinn Therapeutics Inc. of Bridgewater, N.J. Cachexia (pronounced kuh-KEK-see-uh) is commonly defined as the unintentional loss of 5% or more of a person's weight within a six-month period. Crucially, it's muscle that slides off one's frame, often with fat as well. It's associated with advanced cancers as well as HIV, heart failure and kidney disease. In layman's terms, it means "the patient looks awful, they look weak, they've lost much of their body mass," Goldberg says. Cachexia is especially prevalent in pancreatic and lung cancers. People with the condition also tend to lose their appetites, but eating more does not help because the body's metabolism is operating at a higher-than-normal rate, says Vickie Baracos, a metabolism researcher at the University of Alberta in Edmonton. "The controls are not operating properly," she says. "It's sort of like having your thermostat turned up and the window left open at the same time." Given current rates of obesity, muscle wasting is sometimes hidden behind a layer of fat. "You can have somebody who technically looks obese, but they have the muscle mass of a concentration camp victim," says Dr. Mitchell Steiner, a urologic oncologist who co-founded GTx and now serves as the company's chief executive. MORE Introduction Cannabis sativa has been cultivated for more than 5000 y both to obtain fibers for manufacturing of textiles and to provide a variety of extracts for medicinal and recreational use. To the present, marijuana and other psychoactive derivatives of Cannabis sativa represent the most widely illegal drug consumed in the Western world. However, despite the social problems related to the abuse of these substances, scientific and social communities have recently started to be aware of the therapeutic potentials of cannabinoids and of new synthetic compounds interfering with the endogenous cannabinoid system. Since 300 AD, it was observed that Cannabis can stimulate hunger and increase appetite, particularly for sweet and palatable food. However, only a few years ago this phenomenon was seriously taken into consideration in research. After the discovery of cannabinoid receptors and their endogenous ligands (endocannabinoids), the existence of an endogenous cannabinoid system has been proposed, providing a physiological basis for the biological effects induced by marijuana and its derivatives. The importance of this system is also underlined by the finding of a high degree of evolutionary conservation across species, emphasizing the fundamental physiological role played by cannabinoids in brain function. The endogenous cannabinoid system Cannabinoid research was largely neglected at the beginning of the 20th century, partly because of the political antimarijuana attitude, which officially started in the United States with the Harrison Act in 1914, leading to full prohibition 20 years later. During the 1960s, the sudden increase of the recreational use of Cannabis stimulated the public concern about its negative effects on the health of the consumers. On the other hand, this renewed interest initiated a series of scientific investigations into the numerous chemical constituents of Cannabis and their mechanisms of action, finally leading to the identification of the structure of 9-tetrahydrocannabinol ( 9-THC), the main psychoactive ingredient of marijuana. However, the definitive breakthrough concerning the importance of this system was given by the discovery of cannabinoid receptors and their endogenous ligands. Cannabinoid receptors In 1990, the first cannabinoid receptor (CB1) was cloned, followed 3 y later by the characterization of a second cannabinoid receptor (CB2). Cannabinoid receptors belong to the G protein-coupled receptor superfamily and, to the present, include CB1, CB2 and a splice variant of the CB1 (for a review see Howlett et al). There is important pharmacological and physiological evidence suggesting the existence of other cannabinoid receptor subtypes that have not yet been cloned. Typically, the activation of cannabinoid receptors modulates adenylate-cyclase, potassium and calcium channels and signal-regulated kinases. Moreover, cannabinoid receptors are able to crosstalk with other neurotransmitter receptor systems, for example, recruiting by this way other intracellular signal transduction pathways. Given its wide distribution in the central nervous system (CNS) CB1 was considered as the 'brain-type' cannabinoid receptor, whereas CB2, mainly expressed in immune cells, was considered as its 'peripheral' counterpart. However, this classification does not hold true anymore as many studies show expression of CB1 also in peripheral tissues. On the other hand, CB2 was also localized in brain-derived immune cells. In the CNS, CB1 is predominantly expressed presynaptically, modulating the release of neurotransmitters, including -aminobutyric acid (GABA), dopamine, noradrenaline, glutamate and serotonin. 9-THC-mediated behavioral effects include ataxia, analgesia, hypothermia, euphoria, short-term memory deficits and other cognitive impairments. They are mediated by CB1 as suggested by the expression of this receptor in brain areas implicated in these functions and by the lack of these effects in CB1-deficient mice. Endogenous cannabinoids The presence of specific receptors mediating the actions of marijuana and its derivatives strongly stimulated the search for endogenous ligands for cannabinoid receptors. The first endogenous cannabinoid, arachidonoyl ethanolamide, was identified from the porcine brain in 1992 and was named anandamide, from the Sanskrit word 'ananda' that means internal bliss. Anandamide is able to reproduce most of the typical behavioral effects of 9-THC in rodents and shares the same G protein-mediated actions on adenylate cyclase and Ca2+ channels with 9-THC (for a review see Di Marzo et al). This substance binds both to CB1 and CB2, with a higher affinity to CB1 and is present at highest concentration in hippocampus, cortex, thalamus and cerebellum of different species including humans. Since the discovery of this ligand, other polyunsaturated fatty acid derivatives, acting as functional agonists of cannabinoid receptors, have been characterized and collectively termed endocannabinoids. As an example, Noladin ether is the most recent ether-type endocannabinoid identified only 1 y ago. Among these compounds, 2-arachidonoylglycerol (2-AG), identified in canine gut in a search for endogenous ligands selective for CB2, displays a lower affinity for CB1; nevertheless, it represents the most abundant endocannabinoid in the brain. In contrast to classical neurotransmitters, endocannabinoids do not appear to be stored in the interior of synaptic vesicles, because of the high lipophilicity of these ligands. In fact, phospholipid molecules within the cellular membrane were shown to serve as precursors and storage depots for anandamide synthesis. Anandamide is produced from such membrane phospholipids (eg N-arachidonoyl phosphatidyl ethanolamine), after cleavage of the phosphodiester bond by an as-yet-unidentified phospholipase D that is activated by Ca2+ ions. Endocannabinoids, like 'classical' neurotransmitters, are released from neurons following membrane depolarization and Ca2+ influx into the cells, are inactivated by a reuptake mechanism, involving facilitated transport by an as-yet-unisolated anandamide membrane transporter, and hydrolyzed by the enzyme fatty acid amide hydrolase in neurons and astrocytes. Cannabis Treatment: Anorexia and Cachexia An appetite enhancing effect of THC is observed with daily divided doses totalling 5 mg. When required, the daily dose may be increased to 20 mg. In a long-term study of 94 AIDS patients, the appetite-stimulating effect of THC continued for months, confirming the appetite enhancement noted in a shorter 6 week study. THC doubled appetite on a visual analogue scale in comparison to placebo. Patients tended to retain a stable body weight over the course of seven months. A positive influence on body weight was also reported in 15 patients with Alzheimer’s disease who were previously refusing food. source Covers body composition and muscle loss in both normal lifespan progression and disease conditions, offering research results and clinical innovation. The first scientific journal dedicated to research on cachexia and sarcopenia Presents research on both typical ageing progression and disease-related changes Covers both research and clinical topics Changes in body composition, especially in skeletal muscle, are key elements in the ageing process and in the pathophysiology of chronic illness. The Journal of Cachexia, Sarcopenia and Muscle presents research on these debilitating conditions, and on body composition and physiological and pathophysiological changes during the lifespan, and in response to disease. more Coverage includes research on the functional importance of fat tissue and mechanisms leading to lipolysis, and studies on mechanisms of muscle wasting, as well as better screening and evaluation options and enhanced biomarkers through validated complementary investigations. The Journal is a reliable resource on clinical care, including patients suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis and sepsis. The Journal of Cachexia, Sarcopenia and Muscle benefits physicians, biochemists, biologists, dieticians, pharmacologists, and students. Related subjects » Family & Geriatric Medicine - Internal Medicine - Molecular Medicine - Oncology & Hematology - Pharmaceutical Science Understanding Cachexia Symptoms, Signs, Causes, and Treatments By Lynne Eldridge MD, About.com Guide Updated April 03, 2012 About.com Health's Disease and Condition content is reviewed by the Medical Review Board My link Cachexia is a syndrome that is characterized by symptoms of unintentional weight loss, progressive muscle wasting, and a loss of appetite. Present in at least 50% of people with advanced cancer, it's estimated that it contributes directly to 20% of cancer deaths. Even though the symptoms and signs of cachexia are usually noticed late in the course of cancer, we're learning that the process leading to muscle wasting begins very early on after a diagnosis of cancer. In such, cachexia is often present before any weight loss occurs. Cachexia is sometimes referred to as a paraneoplastic syndrome, which simply means symptoms that are caused by substances made by a cancer or by the body's reaction to cancer. It might seem like cachexia should be easily treated at first glance, but effective treatments are lacking. This is because cachexia is more than just a lack of calories in the body. Cancer Cachexia Cachexia is seen frequently with cancer, but is also seen with diseases such as AIDS/HIV, heart failure, emphysema, and kidney failure. With regard to cancer, it is seen most frequently with lung cancer, pancreatic cancer, and stomach cancer. Cachexia not only worsens survival for people with cancer, but it interferes with quality of life. People with cachexia are less able to tolerate treatments, such as chemotherapy, and often have more side effects. For those who have surgery, postoperative complications are more common. Cachexia also worsens cancer fatigue, one of the most annoying symptoms of cancer. read more here Signs and Symptoms The major symptoms of cachexia include: Involuntary (unintentional) weight loss -- Weight loss with cachexia is involuntary, meaning that it occurs without trying. Yet it goes further than unintentional weight loss. Weight loss may occur even though you are getting an adequate amount of calories in your diet, and if calorie intake outweighs output of energy. Skeletal muscle wasting -- Muscle wasting is a hallmark of cachexia and occurs along with loss of fat. It can also be fairly insidious. In people who are overweight at the time of their diagnosis, significant loss of muscle mass can occur without an obvious outward appearance of weight loss. Anorexia/loss of appetite -- Loss of appetite is another symptom of cachexia, and again, this symptom is somewhat different than ordinary "loss of appetite" symptoms. With cachexia, it is not simply a decreased desire for food, but more of a loss of a desire to eat. Lowered quality of life -- Muscle wasting can diminish your ability to walk and participate in activities that would ordinarily be enjoyable. What Causes Cachexia? Cachexia may be caused by "tumor factors" -- substances manufactured and secreted by a tumor, or by the "host response." Host response simply means the body's response to a tumor. The response of the immune system to cancer and other causes of cachexia is being studied to try and understand the underlying factors behind cachexia. Cachexia is dominated by catabolic metabolism. If you think of normal metabolism being the building of tissue and muscle (anabolic metabolism), the opposite is true with cachexia, which is the breakdown of normal bodily processes. Evaluation There are several ways that cachexia can be evaluated. Some of these measures include: Body mass index (BMI) -- Body mass index describes not only relative body weight, but can give more information about a healthy weight. BMI is calculated using a formula of height and weight. Lean muscle mass -- Measuring body composition can help determine the ratio of lean muscle mass to body fat. Tests used to do this may include skin folds and bioimpedance. Food intake diaries -- Keeping a food diary is an important activity when looking to prevent or cope with cachexia. At the same time, it's important to keep in mind that the malnutrition of cachexia can occur even with an adequate intake of calories. Blood tests -- Some lab tests that are useful in evaluating cachexia include white blood cell counts (WBC), serum albumin, transferin levels, uric acid, and inflammatory markers, such as C-reactive protein (CRP). Tackling the Conundrum of Cachexia in Cancer Source http://www.cancer.go...in/110111/page5 By some estimates, nearly one-third of cancer deaths can be attributed to a wasting syndrome called cachexia that can be devastating for patients and their families. Characterized by a dramatic loss of skeletal muscle mass and often accompanied by substantial weight loss, cachexia (pronounced kuh-KEK-see-uh) is a form of metabolic mutiny in which the body overzealously breaks down skeletal muscle and adipose tissue, which stores fat. Patients suffering from cachexia are often so frail and weak that walking can be a Herculean task. Cachexia occurs in many cancers, usually at the advanced stages of disease. It is most commonly seen in a subset of cancers, led by pancreatic and gastric cancer, but also lung, esophageal, colorectal, and head and neck cancer. Despite cachexia's impact on mortality and data strongly suggesting that it hinders treatment responses and patients' ability to tolerate treatment, researchers who study muscle wasting say it has not received the attention it deserves. No effective therapies have been developed to prevent or hamper its progression. Even for patients who are able to eat—appetite suppression or anorexia is a common cachexia symptom—improved nutrition often offers no respite. There really is an enormous therapeutic opportunity here. —Dr. GoldbergAnd yet, over the last few years, researchers have begun to better understand the underlying biology of cancer-related cachexia. Findings from several studies point to potentially powerful therapeutic approaches, and a number of clinical trials of investigational drugs and drugs approved for other uses have been conducted or are under way. "It's exciting to see several avenues of investigation coming to the forefront and trials moving forward," said Dr. Aminah Jatoi, a medical oncologist at the Mayo Clinic Comprehensive Cancer Center. "It's important that oncologists be aware of these trials and offer participation to their patients," said Dr. Jatoi, a member of an international group of clinicians and researchers who earlier this year published a consensus statement to more precisely define cancer-related cachexia. The publication also provided a preliminary classification system for the condition—akin in some respects to the staging system used for tumors. (See the sidebar.) Cachexia isn't limited to cancer. It is commonly seen in people with AIDS and chronic forms of kidney disease and heart failure, among other conditions, as well as in those who have suffered severe trauma and burns, said Dr. Alfred Goldberg of the Harvard University School of Medicine, whose research on muscle wasting and protein degradation eventually led to the development of the cancer drug bortezomib (Velcade). With so many potential clinical applications, Dr. Goldberg said, "There really is an enormous therapeutic opportunity here." Why and How Cachexia Happens The consensus statement is a good beginning, according to another co-author, Dr. Mellar Davis of the Cleveland Clinic Taussig Cancer Center. But researchers still need to dig deeper into how cachexia develops in patients with cancer, Dr. Davis continued, and how its course is influenced by everything from nutrition and physical activity to disease-specific factors, such as reduced testosterone levels caused by cancer therapy or opioids to treat pain. Multiple factors are clearly at play in cachexia development and progression, Dr. Goldberg explained. He believes that at its core cachexia is "more of a host response that's evolved to fight fasting, injury, or disease," he said. During this response, the body is trying to obtain additional energy stores from muscle, in the form of amino acids, to convert into glucose to keep the brain functioning. The problem, he continued, "is that we can't turn off this response to the cancer, even when we can provide the patient with essential nutrients." Many studies suggest that inflammation "is a unifying theme of cachexia across many diseases, including cancer," said Dr. Teresa Zimmers of the Jefferson Kimmel Cancer Center in Philadelphia. The inflammation is caused in part by the body's immune response to the tumor, which results in the production of pro-inflammatory cytokines, explained Dr. Konstantin Salnikow, of NCI's Division of Cancer Biology (DCB). Although these cytokines can help to kill tumor cells, some also appear to tilt the body's metabolism toward catabolism, the breakdown of muscle proteins and fat. Elevated levels of several cytokines in particular have been closely associated with cachexia and mortality in cancer patients. In NCI-supported mouse model studies, for example, Dr. Zimmers has shown that elevated levels of the cytokine IL-6 can induce cachexia. She and others have begun to unravel some of the potential mechanisms by which IL-6 may do this. Goverments Search Despite the incomplete understanding of the underlying biology of cancer-related cachexia, a few potential therapies are moving into early human trials. More than one drug will likely be needed to successfully combat cachexia, particularly if it's at an advanced stage, said Dr. Barbara Spalholz, also of DCB. "We may have to hit different combinations of targets, depending on the type of cancer and other factors," she said. The agent that appears to be the furthest along is the selective androgen receptor modulator GTx-024 (Ostarine), developed by GTx Inc., based in Memphis, TN. In August, GTx launched two phase III clinical trials of the investigational agent, dubbed POWER1 and POWER2, for the prevention or treatment of cachexia in patients with advanced non-small cell lung cancer. More of their report here References_________________________________________________________________________________________________________________________________________________________________________________ 1. ^ http://www.merriam-w...ionary/Cachexia 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1169. ISBN 1-4160-2999-0. 3. ^ Lainscak M, Podbregar M, Anker SD (December 2007). "How does cachexia influence survival in cancer, heart failure and other chronic diseases?". Curr Opin Support Palliat Care 1 (4): 299–305. doi:10.1097/SPC.0b013e3282f31667. 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  10. OBESITY - Cannabis Obesity to be cured by Marijuana? A British pharmaceuticals company is planning to start trials on humans for a treatment for [tag-tec]obesity[/tag-tec] using [tag-tec]marijuana[/tag-tec]. They hasten to add that at this stage it is purely experimental. Of course marijuana has long been known to be a stimulus for hunger but GW pharma plc claim that they have derived a treatment from marijuana itself that could help suppress hunger. They go on to explain that the [tag-tec]marijuana plant[/tag-tec] has 70 different [tag-tec]cannabinoids[/tag-tec] in it and that each of these has an entirely different effect on the human body. Some stimulate your hunger whilst others suppress your hunger. GW say that they will begin trials later in 2007. All drugs have to pass a rigorous three stages of tests before it can be assessed by regulators and only then can a new drug be released. They added that this could take several years. I will keep my ear to the ground and let you know of any developments, as and when they happen. source: http://www.dreambody...d-by-marijuana/ How marijuana could help cure obesity-related diseases A British company says that two compounds found in marijuana leaves could treat patients whose weight puts them at high risk for heart disease and stroke According to a new British study, marijuana leaves (not the buds that Willie Nelson loves so dearly) contain two compounds that boost the metabolism of mice, leading to lower levels of fat and cholesterol in the body — the latest addition to a growing body of evidence that marijuana may be useful in countering ailments related to obesity. One study in March found that a brain chemical similar in structure to an active compound in cannibis could help people shed weight, while another study last September concluded that pot smokers were less likely to be obese than non-potheads, though for reasons that remain unclear. The researchers at Britain's GW Pharmaceuticals who are responsible for the latest weed development are already testing the two compounds on humans. Here, a guide to their findings: So the company is allowed to grow and dispense marijuana? Yes. Although marijuana is illegal in England, says Doug Barry at Jezebel, GW Pharmaceuticals, an "enormous multinational drug corporation equipped with all the magic passwords for dodging government regulations," was granted a license to grow the plant in specially constructed greenhouses at a secret location in the south of England. SEE MORE: Invented: Marijuana that doesn't get you high http://www.youtube.com/watch?v=u8WCdANlf_I London -- Human trials of an experimental treatment for obesity derived from cannabis, which is commonly associated with stimulating hunger, are scheduled to begin in the second half of this year, Britain's GW Pharmaceuticals Plc announced Tuesday. Several other companies, such as Sanofi-Aventis, which is investigating Acomplia, are working on new drugs that will switch off the brain circuits that make people hungry when they smoke cannabis. GW Pharma, however, says it has derived a treatment from cannabis that could help suppress hunger. "The cannabis plant has 70 different cannabinoids in it and each has a different affect on the body," GW Managing Director Justin Gover told Reuters in a telephone interview. "Some can stimulate your appetite, and some in the same plant can suppress your appetite. It is amazing both scientifically and commercially," he said. Drugs have to pass three stages of tests in humans before being eligible for approval by regulators in a process that takes many years. Sanofi-Aventis' Acomplia, which it believes can achieve $3 billion in annual sales, is already on sale in Europe and it is waiting for a U.S. regulatory decision in April. Several other big drug companies also already have similar products to Acomplia in clinical trials. GW is best known for developing Sativex, a treatment derived from cannabis that fights spasticity in multiple sclerosis patients. Sativex, an under-the-tongue spray, has been approved in Canada, but has hit delays with regulators in Britain. GW submitted Sativex for assessment by several European regulators in September, and hopes to secure approval for the UK, Denmark, Spain and the Netherlands in the second half of this year at the earliest, the company said on Tuesday. GW's marijuana plants are grown indoors in a secret location in Southern England. ScienceDaily (May 8, 2008) — Anti-obesity drugs that work by blocking brain molecules similar to those in marijuana could also interfere with neural development in young children, according to a new study from MIT's Picower Institute for Learning and Memory. Marijuana is known to be an appetite stimulant, and a new class of anti-obesity drugs--such as rimonabant (trade name Acomplia) developed by Sanofi-Aventis and awaiting approval for use in the United States--work by blocking brain receptors that bind to marijuana and other cannabinoids. Marijuana, derived from the plant Cannabis sativa, contains special active compounds that are referred to collectively as cannabinoids. But other cannabinoids (endocannabinoids) are generated naturally inside the body. The MIT study, which was done in mice, found that blocking cannabinoid receptors could also suppress the adaptive rewiring of the brain necessary for neural development in children. The work is reported in the May 8 issue of Neuron. "Our finding of a profound disruption of cortical plasticity in juvenile mice suggests caution is advised in the use of such compounds in children," wrote lead author Mark F. Bear, director of the Picower Institute and Picower Professor of Neuroscience. The researchers investigated plasticity--the brain's ability to change in response to experience--by temporarily depriving newborn mice of vision in one eye soon after birth. This well-known experiment induces a long-lasting loss of synapses that causes blindness in the covered eye, while synapses shift to the uncovered eye. How and where this synaptic shift occurs in the primary visual cortex has remained controversial. Understanding the mechanism behind this phenomenon is key because the same brain mechanisms are used for normal development and may go awry in conditions that cause developmental delays in humans, and may reappear in old age and contribute to synaptic loss during Alzheimer's disease, Bear said. In mice, the MIT researchers found, even one day of deprivation from one eye starts the shift to dominance of the uncovered eye. But injecting the mice with a cannabinoid receptor blocker halted the shift in certain brain regions, indicating that cannabinoids play a key role in early synaptic development. Blocking cannabinoids receptors could thwart this developmental process, the researchers said. This work is supported by the National Eye Institute and the National Institute of Mental Health. source: http://www.scienceda...80507133326.htm
  11. Hey everyone. I hope for those reading, things in your life are good and you're happy. I don't mean to be a debbie downer but I don't feel I have many people to talk to. My situation really sucks. I was mis-diagnosed many times by doctors. Ended up in the emergency room. Was in bad shape. Things happened so fast, next thing I know I'm laying on a bed being irradiated everyday along with a pump surgically placed in my chest (right next to my heart) which had a chemo bag hooked up to it slowly pumping in poison even while I slept. Now that all that's over and I'm healing up from all the damage they have already done, now they want to cut a bunch of stuff out. Important stuff. I am 30 years old. What's sad is I felt better. But now I can feel it growing back inside me. The throbbing pain is starting to get worse. My insurance is only willing to cover me for conventional treatment. Meaning cutting me all up and more chemo. I can't and won't do that. I have been scrabbling doing research. Really working hard and eating as healthy as possible but I already was like that. I think I was exposed to something while deployed. I was planning on flying out to OR and trying to get my card since OR is the only state that doesn't require you to be a state resident. The only thing is i don't know any one out there. I have money saved up and would be able to fly out there and stay for a month or two. If I end up going to OR and not being able to get my hands on high concentrated medicine and spending what I had for the trip, lodging +medicine cost, not only would it take all my savings, it would take whatever hope I had left and possibly my life. The only hope I have now is finding some way to get this medicine and not ruining my life or dying in the process. But I guess my life is pretty much ruined. I don't have options. No good options at least. I wish we lived in a better world. A world where we weren't being systematically wiped out, just slowly and painfully so "they" can make money off it. I just can't believe something so amazing like cannabis can be illegal while on every corner in America there is a fast food place or quickie mart selling gmo artificial poison legally. That should make everyone want to scream this is not right! A plant that would help me I can't get. And I shouldn't have to be even doing this. We live in the year 2013. I shouldn't nor anyone be in this position. Spending hours online searching and reading. All your research leads you to oil. Even the National Cancer Institute's own research shows nothing but beneficial activity in the cannabinoid system, anti-inflammatory properties, anti-tumor properties and so much more. It truely is an alien plant to me. Nothing else like it anywhere. But it's just not right that because I am from a certain state or country, I can't have access to the medicine I need, medicine that would help. I have to use everything I have to go across the country and it's not even a guarantee I can get it. It's hard to have any hope after getting all this out. I'm afraid it's going to spread...... I'm a good person. I didn't deserve this, and neither does anyone else. Sorry for my vent. I hope I didn't ruin anybody's night. If anyone could help I would forever be in your debt. This just wasn't the plan.. Thanks for reading..
  12. Multiple Sclerosis / Muscle Spasms A.D.A.M. Medical Encyclopedia. Multiple sclerosis MS; Demyelinating diseaseLast reviewed: September 26, 2011. Multiple sclerosis is an autoimmune disease that affects the brain and spinal cord (central nervous system). Causes, incidence, and risk factors Multiple sclerosis (MS) affects women more than men. The disorder is most commonly diagnosed between ages 20 and 40, but can be seen at any age. MS is caused by damage to the myelin sheath, the protective covering that surrounds nerve cells. When this nerve covering is damaged, nerve signals slow down or stop. The nerve damage is caused by inflammation. Inflammation occurs when the body's own immune cells attack the nervous system. This can occur along any area of the brain, optic nerve, and spinal cord. It is unknown what exactly causes this to happen. The most common thought is that a virus or gene defect, or both, are to blame. Environmental factors may play a role. You are slightly more likely to get this condition if you have a family history of MS or live in an part of the world where MS is more common. Symptoms Symptoms vary, because the location and severity of each attack can be different. Episodes can last for days, weeks, or months. These episodes alternate with periods of reduced or no symptoms (remissions). Fever, hot baths, sun exposure, and stress can trigger or worsen attacks. It is common for the disease to return (relapse). However, the disease may continue to get worse without periods of remission. Because nerves in any part of the brain or spinal cord may be damaged, patients with multiple sclerosis can have symptoms in many parts of the body. Muscle symptoms: Loss of balance Muscle spasms Numbness or abnormal sensation in any area Problems moving arms or legs Problems walking Problems with coordination and making small movements Tremor in one or more arms or legs Weakness in one or more arms or legs Bowel and bladder symptoms: Constipation and stool leakage Difficulty beginning to urinate Frequent need to urinate Strong urge to urinate Urine leakage (incontinence) Eye symptoms: Double vision Eye discomfort Uncontrollable rapid eye movements Vision loss (usually affects one eye at a time) Numbness, tingling, or pain Facial pain Painful muscle spasms Tingling, crawling, or burning feeling in the arms and legs Other brain and nerve symptoms: Decreased attention span, poor judgment, and memory loss Difficulty reasoning and solving problems Depression or feelings of sadness Dizziness and balance problems Hearing loss Sexual symptoms: Problems with erections Problems with vaginal lubrication Speech and swallowing symptoms: Slurred or difficult-to-understand speech Trouble chewing and swallowing Fatigue is a common and bothersome symptoms as MS progresses. It is often worse in the late afternoon. Signs and tests Symptoms of MS may mimic those of many other nervous system disorders. The disease is diagnosed by ruling out other conditions. People who have a form of MS called relapsing-remitting may have a history of at least two attacks, separated by a period of reduced or no symptoms. The health care provider may suspect MS if there are decreases in the function of two different parts of the central nervous system (such as abnormal reflexes) at two different times. A neurological exam may show reduced nerve function in one area of the body, or spread over many parts of the body. This may include: Abnormal nerve reflexes Decreased ability to move a part of the body Decreased or abnormal sensation Other loss of nervous system functions An eye examination may show: Abnormal pupil responses Changes in the visual fields or eye movements Decreased visual acuity Problems with the inside parts of the eye Rapid eye movements triggered when the eye moves Tests to diagnose multiple sclerosis include: Lumbar puncture (spinal tap) for cerebrospinal fluid tests, including CSF oligoclonal banding MRI scan of the brain and MRI scan of the spine are important to help diagnose and follow MS Nerve function study (evoked potential test) Is marijuana an effective treatment for spasticity disorders such as multiple sclerosis? Movement Disorders stated in a Sep. 2004 article titled "Survey on Cannabis Use in Parkinson's Disease" by researchers from the Movement Disorders Centreat the Department of Neurology at Charles University, Prague, Czech Republic: "An anonymous questionnaire sent to all patients attending the Prague Movement Disorder Centre revealed that 25% of 339 respondents had taken cannabis and 45.9% of these described some form of benefit.... The late onset of cannabis action is noteworthy. Because most patients reported that improvement occurred approximately two months after the first use of cannabis, it is very unlikely that it could be attributed to a placebo reaction." More Pro's and Cons People with multiple sclerosis and other diseases that cause severe muscle spasms, spasticity and tremors have used cannabis for a very long time, and have consistently reported that it relieves their symptoms. In what is perhaps the earliest medical report on the use of cannabis to treat muscle spasms, Dr. William O’Shaughnessy, a British physician working in India, reported in 1842 that cannabis extracts effectively controlled the spasticity he observed in cases of tetanus, and in 1890 More Cannabis has also been shown to be effective in relieving muscle spasms and spasticity associated with a number of other illnesses such as irritable bowel syndrome, premenstrual dysphoric disorder (PMDD) and PMS, cerebral palsy, Parkinson’s Disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), spinal cord injury and other nerve injuries, and may also relieve the bronchial spasms that cause asthma, though little formal research has been done on cannabis in any of these conditions. Alan Shackelford, M.D., graduated from the University of Heidelberg School of Medicine and trained at major teaching hospitals of Harvard Medical School in internal medicine, nutritional medicine and hyperalimentation and behavioral medicine. He is principle physician for Intermedical Consulting, LLC and Amarimed of Colorado, LLC and can be contacted at Amarimed.com. Article from Culture Magazine and republished with special permission The question of whether marijuana (Cannabis sativa) should be used for symptom management in MS is a complex one. It is generally agreed that better therapies are needed for distressing symptoms — including pain, tremor, and spasticity — that may not be sufficiently relieved by available treatments. Yet there are serious uncertainties about the benefits of marijuana relative to its side effects. The fact that marijuana is an illegal drug in many states and by federal statute (see in the News) further complicates the issue. Some people with MS report that smoking marijuana relieves several of their MS symptoms. However, for any therapy to be recognized as an effective treatment, this kind of subjective, anecdotal reporting needs to be supported by carefully gathered objective evidence of safety and benefit. Unfortunately, it has proven difficult to do carefully controlled clinical trials of marijuana. One reason for this is that marijuana is psychoactive and makes people feel "high." This means that people taking the active drug during a clinical trial usually become aware of it — thus "unblinding" the study and possibly biasing results. Studies completed thus far have not provided convincing evidence that marijuana or its derivatives provide substantiated benefits for symptoms of MS. Conflicting results of previous research, coupled with the need for additional therapies to treat symptoms of MS, make it important that more research be done on the potential of marijuana and its derivatives. The National MS Society is funding a well controlled study on the effectiveness of different forms of marijuana to treat spasticity in MS, and established a task force to examine the use of Cannabis in MS to review what is currently known about its potential. This task force had made specific recommendations on the research that still needs to be done to answer pressing questions about the potential effectiveness and safety of marijuana and its derivatives in treating MS. Download Recommendations Regarding the Use of Cannabis in Multiple Sclerosis (.pdf) Early Studies Showed Mixed Results and Some Side Effects Well known for its mind-altering properties, marijuana is produced from the flowering top of the hemp plant, Cannabis sativa. Early studies explored the role of THC (tetrahydrocannabinol — an active ingredient in marijuana) or smoked marijuana in treating spasticity, tremor, and balance control in small numbers of people with MS. Most of these studies were done with THC. Because THC can be given by mouth, it is easier to control the dose. The results of these studies were mixed, and participants reported a variety of uncomfortable side effects. In addition, smoked marijuana poses health risks that are at least as significant as those associated with tobacco. For spasticity (unusual muscle tension or stiffness) Studies of THC for spasticity have had mixed results. While some people reported feeling "looseness" and less spasticity, this could not always be confirmed by objective testing done by physicians. Even at its best, effects lasted less than three hours. Side effects, especially at higher doses, included weakness, dry mouth, dizziness, mental clouding, short-term memory impairment, space-time distortions and lack of coordination. For tremor (uncontrolled movements) In a small study of THC involving eight seriously disabled individuals with significant tremor and ataxia (lack of muscle coordination), two people reported improvement in tremor that could be confirmed by an examination by a physician and another three reported improvement in tremor that could not be confirmed. All eight patients taking THC experienced a "high," and two reported feelings of discomfort and unease. For balance Smoked marijuana was shown to worsen control of posture and balance in 10 people with MS and 10 who did not have MS. All 20 study participants reported feeling "high." National Academy of Sciences/ Institute of Medicine Report A 1999 report by the National Academy of Sciences/Institute of Medicine on the medical uses of marijuana raised additional questions. While the report concluded that smoked marijuana does not have a role in the treatment of MS, there remained the possibility that specific compounds derived from marijuana might reduce some MS symptoms, particularly MS-related spasticity. Well designed and controlled studies of the therapeutic potential of marijuana compounds (called cannabinoids) were indicated, in conjunction with the development of safe, reliable drug delivery technology. Study on Marijuana Derivatives in Mice Investigators in the United Kingdom and United States tested the ability of two marijuana derivatives and three synthetic cannabinoids to control spasticity and tremor, symptoms of the MS-like disease, EAE, in mice. The results, published in the March 2, 2000 issue of Nature, suggested that four different cannabinoids could temporarily relieve spasticity and/or tremor. While the study suggested that similar derivatives of marijuana might be developed for human use, it was clear that the psychoactive effects of these cannabinoids would need to be reduced sufficiently to make them a safe and comfortable treatment for people with MS. Received 18 August 1999;accepted 20 January 2000 References 1. Baker, D. et al. Induction of chronic relapsing experimental allergic encephalomyelitis in Biozzi mice. J. Neuroimmunol. 28, 261-270 (1990). 2. Consroe, P., Musty, R., Rein, J., Tillery, W. & Pertwee, R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur. Neurol. 38, 44-48 (1997). 3. Consroe, P. Cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol. Dis. 5, 534-551 (1998). Links 4. Petro, D. J. & Ellenberger, C. Treatment of human spasticity with 9- tetrahydrocannabinol. J. Clin. Pharmacol. 21 (suppl.), 413-416 (1981). 5. Clifford, D. B. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann. Neurol. 13, 669-671 (1983). Links 6. Ungerleider, J. T., Andyrsiak, T., Fairbanks, L., Ellison, G. W. & Myers, L. W. 9-THC in the treatment of spasticity associated with multiple sclerosis. Adv. Alcohol Substance Abuse 7, 39-50 (1987). 7. Martyn, C. N., Illis, L. S. & Thom, J. Nabilone in the treatment of multiple sclerosis. Lancet 345, 579 (1995). Links 8. Pertwee, R. G. Pharmacology of cannabinoid receptor ligands. Curr. Med. Chem. 6, 635-664 (1999). Links 9. Lyman, W. D., Sonett, J. R., Brosnan, C. F., Elkin, R. & Bornstein, M. B. 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J. Neuroimmunol. 23, 73-81 (1989). Links 10. Wirguin, I. et al. Suppression of experimental autoimmune encephalomyelitis by cannabinoids. Immunopharmacology 28, 209-214 (1994). Links 11. Heller, A. H. & Hallet, M. Electrophysiological studies with the spastic mutant mouse. Brain Res. 234, 299-308 (1982). Links 12. Chai, C. K. Hereditary spasticity in mice. J. Heredity 52, 241-243 (1961). 13. Pertwee, R. G. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Therapeut. 74, 129-180 (1997). 14.Breivogel, C. S. & Childers, S. R. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol. Dis. 5, 417-431 (1998). Links 15. Landsman, R. S., Burkey, T. H., Consroe, P., Roeske, W. R. & Yamamura, H. I. SR141716A is an inverse agonist at the human cannabinoid CB1 receptor. Eur. J. Pharmacol. 334, R1-R2 (1997). Links 16. Portier, M. et al. SR144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist. J. Pharmacol Exp. Ther. 288, 582-589 (1999). Links 17. Calignano, A., La Rana, G., Giuffrida, A. & Piomelli, D. Control of pain initiation by endogenous cannabinoids. Nature 394, 277-281 (1998). Links 18. Giuffrida, A. et al. Dopamine activation of endogenous cannabinoid signalling in dorsal striatum. Nature Neurosci. 2, 358-363 (1999). Links 19. Huffman, J. W. et al. 3-(1,1-Dimethylbutyl)-1-deoxy-9-THC and related compounds: synthesis of selective ligands for the CB2 receptor. Bioorg. Med. Chem. 7, 2905-2914 (1999). Links 20. Noth, J. Trends in the pathophysiology and pharmacotherapy of spasticity. J. Neurol. 238, 131-139 (1991). Links Acknowledgements. The authors would like to thank the Multiple Sclerosis Society of Great Britain and Northern Ireland, the Medical Research Council, the National Institute on Drug Abuse and the Wellcome Trust for their financial support. Nature © Macmillan Publishers Ltd 2000 Registered No. 785998 England. Smoked Cannabis Reduces Some Symptoms of Multiple Sclerosis Controlled trial shows improved spasticity, reduced pain after smoking medical marijuana A clinical study of 30 adult patients with multiple sclerosis (MS) at the University of California, San Diego School of Medicine has shown that smoked cannabis may be an effective treatment for spasticity – a common and disabling symptom of this neurological disease. The placebo-controlled trial also resulted in reduced perception of pain, although participants also reported short-term, adverse cognitive effects and increased fatigue. The study will be published in the Canadian Medical Association Journal on May 14. Principal investigator Jody Corey-Bloom, MD, PhD, professor of neurosciences and director of the Multiple Sclerosis Center at UC San Diego, and colleagues randomly assigned participants to either the intervention group (which smoked cannabis once daily for three days) or the control group (which smoked identical placebo cigarettes, also once a day for three days). After an 11-day interval, the participants crossed over to the other group. “We found that smoked cannabis was superior to placebo in reducing symptoms and pain in patients with treatment-resistant spasticity, or excessive muscle contractions,” said Corey-Bloom. Earlier reports suggested that the active compounds of medical marijuana were potentially effective in treating neurologic conditions, but most studies focused on orally administered cannabinoids. There were also anecdotal reports of MS patients that endorsed smoking marijuana to relieve symptoms of spasticity. However, this trial used a more objective measurement, a modified Ashworth scale which graded the intensity of muscle tone by measuring such things as resistance in range of motion and rigidity. The secondary outcome, pain, was measured using a visual analogue scale. The researchers also looked at physical performance (using a timed walk) and cognitive function and – at the end of each visit – asked patients to assess their feeling of “highness.” Although generally well tolerated, smoking cannabis did have mild effects on attention and concentration. The researchers noted that larger, long-terms studies are needed to confirm their findings and determine whether lower doses can result in beneficial effects with less cognitive impact. The current study is the fifth clinical test of the possible efficacy of cannabis for clinical use reported by the University of California Center for Medicinal Cannabis Research (CMCR). Four other human studies on control of neuropathic pain also reported positive results. “The study by Corey Bloom and her colleagues adds to a growing body of evidence that cannabis has therapeutic value for selected indications, and may be an adjunct or alternative for patients whose spasticity or pain is not optimally managed,” said Igor Grant, MD, director of the CMCR, which provided funding for the study. Additional contributors include Tanya Wolfson, Anthony Gamst, PhD, Shelia Jin, MD, MPH, Thomas D. Marcotte, PhD, Heather Bentley and Ben Gouaux, all from UC San Diego School of Medicine. Press Release From University Of California, San Diego
  13. PAU D'ARCO TEA - HEALTH BENEFITS The following is a summary of some of the effects of pau d'arco / lapacho and/or any of its constituents that have been validated by modern research: 1. PAU D'ARCO TEA - Laxative effect. Regular use of lapacho will maintain regularity of bowel movements. This property is undoubtedly due to the presence of the napthaquinones and anthraquinones. Users of lapacho universally report a pleasant and moderate loosening of the bowels that leads to greater regularity without any unpleasant side-effects such as diarrhea. 2. PAU D'ARCO TEA - Anti-cancer effect. The greater part of the basic research on lapacho, both in the United States and in other countries has dealt directly with the cancer question. Obviously, this issue is of great importance. The absence of side effects makes lapacho a treatment of choice even in conjunction with standard forms of therapy. The user has nothing to lose and much to gain from the judicious use of Pau d'arco. "I had a large tumor in my brain. Traditional treatment produced only minor success. Then I began to use lapacho tea. After several weeks a CAT scan showed that the tumor was totally gone. The doctors couldn't believe it because they had classified my case as basically untreatable." 3. PAU D'ARCO TEA - Anti-oxidant effect. In vitro trials show definite inhibition of free radicals and inflammatory leukotrienes by lapacho constituents. This property might underlie the effectiveness of lapacho against skin cancer, and definitely helps to explain observed anti-aging effects. Modern science has recently uncovered the importance of free radicals in the generation of many debilitating diseases, from cancer to arthritis. Among the antioxidants few have greater potency than lapacho and other constituents of lapacho. 4. PAU D'ARCO TEA - Analgesic effect. The administration of lapacho is consistently credited in reports issuing from South American clinics as a primary modality for lessening the pain associated with several kinds of cancer, especially cancer of the prostate, liver or breast. Arthritic pain has also been relieved with lapacho ingestion. 5. PAU D'ARCO TEA - Antimicrobial/anti-parisiticidal effects. includes inhibition and destruction of gram positive and acid-fast bacteria (B. subtilis, M. pyogenes aureus, etc.), yeasts, fungi, viruses and several kinds of parasites. Two troublesome families of viruses inhibited by lapachol are noteworthy: Herpes viruses and HIV's. Together, these viruses account for much of the misery of mankind. The anti malarial activity of lapacho spawned a great deal of research interest in the early decades of this century. A 1948 article reviewed the progress and indicated that the N-factors, especially lapachol, were among the most promising anti malarial substances known at that time. Lapacho's immunostimulating action is due in part to its rather potent antimicrobial effects. "I began using pau d'arco tea about 3 mos. ago. I immediately experienced a surge of energy within half-an-hour I was up dancing which is pretty amazing considering I've got MS and spent most of the Spring in a wheelchair. Within 2 days I noticed a lessening of pain and muscle spasms which was fantastic . . . my urinary, bowel and digestive functions have vastly improved . . . There is no doubt that the MS has greatly improved with the herbs as I quit using them for a week and all the old symptoms return. I start the tea again and they subside., I've repeated this scenario three times." 6. PAU D'ARCO TEA - Anti-fungal effect. Lapacho is often singled out as the premier treatment for Candida or yeast infections. Lapachol, N-factors and xyloidone appear to be the primary active principles.9/10 By the mid 70's the list of N-factors that inhibited Candida albicans and other fungi had grown to several dozen. It would be misleading to categorically state that the N-factors in lapacho have proven antimicrobial and anti fungal activity in and of themselves. Studies have shown that the manner in which they occur in the plant must be taken into consideration. We know, for example, that anti fungal activitys lost when the N-factors are tightly bound to highly water-soluble or highly fat-soluble groups. It has not been clearly determined how the N-factors occur in lapacho. N-factors, obtainable from various chemical supply companies, have become favorite testing agents in government/university labs due to the rise in yeast infections resulting from increased use of cytotoxic drugs, corticosteroids, antibiotics and immunosuppressants. An interesting application has been reported in which toe and fingernail fungi infections are relieved by soaking these appendages in lapacho tea off and on for a couple of weeks. 7. PAU D'ARCO TEA - Anti-inflammatory. The anti-inflammatory and healing action of lapacho extracts was demonstrated in a study in which purple lapacho extract was administered to patients with cervicitis and cervico-vaginitis, conditions resulting variously from infections (candida albicans, trichomonas vaginalis), chemical irritations and mechanical irritation. The lapacho extract was applied intra-vaginally via gauze tampons soaked in the extract, and renewed every 24 hours. The treatment proved to be highly effective. One wonders what might happen were the tampon method combined with the ingestion of strong teas. The anti-inflammatory action of lapacho might also account for its observed tendency to reduce the pain, inflammation and other symptoms of arthritis. Anecdotal accounts of complete recovery are even available. As yet virtually untested in research settings, the purported ability of this plant to reduce symptoms of joint disease may be ultimately validated and added to the growing list of benefits to be enjoyed by the daily ingestion of lapacho tea. "I recently had a violent M.S. attack. I lost my balance, lost vision in my left eye and had excruciating pain in my left leg. I went to bed, took the anti-siezure medication and an analgesic. I drank about 1-1/2 quarts of lapacho. Within 6 hours I was up stuffing turkey. Usually these episodes lay me up for weeks. I am convinced the lapacho and mate made the difference." 8. PAU D'ARCO TEA - Other beneficial effects. Routine screenings have revealed several minor properties of lapacho that might occur if needed in certain individuals: diuretic, sedative, decongestant, and hypotensive, to name a few. "I started drinking the red lapacho because I had read a testimonial letter that indicated that its daily use had been effective against the pain of arthritis. I was skeptical to say the least. Prior to drinking the tea I could not stand on a hard surface for more than 5 minutes because the pain was excruciating in my hip . . . Since drinking the red lapacho regularly I have been on my feet for two or three hours without pain. Now the doctor tells me the tissues in my hip are regenerating!" "During exploratory surgery it was noted that I had ovarian, stomach, intestine & liver cancer. I was told I had approximately 4 to 6 months to live. I made up my mind to fight. I went for chemotherapy, drank a quart of red lapacho tea, an ounce of aloe vera juice and took various vitamins daily. After 11 mos. the physicians could not believe what they found (no cancer). I continue to have regular check-ups and have proved to be a 'miracle case'." A Note on Nausea: In the human study reported above, some patients dropped out of the experiment due to nausea. This is a common observation in some, but certainly not all, people who begin to experience the cleansing action of lapacho (and other healthful herbs). As toxins (and toxic medicines) and wastes are drawn out of the cells, or flushed out, or physiologically expelled from the cells, through the action of the herb, they tend at times to accumulate in the blood, lymph, lymph nodes, skin, liver and kidneys awaiting the opportunity to be expelled from the body. Backing up, they can, on occasion produce sensations such as nausea; the body may even try to rid itself of some toxic substances by vomiting. Not to worry. These transient signs dissipate once the toxins are moving freely from the body. They are a positive sign that the herb is working. Remember the body only has three basic processes for getting rid of wastes: lower bowel movement, sweating, urinating. The use of lapacho can so overload these processes in the early stages that discomfort may be produced. "My wife was dying of cancer. She has a malignant tumor on her temple. The pain was so intense the doctors wanted to keep her sedated in the hospital until she died. We decided not to give up. For three weeks now she has been drinking purple lapacho tea. The tumor looks much better; it began draining and no longer looks so 'angry.' The pain is much less, and she can get up and move around the house. Our M.D. is impressed! . . . Now we have hope!" TOXICITY While there can be no doubt that lapacho is very toxic to many kinds of cancer cells, viruses, bacteria, fungi, parasites and other kinds of microorganisms, the substance appears to be without any kind of significant toxicity to healthy human cells. The side-effects mainly encountered, and usually with isolated lapacho constituents, are limited to nausea and anticoagulant effects in very high doses, a tendency to loosen the bowels, and diarrhea in very high doses. As indicated earlier, some nausea should be expected as a natural consequence of the detoxification process. The FDA gave lapacho a clean bill of health in 1981. Some trials have indicated that lapachol has anti-vitamin K action. Other constituents have a pro-vitamain K action; it is likely, therefore, that the two actions cancel each other out (except possibly when one or the other is necessary--as one would expect from an herbal tonic). Perhaps the most significant study on toxicity was published in 1970 by researchers from the Chase Pfizer & Co., Inc. Looking specifically at lapachol, these investigators found that all signs of lapachol toxicity in animals were completely reversible and even self limiting, i.e., over time the signs of toxicity decreased and even disappeared within the time constraints of the study. The most severe kinds of self-limiting side-effects they observed were an anti-vitamin K effect, anemia, and significant rises of metabolic and protein toxins in the blood stream. The diminution of these signs indicates that lapacho initiates an immediate "alterative" or "detoxification" effect on the body's cells. Once the cells are "cleaned up," the signs of toxicity disappear. This effect is quite common among herbal tonics. Clinical studies showed that Pau D'Arco has no contraindications, no incompatabilities, and has been proven to be non-toxic. However, the most innocuous of agents, even oxygen, could finally become toxic if taken in too large enough amounts. A little common sense goes a long way!
  14. Where is she? Where's Mykayla? There she is! rolling in the green grass, giggling away, up and running, she's off to adventure... twinkling sapphire eyes, hazel toned mahogany hair, and a leopards pelt worth of creamy umber freckles... that's our baby girl right there... full of life, independent, determined, stubborn, curious, imaginative, spirited, enthusiastic, intelligent, artistic, an amazing big sister and so full of life that she is always bubbling over with happiness... our daughter has this flair about her, she lives life to the fullest. She is so special to us; she is her sister Ryleigh's special best friend in life... One day she woke up tired... she didn't feel like playing much. She was just a little tired. We noticed she was coughing a little bit... so we let her sit around and watch movies for the day. She wasn't too hungry, she just wanted to snack. We thought she had a bug, so off to urgent care we went. Strep throat was what we were told it was. Awesome strep is not that bad, antibiotics and rest, maybe some salt water gargle here or there, standard treatment for strep... Two weeks or so pass, she still has this lingering cough... it sounds very much like an allergic cough, and given the season it fit. Well that cough and the random sneezes. Then the stomach aches. Daddy, mommy, I hurt, it’s my belly. Strange. So we called a pediatrician and set up an appointment. After a few selective questions and a relatively quick appointment we were hustled out the door with the advice to discontinue milk and dairy in her diet. OK doc, you bet. Sorry Sweetheart no more cheese, butter, milk, mac and cheese, yogurt, you know the drill... buy the almond milk and alternative cheeses, replacement comfort foods and put your foot down when she gets to missing all the old foods. such a struggle to eat. Two weeks go by, the cough is still there, even more apparent however. louder, more forceful, and a raspy. The dietary changes led to no more bed wetting but the stomach pains did not subside. Now they were constant. Added to that were the complaints of back and joint pain. She was tired all the time. We noticed she was short of breathe... what is going on? She hasn't ever had allergies before. She is our healthy daughter. Time to go to the doctor again. What was he thinking? Lactose intolerance? Then came the night sweats and the labored breathing. Every night became a decision to go to the ER or not. Finally the appointment. The doctor listened, he ran some tests. A lot of people came to see the results... who are all these people? Why are they looking at us this way? We found a large mass. Then came the Whirlwind... extra tests, children's hospital called, sent home, pack pack pack, time to go to Portland... drive drive drive, check in, go over the stories time and time again, what has Mykayla been like? Any exposures? Poke prod, touch, listen, question, wonder, be scared... wait stop! What is going on? Acute Lymphoblastic Leukemia... A cancer of the blood and bone-marrow. A tumor literally the size of a basketball in her chest. Not Strep, not lactose intolerance, not allergies nor a cold... cancer. For some reason this little angel's life path has brought a journey of this magnitude into her life. It is terrifying. It is strengthening, it is sad... we have heavy hearts and melancholy minds...no parent should have to watch their child go through this. Children are innocent. They are not deserving of a disease such as this... Mykayla has a treatment plan in place for chemotherapy. She is receiving a multitude of chemotherapy drugs both intravenously and through intramuscular injections. She has to undergo treatment for the next three years. Until she is 10. she will lose her hair, feel nausea, pain and depression. She wont feel like a child. She wont feel like herself. but it always gets worse before it gets better. She will have to pull from the deepest within herself to fight this off. She will have to be determined, resilient, strong and unyielding... good thing our little girl is all of these things. B. This was written before Cannabis Therapy... A little prologue to Brave Mykayla. The picture is one of Mykayla before diagnosis...
  15. Lymphoblasts are immature cells which typically differentiate to form mature lymphocytes. Normally lymphoblasts are found in the bone marrow only, but in acute lymphoblastic leukemia (ALL), lymphoblasts proliferate uncontrollably and are found in large numbers in the peripheral blood smear. July 14th 2012 (diagnosis day and steroid treatment began) Mykayla’s Lymphoblast percentage in her blood smear was 33% July 15th 2012 - 51% Lymphoblasts in Mykayla’s blood smear July 16th 2012 – 11% Lymphoblasts in Mykayla’s blood smear (began chemotherapy) July 17th 2012 – 14% Lymphoblasts in Mykayla’s blood smear July 18th 2012 – 16% Lymphoblasts in Mykayla’s blood smear July 19th 2012 – 3% Lymphoblasts in Mykayla’s blood smear July 20th 2012 – 29% Lymphoblasts in Mykayla’s blood smear (got released from hospital) July 23rd 2012 – 31% Lymphoblasts in Mykayla’s blood smear July 24th 2012 – BEGAN CANNABIS OIL (RICK SIMPSON OIL, WHOLE EXTRACT CANNABIS OIL) July 26th 2012 – 5% Lymphoblasts in Mykayla’s blood smear July 30th 2012 – 3% Lymphoblasts in Mykayla’s blood (doctor spoke to us about Mykayla’s Lymphoblast count failing to go down to 0 and said that a Bone Marrow Transplant MAY BE in our near future because her blasts are not gone from her blood. August 2nd 2012 – 0% blasts August 6th 2012 – 0% blasts August 13th 2012 – 0% blasts August 20th 2012 – 0% blasts TODAY – 0% blasts! July 30th 2012 was THE VERY LAST TIME THEY HAVE FOUND LYMPHOBLASTS IN MYKAYLA’S BLOOD SMEAR!!!! The very next time we saw the oncologist they told us Mykayla was in remission. Some may say that cannabis does not “cure” cancer… I am not saying the steroids and chemo didn’t help… but this right here shows something… proof enough for me! Some say cannabis is inappropriate for children… We Say cancer is inappropriate for children. <3 PeaceloveCURE
  16. Humble fly key in fight against cancer and motor neuron disease Fruit fly: Scientists in Edinburgh study the flies to try and understand more about humans.The Obbard Lab/University of Edinburgh Without making firm predictions, Professor Finnegan believes the continued work of scientists on the fruit fly in Edinburgh and beyond could help - one day - find a treatment for MND or some cancers. He added: “No disease has been cured because of studies of drosophila, but we are getting a better understanding of the biology behind quite a number of diseases like cancer. “We believe eventually, maybe in five or ten years, we will be able to predict something that will intervene and stop disease. “Drosophila can be used as an organism to investigate potential drugs. In general, it [the fruit fly] has been hugely important. Drosophila is the most important experimental animal, and has had the most influence. “In most cases, the use of drosophila is leading to a greater understanding on what goes wrong - motor neuron disease, for example. “We all believe that if we understand what goes wrong, we have a fighting chance of addressing it. “I think it is quite reasonable to suppose that research involving drosophila will identify targets for drugs that can be used to treat some forms of cancer.” Research progress Giusy Pennetta, a 45-year-old lecturer in neuroscience at the university, also believes the fruit fly will help play a key role in the search for a cure of conditions like MND. She works in the Euan MacDonald Centre for Motor Neurone Disease Research. The scientist said: “Our final goal is to understand the complex molecular network controlling the function of the neurons that die in the patient. “We will be able to decide a therapy that will be efficient. When we know exactly what is going on, we can develop a therapy to cure the disease.” At the moment, Ms Pennetta and her team are collaborating with Imperial College London to look at human patients and identify if what they have found in flies also happens with a human patient. She added: “We have progressed enormously. In just more than ten years, we have learned quite a lot and there is still a lot to learn.” In the past few years, the University of Edinburgh has used research into fruit flies in a wide variety of fields. Last November, scientists identified a gene which they claim could help solve the problem of infertility in humans. Work into the sexual reproduction of species which mate with a partner, instead of reproducing asexually, and studies into protecting against diseases like SARS are amongst other recent research. Professor Margarete Heck is another scientist at the University of Edinburgh who uses fruit flies. The 53-year-old professor of Cell Biology and Genetics uses the insect to determine how chromosomes - groups of DNA - are formed. “It is a very cheap system and easy to grow,” she said. “The genes that we have are conserved in the fly so we can very readily, once we identify a gene in the fly, find out about how human cells work. “I think Edinburgh plays a very significant role in this particular field. We have research groups looking at drosophila studying many problems - diseases, the nervous system and how cells move around.” Professor Heck is just one example of how University of Edinburgh scientists are at the frontline of fruit flies research. She is currently working on a project which could lead to a treatment for Type 2 Diabetes. One day, these scientists on own doorstep may discover the key to treating some of the conditions which affect millions of people across the globe. For now though, it is back to the lab with the fruit flies. source
  17. Killing bacteria with cannabis Pharmacists and chemists have found another use for the multipurpose cannabis as a source of antibacterial chemicals for multidrug resistant bacteria. Ironically, inhaling cannabis is known to damage the lung's ability to fend off invading pathogens, but the ingredients in cannabis, particularly the cannabinoids, have antiseptic properties. Although scattered research has been conducted since the 1950s, no comprehensive study existed that relates the structure of cannabinoids with antibacterial activity. Giovanni Appendino, Simon Gibbons, and coworkers attempted to remedy that problem by examining the activity of five common cannabinoids and their synthetic derivatives. Five of the most common cannabinoids. All five cannabinoids (THC, CBD, CBG, CBC, and CBN) were potent against bacteria. Notably, they performed well against bacteria that were known to be multidrug resistant, like the strains of MRSA that plagued U.K. hospitals. CBD and CBG have the most potential for consumer use because they are nonpsychotropic. Besides identifying antibacterial capability, the researchers wanted to figure out why these cannabinoids are so good at killing bacteria. They obviously are very effective at specifically targeting some vital process in the bacteria. Unfortunately, even after extensive work at modifying the cannabinoids and comparing their activities, that targeting mechanism remains a mystery. The scientists were able to figure out that the position of the n-pentyl chain (orange) relative to the terpenoid moiety (blue) serves to control lipid affinity. These cannabinoids are promising enough to warrant rigorous clinical trials. They are applicable as topical antiseptics, biodegradable antibacterial compounds for cosmetics, and systematic antibacterial agents. J. Nat. Prod., 2008. DOI: 10.1021/np8002673 Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated. All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Δ9-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance. Activity was remarkably tolerant to the nature of the prenyl moiety, to its relative position compared to the n-pentyl moiety (abnormal cannabinoids), and to carboxylation of the resorcinyl moiety (pre-cannabinoids). Conversely, methylation and acetylation of the phenolic hydroxyls, esterification of the carboxylic group of pre-cannabinoids, and introduction of a second prenyl moiety were all detrimental for antibacterial activity. Taken together, these observations suggest that the prenyl moiety of cannabinoids serves mainly as a modulator of lipid affinity for the olivetol core, a per se poorly active antibacterial pharmacophore, while their high potency definitely suggests a specific, but yet elusive, mechanism of activity. Several studies have associated the abuse of marijuana (Cannabis sativa L. Cannabinaceae) with an increase in opportunistic infections,(1) and inhalation of marijuana has indeed been shown to interfere with the production of nitric oxide from pulmonary macrophages, impairing the respiratory defense mechanisms against pathogens and causing immunosuppression.(2) The association of C. sativa with a decreased protection against bacterial infections is paradoxical, since this plant has long been known to contain powerful antibacterial agents.(3) Thus, preparations from C. sativa were investigated extensively in the 1950s as highly active topical antiseptic agents for the oral cavity and the skin and as antitubercular agents.(3) Unfortunately, most of these investigations were done at a time when the phytochemistry of Cannabis was still in its infancy, and the remarkable antibacterial profile of the plant could not be related to any single, structurally defined and specific constituent. Evidence that pre-cannabidiol (1a) is a powerful plant antibiotic was, nevertheless, obtained,(4) and more recent investigations have demonstrated, to various degrees, antibacterial activity for the nonpsychotropic cannabinoids cannabichromene (CBC, 2),(5) cannabigerol (CBG, 3b),(6) and cannabidiol (1b),(7) as well as for the psychotropic agent Δ9-tetrahydrocannabinol (THC, 4b).(7) These observations, and the inactivity of several noncannabinoid constituents of C. sativa as antibacterial agents, suggest that cannabinoids and their precursors are the most likely antibacterial agents present in C. sativa preparations.(8) However, differences in bacterial strains and end-points make it difficult to compare the data reported in these scattered studies, and the overall value of C. sativa as an antibacterial agent is therefore not easy to assess. There are currently considerable challenges with the treatment of infections caused by strains of clinically relevant bacteria that show multidrug-resistance (MDR), such as methicillin-resistant Staphylococcus aureus (MRSA) and the recently emerged and extremely drug-resistant Mycobacterium tuberculosis XDR-TB. New antibacterials are therefore urgently needed, but only one new class of antibacterial has been introduced in the last 30 years.(9) Despite the excellent antibacterial activity of many plant secondary metabolites(10) and the ability of some of them to modify the resistance associated with MDR strains(11) and efflux pumps,(12) plants are still a substantially untapped source of antimicrobial agents. These considerations, as well as the observation that cross-resistance to microbial and plant antibacterial agents is rare,(10) make C. sativa a potential source of compounds to address antibiotic resistance, one of the most urgent issues in antimicrobial therapy. To obtain structure−activity data and define a possible microbiocidal cannabinoid pharmacophore, we investigated the antibacterial profile of the five major cannabinoids, of their alkylation and acylation products, and of a selection of their carboxylic precursors (pre-cannabinoids) and synthetic positional isomers (abnormal cannabinoids). Results and Discussion The antibacterial cannabinoid chemotype is poorly defined, as is the molecular mechanism of its activity. Since many simple phenols show antimicrobial properties, it does not seem unreasonable to assume that the resorcinol moiety of cannabinoids serves as the antibacterial pharmacophore, with the alkyl, terpenoid, and carboxylic appendices modulating its activity. To gain insight into the microbiocidal cannabinoid pharmacophore, we have investigated how the nature of the terpenoid moiety, its relative position compared to the n-pentyl group, and the effect of carboxylation of the resorcinyl moiety are translated biologically, assaying the major cannabinoids and a selection of their precursors and regioisomeric analogues against drug-resistant bacteria of clinical relevance. Within these, we have selected a panel of clinically relevant Staphylococcus aureus strains that includes the (in)famous EMRSA-15, one of the main epidemic methicillin-resistant strains,(13) and SA-1199B, a multidrug-resistant strain that overexpresses the NorA efflux mechanism, the best characterized antibiotic efflux pump in this species.(14) SA-1199B also possesses a gyrase mutation that, in addition to NorA, confers a high level of resistance to certain fluoroquinolones. A macrolide-resistant strain (RN4220),(15) a tetracycline-resistant line overexpressing the TetK efflux pump (XU212),(16) and a standard laboratory strain (ATCC25923) completed the bacterial panel. Δ9-Tetrahydrocannabinol (THC, 4b), cannabidiol (CBD, 1b), cannabigerol (CBG, 3b), cannabichromene (CBC, 2), and cannabinol (CBN, 5) are the five most common cannabinoids.(17) They could be obtained in high purity (>98%) by isolation from strains of C. sativa producing a single major cannabinoid (THC, CBD, CBG), by total synthesis (CBC),(6) or by semisynthesis (CBN).(18) Their antimicrobial properties are listed in Table 1. All compounds showed potent antibacterial activity, with MIC values in the 0.5−2 μg/mL range. Activity was exceptional against some of these strains, in particular the multidrug-resistant (MDR) SA-1199B, which has a high level of resistance to certain fluoroquinolones. Also noteworthy is the potent activity demonstrated against EMRSA-15 and EMRSA-16, the major epidemic methicillin-resistant S. aureus strains occurring in U.K. hospitals.(13, 19) These activities compare highly favorably with the standard antibiotics for these strains. The potent activity against strains possessing the NorA and TetK efflux transporters suggests that cannabinoids are not substrates for the most common resistance mechanisms to current antibacterial agents, making them attractive antibacterial leads. Table 1. MIC (μg/mL) Values of Cannabinoids and Their Analogues toward Various Drug-Resistant Strains of Staphylococcus aureusab compoundSA-1199BRN-4220XU212ATCC25923EMRSA-15EMRSA-161a2222221b1110.51122212223a4244243b1111213f64c64ccc4a8484844b211120.5511111c61111117210.512c8323216161632106464641286464norfloxacin321410.5128erythromycin0.2564>1280.25>128>128tetracycline0.250.251280.250.1250.125oxacillin0.250.251280.12532>128 a Compounds 1c−g, 3c−e, 3g, and 9 exhibited MIC values of >128 μg/mL for all organisms in which they were evaluated. b Compound 11 exhibited MIC values of >256 μg/mL for all organisms in which they were evaluated. c Not tested. Given their nonpsychotropic profiles, CBD (1b) and CBG (3b) seemed especially promising, and were selected for further structure−activity studies. Thus, acetylation and methylation of their phenolic hydroxyls (compounds 1c−e and 3c−e, respectively) were both detrimental for activity (MIC >100 μg/mL), in accordance with the essential role of the phenolic hydroxyls in the antibacterial properties. However, in light of the potent activity of the monophenols CBC (2), THC (4b), and CBN (5), it was surprising that monomethylation of the diphenols CBD (1b) and CBG (3b) was so poorly tolerated in terms of antibacterial activity. Cannabinoids are the products of thermal degradation of their corresponding carboxylic acids (pre-cannabinoids).(17) Investigation of the antibacterial profile of the carboxylated versions of CBD, CBG, and THC (compounds 1a, 3a, and 4a, respectively) showed a substantial maintenance of activity. On the other hand, methylation of the carboxylic group (compounds 1f and 3f, respectively) caused a marked decrease of potency, as did esterification with phenethyl alcohol (compounds 1g and 3g, respectively). This operation is associated with a potentiation of the antibacterial properties of phenolic acids, as exemplified by phenethyl caffeate (CAPE), the major antibacterial from propolis, compared to caffeic acid.(20) Remarkably, the synthetic abnormal cannabinoids abn-CBD (6)(21) and abn-CBG (7)(22) showed antibacterial activity comparable to, although slightly less potent than, their corresponding natural products, while olivetol (10) showed modest activity against all six strains, with MICs of 64−128 μg/mL, and resorcinol (11) did not exhibit any activity even at 256 μg/mL. Thus, the pentyl chain and the monoterpene moiety greatly enhance the activity of resorcinol. Taken together, these observations show that the cannabinoid antibacterial chemotype is remarkably tolerant to structural modification of the terpenoid moiety and its positional relationship with the n-pentyl chain, suggesting that these residues serve mainly as modulators of lipid affinity, and therefore cellular bioavailability. This view was substantiated by the marked decrease of activity observed when the antibacterial activity of CBG (3b) was compared to that of its polar analogue carmagerol (8).(23) The results against the resistant strains confirm this suggestion, and it is likely that the increased hydrophilicity caused by the addition of two hydroxyls greatly reduces the cellular bioavailability by substantially reducing membrane permeability. Conversely, the addition of a further prenyl moiety, as in the bis-prenylated cannabinoid 9,(21) while increasing membrane solubility, may result in poorer aqueous solubility and therefore a lower intracellular concentration, similarly leading to a substantial loss of activity. A single unfunctionalized terpenyl moiety seems therefore ideal in terms of lipophilicity balance for the antibacterial activity of olivetol derivatives. The great potency of cannabinoids suggests a specific interaction with a bacterial target, whose identity is, however, still elusive. This article references 30 other publications. 1. Caiffa, W. T., Vlahov, D., Graham, N. M. H., Astemborski, J., Solomon, L., Nelson, K. E., and Munoz, A. Am. J. Resp. Crit. Care Med. 1994 150 1593 1598 2. Roth, M. D., Whittaker, K., Salehi, K., Tashkin, D. P., and Baldwin, G. C. J. Neuroimmunol. 2004 147 82 86[CrossRef], [PubMed], [CAS] 3. (a) Krjci, Z. Lekarske Listy 1952 7 500 503 ; Chem. 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  18. Ya gotta read this, it's unbelievable! http://tokesignals.com/worth-repeating-its-official-cannabinoids-kill-all-types-of-cancer-2/
  19. AMYOTROPHIC LATERAL SCLEROSIS Edit by Author, 1/15/2013 Some of the source links below are now dead. I was only allowed to take one third of the original content. And leave links. I give you permission to use one third also. Or search out the videos first and and take them from there. http://www.youtube.com/watch?v=Dp4q8YNF9o4 What Types of Nerves Make Your Body Work Properly? (from Living with ALS, Manual 1: What's It All About?) The body has many kinds of nerves. There are those involved in the process of thinking, memory, and of detecting sensations (such as hot/cold, sharp/dull), and others for vision, hearing, and other bodily functions. The nerves that are affected when you have ALS are the motor neurons that provide voluntary movements and muscle power. Examples of voluntary movements are your making the effort to reach for the phone or step off a curb; these actions are controlled by the muscles in the arms and legs. The heart and the digestive system are also made of muscle but a different kind, and their movements are not under voluntary control. When your heart beats or a meal is digested, it all happens automatically. Therefore, the heart and digestive system are not involved in ALS. Breathing also may seem to be involuntary. Remember, though, while you cannot stop your heart, you can hold your breath - so be aware that ALS may eventually have an impact on breathing. Although the cause of ALS is not completely understood, the recent years have brought a wealth of new scientific understanding regarding the physiology of this disease. Source Marijuana's Potential Exciting Researchers in Treatment of ALS, Parkinson's Disease A Legal Mood Lifter: Researchers are investigating a new antidepressant and pain reliever that works like cannabis (marijuana), without the illegal side effects. A decade ago, when Daniele Piomelli went to scientific conferences, he was often the only researcher studying cannabinoids, the class of chemicals that give marijuana users a high. His work often drew snickers and jokes, but no more. At the annual Society for Neuroscience conference recently, scientists here delivered almost 200 papers on the subject. Why the attention? Many scientists believe cannabis-like drugs might be able to treat a wide range of diseases, far beyond the nausea and chronic pain typically treated with medical cannabis. Researchers here presented tantalizing evidence that cannabinoid drugs can help treat amyotrophic lateral sclerosis, known as ALS or Lou Gehrig's disease, Parkinson's disease and obesity. Other researchers are studying whether the compounds can help victims of stroke and multiple sclerosis. Although the chemicals work on the same area of the nervous system, the new drugs are much more refined and targeted than cannabis, with few of its side effects. "Cannabinoids have a lot of pharmaceutical potential," said Piomelli, a neuroscientist at the University of California at Irvine. "A lot of people are very excited" Although the federal government opposes the use of medical marijuana, it generally doesn't restrict cannabinoid research, most of which doesn't involve the cannabis plant itself. Scientists who use Marinol, a legal but tightly regulated marijuana-like drug, do need government permission. Because the cannabinoid system wasn't discovered until the late 1980s, decades after serotonin, dopamine and other neurotransmitters, researchers still know relatively little about how it works. Like all neurotransmitter networks, the cannabinoid system consists of a series of chemical pathways through the brain and nervous system. Cannabis produces its effects by activating this pathway, primarily through the effects of tetrahydrocannabinol, or THC, the drug's main active ingredient. Over the past decade, researchers have been following these abundant trails to determine their real purpose. "You don't have them there to get stoned. So, there must be internal reasons," said Andrea Giuffrida, a neuroscientist at the University of Texas Health Sciences Center in San Antonio. Researchers have learned that endogenous cannabinoids, internal brain chemicals that activate the system, play a role in tissue protection, immunity and inflammation, among other functions. The cannabinoid system also appears to exert wide influence, modulating the release of dopamine, serotonin and other neurotransmitters. Giuffrida and others believe cannabinoids can treat degenerative disorders such as Parkinson's disease and ALS. At the conference, Giuffrida announced that a cannabinoid drug wards off Parkinson's-like effects in mice. The disorder, which afflicts more than 1 million Americans, destroys neurons in a key part of the brain, causing patients to lose control over movement. Giuffrida, with colleagues David Price and James Roberts, injected mice with a chemical called MPTP, which mimics Parkinson's damage. When some of the animals subsequently received a drug that blocks cannabinoid receptors, their nerve cells suffered far less damage than did the cells of the other mice. This was the first demonstration that a cannabinoid drug can have this effect. Although he is not sure how the anti-cannabinoid compound works, Giuffrida suspects it protects neurons by reducing inflammation, a key component in Parkinson's. Cannabinoids might also slow down ALS, which destroys neurons that control muscles until victims become paralyzed, unable to breathe on their own. Neuroscientist Mary Abood first became interested in cannabinoids after hearing about ALS patients who got some relief from smoking cannabis. So she began animal experiments at the California Pacific Medical Center in San Francisco. In her study, mice with a variant of ALS were given a combination of THC and cannabidiol, another compound found in cannabis. Both substances are cannabinoid agonists, chemicals that activate the cannabinoid system. Abood measured the course of the ailment by testing how long the mice could stand on a rod that was slowly rotating. The treatment delayed disease progression by more than seven days and extended survival by six days. In human terms, this would amount to about three years. That's a significant improvement over the only existing ALS drug, riluzole, which extends life by two months. "I was very excited when I got my initial results," Abood said. Also at the conference, researchers at the Institute of Neurology in London announced results that corroborated her findings. Cannabinoids have also helped some human ALS patients in one small trial, and Abood is trying to get funding for a larger one. If cannabinoids can shield human neurons from harm, researchers say, they might prove useful against other neurological diseases, including mental illness. Scientists are looking at whether cannabinoids can treat multiple sclerosis, epilepsy and Huntington's disease, while Giuffrida is beginning a study of their effect on schizophrenia. Advocates of medical cannabis have long argued that the drug can be useful for treating many conditions, particularly chronic pain, nausea and glaucoma (in the latter, cannabis works by temporarily decreasing pressure around the eye). Although they don't dispute this view, most researchers believe there are better, more precise ways to stimulate the cannabinoid system. They believe cannabis has too many negatives to be a truly effective drug, with side effects that include memory problems, decreased immunity and possibly addiction. (Some researchers dispute this "addictive" claim.) Cannabis has another drawback. From a scientific standpoint, Giuffrida says, it's "a very dirty drug." It contains more than 300 compounds, 60 of which affect the cannabinoid system. Scientists don't understand what most of these substances do or how they work together. This complexity makes it hard for researchers to pinpoint cannabis' effects. One cannabinoid, Marinol, is available legally. The compound, which contains THC in a pill form, is usually prescribed for nausea and for appetite loss among AIDS patients. But Marinol has the same psychoactive effects as cannabis. "So the key", Piomelli says, "is getting the effects without the side effects." To that end, Piomelli has developed a compound called URB597, which doesn't flood the body with cannabinoids, as Marinol and cannabis do. Instead, it slows the breakdown of the cannabinoids in the system. He thinks the drug may help treat pain, anxiety and even depression without making patients stoned and forgetful. He and others are testing it on animals. SOURCE http://www.illinoisn...ent/view/600/1/ http://www.youtube.com/watch?v=-qFSMXEYC3c Survey of Cannabis Use in Patients with Amyotrophic Lateral Sclerosis Dagmar Amtmann, PhD Patrick Weydt, Md Kurt L. Johnson, PhD Mark P. Jensen, PhD Gregory T. Carter, M.D. Abstract Cannabis (marijuana) has been proposed as treatment for a widening spectrum of medical condtions and has many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). This study is the first, anonymous survey of persons with ALS regarding the use of cannabis. There were 131 respondents, 13 of whom reported using cannabis in the last 12 months. Although the small number of people with ALS that reported using cannabis limits the interpretation of the survey findings, the results indicate that cannabis may be moderately effective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling. Cannabis was reported ineffective in reducing difficulties with speech and swallowing, and sexual dysfuction. The longest relief was reported for depression (approximately two to three hours). Key words: pain, palliative care, cannabis, medicinal marijuana, amyotrophic lateral sclerosis. Introduction Amyotrophic lateral sclerosis (ALS), with an incident rate of five to seven per 100,000 population, is the most common form of adult motor neuron disease.1-3 ALS is a rapidly progerssive neuromuscular disease that destroys both upper and lower motor neurons, ultimately causing death, typically from respiratory failure. The vast majority of ALS is acquired and occurs sporadically. There is not yet a known cure for ALS. 4-6 ALS patients may present with any number of clinical symptoms, including weakness, spasticity, cachexia, dysarthria and drooling, and pain secondary to immobility, among others.7-8 Previous studies have reported both direct and theoretical applications for using cannabis to manage some of these ALS symptoms.9-11 Cannabis has easily observable clinical effects with rapid onset (e.g., analgesia, muscle relaxation, dry mouth). Moreover, some components of marijuana (not inhaled smoke) have been shown in laboratory studiues to have neuroprotective properties that may help prolong neuronal cell survival over extended time.12-16 Marijuana is a complex plant, containing over 400 chemicals.17 Approximately 60 are cannabinoids, chemically classified as 21 carbon terpenes.17,18 Among the most psychoactive of these is delta-9-tetrahydrocannabinol (THC).17,18 Because of this biochemical complexity, characterizing the clinical pharmacology of marijuana is difficult. The clinical pharmacology of marijuana containing high concentrations of THC may well differ from plant material containing small amounts of THC and higher amounts of the other cannabinoids. The bioavailability and pharmacokinetics of inhaled marijuana are also substantially different from those taken by ingestion. The cannabinoids are all lipid soluble compounds and are not soluble in water.19 Besides THC, which is the active ingredient in dronabinol, varying proportions of other cannabinoids, mainly cannabidiol (CBD) and cannabinol (CBN), are also present in marijuana and may modify the pharmacology of the THC as well as have distinct effects of their own. CBD is not psychoactive but has significant anticonvulsant and sedative pharmacologic properties and may interact with THC.20-21 The concentration of THC and other cannabinoids in marijuana varies greatly depending on growing conditions, plant genetics, and processing after harvest.21 In the usual mixture of leaves and stems distributed as marijuana, concentration of THC ranges from 0.3 percent to 4 percent by weight.21,22 However, specially grown and selected marijuana can contain 15 percent or more THC. Thus, one gram of marijuana might contain as little as three milligrams of THC or more than 150 mg.21 THC is a potent psychoactive drug, and large doses may produce mental and perceptual effects similar to hallucinogenic drugs.23,24 Despite this, THC and other cannabinoids have low toxicity, and lethal doses in humans have not been described.25,26 Despite risk for bronchitis, the main advantage of smoking is rapid onset of effect and easy dose titration. When marijuana is smoked, cannabinoids in the form of an aerosol in the inhaled smoke are rapidly absorbed and delivered to the brain, as would be expected of a highly lipid-soluble drug.27,28 However, smoking anything, including marijuana, carries health risks for the lungs and airway system. A healthier option is vaporization. Because the cannabinoids are volatile, they will vaproize at a temperature much lower than actual combustion.24 Heated air can be drawn through marijuana and the active compounds will vaporize, which can then be inhaled. This delivers the substance in a rapid manner that can be easily titrated to desired effect.29 Vaporization therefore removes most of the health hazards of smoking.27 The medicinal use of cannabis is better documented in multiple sclerosis (MS) than in other clinical conditions, although evidence tends to be anecdotal, and no controlled clinical trials of medicinal marujuana use in MS have been published.30-39 With respect to pain, the concominant use of cannabis with narcotics may be beneficial, because the cannabinoid receptor system appears to be discrete from that of opioids.40-45 In that regard, the antiemetic effect of cannabis may also help with the nausea sometimes associated with narcotic medications. Untoward effects of cannabis include potentially significant psychoactive properties, which may produce a sense of well-being or euphoria but can also induce anxiety, confusion, paranoia, and lethargy.46 To date there have not yet been any empirical studies to investigate the use of cannabis for medicinal purposes in ALS. The purpose of this survey was to gather preliminary data on the extent of use of cannabis among persons with ALS (PALS) and to learn which of the symptoms experienced by PALS are reported to be alleviated by the use of cannabis. Metohdology Participants in this survey were recruited from the ALS Digest (the Digest), an electronic discussion list published weekly to serve the worldwide ALS community, including patients, families, caregivers, and providers. The Digest serves as a forum for discussion of issues related to ALS and is not intended to provide medical advice on individual health matters. The Digest can be viewed at www.alslinks.com. Currently there are over 5,600 subscribers in 80 countries worldwide. However, the number of subscribers with ALS is not known. The editor is not a physician and the Digest is not peer reviewed. An e-mail invitation to participate was posted to the Digest four times over two months. The survey was available online from January 6 through March 2, 2003, approximately eight consecutive weeks. Any subscriber with ALS was invited to participate on a voluntary and anonymous basis. The sponsoring institution human subjects review board approved the study protocol. A Web-based survey tool developed by the University of Washignton was used to collect responses. The tool uses SSL encryption for transferred data, and all identifying information was stored in a code translation table separate from the actual data to protect the privacy of respondents. The University of Washington human subjects review board has approved this tool for research purposes. PALS who wanted to participate were given a Web site address that introduced the survey and provided a link to the survey site. The invitation to participate did not mention cannabis or marijuana, in order to discourage participation by individuals who do not have ALS but might otherwise be interested in promoting legalization of marijuana. The sruvey was titled "A survey of ALS Patients Who Use Alternative Therapies to Treat Symptoms." It was presumed by the investigatiors that the diagnostic information provided by the survey participants was accurate (i.e., no medical records were reviewed to confirm their diagnosis). In addition to a series of questions related to the ALS symptoms, the use of cannabis, and its effectiveness in alleviating the symptoms of ALS, participants were also asked to provide demographic and diagnostic information. The survey was anonymous and it is therefore impossible to conclusively determine whether all respondents were individuals with ALS. However, the first six questions of the survey asked about how and when the respondent was diagnosed with ALS and specifically asked those who were not diagnosed with ALS by a physician to not fill out the survey. The authors carefully studied the demographic and diagnostic information provided by each respondent for completeness, consistency, and plausiblity. Records with the diagnostic information missing were excluded from the analysis. Many participants offered extensive information about other alternative therapies they use, and the general comments appeared to reflect experiences of individuals living with ALS. Results A total of 137 responses were received. Four responses were excluded because of duplicate submission (i.e. the same person inadvertently submitting more than one survey by hitting the submit key more than once) and two because of failure to complete most of the questions of the survey. Eletronic logs of all submissions were inspected for repeated entries from the same Internet protocol (IP) address. None were found. A total of 131 responses were retained for analysis. The demographics of the sample are shown in Table 1. Seventy-five percent of the respondents were male and 90 percent were caucasian. The average age of participants was 54 years [standard deviation(sd)=11], with no significant difference between the genders [Mean(M) mean(m)=54 for=for males,=males, sd=12.5 m=53 females,=females,]. Eighty-four percent of the respondents were married or living with a significant other, 17 percent were employed (full time or part-time), 64 percent were unemployed or retired due to disability, and 18 percent were retired due to age. Respondents reported high levels of education, with only 13 percent with high school education or less and 62 percent with college education or higher. The time since ALS diagnosis ranged from one month to 24 years. The median time since diagnosis (i.e., duration) was three years, the mean duration was approximately four years (M=4.4, SD=4.0). About a half of the sample reported they used a wheelchair usually or always, and about 20 percent reported no restrictions in mobility. Eighty-one percent of the respondents filled out the survey independently while 19 percent reported that they required assistance from others. One-half of the participants were taking Riluzole. The majority of participants (69 percent) reported that they live in the Unted States, 8 percent in Canada, and 5 percent in Australia. Six percent of the participants live in Europe, while the rest (12 percent) of the respondents reported that they were from Africa, India, Israel, Brazil, Ecuador, Guatemala, or Argentina. Fifty-three participants (41 percent) reported drinking alcohol, 14 (11 percent) reported that they use tobacco, and four (3 percent) reported consuming both alcohol and tobacco. Use of cannabis Seventy-seven respondents (60 percent) reported that they never used cannabis, and 41 (31 percent) used cannabis in teenage or college years only. Thirteen respondents (10 percent) reported using cannabis in the last 12 months, and their demographics are outlined in Table 2. Those who reported using cannabis in the last 12 months were all male and all lived in the US. Ten of those who reported using cannabis in the last 12 months also responded affirmatively to the question that asked about the use of cannabis during the teenage, college, and adult years. All of those who reported using cannabis in the last 12 months also reported that they used cannabis at some point in their lives before they were diagnosed with ALS. Six of the cannabis users reported that they lived in a state where medical cannabis is legal, and four lived in a state where medical cannabis is illegal. The remaining three respondents were not sure whteher medical cannabis was legal in their state. There were no statistcally significant differences between the cannabis users and non-users (see Table 2) on any demographic variable (age, marital status, employment status, education level, time since diagnosis, mobility status). None of those who reported using cannabis in the past 12 months reported tobacco use, but all reported drinking alcohol. Eight cannabis users reported smoking cannabis in the last three months. Two respondents reported smoking cannabis infrequently (less often than once a month), one reported smoking one to two times a week, and three reported daily use. No respondents reported only breathing vaporized cannabis, although one participant reported using vaporized cannabis in addition to smoking and using medicinal cannabis. Two participants reported eating cannabis, one in addition to smoking it. Three respondents used medicinal cannabinoids (i.e., Dronabinol). Of the three respondents who used medicinal cannabinoids, one reported using only medicinal cannabinoids, one also smoked cannabis, and one both smoked as well as breathed vaporized cannabis. Symptoms The intensity of ALS-related symptoms was quantified by asking respondents to rate how much they experience each of the symptoms on a five-point scale ranging from "not at all" (0) to "very much" (4). The most frequent sympotm was weakness, followed by speech difficulties, drooling and swalowing difficulties. The intnesity of symptoms reported by respondents who did not use cannabis was not statistically significantly idfferent from the symptom intensity reported by the cannabis users [F(10, 120)=120) 1.07,=1.07, p=.39]. A summary of symptoms and their intensity is listed in Table 3. The ammount of relief attributed to cannabis use was assessed by asking the respondents to rate the degree to which cannabis alleviates each symptom on a five-point scale ranging from "not at all" (0) to "completely relieves the symptom" (4). Respondents reported that the use of cannabis helped moderately for depression, appetite loss, spasticity, drooling, and pain. All cannabis users who reported symptoms of appetite loss and depression also reported that cannabis reduced these symptoms. None of the cannabis users reported any reduction in difficulties with swallowing and speech or sexual dysfunction. The duration of symptom relief was measured on a scale from 0 (no relief) to 6 (more than nine hours). Respondents reported the most lasting relief (on average two to three hours) for depression. The loss of appetite, drooling, shortness of breath, spasticity, and pain were reported to be relieved on average for approximately one hour or less. Table 4 provides a summary of symptoms reported by the cannabis users. Level of relief was reported on a five-point scale ranging from "not at all" (0) to "completely relieves the symptom" (4). The duration of sumptom relief was measured on a scale from "no relief" (0), "less than one hour" (1), "two to three hours" (2), "four to five hours" (3), "six to seven hours" (4), "eight to nine hours" (5), "more than nine hours" (6). Discussion There is an increasing amount of research concerning the medicinal effects of cannabinoids. For example, cannabinoids have been reported to reduce chemotherapy-induced nausea and vomiting, lower intraocular pressure in patients with glaucoma, reduce anorexia in patients with cancer and AIDS-associated weight loss, and reduce pain and spasticity in MS.30-39 Cannabinoids, the active ingredients in marijuana, may also have properties that may be applicable to the management of ALS.9,10 However, to date no empirical studies of use and effectiveness of cannabis for symptom management by PALS have been published. Approximately 10 percent of the survey respondents reported using cannabis. This is a lower rate than the frequency of use reported by other patient populations, including MS, AIDS, and cancer patients.10,30,31 However, the pattern of symptom relief reported by the small number of PALS who reported using cannabis for symptom management by people with other conditions, including MS.30,35,36 Cannabis users reported that cannabis smoking was most effective at reducing depression, appetite loss, pain, spasticity, drooling, and weakness. The factor that most predicted current use of cannabis by PALS was reported previous use (presumably recreational). The survey had a number of limitations. First, the survey results reported here are based on a relatively small number of respondents (131) and on reports of 13 cannabis users, and may not be representative of the patterns of cannabis use in the ALS population by people with ALS in general. Second, 75 percent of the respondents were male, 25 percent were female. Men appear to be about 1.5 times more likely to be affected with ALS than women,7,8 so the percentage of female participants is slightly lower than expected in the general ALS population (about 33 percent). Published studies of Internet use consistently report that females are less likely to use the Internet for reasons that may be independent of income and estimate that only about one-third of Internet users are women.47,48 This may account for the lower than expected participation by women with ALS. A third limitation of the study is that a disproportionate number of the survey respondents were white (90 percent) and all cannabis users were white. There is some evidence that whites may be at higher risk for ALS though most researchers agree that ALS equally affects people of all races.49,50 Racial discrepancies in rates of ALS may be due to poorer access to healthcare for minority populations in the US, particularly access to tertiary referral centers, where the ALS diagnosis is often made. Published studies report that over 80 percent of Internet users are white;48 this is the most likely explanation for the disproportionate perticipation by Caucasians in this survey. Fourth, Internet users tend to be highly educated. Almost 60 percent repoert having at least one degree.48 Those with higher education are more likely to own computer equipment and to use it to connect to the Internet.51 The results of the survey we report here provide further evidence for this trend, with only 13 respondents (10 percent) reported having high school education or less. Finally, none of the participants from the countries where cannabis use is prevalent (India) or legal for medical uses (Australia, Canada) reported using cannabis. The most likely explanation for this finding is the small number of perticipants from these countries; only one respondent was from India, six from Australia, and eleven from Canada. In general, professionals with university degrees living in households with disposable incomes sufficient to purchase technology tools are likely to be over-represented in Internet surveys. Women, minorities, the elderly, those who liveon social assistance disability payments, or who earn minimum wages, are much less likely to participate.48,51 Privacy is a major issue associated with Web-based methodology. When the Internet is used for research, especially for research on sensitive issues (such as using substances that are illegal under federal law and most state laws), protecting the privacy of the participants is paramount. By making the survey anonymous, the authors protected the privacy of the respondents but gave up the ability to verify respondent' diagnoses or prevent repeated or malicious submittals. Although the records showed that no two responses were submitted from the same IP address, the IP address identifies the computer, not the user. Therefore, it cannot be conclusively determined that one respondent did not submit more than one response using different computers. The low response rate might be explained by many factors. First, we do not know how many participants in the electronic discussion list that was used to recruit participants have ALS. It is possible, even likely, that a large majority of the participants are family members, service providers, and advocates. Second, the respondents who do not use alternative therapies may have been less likely to respond. It is unclear what percentage of people with ALS use alternative therapies. A recent survey from Germany suggests that about half of the ALS patients there use complementary and alternative medicine.52 Some respondents who do not use alternative therapies such as vitamins and supplements, but do use cannabis to manage their symptoms may not have considered cannabis to be an "alternative therapy" and decided not to participate. Many respondents provided information on vitamins, supplements, and other alternative therapies in the write-in spaces of the survey even though they were nto asked about these therapies directly, probably because the respondents had anticipated the survey would gather informationon those topics. Third, even though the invitation as well as the introduction to the survey clearly stated that the survey was anonymous and there was no way for the researchers to associate a specific response with a specific respondent, many may have been individuals who are generally suspicious of providing information via the Internet and may have decided not to participate for this reason. Despite the limitations of this study noted above, these preliminary findings support the need for further research into the potential benefits of cannabis use for the clinical management of some ALS symptoms. These include pain, which was one of the symptoms identified in a recent study as not being sufficiently addressed in ALS.53 Further research is needed to see if the current findings can be confirmed using non-Internet-based survey methodology with a defined sample. It would also be informative to inquire about cannabis use within the context of subject beliefs about the efficacy of various alternative and complimentary approaches and their engagement and satisfaction with those approaches. Acknowledgements Funding for this research was provided by grants from the National Institute on Disability and Rehabilitation Research, Washington, DC and from the National Institutes of Health References 1. Norris F, Sheperd R, Denys E, Et al.: Onset, natural history and outcome in idiopathic adult motor neuron disease. J Neurol Sci. 1993; 118(1); 48-55. 2. Ringel SP, Murphy JR, Alderson MK, et al.: The natural history of amyotrophic lateral sclerosis. Neurology. 1993; 43(7): 1316-1322. 3. Neilson S, Tobinson I, Nymoen EH: Longitudinal analysis of amyotrophic lateral sclerosis mortality in Norway, 1966-1989: Evidence for a susceptible subpopulation. J Neurol Sci. 1994; 122(2): 148-154. 5. Eisen A: Amyotropic lateral sclerosis is a multifactorial disease. 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Leone M, Chandra V, Schoenberg BS: Motor neuron disease in the United States, 1971 and 1973-1978: Patterns of mortality and associated conditions at the time of death. Neurology. 1987; 37(8): 1339-1343. 50. Lilenfeld DE, Chan E, Ehland J, et al.: Rising mortality from motoneuron disease in the USA, 1962-84. Lancet. 1989; 1(8640): 710-713. 51. Kaye S: Computer and Internet Use Among People with Disabilities. Washington, DC: NIDRR, US Dept. of Education, 2000. 52. Wasner M, Klier H, Borasio GD: The use of alternative medicine by patients with amyotrophic lateral sclerosis. J Neurol Sci. 2001; 191(1-2): 151-154. 53. Mandler RN, Anderson FA, Miller RG, et al.: ALS C.A.R.E. Study Group. The ALS patient care database: insights in to end-of-life care in ALS. Amyotroph Lateral Scler Other Motor Neruon Disord. 2001; 2(4): 203-208 source: http://www.cannabism...rts/carter4.php Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Raman C, McAllister SD, Rizvi G, Patel SG, Moore DH, Abood ME. Forbes Norris MDA/ALS Research Center, 2351 Clay Street, Suite 416, California Pacific Medical Center, San Francisco, CA 94115, USA. Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSOD(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Delta(9)-THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Delta(9)-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Delta(9)-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS. source: http://www.ncbi.nlm....Pubmed_RVDocSum
  20. Cannabis cured my Cancer Causes, incidence, and risk factors Prostate cancer is the most common cause of death from cancer in men over age 75. Prostate cancer is rarely found in men younger than 40. People who are at higher risk include: African-American men, who are also likely to develop cancer at every age Men who are older than 60 Men who have a father or brother with prostate cancer Other people at risk include: Men who have been around agent orange Men who use too much alcohol Farmers Men who eat a diet high in fat, especially animal fat Tire plant workers Painters Men who have been around cadmium Prostate cancer is less common in people who do not eat meat (vegetarians). A common problem in almost all men as they grow older is an enlarged prostate. This is called benign prostatic hyperplasia, or BPH. It does not raise your risk of prostate cancer. However, it can increase your PSA blood test results. Symptoms The PSA blood test is often done to screen men for prostate cancer. Because of PSA testing, most prostate cancers are now found before they cause any symptoms. The symptoms listed below can occur with prostate cancer, usually at a late stage. These symptoms can also be caused by other prostate problems: Delayed or slowed start of urinary stream Dribbling or leakage of urine, most often after urinating Slow urinary stream Straining when urinating, or not being able to empty out all of the urine Blood in the urine or semen Bone pain or tenderness, most often in the lower back and pelvic bones (only when the cancer has spread) Signs and tests A biopsy is needed to tell if you have prostate cancer. A sample of tissue is removed from the prostate and sent to a lab. Your doctor may recommend a prostate biopsy if: You have high PSA level A rectal exam shows a large prostate or a hard, uneven surface The results are reported using what is called a Gleason grade and a Gleason score. The Gleason grade tells you how fast the cancer might spread. It grades tumors on a scale of 1 - 5. You may have different grades of cancer in one biopsy sample. The two main grades are added together. This gives you the Gleason score. The higher your Gleason score, the more likely the cancer is to have spread past the prostate: Scores 2 - 5: Low-grade prostate cancer Scores 6 - 7: Intermediate- (or in the middle-) grade cancer. Most prostate cancers fall into this group. Scores 8 - 10: High-grade cancer The following tests may be done to determine whether the cancer has spread: CT scan Bone scan The PSA blood test will also be used to monitor your cancer after treatment. Often, PSA levels will begin to rise before there are any symptoms. An abnormal digital rectal exam may be the only sign of prostate cancer (even if the PSA is normal). Treatment Treatment depends on many things, including your Gleason score and your overall health. Your doctor will discuss your treatment options. For early-stage prostate cancer, this may include: Surgery (radical prostatectomy) Radiation therapy, including brachytherapy and proton therapy If you are older, your doctor may recommend simply monitoring the cancer with PSA tests and biopsies. If the prostate cancer has spread, treatment may include: Hormone therapy (medicines to reduce testosterone levels) Surgery Chemotherapy Surgery, radiation therapy, and hormone therapy can affect your sexual desire or performance. Problems with urine control are common after surgery and radiation therapy. Discuss your concerns with your health care provider. After treatment for prostate cancer, you will be closely watched to make sure the cancer does not spread. This involves routine doctor check-ups, including PSA blood tests (usually every 3 months to 1 year). See also: Prostate cancer - stages Prostate radiation - discharge Support Groups You can ease the stress of illness by joining a support group whose members share common experiences and problems. See: Support group - prostate cancer Expectations (prognosis) How well you do depends on whether the cancer has spread outside the prostate gland and how abnormal the cancer cells are (the Gleason score) when you are diagnosed. Many patients can be cured if their prostate cancer has not spread. Some patients whose cancer has not spread very much outside the prostate gland can also be cured. Hormone treatment can improve survival, even in patients who cannot be cured. Complications The complications of prostate cancer are mostly due to different treatments. Calling your health care provider Discuss the advantages and disadvantages to PSA screening with your health care provider. Prevention You may lower your risk of prostate cancer by eating a diet that is: High in omega-3 fatty acids Low-fat Similar to the traditional Japanese diet Vegetarian Finasteride (Proscar, generic) and dutasteride (Avodart) are drugs used to treat prostate enlargement (benign prostatic hyperplasia, or BPH). If you do not have prostate cancer and your PSA score is 3.0 or lower, ask your health care provider about the pros and cons of taking these drugs to prevent prostate cancer. References Theoret MR, Ning YM, Zhang JJ, et al. The risks and benefits of 5a-reductase inhibitors for prostate-cancer prevention. N Engl J Med. 2011 Jun 15. Antonarakis ES, Eisenberger MA. Expanding treatment options for metastatic prostate cancer. N Engl J Med. 2011 May 26;364:2055-2058. Andriole GL, Crawford ED, Grubb RI 3rd, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319. Babaian RJ, Donnelly B, Bahn D, Baust JG, Dineen M, Ellis D, et al. Best practice statement on cryosurgery for the treatment of localized prostate cancer. J Urol. 2008;180:1993-2004. Schrader FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328. Walsh PC. Chemoprevention of prostate cancer. N Engl J Med. 2010 Apr 1;362(13):1237-8. Wilt TJ, MacDonald R, et al. Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med. 2008;148(6):435-448. Review Date: 9/19/2011. Reviewed by: Louis S. Liou, MD, PhD, Chief of Urology, Cambridge Health Alliance, Visiting Assistant Professor of Surgery, Harvard Medical School. Also reviewed by David Zieve, MD, MHA, Arachidonoylglycerol A Novel Inhibitor of Androgen-Independent Prostate Cancer Cell Invasion Kasem Nithipatikom1, Michael P. Endsley1, Marilyn A. Isbell1, John R. Falck3, Yoshiki Iwamoto2, Cecilia J. Hillard1 and William B. Campbell1 Departments of 1 Pharmacology and Toxicology and 2 Urology, Medical College of Wisconsin, Milwaukee, Wisconsin; and 3 Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas Endocannabinoids have been implicated in cancer. Increasing endogenous 2-arachidonoylglycerol (2-AG) by blocking its metabolism inhibits invasion of androgen-independent prostate cancer (PC-3 and DU-145) cells. Noladin ether (a stable 2-AG analog) and exogenous CB1 receptor agonists possess similar effects. Conversely, reducing endogenous 2-AG by inhibiting its synthesis or blocking its binding to CB1 receptors with antagonists increases the cell invasion. 2-AG and noladin ether decrease protein kinase A activity in these cells, indicating coupling of the CB1 receptor to downstream effectors. The results suggest that cellular 2-AG, acting through the CB1 receptor, is an endogenous inhibitor of invasive prostate cancer cells. source: http://cancerres.aac...ract/64/24/8826 Activation of Signal Transducer and Activator of Transcription 5 in Human Prostate Cancer Is Associated with High Histological Grade Hongzhen Li1, Tommi J. Ahonen4, Kalle Alanen5, Jianwu Xie1, Matthew J. LeBaron1, Thomas G. Pretlow7, Erica L. Ealley1, Ying Zhang2, Martti Nurmi6, Baljit Singh3,1, Paula M. Martikainen8 and Marja T. Nevalainen1 Departments of 1 Oncology, 2 Biostatistics Unit, and 3 Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC; Departments of 4 Anatomy and Cell Biology and 5 Pathology, Institute of Biomedicine, University of Turku, Turku, Finland; 6 Department of Surgery, University Hospital of Turku, Turku, Finland; 7 Department of Pathology, Case Western Reserve Medical Center, Cleveland, Ohio; and 8 Deptartment of Pathology, Tampere University Hospital, Tampere, Finland We have recently identified signal transducer and activator of transcription 5 (Stat5) as a critical survival factor for prostate cancer cells. We now report that activation of Stat5 is associated with high histological grade of human prostate cancer. Specifically, immunohistochemical analysis demonstrated a strong positive correlation with activation of Stat5 and high Gleason score in 114 human prostate cancers. To investigate the mechanisms underlying constitutive activation of Stat5 in prostate cancer, a dominant-negative mutant of Janus kinase 2 (Jak2) was delivered by adenovirus to CWR22Rv cells. Dominant-negative-Jak2 effectively blocked the activation of Stat5 whereas wild-type Jak2 enhanced activation, indicating that Jak2 is the main kinase that phosphorylates Stat5 in human prostate cancer cells. A ligand-induced mechanism for activation of Stat5 in prostate cancer was suggested by the ability of prolactin (Prl) to stimulate activation of both Jak2 and Stat5 in CWR22Rv human prostate cancer cells and in CWR22Rv xenograft tumors. In addition, Prl restored constitutive activation of Stat5 in five of six human prostate cancer specimens in ex vivo long-term organ cultures. Finally, Prl protein was locally expressed in the epithelium of 54% of 80 human prostate cancer specimens with positive correlation with high Gleason scores and activation of Stat5. In conclusion, our data indicate that increased activation of Stat5 was associated with more biologically aggressive behavior of prostate cancer. The results further suggest that Jak2 is the principal Stat5 tyrosine kinase in human prostate cancer, possibly activated by autocrine/paracrine Prl. source: http://cancerres.aac...ract/64/14/4774 Suppression of Nerve Growth Factor Trk Receptors and Prolactin Receptors by Endocannabinoids Leads to Inhibition of Human Breast and Prostate Cancer Cell Proliferation1 Dominique Melck, Luciano De Petrocellis, Pierangelo Orlando, Tiziana Bisogno, Chiara Laezza, Maurizio Bifulco and Vincenzo Di Marzo Istituto per la Chimica di Molecole di Interesse Biologico (D.M., T.B., V.D.M.), Istituto di Cibernetica (L.D.P.), and Istituto di Biochimica delle Proteine ed Enzimologia (P.O.), Consiglio Nazionale delle Ricerche, 80072 Arco Felice (NA); and Centro di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II (C.L., M.B.), 80131 Naples, Italy Address all correspondence and requests for reprints to: Dr. Vincenzo Di Marzo, Istituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, 80072 Arco Felice (NA), Italy. E-mail: vdm@trinc.icmib.na.cnr.it. Anandamide and 2-arachidonoylglycerol (2-AG), two endogenous ligands of the CB1 and CB2 cannabinoid receptor subtypes, inhibit the proliferation of PRL-responsive human breast cancer cells (HBCCs) through down-regulation of the long form of the PRL receptor (PRLr). Here we report that 1) anandamide and 2-AG inhibit the nerve growth factor (NGF)-induced proliferation of HBCCs through suppression of the levels of NGF Trk receptors; 2) inhibition of PRLr levels results in inhibition of the proliferation of other PRL-responsive cells, the prostate cancer DU-145 cell line; and 3) CB1-like cannabinoid receptors are expressed in HBCCs and DU-145 cells and mediate the inhibition of cell proliferation and Trk/PRLr expression. ß-NGF-induced HBCC proliferation was potently inhibited (IC50 = 50–600 nM) by the synthetic cannabinoid HU-210, 2-AG, anandamide, and its metabolically stable analogs, but not by the anandamide congener, palmitoylethanolamide, or the selective agonist of CB2 cannabinoid receptors, BML-190. The effect of anandamide was blocked by the CB1 receptor antagonist, SR141716A, but not by the CB2 receptor antagonist, SR144528. Anandamide and HU-210 exerted a strong inhibition of the levels of NGF Trk receptors as detected by Western immunoblotting; this effect was reversed by SR141716A. When induced by exogenous PRL, the proliferation of prostate DU-145 cells was potently inhibited (IC50 = 100–300 nM) by anandamide, 2-AG, and HU-210. Anandamide also down-regulated the levels of PRLr in DU-145 cells. SR141716A attenuated these two effects of anandamide. HBCCs and DU-145 cells were shown to contain 1) transcripts for CB1 and, to a lesser extent, CB2 cannabinoid receptors, 2) specific binding sites for [3H]SR141716A that could be displaced by anandamide, and 3) a CB1 receptor-immunoreactive protein. These findings suggest that endogenous cannabinoids and CB1 receptor agonists are potential negative effectors of PRL- and NGF-induced biological responses, at least in some cancer cells. source: http://endo.endojour...tract/141/1/118 Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes Arkaitz Carracedo1, Meritxell Gironella2, Mar Lorente1, Stephane Garcia2, Manuel Guzmán1, Guillermo Velasco1 and Juan L. Iovanna2 1 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain and 2 U624 Institut National de la Sante et de la Recherche Medicale, Marseille, France Requests for reprints: Guillermo Velasco, Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, c/ José Antonio Novais s/n, 28040 Madrid, Spain. Phone: 34-91-394-4668; Fax: 34-91-394-4672; E-mail: gvd@bbm1.ucm.es. Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue. Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, ( increased ceramide levels, and © up-regulated mRNA levels of the stress protein p8. These effects were prevented by blockade of the CB2 cannabinoid receptor or by pharmacologic inhibition of ceramide synthesis de novo. Knockdown experiments using selective small interfering RNAs showed the involvement of p8 via its downstream endoplasmic reticulum stress–related targets activating transcription factor 4 (ATF-4) and TRB3 in 9-tetrahydrocannabinol–induced apoptosis. Cannabinoids also reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue. In conclusion, results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress–related genes ATF-4 and TRB3. These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer. (Cancer Res 2006; 66(13): 6748-55) source: http://cancerres.aacrjournals.org/cgi/cont...ract/66/13/6748
  21. Spain Study Confirms Hemp Oil Cures Cancer Without Side Effects “The medical science is strongly in favor of THC laden hemp oil as a primary cancer therapy, not just in a supportive role to control the side effects of chemotherapy. The International Medical Verities Association is putting hemp oil on its cancer protocol. It is a prioritized protocol list whose top five items are magnesium chloride, iodine, selenium, Alpha Lipoic Acid and sodium bicarbonate. It makes perfect sense to drop hemp oil right into the middle of this nutritional crossfire of anti cancer medicines, which are all available without prescription. Hemp oil has long been recognised as one of the most versatile and beneficial substances known to man. Derived from hemp seeds (a member of the achene family of fruits) it has been regarded as a superfood due to its high essential fatty acid content and the unique ratio of omega3 to omega6 and gamma linolenic acid (GLA) – 2:5:1. Hemp oil, is known to contain up to 5% of pure GLA, a much higher concentration than any other plant, even higher than spirulina. For thousands of years, the hemp plant has been used in elixirs and medicinal teas because of its healing properties and now medical science is zeroing in on the properties of its active substances. Both the commercial legal type of hemp oil and the illegal THC laden hemp oil are one of the most power-packed protein sources available in the plant kingdom. Its oil can be used in many nutritional and transdermal applications. In other chapters in my Winning the War on Cancer book we will discuss in-depth about GLA and cancer and also the interesting work of Dr. Johanna Budwig. She uses flax seed oil instead of hemp oil to cure cancer – through effecting changes in cell walls – using these omega3 and omega6 laden medicinal oils. Read more
  22. Int J Oncol. 2012 May 14. doi: 10.3892/ijo.2012.1476. [Epub ahead of print] Cannabinoid-associated cell death mechanisms in tumor models (Review). Calvaruso G, Pellerito O, Notaro A, Giuliano M. Source Department of Experimental Biomedicine and Clinical Neuroscience, Section of Biochemical Sciences, University of Palermo, 90129 Palermo, Italy. Abstract In recent years, cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to findings that they can affect the viability and invasiveness of a variety of different cancer cells. Moreover, in addition to their inhibitory effects on tumor growth and migration, angiogenesis and metastasis, the ability of these compounds to induce different pathways of cell death has been highlighted. Here, we review the most recent results generating interest in the field of death mechanisms induced by cannabinoids in cancer cells. In particular, we analyze the pathways triggered by cannabinoids to induce apoptosis or autophagy and investigate the interplay between the two processes. Overall, the results reported here suggest that the exploration of molecular mechanisms induced by cannabinoids in cancer cells can contribute to the development of safe and effective treatments in cancer therapy. PMID:22614735 [PubMed - as supplied by publisher] My link Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation Δ9-Tetrahydrocannabinol, the main active component of marijuana, induces apoptosis of transformed neural cells in culture. Here, we show that intratumoral administration of Δ9-tetrahydrocannabinol and the synthetic cannabinoid agonist WIN-55,212-2 induced a considerable regression of malignant gliomas in Wistar rats and in mice deficient in recombination activating gene 2. Cannabinoid treatment did not produce any substantial neurotoxic effect in the conditions used. Experiments with two subclones of C6 glioma cells in culture showed that cannabinoids signal apoptosis by a pathway involving cannabinoid receptors, sustained ceramide accumulation and Raf1/extracellular signal-regulated kinase activation. These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas. My link 15 Rats with "incurable" brain tumors treated with THC infusions:3 die, 9 live up to twice as long as untreated Rats, 3 had tumors completely eliminated.Effective treatment: 60% Complete cure: 20% Cancer Killed by Cannabis - Weed - Pot - Marijuana finds UCLA research and others Full-length Doc Marijuana cures cancer - US government has known since 1974
  23. Marijuana Chemical May Fight Brain Cancer Active Component In Marijuana Targets Aggressive Brain Cancer Cells, Study Says By Kelli Miller Stacy WebMD Health News Reviewed by Louise Chang, MD The active chemical in marijuana promotes the death of brain cancer cells by essentially helping them feed upon themselves, researchers in Spain report. Guillermo Velasco and colleagues at Complutense University in Spain have found that the active ingredient in marijuana, THC, causes brain cancer cells to undergo a process called autophagy. Autophagy is the breakdown of a cell that occurs when the cell essentially self-digests. The team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and people with brain tumors. When mice with the human brain cancer cells received the THC, the tumor growth shrank. Two patients enrolled in a clinical trial received THC directly to the brain as an experimental treatment for recurrent glioblastoma multiforme, a highly aggressive brain tumor. Biopsies taken before and after treatment helped track their progress. After receiving the THC, there was evidence of increased autophagy activity. The findings appear in the April 1 issue of the Journal of Clinical Investigation. The patients did not have any toxic effects from the treatment. Previous studies of THC for the treatment of cancer have also found the therapy to be well tolerated, according to background information in journal article. Study authors say their findings could lead to new strategies for preventing tumor growth. source : http://www.webmd.com...ht-brain-cancer Marijuana May Stall Brain Tumor Growth Active Ingredient in Marijuana Inhibits Cancer Growth in Early Study By Jennifer Warner WebMD Health News Reviewed by Michael W. Smith, MD Aug. 15, 2004 -- The active ingredient in marijuana may help fight brain tumors, a new study suggests. Researchers say the cannabinoids found in marijuana may aid in brain tumor treatment by targeting the genes needed for the tumors to sprout blood vessels and grow. Their study showed that cannabinoids inhibited genes needed for the production of vascular growth factor (VEGF) in laboratory mice with glioma brain tumors and two patients with late-stage glioblastoma multiforme, a form of brain cancer. VEGF is a protein that stimulates blood vessels to grow. Tumors need an abundant blood supply because they generally grow rapidly. So when VEGF is blocked, tumors starve from lack of blood supply and nutrients. Blocking of VEGF constitutes one of the most promising tumor-fighting approaches currently available, says researcher Manuel Guzman, professor of biochemistry and molecular biology, at the Complutense University in Madrid, Spain, in a news release. Guzman says the findings suggest VEGF may be a new target for cannabinoid-based treatments. Previous studies have shown that cannabinoids could inhibit the growth of tumor-associated blood vessels in mice, but until now little was known about how they worked. The results of the study appear in the Aug. 15 issue of the journal Cancer Research. Cannabinoids May Help Starve Tumors In the study, researchers looked at the effects of cannabinoid treatment on gliobastoma multiforme, a form of brain cancer that affects about 7,000 Americans each year. It's considered one of the deadliest forms of cancer and usually results in death within one to two years after diagnosis. Treatment typically involves surgery, followed by radiation and/or chemotherapy. But despite these efforts to destroy the tumor, this type of brain tumor often survives and starts growing again, which is why researchers are looking for novel ways to attack it. In order to grow, all tumors require a network of blood vessels to feed them, and they create this network through a process known as angiogenesis. VEGF is critical to this process. In the first part of the study, researchers induced brain cancer in mice and then treated them with cannabinoids. They then analyzed the genes associated with the growth of blood vessels in the tumor and found that cannabinoids inhibited several of the genes related to VEGF. In the second part of the study, researchers injected cannabinoids into tumor samples taken from two human glioblastoma patients. "In both patients, VEGF levels in tumor extracts were lower after cannabinoid inoculation," says Guzman. Researchers say more study is needed but the results suggest that cannabinoid-based therapies may offer a new alternative for treatment of these otherwise untreatable brain tumors. source: http://www.webmd.com...in-tumor-growth http://www.youtube.com/watch?v=HVGlfcP3ATI Human Brains Make Their Own 'Marijuana' ScienceDaily (Apr. 20, 2009) — U.S. and Brazilian scientists have discovered that the brain manufactures proteins that act like marijuana at specific receptors in the brain itself. This discovery may lead to new marijuana-like drugs for managing pain, stimulating appetite, and preventing marijuana abuse. "Ideally, this development will lead to drugs that bind to and activate the THC receptor, but are devoid of the side effects that limit the usefulness of marijuana," said Lakshmi A. Devi of the Department of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine in New York and one of the senior researchers involved in the study. "It would be helpful to have a drug that activated or blocked the THC receptor, and our findings raise the possibility that this will lead to effective drugs with fewer side effects." Scientists made their discovery by first extracting several small proteins, called peptides, from the brains of mice and determining their amino acid sequence. The extracted proteins were then compared with another peptide previously known to bind to, but not activate, the receptor (THC) affected by marijuana. Out of the extracted proteins, several not only bound to the brain's THC receptors, but activated them as well. "The War on Drugs has hit very close to home," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Last year, scientists found that our skin makes its own marijuana-like substance. Now, we see that our brain has been making proteins that act directly on the marijuana receptors in our head. The next step is for scientists to come up with new medicines that eliminate the nasty side of pot—a better joint, so to speak." source: http://www.scienceda...90420151240.htm Active Ingredient in Marijuana Kills Brain Cancer Cells Experts say finding worth further study, but patients shouldn't light up just yet Posted April 1, 2009 By Alan Mozes HealthDay Reporter WEDNESDAY, April 1 (HealthDay News) -- New research out of Spain suggests that THC -- the active ingredient in marijuana -- appears to prompt the death of brain cancer cells. The finding is based on work with mice designed to carry human cancer tumors, as well as from an analysis of THC's impact on tumor cells extracted from two patients coping with a highly aggressive form of brain cancer. Explaining that the introduction of THC into the brain triggers a cellular self-digestion process known as "autophagy," study co-author Guillermo Velasco said his team has isolated the specific pathway by which this process unfolds, and noted that it appears "to kill cancer cells, while it does not affect normal cells." Velasco is with the department of biochemistry and molecular biology in the School of Biology at Complutense University in Madrid. The findings were published in the April issue of The Journal of Clinical Investigation. The Spanish researchers focused on two patients suffering from "recurrent glioblastoma multiforme," a fast-moving form of brain cancer. Both patients had been enrolled in a clinical trial designed to test THC's potential as a cancer therapy. Using electron microscopes to analyze brain tissue taken both before and after a 26- to 30-day THC treatment regimen, the researchers found that THC eliminated cancer cells while it left healthy cells intact. The team also was able, in what it described as a "novel" discovery, to track the signaling route by which this process was activated. These findings were replicated in work with mice, which had been "engineered" to carry three different types of human cancer tumor grafts. "These results may help to design new cancer therapies based on the use of medicines containing the active principle of marijuana and/or in the activation of autophagy," Velasco said. Outside experts suggested that more research is needed before advocating marijuana as a medicinal intervention for brain cancer. Dr. John S. Yu, co-director of the Comprehensive Brain Tumor Program in the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center in Los Angeles, said the findings were "not surprising." "There have been previous reports to this effect as well," he said. "So this is yet another indication that THC has an anti-cancer effect, which means it's certainly worth further study. But it does not suggest that one should jump at marijuana for a potential cure for cancer, and one should not urge anyone to start smoking pot right away as a means of curing their own cancer." But that's exactly what many brain cancer patients have been doing, said Dr. Paul Graham Fisher, the Beirne Family director of Neuro-Oncology at Stanford University. "In fact, 40 percent of brain tumor patients in the U.S. are already using alternative treatments, ranging from herbals to vitamins to marijuana," he said. "But that actually points out a cautionary tale here, which is that many brain cancer patients are already rolling a joint to treat themselves, but we're not really seeing brain tumors suddenly going away as a result, which we clearly would've noticed if it had that effect. So we need to be open-minded. But this suggests that the promise of THC might be a little over-hoped, and certainly requires further investigation before telling people to go out and roll a joint." source: http://health.usnews...ain-cancer.html Ted Kennedy's Brain Cancer Can Be Fought The senator, like the author, was struck by a sudden seizure. She has outlasted a grim prognosis By Bernadine Healy, M.D. Posted May 20, 2008 I have been praying for Sen. Ted Kennedy since Saturday, when he was rushed to the hospital because of an out-of-the-blue seizure. I knew all too well that the most likely diagnosis, considering his presentation and age, was a brain tumor. Today we hear it's a malignant glioma in the left parietal lobe of his brain, a dominant area that controls, among other functions, the ability to comprehend and express words. As he and his family are trying hard, no doubt, to digest this shocking news, they must also face the dark stories that are being blasted all over the airways about his illness—almost as if he were no longer with us. It brings chills to me, not just as a doctor who has cared for many with serious illness but also as a patient who, like the senator, once had a sudden seizure that led to the detection of a malignant glioma. Mine, too, was in the left parietal lobe. As I commented in my book Living Time and in an excerpt in U.S.News last year about my own battle with brain cancer, gliomas are rare and often forgotten tumors that strike fear into anyone's heart—in part because we have known so little about them. Though the senator's doctors have not yet shared details of his exact tumor type, those particulars will be crucial, because all malignant gliomas are not created equal. In the coming days we will learn more about his outlook. But it is worth remembering that prognoses are estimates—and can be misleading. When I was diagnosed, it looked like I would not see my 12-year-old daughter complete middle school. This past weekend, she graduated from college. To a large degree, the prognosis in brain cancer depends on a given tumor's characteristics—how it looks under the microscope, its genetic profile (which increasingly guides newer and better therapies), and, importantly, how it responds to treatment. In other words, Senator Kennedy's outlook depends on the traits of his particular tumor—as well as the patient himself. And if there is one thing we know about this patient, it's that he's a determined fighter. http://health.usnews...lated-links:TOP Can Cannabis Cure Brain Cancer? Apr 3, 2009 In another boost for the cred of marijuana as a potential valuable medicine, researchers in Spain have found that cannabis could be a treatment and perhaps a future cure for brain cancer - in a study done on both rats and humans: Hope Ted Kennedy gets the word. WASHINGTON (AFP) — The main chemical in marijuana appears to aid in the destruction of brain cancer cells, offering hope for future anti-cancer therapies, researchers in Spain wrote in a study released Thursday. The authors from the Complutense University in Madrid, working with scientists from other universities, found that the active component of marijuana, tetrahydrocannabinol (THC), causes cancer cells to undergo a process called autophagy -- the breakdown that occurs when the cell essentially self-digests. The research, which appears in the April edition of US-published Journal of Clinical Investigation, demonstrates that THC and related "cannabinoids" appear to be "a new family of potential antitumoral agent." The authors wrote that the chemical may prove useful in the development of future "antitumoral agents." source: http://www.fodors.co...rain-cancer.cfm The active chemical in marijuana promotes the death of brain cancer cells by essentially helping them feed upon themselves, researchers in Spain report. Guillermo Velasco and colleagues at Complutense University in Spain have found that the active ingredient in marijuana, THC, causes brain cancer cells to undergo a process called autophagy. Autophagy is the breakdown of a cell that occurs when the cell essentially self-digests. The team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and people with brain tumors. When mice with the human brain cancer cells received the THC, the tumor growth shrank. Two patients enrolled in a clinical trial received THC directly to the brain as an experimental treatment for recurrent glioblastoma multiforme, a highly aggressive brain tumor. Biopsies taken before and after treatment helped track their progress. After receiving the THC, there was evidence of increased autophagy activity. The findings appear in the April 1 issue of the Journal of Clinical Investigation. The patients did not have any toxic effects from the treatment. Previous studies of THC for the treatment of cancer have also found the therapy to be well tolerated, according to background information in journal article. Study authors say their findings could lead to new strategies for preventing tumor growth. Ref: http://www.webmd.com...ht-brain-cancer How Medical Marijuana Works The Therapeutic Uses of Cannabis and Cannabinoids There are over 400 natural compounds in medical marijuana and, of these, eighty are only found in cannabis plants. These eighty special compounds are known as cannabinoids. Cannabinoids relieve symptoms of illness by attaching to receptors in the brain that look for similar compounds that occur in the human body, such as dopamine. There are five major cannabinoids in medical marijuana that are particularly effective for relieving symptoms of illness, and each one produces different physical and psychological effects. This is why certain strains of medical marijuana are bred to have different amounts of each cannabinoid and are recommended for different conditions. Major Cannabinoids in Medical Marijuana What THC Is and Its Effects THC stands for delta-9-tetrahydrocannibinol. It is probably the best known cannabinoid present in medical marijuana. Physically it acts as a muscle relaxant and anti-inflammatory and psychologically it acts as a stimulant. This makes medical marijuana strains high in THC a good choice for patients who need relief while also to remain alert and active. THC in medical marijuana acts in the following ways: anti-epileptic anti-inflammatory anti-depressant stimulates appetite lowers blood pressure What CBD Is and Its Effects CBD stands for cannabidiol. Cannabidiol actually reduces the psychological effects of medical marijuana. For most patients, a strain that has high THC and high cannabidiol will have fewer “mental” effects and more physical ones. High cannabidiol medical marijuana strains, like Blueberry and Harlequin, are especially effective for illnesses with strong physical symptoms. Cannabidiol’s effects include: reduced pain reduced anxiety reduced nausea sedative effects anti-convulsive anti-schizophrenic What CBN Is and Its Effects CBN is cannabinol, not to be confused with Cannabidiol. Cannabinol is very similar to THC, but has less psychological effects. It is produced as THC breaks down within the medical marijuana plant. High THC will make cannabinol’s effects stronger, and very high cannabinol concentrations can produce undesirably strong head highs. Cannabinol levels tend to be high in medical marijuana strains like Strawberry Haze and Blue Rhino, which can be particularly helpful for: lowering pressure in the eye (such as with glaucoma) analgesic anti-seizure What CBC Is and Its Effects CBC stands for cannabichromene. Cannabichromene’s main action is to enhance the effects of THC. High cannabichromene levels will make a high-THC medical marijuana strain much more potent. Cannabichromene working together with THC is known to be a: sedative analgesic anti-inflammatory What CBG Is and Its Effects CBG is an abbreviation for cannabigerol. Cannabigerol has no psychological effects on its own, and is not usually found in high amounts in most medical marijuana. Scientists believe that cannabigerol is actually one of the oldest forms of cannabinoids, meaning it is essentially a “parent” to the other cannabinoids found in medical marijuana. It also has anti-microbial properties. Cannabigerol has physical effects such as: lowering pressure in the eye anti-inflammatory sedative sleep assistance Combining Strains Alone, none of the five major cannabinoids are as effective as when they work together. These five cannabinoids also work with the minor compounds in marijuana, and this is probably one reason that medical marijuana replacements like Marinol do not work very well. Professional medical marijuana growers can analyze their medical marijuana strains to breed and grow medication for patients with the desired range of levels of each major cannabinoid. Using this knowledge of what each compound does helps medical marijuana pharmacists, or budtenders, find the right combination for patients to treat specific conditions and find maximum relief.
  24. http://www.youtube.com/watch?v=yj72e5q61Fs Marijuana and ADD By: Kort E Patterson Year Written: 2000 Therapeutic uses of Medical Marijuana in the treatment of Attention Deficit Disorder --------------------------------- Note: The following research was part of a petition filed in 1999 to add Attention Deficit Disorder to the Oregon Medical Marijuana Act. The Oregon Health Division continues to refuse to add mental conditions such as ADD to the list of OMMA "covered conditions". The Health Division claims that medical marjuana isn't effective for mental conditions even though the primary justification for marijuana prohibition is its alleged psycho-active effectiveness. --------------------------------- At first glance it might seem counter-intuitive to use a medication that has a public perception of decreasing attention to treat a condition whose primary symptom is a deficit of attention. But just as taking stimulants often calms those with hyperactivity, medical marijuana improves the ability to concentrate in some types of ADD. Categorizing The Condition Attention Deficit Disorder (ADD) is a very broad category of conditions that share some symptoms but appear to result from different underlying causes. Most seem to involve, at least in part, imbalances in neural transmitter levels and functions. Some experts in the field expect that the broad category of ADD will be refined in the future, with many conditions that are now diagnosed as ADD being recognized as separate disorders. The particular type of ADD under consideration for treatment with medical marijuana might better be termed "Racing Brain Syndrome" (RBS). A useful analogy for this mental condition is that of a centrifugal pump that is being over-driven. As the pump speed increases, cavitation sets in and the pump's output decreases. The faster the pump is driven the greater the cavitation until a point is reached where large amounts of energy are being input but nothing is being output. Without medication there is a sensation that thoughts flash through the brain too fast to "think" them. Medical marijuana slows the brain down sufficiently to achieve impressive improvements in functionality. This syndrome probably only afflicts a small minority of all those diagnosed with ADD. The condition doesn't respond to the standard ADD medications, indicating that it results from different underlying processes than other forms of ADD. Individuals with types of ADD that do respond to the standard ADD medications also tend to have a far different reaction to medical marijuana than those with RBS. At this point in our limited understanding of the condition, it appears that RBS would make a good candidate to be redefined as a separate condition outside of the general diagnosis of ADD. Treating ADD/RBS With Medical Marijuana There is some evidence available that medical marijuana has been found to be an effective medication for some types of ADD by other researchers in the field.(1) Unfortunately, ADD encompasses such a variety of conditions that the limited amount of research in the field leaves many of the effective therapeutic mechanisms under-investigated. Considering the regulatory difficulties in researching the effects of medical marijuana, it isn't surprising that the information regarding medical marijuana and ADD is largely anecdotal(2). Individuals with RBS tend to have a very low tolerance for most stimulants, and report even caffeine aggravates their disorder. The one exception appears to be low doses of Dextrostat. While Dextrostat does have a calming effect, it fails to address the higher level mental functions needed for complex intellectual demands. Larger doses of Dextrostat tend to produce undesirable mental and physical stimulation, greatly limiting the level of medication that can be tolerated. Medical marijuana remains the only single medication that provides an adequate solution for RBS, and remains a necessary component in a multi-drug approach. Dextrostat does appear to reduce the amount of medical marijuana needed by individuals with RBS to achieve a functional mental state. This reduction probably justifies continuing with Dextrostat as a means of reducing the quantity of medical marijuana that must consumed, as well as allow those with RBS to gain the maximum benefit possible within the quantity limitations of the OMMA. The green leaves of certain strains of medical marijuana appear to provide the best therapeutic effects for RBS. Experiments with Marinol seem to indicate that THC is involved, but is not the primary therapeutic agent. The therapeutic agent(s) most useful in treating RBS appear to be present in relatively low concentrations in medical marijuana. As such those with this condition must consume a larger quantity of medical marijuana in order to ingest a sufficient dosage of the target agent(s). This would explain why dried low-THC green leaves appear to be the most effective treatment. The patient can consume enough of this low-THC marijuana to acquire the levels of the needed active agent(s) necessary to treat the condition without in the process consuming sufficient THC to become intoxicated. Underlying Cause of RBS It has long been suspected that RBS involved a deficit of one or more neural transmitters. It was observed as long ago as the 1970's that high levels of adrenaline had a residual therapeutic effect in those with RBS. The effect was first noted in those engaged in such activities as skydiving. Individuals with RBS reported that their mental functions were improved in the days following skydiving. It was first assumed that adrenaline stimulated the production of all neural transmitters - including those that were in deficit. It's now thought that while adrenaline initially acts as a stimulant of neural transmitter production, it has a secondary effect of depleting neural transmitters. The limited effectiveness of Dextrostat, as well as additional information about the secondary effects of adrenaline, suggests the possibility that at least part of the underlying cause of RBS may also be a surplus of one or more neural transmitters. The partial solution offered by Dextrostat also suggests that at least some part of the condition results from those neural transmitters and/or hormones that are influenced by both Dextrostat and medical marijuana. The failure of Dextrostat to provide a complete solution suggests two possible alternatives: (1) that the effects of Dextrostat and medical marijuana are additive - with both influencing the same neural transmitters and/or hormones, and together delivering the required level of therapeutic effect; or (2) that the condition is the result of multiple imbalances, some of which are unaffected by Dextrostat, but all of which appear to be affected by medical marijuana. Potential Beneficial Therapeutic Effects The research that has been done on the therapeutic effects of medical marijuana on other conditions provides a number of potential mechanisms that may be involved in RBS. The following are documented effects of medical marijuana that appear to have some potential for involvement. Perhaps the most obvious possibility is suggested by the fact that both Dextrostat and medical marijuana influence the release and/or functions of serotonin(3)(4). Since both Dextrostat and medical marijuana appear to decrease the apparent availability and effectiveness of serotonin, it would appear possible that a surplus of serotonin is involved in some way. There are over 60 cannabinoids and cannabidiols present in medical marijuana. The effect of most of these substances is at present largely unknown.(5) The discovery of a previously unknown system of cannabinoid neural transmitters is profound.(6) The different cannabinoid receptor types found in the body appear to play different roles in normal human physiology.(5) An endogenous cannabinoid, arachidonylethanolamide, named anandamide, has been found in the human brain. This ligand inhibits cyclic AMP in its target cells, which are widespread throughout the brain, but demonstrate a predilection for areas involved with nociception. The exact physiological role of anandamide is unclear, but preliminary tests of its behavioral effects reveal actions similar to those of THC.(7) Cannabinoid receptors appear to be very dense in the globus pallidus, substantia nigra pars reticulata (SNr), the molecular layers of the cerebellum and hippocampal dentate gyrus, the cerebral cortex, other parts of the hippocampal formation, and striatum - with the highest density being in the SNr. The Neocortex has moderate receptor density, with peaks in superficial and deep layers. Very low and homogeneous density was found in the thalamus and most of the brainstem, including all of the monoamine containing cell groups, reticular formation, primary sensory, visceromotor and cranial motor nuclei, and the area postrema. The hypothalamus, basal amygdala, central gray, nucleus of the solitary tract, and laminae I-III and X of the spinal cord showed slightly higher but still sparse receptor density.(5) While there are cannabinoid receptors in the ventromedial striatum and basal ganglia, which are areas associated with dopamine production, no cannabinoid receptors have been found in dopamine-producing neurons. According to the congressional Office of Technology Assessment, research over the last 10 years has proved that marijuana has no effect on dopamine-related brain systems.(6) However, cannabidiol has been shown to exert anticonvulsant and antianxiety properties, and is suspected by some to exert antidyskinetic effects through modulation of striatal dopaminergic activity.(3) It's been suggested that the cannabinoid receptors in the human brain play a role in the limbic system, which in turn plays a central role in the mechanisms which govern behavior and emotions. The limbic system coordinates activities between the visceral base-brain and the rest of the nervous system. Cannabis acts on memory by way of the receptors in the limbic system's hippocampus, which "gates" information during memory consolidation.(6) In addition, some effects of cannabinoids appear to be independent of cannabinoid receptors. The variety of mechanisms through which cannabinoids can influence human physiology underlies the variety of potential therapeutic uses for medical marijuana.(8) When the effects of cannabis on a "normal" brain are tracked on an electroencephalogram (EEG), there is an initial speeding up of brain wave activity and a reactive slowing as the drug effects wear off. The higher the dosage, the more intense the effects and longer the experience. There is an increase in mean-square alpha energy levels and a slight slowing of alpha frequency.(5) There is also an increase of beta waves reflecting increased cognitive activity. The distortion of time resulting from the "speeding up of thoughts" causes a subjective perception that there is a slowing of time.(9) As the cannabis effects wear off, stimulation gives way to sedation. The cognitive activity of the beta state gives way to alpha and theta frequencies. Theta waves are commonly associated with visual imagery. These images interact with thinking and disrupt the train of thought. Thinking can be distracted by these intrusions, with thought contents being modified to some extent depending on dose, expectations, setting, and personality.(9) Cannabis decreases emotional reactivity and intensity of affect while increasing introspection as evidenced by the slowing of the EEG after initial stimulation. Obsessive and pressured thinking is replaced by introspective free associations. Emotional reactivity is moderated and worries become less pressing.(10) Cannabis causes a general increase in cerebral blood flow (CBF). This increase in blood circulation is due to decreased peripheral resistance, which is in turn due to the dilation of the capillaries in the cerebral cortex. Changes in CBF affect the mental processes of the brain, with increases stimulating cognition, while decreases accompany sedation.(9) Relative Safety of Medical Marijuana "Marijuana is the safest therapeutically active substance known to man... safer than many foods we commonly consume." DEA Judge Francis L. Young, Sept. 6, 1988 "After carefully monitoring the literature for more than two decades, we have concluded that the only well-confirmed deleterious physical effect of marihuana is harm to the pulmonary system." Grinspoon M.D., James B. Bakalar, Medical Marijuana has been in use for thousands of years, and in spite of substantial efforts to find adverse effects, it remains the safest medication available for RBS. There has never been a single known case of lethal overdose. The ratio of lethal to effective dose for medical marijuana is estimated to be as 40,000 to 1. By comparison, the ratio is 3-50 to 1 for secobarbital and 4-10 to 1 for alcohol.(11) During the 1890s the Indian Hemp Drugs Commission interviewed some eight hundred people and produced a report of more than 3000 pages. The report concluded that "there was no evidence that moderate use of cannabis drugs produced any disease or mental or moral damage, or that it tended to lead to excess any more than the moderate use of whiskey."(12) The Mayor's Committee on Marihuana examined chronic users in New York City who had averaged seven marihuana cigarettes a day for eight years and "showed no mental or physical decline."(13) Several later controlled studies of chronic heavy use failed to establish any pharmacologically induced harm.(14) A subsequent government sponsored review of cannabis conducted by the Institute of Medicine, a branch of the National Academy of Sciences, also found little evidence of its alleged harmfulness.(15) Several studies in the United States found that fairly heavy marihuana use had no effects on learning, perception, or motivation over periods as long as a year.(16) Studies of very heavy smokers in Jamaica, Costa Rica, and Greece "found no evidence of intellectual or neurological damage, no changes in personality, and no loss of the will to work or participate in society."(17) The Costa Rican study showed no difference between heavy users (seven or more marihuana cigarettes a day) and lighter users (six or fewer cigarettes a day).(18) In addition, none of the studies involving prolonged and heavy use of medical marijuana have shown any effects on mental abilities suggestive of impairment of brain or cerebral function and cognition.(2) The inhalation of the combustion products of burning plant material is the cause of the only well-confirmed deleterious physical effects of medical marijuana. These adverse effects can be eliminated by using one of the non-combustion means of ingesting the mediation. Marijuana can be eaten in foods or inhaled using a vaporizer. The therapeutic agents in medical marijuana vaporize at around 190 degrees centigrade, while it takes the heat of combustion of around 560 degrees centigrade to generate the harmful components of marijuana smoke. A vaporizer heats the medical marijuana to the point where the therapeutic agents are released and can be inhaled, without getting the plant material hot enough to burn.(19) Cannabis And Blood Pressure Research Proposal 1. Possible Therapeutic Cannabis Applications for Psychiatric Disorders, Tod H. Mikuriya, M.D. 2. Marihuana, The Forbidden Medicine, Lester Grinspoon M.D., James B. Bakalar, Yale University Press, 1997 3. MARIJUANA AND TOURETTE'S SYNDROME, Journal of Clinical Psychopharmacology, Vol. 8/No. 6, Dec 1988 4. CANNABINOIDS BLOCK RELEASE OF SEROTONIN FROM PLATELETS INDUCED BY PLASMA FROM MIGRAINE PATIENTS, Int J Clin Pharm. Res V (4) 243-246 (1985), Volfe Z., Dvilansky A., Nathan I. Blood Research, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, P.O. Box 151, Beer-Sheva 84101, Israel. 5. Nelson, P. L. (1993). A critical review of the research literature concerning some biological and psychological effects of cannabis. In Advisory Committee on Illicit Drugs (Eds.), Cannabis and the law in Queensland: A discussion paper (pp. 113-152). Brisbane: Criminal Justice Commission of Queensland. 6. Marijuana And the Brain, by John Gettman, High Times, March, 1995 7. Cannabis for Migraine Treatment: The Once and Future Prescription?: An Historical and Scientific Review; Ethan B. Russo, M.D. 8. Marijuana and Medicine, Assessing the Science Base, Janet E. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr., Editors Division of Neuroscience and Behavioral Health, INSTITUTE OF MEDICINE 9. Marijuana Medical Handbook, by Tod Mikuriya, M.D. 10. Medicinal Uses of Cannabis, Tod H. Mikuriya, M.D. ©1998 11. Marihuana as Medicine: A Plea for Reconsideration; Lester Grinspoon M.D., James B. Bakalar; Journal of the American Medical Association (JAMA); June 1995 12. Report of the Indian Hemp Drugs Commission, 1893-1894, 7 vols. (Simla: Government Central Printing Office, 1894); D. Solomon, ed., The Marihuana Papers (Indianapolis: Bobbs-Merrill, 1966). 13. Mayor's Committee on Marihuana, The Marihuana Problem in the City of New York (Lancaster, Pa.: Jacques Cattell, 1944). 14. M. H. Beaubrun and F Knight, "Psychiatric Assessment of Thirty Chronic Users of Cannabis and Thirty Matched Controls," American journal of Psychiatry 130 (1973): 309; M. C. Braude and S. Szara, eds., The Pharmacology of Marihuana, 2 vols. (New York: Raven, 1976); R. L. Dombush, A. M. Freedman, and M. Fink, eds., "Chronic Cannabis Use," Annals of New Yorh Academy of Sciences 282 (1976); J. S. Hochman and N. Q. Brill, "Chronic Marijuana Use and Psychosocial Adaptation," American journal of Psychiatry 130 (1973):132; Rubin and Comitas, Ganja in Jamaica. 15. Institute of Medicine, Marijuana and Health (Washington, D.C.: National Academy of Sciences, 1982). 16. C. M. Culver and F W King, "Neurophysiological Assessment of Undergraduate Marihuana and LSD Users," Archives of General Psychiatry 31 (1974): 707-711; P.J. Lessin and S. Thomas, "Assessment of the Chronic Effects of Marijuana on Motivation and Achievement: A Preliminary Report," in Pharmacology of Marihuana, ed. Braude and Szara, 2:681-684. 17. Cognition and Long-Term Use of Ganja (Cannabis), Reprint Series, 24 July 1981, Volume 213, pp. 465-466 SCIENCE, Jeffrey Schaeffer, Therese Andrysiak, and J. Thomas Ungerleider Copyright 1981 by the American Association for the Advancement of Science 18. Rubin and Comitas, Ganja in Jamaica; W E. Carter, ed., Cannabis in Costa Rica: A Study of Chronic Marihuana Use (Philadelphia: Institute for the Study of Human Issues, 1980); C. Stefariis, J. Boulougouris, and A. I-iakos, "Clinical and Psychophysiological Effects of Cannabis in Long-term Users," in Pharmacology of Marihuana, ed. Braude and Szara, 2:659-666; P Satz, J. M. Fletcher, and L. S. Sutker, "Neurophysiologic, Intellectual, and Personality Correlates of Chronic Marihuana Use in Native Costa Ricans," Annals of the New York Academy of Sciences 282 (1976): 266-306. 19. Is Marijuana The Right Medicine For You?; Bill Zimmerman Ph.D., Rick Bayer M.D., and Nancy Crumpacker M.D.; (1998): pp. 125; Keats Publishing Inc. source: http://www.kortexplores.com/node/133 © International Association for Cannabis as Medicine1Case report Cannabis improves symptoms of ADHD http://66.218.69.11/...&...=1&.intl=us Cannabis as a medical treatment for attention deficit disorder "Why would anyone want to give their child an expensive pill... with unacceptable side effects, when he or she could just go into the backyard, pick a few leaves off a plant and make tea for him or her instead? Cannabinoids are a very viable alternative to treating adolescents with ADD and ADHD" WASHINGTON - As a California pediatrician and 49-year-old mother of two teenage daughters, Claudia Jensen says pot might prove to be the preferred medical treatment for attention deficit disorder - even in adolescents. While some wonder whether Jensen was smoking some wacky weed herself, the clinician for low-income patients and professor to first-year medical students at the University of Southern California said her beliefs are very grounded: The drug helps ease the symptomatic mood swings, lack of focus, anxiety and irritability in people suffering from neuropsychiatric disorders like ADD and attention deficit/hyperactivity disorder. "Cannabinoids are a very viable alternative to treating adolescents with ADD and ADHD.I have a lot of adult patients who swear by it." Under California state law, physicians are allowed to recommend to patients the use of cannabis to treat illnesses, although the federal government has maintained that any use of marijuana - medicinal or otherwise - is illegal. The federal courts have ruled that physicians like Jensen cannot be prosecuted for making such recommendations. Jensen said she regularly writes prescriptions recommending the use of cannabis for patients -particularly those suffering pain and nausea from chronic illnesses, such as AIDS, cancer, glaucoma and arthritis. She has also worked with one family of a 15-year-old - whose family had tried every drug available to help their son, who by age 13 had become a problem student diagnosed as suffering from ADHD. Under Jensen’s supervision, he began cannabis treatment, settling it on in food and candy form, and he has since found equilibrium and regularly attends school. But not everyone is so high on the idea of pot for students with neurological illnesses. Subcommittee Chairman Mark Souder, R-Ind., who invited Jensen to testify after reading about her ideas in the newspaper, was hardly convinced by her testimony. "I do believe that Dr. Jensen really wants to help her patients, but I think she is deeply misguided when she recommends cannabis to teenagers with attention deficit disorder or hyperactivity," he told Foxnews.com. "There is no serious scientific basis for using marijuana to treat those conditions, and Dr. Jensen didn’t even try to present one." Dr. Tom O’Connell, a retired chest surgeon who now works with patients at a Bay Area clinic for patients seeking medical marijuana recommendations, is working on it. He said cannabis not only helps pain, but also can treat psychological disorders. He is currently conducting a study of hundreds of his patients, whom he said he believes have been self-medicating with pot and other drugs for years, and he hopes to publish a paper on the subject soon. "My work with cannabis patients is certainly not definitive at this point, but it strongly suggests that the precepts upon which cannabis prohibition have been based are completely spurious," O’Connell said. Worse yet, he added, the prohibition has successfully kept certain adolescents away from pot who now turn to tobacco and alcohol instead. Jensen, who said she believes Souder invited her to testify to "humiliate me and incriminate me in some way," suggested that a growing body of evidence is being developed to back medical cannabis chiefly for chronic pain and nausea. She said it is difficult, however, for advocates like herself to get the funding and permission to conduct government-recognized tests on ADD/ADHD patients. "Unfortunately, no pharmaceutical companies are motivated to spend the money on research, and the United States government has a monopoly on the available cannabis and research permits," she told Congress. Studies done on behalf of the government, including the 1999 Institute of Medicine’s "Marijuana and Medicine: Assessing the Science Base," found that cannabis delivers effective THC and other cannabinoids that serve as pain relief and nausea-control agents. But these same studies warn against the dangers of smoking cannabis and suggest other FDA-approved drugs are preferable. "We know all too well the dangerous health risks that accompany (smoking)," said Rep. Elijah Cummings, D-Md., ranking member on the subcommittee, who like Souder, was not impressed by Jensen’s arguments. "It flies in the face of responsible medicine to advocate a drug that had been known to have over 300 carcinogens and has proven to be as damaging to the lungs as cigarette smoking," added Jennifer Devallance, spokeswoman for the White House Office of Drug Control Policy. The government points to Food and Drug Administration-approved Marinol, a THC-derived pill that acts as a stand-in for marijuana. But many critics say there are nasty side effects, and it’s too expensive for the average patient. On the other hand, Jensen and others say cannabinoids can be made into candy form, baked into food or boiled into tea. They say that despite the FDA blessing, giving kids amphetamines like Ritalin for ADD and other behavioral disorders might be more dangerous. "Ritalin is an amphetamine - we have all of these youngsters running around on speed," said Keith Stroup, spokesman for the National Organization for the Reform of Marijuana Laws. "Although it flies in the face of conventional wisdom, it’s nevertheless true that cannabis is far safer and more effective than the prescription agents currently advocated for treatment of ADD-ADHD," O’Connell said. Stroup said if Souder’s intention was to harangue Jensen, he was unsuccessful in the face of her solid and articulate testimony on April 1."It was a good day for her, and a good day for medical marijuana in Congress," he said. Nick Coleman, a subcommittee spokesman, said Souder doesn’t "try to humiliate people. "But to promote medical cannabis for teenagers with ADD... he does not feel that is a sound and scientific medical practice," Coleman said. While the issue of treating adolescents with medical marijuana is fairly new, the idea of using pot to treat chronically and terminally ill patients is not. Nine states currently have laws allowing such practices. A number of lawmakers on both sides of the aisle have added that they want the states to decide for themselves whether to pursue medical marijuana laws. Among those lawmakers are Reps. Ron Paul, R-Texas, a physician; Dana Rohrabacher, R-Calif.; and Barney Frank, D-Mass. "(Rep. Paul) believes there are some legitimate applications," like for pain and nausea, said spokesman Jeff Deist. "But the real issue is that states should decide for themselves." source: http://www.chanvre-i...-treatment.html Marijuana and ADD Therapeutic uses of Medical Marijuana in the treatment of Marijuana and ADD By Kort E Patterson Sam’s Story; Autism & Medical Marijuana Sam’s Story, Using Medical Cannabis to Treat Autism Spectrum Disorder ADD, ADHD & Medical Marijuana It was mentioned in the Portland newspaper that the Oregon Health Division is considering allowing medical marijuana to be used to treat Attention Deficit Disorder (ADD) under the Oregon Medical Marijuana Act. At first glance it might seem counter-intuitive to use a medication that has a public perception of decreasing attention to treat a condition whose primary symptom is a deficit of attention. But just as taking stimulants often calms those with hyperactivity, medical marijuana improves the ability to concentrate in some types of ADD. Categorizing The Condition Attention Deficit Disorder (ADD) is a very broad category of conditions that share some symptoms but appear to result from different underlying causes. Most seem to involve, at least in part, imbalances in neural transmitter levels and functions. Some experts in the field expect that the broad category of ADD will be refined in the future, with many conditions that are now diagnosed as ADD being recognized as separate disorders. The particular type of ADD under consideration for treatment with medical marijuana might better be termed "Racing Brain Syndrome" (RBS). A useful analogy for this mental condition is that of a centrifugal pump that is being over-driven. As the pump speed increases, cavitation sets in and the pump's output decreases. The faster the pump is driven the greater the cavitation until a point is reached where large amounts of energy are being input but nothing is being output. Without medication there is a sensation that thoughts flash through the brain too fast to "think" them. Medical marijuana slows the brain down sufficiently to achieve impressive improvements in functionality. This syndrome probably only afflicts a small minority of all those diagnosed with ADD. The condition doesn't respond to the standard ADD medications, indicating that it results from different underlying processes than other forms of ADD. Individuals with types of ADD that do respond to the standard ADD medications also tend to have a far different reaction to medical marijuana than those with RBS. At this point in our limited understanding of the condition, it appears that RBS would make a good candidate to be redefined as a separate condition outside of the general diagnosis of ADD. Treating ADD/RBS With Medical Marijuana There is some evidence available that medical marijuana has been found to be an effective medication for some types of ADD by other researchers in the field.(1) Unfortunately, ADD encompasses such a variety of conditions that the limited amount of research in the field leaves many of the effective therapeutic mechanisms under-investigated. Considering the regulatory difficulties in researching the effects of medical marijuana, it isn't surprising that the information regarding medical marijuana and ADD is largely anecdotal(2). Individuals with RBS tend to have a very low tolerance for most stimulants, and report even caffeine aggravates their disorder. The one exception appears to be low doses of Dextrostat. While Dextrostat does have a calming effect, it fails to address the higher level mental functions needed for complex intellectual demands. Larger doses of Dextrostat tend to produce undesirable mental and physical stimulation, greatly limiting the level of medication that can be tolerated. Medical marijuana remains the only single medication that provides an adequate solution for RBS, and remains a necessary component in a multi-drug approach. Dextrostat does appear to reduce the amount of medical marijuana needed by individuals with RBS to achieve a functional mental state. This reduction probably justifies continuing with Dextrostat as a means of reducing the quantity of medical marijuana that must consumed, as well as allow those with RBS to gain the maximum benefit possible within the quantity limitations of the OMMA. The green leaves of certain strains of medical marijuana appear to provide the best therapeutic effects for RBS. Experiments with Marinol seem to indicate that THC is involved, but is not the primary therapeutic agent. The therapeutic agent(s) most useful in treating RBS appear to be present in relatively low concentrations in medical marijuana. As such those with this condition must consume a larger quantity of medical marijuana in order to ingest a sufficient dosage of the target agent(s). This would explain why dried low-THC green leaves appear to be the most effective treatment. The patient can consume enough of this low-THC marijuana to acquire the levels of the needed active agent(s) necessary to treat the condition without in the process consuming sufficient THC to become intoxicated. Underlying Cause of RBS It has long been suspected that RBS involved a deficit of one or more neural transmitters. It was observed as long ago as the 1970's that high levels of adrenaline had a residual therapeutic effect in those with RBS. The effect was first noted in those engaged in such activities as skydiving. Individuals with RBS reported that their mental functions were improved in the days following skydiving. It was first assumed that adrenaline stimulated the production of all neural transmitters - including those that were in deficit. It's now thought that while adrenaline initially acts as a stimulant of neural transmitter production, it has a secondary effect of depleting neural transmitters. The limited effectiveness of Dextrostat, as well as additional information about the secondary effects of adrenaline, suggests the possibility that at least part of the underlying cause of RBS may also be a surplus of one or more neural transmitters. The partial solution offered by Dextrostat also suggests that at least some part of the condition results from those neural transmitters and/or hormones that are influenced by both Dextrostat and medical marijuana. The failure of Dextrostat to provide a complete solution suggests two possible alternatives: (1) that the effects of Dextrostat and medical marijuana are additive - with both influencing the same neural transmitters and/or hormones, and together delivering the required level of therapeutic effect; or (2) that the condition is the result of multiple imbalances, some of which are unaffected by Dextrostat, but all of which appear to be affected by medical marijuana. Potential Beneficial Therapeutic Effects The research that has been done on the therapeutic effects of medical marijuana on other conditions provides a number of potential mechanisms that may be involved in RBS. The following are documented effects of medical marijuana that appear to have some potential for involvement. Perhaps the most obvious possibility is suggested by the fact that both Dextrostat and medical marijuana influence the release and/or functions of serotonin(3)(4). Since both Dextrostat and medical marijuana appear to increase the apparent availability and effectiveness of serotonin, it would appear possible that a deficit of serotonin is involved in some way. There are over 60 cannabinoids and cannabidiols present in medical marijuana. The effect of most of these substances is at present largely unknown.(5) The discovery of a previously unknown system of cannabinoid neural transmitters is profound.(6) The different cannabinoid receptor types found in the body appear to play different roles in normal human physiology.(5) An endogenous cannabinoid, arachidonylethanolamide, named anandamide, has been found in the human brain. This ligand inhibits cyclic AMP in its target cells, which are widespread throughout the brain, but demonstrate a predilection for areas involved with nociception. The exact physiological role of anandamide is unclear, but preliminary tests of its behavioral effects reveal actions similar to those of THC.(7) Cannabinoid receptors appear to be very dense in the globus pallidus, substantia nigra pars reticulata (SNr), the molecular layers of the cerebellum and hippocampal dentate gyrus, the cerebral cortex, other parts of the hippocampal formation, and striatum - with the highest density being in the SNr. The Neocortex has moderate receptor density, with peaks in superficial and deep layers. Very low and homogeneous density was found in the thalamus and most of the brainstem, including all of the monoamine containing cell groups, reticular formation, primary sensory, visceromotor and cranial motor nuclei, and the area postrema. The hypothalamus, basal amygdala, central gray, nucleus of the solitary tract, and laminae I-III and X of the spinal cord showed slightly higher but still sparse receptor density.(5) While there are cannabinoid receptors in the ventromedial striatum and basal ganglia, which are areas associated with dopamine production, no cannabinoid receptors have been found in dopamine-producing neurons. According to the congressional Office of Technology Assessment, research over the last 10 years has proved that marijuana has no effect on dopamine-related brain systems.(6) However, cannabidiol has been shown to exert anticonvulsant and antianxiety properties, and is suspected by some to exert antidyskinetic effects through modulation of striatal dopaminergic activity.(3) It's been suggested that the cannabinoid receptors in the human brain play a role in the limbic system, which in turn plays a central role in the mechanisms which govern behavior and emotions. The limbic system coordinates activities between the visceral base-brain and the rest of the nervous system. Cannabis acts on memory by way of the receptors in the limbic system's hippocampus, which "gates" information during memory consolidation.(6) In addition, some effects of cannabinoids appear to be independent of cannabinoid receptors. The variety of mechanisms through which cannabinoids can influence human physiology underlies the variety of potential therapeutic uses for medical marijuana.(8) When the effects of cannabis on a "normal" brain are tracked on an electroencephalogram (EEG), there is an initial speeding up of brain wave activity and a reactive slowing as the drug effects wear off. The higher the dosage, the more intense the effects and longer the experience. There is an increase in mean-square alpha energy levels and a slight slowing of alpha frequency.(5) There is also an increase of beta waves reflecting increased cognitive activity. The distortion of time resulting from the "speeding up of thoughts" causes a subjective perception that there is a slowing of time.(9) As the cannabis effects wear off, stimulation gives way to sedation. The cognitive activity of the beta state gives way to alpha and theta frequencies. Theta waves are commonly associated with visual imagery. These images interact with thinking and disrupt the train of thought. Thinking can be distracted by these intrusions, with thought contents being modified to some extent depending on dose, expectations, setting, and personality.(9) Cannabis decreases emotional reactivity and intensity of affect while increasing introspection as evidenced by the slowing of the EEG after initial stimulation. Obsessive and pressured thinking is replaced by introspective free associations. Emotional reactivity is moderated and worries become less pressing.(10) Cannabis causes a general increase in cerebral blood flow (CBF). This increase in blood circulation is due to decreased peripheral resistance, which is in turn due to the dilation of the capillaries in the cerebral cortex. Changes in CBF affect the mental processes of the brain, with increases stimulating cognition, while decreases accompany sedation.(9) Relative Safety of Medical Marijuana "Marijuana is the safest therapeutically active substance known to man... safer than many foods we commonly consume." DEA Judge Francis L. Young, Sept. 6, 1988 "After carefully monitoring the literature for more than two decades, we have concluded that the only well-confirmed deleterious physical effect of marihuana is harm to the pulmonary system." Grinspoon M.D., James B. Bakalar, Medical Marijuana has been in use for thousands of years, and in spite of substantial efforts to find adverse effects, it remains the safest medication available for RBS. There has never been a single known case of lethal overdose. The ratio of lethal to effective dose for medical marijuana is estimated to be as 40,000 to 1. By comparison, the ratio is 3-50 to 1 for secobarbital and 4-10 to 1 for alcohol.(11) During the 1890s the Indian Hemp Drugs Commission interviewed some eight hundred people and produced a report of more than 3000 pages. The report concluded that "there was no evidence that moderate use of cannabis drugs produced any disease or mental or moral damage, or that it tended to lead to excess any more than the moderate use of whiskey."(12) The Mayor's Committee on Marihuana examined chronic users in New York City who had averaged seven marihuana cigarettes a day for eight years and "showed no mental or physical decline."(13) Several later controlled studies of chronic heavy use failed to establish any pharmacologically induced harm.(14) A subsequent government sponsored review of cannabis conducted by the Institute of Medicine, a branch of the National Academy of Sciences, also found little evidence of its alleged harmfulness.(15) Several studies in the United States found that fairly heavy marihuana use had no effects on learning, perception, or motivation over periods as long as a year.(16) Studies of very heavy smokers in Jamaica, Costa Rica, and Greece "found no evidence of intellectual or neurological damage, no changes in personality, and no loss of the will to work or participate in society."(17) The Costa Rican study showed no difference between heavy users (seven or more marihuana cigarettes a day) and lighter users (six or fewer cigarettes a day).(18) In addition, none of the studies involving prolonged and heavy use of medical marijuana have shown any effects on mental abilities suggestive of impairment of brain or cerebral function and cognition.(2) The inhalation of the combustion products of burning plant material is the cause of the only well-confirmed deleterious physical effects of medical marijuana. These adverse effects can be eliminated by using one of the non-combustion means of ingesting the mediation. Marijuana can be eaten in foods or inhaled using a vaporizer. The therapeutic agents in medical marijuana vaporize at around 190 degrees centigrade, while it takes the heat of combustion of around 560 degrees centigrade to generate the harmful components of marijuana smoke. A vaporizer heats the medical marijuana to the point where the therapeutic agents are released and can be inhaled, without getting the plant material hot enough to burn.(19) References: 1. Possible Therapeutic Cannabis Applications for Psychiatric Disorders, Tod H. Mikuriya, M.D. 2. Marihuana, The Forbidden Medicine, Lester Grinspoon M.D., James B. Bakalar, Yale University Press, 1997 3. MARIJUANA AND TOURETTE'S SYNDROME, Journal of Clinical Psychopharmacology, Vol. 8/No. 6, Dec 1988 4. CANNABINOIDS BLOCK RELEASE OF SEROTONIN FROM PLATELETS INDUCED BY PLASMA FROM MIGRAINE PATIENTS, Int J Clin Pharm. Res V (4) 243-246 (1985), Volfe Z., Dvilansky A., Nathan I. Blood Research, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, P.O. Box 151, Beer-Sheva 84101, Israel. 5. Nelson, P. L. (1993). A critical review of the research literature concerning some biological and psychological effects of cannabis. In Advisory Committee on Illicit Drugs (Eds.), Cannabis and the law in Queensland: A discussion paper (pp. 113-152). Brisbane: Criminal Justice Commission of Queensland. 6. Marijuana And the Brain, by John Gettman, High Times, March, 1995 7. Cannabis for Migraine Treatment: The Once and Future Prescription?: An Historical and Scientific Review; Ethan B. Russo, M.D. 8. Marijuana and Medicine, Assessing the Science Base, Janet E. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr., Editors Division of Neuroscience and Behavioral Health, INSTITUTE OF MEDICINE 9. Marijuana Medical Handbook, by Tod Mikuriya, M.D. 10. Medicinal Uses of Cannabis, Tod H. Mikuriya, M.D. ©1998 11. Marihuana as Medicine: A Plea for Reconsideration; Lester Grinspoon M.D., James B. Bakalar; Journal of the American Medical Association (JAMA); June 1995 12. Report of the Indian Hemp Drugs Commission, 1893-1894, 7 vols. (Simla: Government Central Printing Office, 1894); D. Solomon, ed., The Marihuana Papers (Indianapolis: Bobbs-Merrill, 1966). 13. Mayor's Committee on Marihuana, The Marihuana Problem in the City of New York (Lancaster, Pa.: Jacques Cattell, 1944). 14. M. H. Beaubrun and F Knight, "Psychiatric Assessment of Thirty Chronic Users of Cannabis and Thirty Matched Controls," American journal of Psychiatry 130 (1973): 309; M. C. Braude and S. Szara, eds., The Pharmacology of Marihuana, 2 vols. (New York: Raven, 1976); R. L. Dombush, A. M. Freedman, and M. Fink, eds., "Chronic Cannabis Use," Annals of New Yorh Academy of Sciences 282 (1976); J. S. Hochman and N. Q. Brill, "Chronic Marijuana Use and Psychosocial Adaptation," American journal of Psychiatry 130 (1973):132; Rubin and Comitas, Ganja in Jamaica. 15. Institute of Medicine, Marijuana and Health (Washington, D.C.: National Academy of Sciences, 1982). 16. C. M. Culver and F W King, "Neurophysiological Assessment of Undergraduate Marihuana and LSD Users," Archives of General Psychiatry 31 (1974): 707-711; P.J. Lessin and S. Thomas, "Assessment of the Chronic Effects of Marijuana on Motivation and Achievement: A Preliminary Report," in Pharmacology of Marihuana, ed. Braude and Szara, 2:681-684. 17. Cognition and Long-Term Use of Ganja (Cannabis), Reprint Series, 24 July 1981, Volume 213, pp. 465-466 SCIENCE, Jeffrey Schaeffer, Therese Andrysiak, and J. Thomas Ungerleider Copyright 1981 by the American Association for the Advancement of Science 18. Rubin and Comitas, Ganja in Jamaica; W E. Carter, ed., Cannabis in Costa Rica: A Study of Chronic Marihuana Use (Philadelphia: Institute for the Study of Human Issues, 1980); C. Stefariis, J. Boulougouris, and A. I-iakos, "Clinical and Psychophysiological Effects of Cannabis in Long-term Users," in Pharmacology of Marihuana, ed. Braude and Szara, 2:659-666; P Satz, J. M. Fletcher, and L. S. Sutker, "Neurophysiologic, Intellectual, and Personality Correlates of Chronic Marihuana Use in Native Costa Ricans," Annals of the New York Academy of Sciences 282 (1976): 266-306. 19. Is Marijuana The Right Medicine For You?; Bill Zimmerman Ph.D., Rick Bayer M.D., and Nancy Crumpacker M.D.; (1998): pp. 125; Keats Publishing Inc. source: http://www.onlinepot...cal/add&mmj.htm
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