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    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. For the millions of American’s suffering with the condition, fibromyalgia and its often severe symptoms affect their quality of life every single day. The condition can make it difficult to complete basic tasks, maintain relationships, and hold a job. Even more unfortunate, there is no cure for the disorder, and available treatments often fall short of providing the relief these patients need. This is why medical marijuana has been considered as a possible treatment for fibromyalgia. Understanding the condition, how it is typically treated, and how cannabis might help, will provide greater insight on how medical marijuana can make a difference from fibromyalgia patients. What is Fibromyalgia?Fibromyalgia is an often misunderstood medical condition that causes chronic pain throughout the body along with other related symptoms. Those with the condition often experience pain, tingling, and tenderness with no obvious cause. They can also experience mental and gastrointestinal symptoms. Many individuals with the condition require complex treatment plans, and some are unresponsive to current medical treatments. Fibromyalgia occurs more commonly in women and in those who have had certain infections, injuries, or emotional trauma. There may also be a genetic component to the condition, as it is more likely in families where one or more members have fibromyalgia. Unfortunately, the exact cause of fibromyalgia has yet to be determined. Individuals with fibromyalgia may experience a wide range of symptoms. The most common symptoms of fibromyalgia include: Pain and/or tenderness throughout the body Trouble sleeping or irregular sleep patterns Fatigue Nausea Irritable bowels and other gastrointestinal issues Irregular appetite Temperature sensitivity Morning stiffness Joint stiffness Headaches Painful menstrual periods Tingling feelings, especially in hands or feet Cognitive and memory issues Mood changes Depression and anxiety Vision problems It is estimated by the National Institute of Arthritis and Musculoskeletal and Skin Diseases that more than five million Americans are affected by fibromyalgia, making the disorder a significant one in the United States. Many individuals with the condition do not experience the relief they need from treatments to conduct normal activities, making it difficult to maintain a role in the workforce and affecting personal relationships. Current Treatments for FibromyalgiaFibromyalgia is known for being difficult to treat, and there is currently no cure for the condition. An estimated 35 to 40 percent of people with fibromyalgia do not find relief from conventional medications and treatments. Even when treatment is possible, it requires a multipronged approach to provide symptom relief. Many patients require multiple medications along with specialized diets, exercise plans, and other lifestyle changes. Some common medication-based treatments include antidepressants, anti-anxiety medications, fibromyalgia medications, opioid painkillers, or extremely expensive growth hormones. These medications each address separate symptoms, requiring the use of more than one prescription for most patients. Additional medications to address nausea, insomnia, and other symptoms of fibromyalgia may also be needed depending on the patient and their unique symptoms. While many find relief with these medications, for those whose fibromyalgia is not responsive treatment current medication fall short. Other therapies to address muscle weakness, aid in pain management, and improve mental state are often recommended as part of a fibromyalgia treatment plan to tackle symptoms that are not corrected with traditional medication. This can range from working with a physical therapist to acupuncture to restrictive diets and costly supplements. Reduced stress and improved sleep may also improve fibromyalgia symptoms. Even with these options, many patients still have been unable to find relief. This is what lead some patients and medical practitioners to suggest that fibromyalgia and medical cannabis might make sense together. As reported by CNN, some patients have found medical marijuana to provide greater relief from fibromyalgia symptoms than a combination of other therapies. Medical Marijuana for FibromyalgiaOne of the main reasons that medical marijuana was first considered for fibromyalgia is its known pain-relieving qualities, but marijuana is also able to treat several of the condition’s other symptoms. Medical cannabis can be prescribed to treat a variety of symptoms and conditions, including nausea, muscle spasms, appetite issues, Crohn’s disease and colitis, and several other conditions, all of which can occur with fibromyalgia. This makes the primary benefit of using marijuana as a fibromyalgia treatment its ability to treat multiple symptoms that previously required the use of multiple medications. Fibromyalgia patients may see a benefit in pain relief, nausea and appetite, bowel issues, mental symptoms and mood issues, and insomnia and sleep issues. This is a huge benefit for many patients who are either unable to find relief or who are dealing with a variety of medications to treat their symptoms. Although more research is needed to determine how medical marijuana may be used to treat or even cure fibromyalgia, several research studies have shown promising results when cannabis was used to treat fibromyalgia patients. As a fibromyalgia treatment marijuana was shown to address multiple symptoms, including fibromyalgia pain, muscle and joint stiffness, overall mood, and ability to relax. Some studies and research related to using marijuana to treat fibromyalgia have shown positive results. In one study where symptoms and mood were tracked by individuals with fibromyalgia, a statistically significant reduction in pain and stiffness and an improvement in relaxation and feelings of well-being were reported by the portion of the group that used cannabis as a treatment. Another study from Canada, has shown that a fibromyalgia marijuana treatment improved sleep for patients, which is often one of the most difficult symptoms to overcome. Doctors there have begun prescribing it to patients as a viable treatment. Other medical research has been geared at the use of medical cannabis and synthetic marijuana to treat chronic conditions like fibromyalgia. In the United States, synthetic marijuana medications have been tested extensively and approved for use in treating certain conditions for cancer patients. Treating Fibromyalgia with Medical MarijuanaWhen treating fibromyalgia cannabis can be used a variety of ways. The studies mentioned above and additional research on marijuana’s medicinal properties have shown that two compounds in cannabis seem to be the most beneficial. This includes THC and CBD, which are cannabinoids. These compounds interact with the body’s endocannabinoid system, which interacts with multiple other systems in the body. For certain medical conditions, a high concentration of either THC or CBD is recommended. Fibromyalgia patients appear to benefit from both compounds, so treatment cannabis strains should contain both. This is because the various symptoms of fibromyalgia are impacted by one or the other. THC assists with certain issues, including sleeping issues and improved mood, while CBD assists with others like pain and spasms. Studies have also looked at the way marijuana is taken when treating fibromyalgia and other similar conditions. Studies have been done using patients who smoked or inhaled marijuana as well as those who took cannabis orally, and both methods were shown to provide similar symptom improvement. Although there are pros and cons to every method of cannabis ingestion, inhaling is generally considered the most effective because it provides relief much faster than other methods. Recent testing has turned to other delivery methods, including a CBD patch which is being looked at for the treatment of fibromyalgia and neuropathic pain. CBD is known for its pain-relieving and anti-inflammatory abilities, and the patch may be a better way to absorb key compounds and control dosing while providing relief directly to the area. Why are People Turning to Marijuana to Treat Fibromyalgia Pain?Although additional research is needed to identify how medical marijuana card online may affect fibromyalgia patients, many have already begun using cannabis to treat their symptoms. Some patients report that marijuana has finally provided them the relief they need after traditional medicines failed them. According to these patients, the link between fibromyalgia and weed is a simple one – it works. This is especially important to individuals who have not found relief for some of the most severe symptoms of fibromyalgia. Additionally, the medications often prescribed to treat fibromyalgia symptoms can have severe side effects. Antidepressant medications can cause nausea, weight gain, sexual problems, insomnia, and more. This can actually worsen some of the symptoms of the disease. Addiction is also a problem, especially in cases where the pain is severe enough for opioid pain medications, which have been shown to be highly addictive. Marijuana provides a solution for fibromyalgia symptoms without the harsh side effects. Fibromyalgia is a condition that can be difficult to treat because of the wide array of symptoms it causes. Traditional treatments fall short of providing relief, and a large percentage of patients do not respond to these therapies. Studies using medical marijuana to treat fibromyalgia symptoms have shown promising results, improving pain levels, stiffness, mood, and sleep quality for some patients, including those who were dissatisfied with other medical options. While more research is needed to fully understand how cannabis and fibromyalgia interact, many patients are making the switch and reporting symptom improvements.
  3. 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.
  4. The List is just too darn big to be sent as one attachment- some email providers simply can't handle it! So, here is the first section of the new January 2014 List- "CONDITIONS and RELATED ARTICLES". It will be the most useful for the majority of folks. Please feel free to forward the List to all of your friends. Every person we educate brings us one vote closer to legalization! Granny edit : ek I have all the parts here, Take em and share em. http://ommppayitforward.bugs3.com/pdf/GSCListJan2014%20Dict.pdf http://ommppayitforward.bugs3.com/pdf/GSCListJan2014CONDITIONS.pdf http://ommppayitforward.bugs3.com/pdf/GSCList%20Jan2014PHYTO.pdf http://ommppayitforward.bugs3.com/pdf/GSCList%20Jan2014SYNTH.pdf http://ommppayitforward.bugs3.com/pdf/GSCListJan2014OLD.pdf http://ommppayitforward.bugs3.com/pdf/GSCListJan2014ENDO.pdf
  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. LowWater

    New Guy, New Site

    Greetings, This, not counting my introductory greeting is my first post. I curate a Pinterest Site on medicinal cannabis targeted toward folks 65 and older. Don't let that disuade you from checking it out. Commentary is most welcome. It's a pleasure to be digitally surrounded by Oregonians. I'm temporarily maroooned in Central New York State - a town called Troy outside of Albany. Imagine Salem, now imagine that you drove 200 miles from where you lived to get to Salem for some weekend excitement. That's Troy. In longhand: http://www.pinterest.com/lowwater/
  7. 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
  8. 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..
  9. 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
  10. 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. Abstr. 1952, 48, 78326 [PubMed] ( Ferenczy, L., Gracza, L., and Jakobey, I. Naturwissenschaften 1958 45 188[CrossRef], [CAS] © Krejci, Z. Pharmazie 1958 13 155 156[PubMed], [CAS] (d) Rabinovich, A. S., Aizenman, B. L., and Zelepukha, S. I. Mikrobiol. Zh 1959 21 40 48 (PubMed ID 14435632) [PubMed] (e) Turner, C. E., Elsohly, M. A., and Boeren, E. G. J. Nat. Prod. 1980 43 169 243[ACS Full Text ], [PubMed], [CAS] 4. Schultz, O. E., and Haffner, G. A. Z. Naturforsch. 1959 14b 98 100[CAS] 5. Turner, C. E., and Elsohly, M. A. J. Clin. Pharmacol. 1981 21 283S 291S[PubMed], [CAS] 6. Elsohly, H. N., Turner, C. E., Clark, A. M., and Elsohly, M. A. J. Pharm. Sci. 1982 71 1319 1323[CrossRef], [PubMed] 7. Van Klingeren, B., and Ten Ham, M. Lab. Chemother. Natl. Inst. Public Health 1976 42 9 12 ; Chem. Abstr. 1976, 85, 14622 [CAS] 8. Molnar, J., Csiszar, K., Nishioka, I., and Shoyama, Y. Acta Microb. Hung. 1986 33 221 231[PubMed], [CAS] 9. Barrett, C. T., and Barrett, J. F. Curr. Opin. Biotechnol. 2003 14 621 626[CrossRef], [PubMed], [CAS] 10. Gibbons, S. Nat. Prod. Rep. 2004 21 263 277[CrossRef], [PubMed], [CAS] 11. Stavri, M., Piddock, L. J. V., and Gibbons, S. J. Antimicrob. Chemother. 2007 59 1247 1260[CrossRef], [PubMed], [CAS] 12. Smith, E. C. J., Kaatz, G. W., Seo, S. M., Wareham, N., Williamson, E. M., and Gibbons, S. Antimicrob. Agents Chemother. 2007 51 4480 4483[CrossRef], [PubMed], [CAS] 13. Richardson, J. F., and Reith, S. J. Hosp. Infect. 1993 25 45 52[CrossRef], [PubMed], [CAS] 14. Kaatz, G. W., Seo, S. M., and Ruble, C. A. Antimicrob. Agents Chemother. 1993 37 1086 1094[PubMed], [CAS] 15. Ross, J. I., Farrell, A. M., Eady, E. A., Cove, J. H., and Cunliffe, W. J. J. Antimicrob. Chemother. 1989 24 851 862[CrossRef], [PubMed], [CAS] 16. Gibbons, S., and Udo, E. E. Phytother. Res. 2000 14 139 140[CrossRef], [PubMed], [CAS] 17. (a) Mechoulam, R., McCallum, N. K., and Burstein, S. Chem. Rev. 1976 76 75 112[ACS Full Text ], [CAS] ( Elsohly, M. A., and Slade, D. Life Sci. 2005 78 539 548[CrossRef], [PubMed], [CAS] 18. (a) Ghosh, R., Todd, A. R., and Wilkinson, S. J. Chem. Soc. 1940 1393 1396[CrossRef] ( Bastola, K. P., Hazekamp, A., and Verpoorte, R. Planta Med. 2007 73 273 275[CrossRef], [PubMed], [CAS] 19. Cox, R. A., Conquest, C., Mallaghan, C., and Maples, R. R. J. Hosp. Infect. 1995 29 87 106[CrossRef], [PubMed], [CAS] 20. Castaldo, S., and Capasso, F. Fitoterapia 2002 73 S1−S6[CrossRef], [PubMed] 21. Razdan, R. K., Dalzell, H. C., and Handrick, G. R. J. Am. Chem. Soc. 1974 96 5860 5865[ACS Full Text ], [PubMed], [CAS] 22. Baek, S. H., Srebnik, M., and Mechoulam, R. Tetrahedron Lett. 1985 26 1083 1086[CrossRef], [CAS] 23. Appendino, G. Unpublished results . 24. Bancroft, E. A. J. Am. Med. Assoc. 2007 298 1803[CrossRef] 25. Mechoulam, R., and Gaoni, Y. Tetrahedron 1965 21 1223 1229[CrossRef], [PubMed], [CAS] 26. Simor, A. E., Stuart, T. L., Louie, L., Watt, C., Ofner-Agostini, M., Gravel, D., Mulvey, M., Loeb, M., McGeer, A., Bryce, E., and Matlow, A. Antimicrob. Agents Chemother. 2007 51 3880 3886[CrossRef], [PubMed], [CAS] 27. McGrath, K. G. Eur. J. Cancer Prev. 2003 12 479 485[CrossRef], [PubMed], [CAS] 28. Hazekamp, A., Peltenburg, A., Verpoorte, R., and Giroud, C. J. Liq. Chromatogr. Rel. Technol. 2005 28 2361 2382[CrossRef], [CAS] 29. Vailancourt, V., and Albizati, K. F. J. Org. Chem. 1992 57 3627 3631[ACS Full Text ] 30. Mechoulam, R., and Gaoni, Y. Tetrahedron 1965 21 1223 1229[CrossRef], [PubMed], [CAS] My link
  11. 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
  12. https://www.youtube.com/embed/kFgrB2Wmh5s?feature=player_embedded The above video shows Colorodo congressman Poll questioning a top DEA official about medicinal marijuana, and it's level of harm in relation to other Schedule 1 drugs. His conclusion is brilliant . . . Must see ! <KZ>
  13. WWII Chemical Exposure Spurs Obesity, Autism, Researcher Says May 21 (Bloomberg) -- The World War II generation may have passed down to their grandchildren the effects of chemical exposure in the 1940s, possibly explaining current rates of obesity, autism and mental illness, according to one researcher. David Crews, professor of psychology and zoology at the University of Texas at Austin, theorized that the rise in these diseases may be linked to environmental effects passed on through generations. His research showed that descendants of rats exposed to a crop fungicide were less sociable, more obese and more anxious than offspring of the unexposed. The results, published today in the Proceedings of the National Academy of Sciences, are part of a growing field of study that suggests environmental damage to cells can cause inherited changes and susceptibility to disease. Crews said his findings are applicable to humans. "We should be very careful about overstating what looks like basic science with public health implications," Feinberg said in an interview. "Currently we don't have enough evidence showing that these fungicides are causing common human disease through an epigenetic mechanism. It's research that's well worth doing, but it's clear that that hasn't been shown." Read more: http://www.sfgate.co...L#ixzz1vYC5xs9j KTLA 5 news Los Angeles has reported on a family in southern California who, after a series of worsening autism symptoms exhibited by their son, resorted to medical marijuana. The results have been wonderful, according to the boy's parents. Ten-year -old Sam's father told reporter Cher Calvin that his son had been hurting other children at school, pulling the television down, destroying furniture, etc .He would have to put the boy in a hold for an hour, while he had spasms, until he eventually calmed down. The parents had consulted the conventional 'experts'; doctors who put Sam on prescription drugs, which resulted in the boy gaining twenty pounds. "He was getting more dangerous, bigger, stronger", recalled Sam's mom. Within 20 minutes effects were clear, recalls the reporter who spent some time with the family. He was "calm, relaxed and social" after taking his "spec of hash" in front of the news crew. "The more I tell people the more comfortable I am", says the mother when asked how she explains this treatment to others. A Dr. Tolcher, consulted by KTLA, says this is intriguing, but needs more research. Read the full article here... Sam’s Story: Using Medical Cannabis to Treat Autism Spectrum Disorder Background on Sam Sam is an eight-year-old male. He was diagnosed with Pervasive Developmental Delay- Not Otherwise Specified (PDD-NOS) when he was two and one-half years old by a pediatric psychiatrist at the M.I.N.D. Institute, UC Davis Medical Center. He was re-diagnosed at the M.I.N.D. Institute in October of 2007 with Autism Spectrum Disorder (ASD). As the psychiatrist told Sam’s mom and I, “Sam is a poster child for ASD”. Sam has lowered cognitive abilities and lowered verbal skills. Sam lives with his mom, dad and his younger sister who is six years of age. She is a typical child with no physical or mental health issues. Sam was adopted at birth. He had no prenatal issues and was a healthy infant. At around 18 months of age he began exhibiting ASD like behaviors and after six months of reassurances by his primary doctors that he was fine Sam was diagnosed with ASD. Since his diagnoses he has received special education services, speech therapy, occupational therapy, and behavioral therapy. He had been on the Gluten-Casein Free Diet (GCFD). He has been treated by a doctor (supposedly one of the best in the country) who treats ASD patients following the Defeat Autism Now (DAN) protocol which emphasizes a “BioMedical” approach established by Dr. Rimland the founder of Autism Society of America and the Autism Research Institute in San Diego, CA. As a family we have spent tens of thousands of dollars trying to help Sam. Even though as a teacher I have full coverage insurance, many of the services and doctors Sam has seen are not covered under my plan. Blue Cross of California still categorizes ASD as a “mental illness” instead of an “organic disorder” which precludes it from receiving the coverage a typical physical illness would be granted. I only mention this because since Sam was diagnosed with ASD we have devoted ourselves to helping him. This devotion has been in the forms of time, effort, education, therapy cost, medical costs, conferences, parent support groups, and most importantly love. Sam’s Strengths Sam loves people and he loves to “be on the go”. He has been to Disneyland four times, been camping many times, and has been to San Diego to visit the zoo, Wild Animal Park and Sea World. Sam loves to go to San Francisco Giant and Sacramento Kings games and loves to travel to San Francisco. Sam is our gift from God and we love him just as he is. Many tears have been shed from worry and from the joy of watching Sam achieve things parents of typical children take for granted. There have many moments of laughter and warmth given to us by our quirky, sweet, lovable, little boy. Purpose of this Journal I write this journal for Sam and other children like him. We almost lost our little boy to ASD and pharmaceuticals. By the grace of God and the help of a little Medical Cannabis (MC) we have him back. Maybe this journal can give other parents hope when all else seems dark and hopeless. Maybe this journal can prompt others to tell their stories if they have treated their ASD child with Medical Cannabis (MC). Even more important would be some legitimate scientific studies conducted to determine the effectiveness of MC to treat symptoms of Autism. I never wanted to be an advocate for Medical Cannabis (MC). I do not drink alcohol, take marijuana, or any other psychoactive drug. However, this experience has been so profound and dramatic that I feel no choice but to speak out on the issue. I understand the political and legal sensitivity of giving an eight-year-old child medical cannabis but if one child and family can be helped from my disclosure any risk to myself is acceptable. As a parent, I only want to help my son. No one ever questioned our decision to give our son the potpourri of pharmaceuticals prescribed by his doctors that, in my opinion, almost destroyed him. My wife and I both have very conservative parents and families who are very much opposed to any type of “illegal” drug use. We have their complete support. They witnessed Sam’s deterioration over the last year and they saw his almost miraculous turn around once we started using the MC. We have only disclosed treating Sam with MC to our closest family. We have shared the information with Sam’s primary pediatrician on the recommendation of Sam’s MC Doctor. The pediatrician has been supportive in an “off the record” manner. He has been Sam’s pediatrician since birth and he knows that we are responsible parents. Sam’s Educational Background Sam has had significant difficulty in school. He did well in preschool but began having constant problems once he entered Kindergarten. After a few months in a Kindergarten Special Day Class (SDC) Sam was removed from his neighborhood school and placed in a more specialized program for children with ASD. In 1st grade he was removed from that program and placed in a very restrictive setting that deals only with ASD kids (also public school). The population of that program was much lower than Sam, i.e., he was the only verbal child out of 12. Throughout this time Sam continued to have severe behavioral problems. To begin the 2007-08 school year he was placed back at his home school. His negative acting out became so intense and frequent that he was only able to attend school for 3 hours each day and was getting sent home at least 2 days each week. He was extremely unhappy at school and this unhappiness seemed to compound the increasing difficulty he was having at home. In December of 2007 Sam was placed in a Non Public School setting due to his aggressive, destructive, unsafe and antisocial behaviors. Data from a Functional Analysis Assessment done over a month period of time by a Behavioral Intervention Specialists (BIP) showed that Sam was having anywhere from 10-20 hitting, pushing, knocking things over, running off incidents per each 3 hour day. In summary, school was a disaster. Sam wasn’t learning anything and the teacher and his one-on-one aide were just trying to prevent him from hurting himself, them, or other children. Medical Intervention with Pharmaceuticals Throughout this time we were encouraged by school personnel and his doctors to keep trying different medications until we found one that would help him. We were told that this could be a long process because kids with ASD were extremely sensitive to medications in general and that there was no one drug that worked for every kid. We were constantly reminded of the success stories of other children. Unfortunately, taking any of the medications prescribed by his doctors never helped Sam. On the contrary, Sam’s mom and I were seeing a dramatic escalation of his anti social behaviors at school and at home. We had never had such intense problems at home. Sam’s condition imminently threatened the safety of our six-year-old daughter whom he began hitting on a regular basis. There were times when I would have to physically restrain Sam because he was in such a rage. He would go around the house yelling and knocking things over as if he were going crazy. He would try to run out of the house at 10 PM in the rain with no shoes on. Our home became a lock down facility. We were all miserable and Sam just kept getting worse. The future looked bleak. All this time we were going through a litany of medications to "help" him. Over a two-year period we did trials with Respirdol and Abilify (atypical antipsychotics), Ritalin and Adderall (amphetamines), Prosac, Paxil and Celexa (serotonin reuptake meds), and Tenex (Guanfacine), which is a blood pressure medication. We have a cupboard full of prescriptions for Sam. We tried different versions of the same type medications. We were encouraged to keep trying a medication until we knew for sure it worked or didn't work. The problem was he was having significant negative reactions to each medication he would try. He gained 10 pounds in 6 weeks on the Respirdol. Some of the meds, like the amphetamines, were obviously ineffective but others like the Abilify, Resperdal, and Paxil took time to develop negative side effects. The last medicine we tried was the Celexa. He was on it for 2 days in December and had a severe negative reaction. To put it bluntly, he "flipped out" on the medication. We stopped giving it to him immediately but the negative effects lingered with Sam for weeks. At that point we took Sam off all medication. His doctors recommended we try Depakote next. At this point, we were fearful that we would be able to manage him at home either with or without medication. Decision to Use Medical Cannabis At this point it was clear that the medications being prescribed by his doctors were not only failing to help Sam but they were harming him. He had gained significant weight, had an increase of aggressive and unpredictable behaviors and, most alarmingly to us, became very distant to those he had always loved so much. He began hitting his grandmothers and sister, and did not engage with his parents as he once did. He even became distant to me, his dad, the one person whom he had always had the most attachment. It was heartbreaking to watch him slip away. It was like the Sammy we had known was disappearing and we feared that he would steadily slip into greater isolation. There were several episodes that were so bad that we considered taking him to the hospital. My wife came to me with the suggestion that we consider treating Sam with Medical Cannabis. She had found information on the Internet that documented another parent’s success in treating her son who had similar characteristics to Sam with Medical Cannabis. I researched the subject myself and found an article written by Dr. Bernard Rimland from the Autism Research Institute that authenticated the parent’s story and stated the he would be more in favor of trying MC before he would more “toxic” pharmaceuticals. The article can be found at the following address (http://www.autism.org/marijuana.html). After discussing it with my wife and Sam’s grandparents, we decided to pursue it further. I knew very little about getting a recommendation from a doctor but was able to contact a doctor in my local area who recommends MC to patients. We had no idea how to obtain marijuana and we didn’t want to do anything illegal. We made an appointment with the MC doctor and gathered up all Sam’s medical and school records The doctor reviewed the case, examined Sam, and educated us on Medical Cannabis. He also made it clear that we would need to share information with Sam’s primary pediatrician. Additionally, we discussed the sensitivity of the issue and the risk that we were taking. As a team, we decided to maintain a “need to know policy” regarding Sam’s new medication. It was decided that school personnel did not need to know. Sam’s mom and I learned that in California a physician can “recommend” MC. It is not called a prescription but a recommendation. We also discovered that we would be able to obtain the MC locally through a Cooperative. Using Medical Cannabis to Treat Sam I have been keeping a journal since the trial began. The entries were daily to begin. After the first three weeks I reported every three to four days. I am not including every journal entry in this paper because it would be too long. January 8th, 2008 Today was the first day we gave Sam MC. We obtained the medicine around 3:00 PM. Because Sam is such a finicky eater we were very concerned about putting the medicine in baked goods. We wanted to give him the same amount of medicine at the same times each day and we knew that the baked goods could be problematic. Sam doesn’t like to eat breakfast before school and has an almost uncanny ability to detect anything that we place in his food. Often, he smells food before eating. Due to these considerations, we decided to give him the MC orally, in the form of Hashish. At 4:00 PM we administered his first dose. We gave him an amount that was about the size of a BB. We rolled the dose into a tight ball and buried it in a spoonful of yogurt. We told him he was taking a new medicine. He chewed the MC when he discovered it in the yogurt. He complained of the taste. We wanted to start out with a very small dose. Sam had been having another horrible day before the dose. After 30 minutes we could see the MC was beginning to have an effect. Sam’s eyes got a little red and got a bit droopy. His behavior became relaxed and far less anxious than he had been at the time we gave him the MC. He started laughing for the first time in weeks. My wife and I were astonished with the effect. It was as if all the anxiety, rage and hostility that had been haunting him melted away. That afternoon and evening his behavior was steady and calm. He started talking to us and interacting with us again. Sam’s was physically more relaxed and began initiating physical contact with the motivation being affection instead of aggression. It was amazing! He went to sleep that night with no problem and slept through the night. January 9th, 2008 Gave Sam about ½ dose (1/2 BB) of MC at 7:00 AM. He was not attending his new school yet so spent the day with Grandparent while we were at work. He had rough morning. Hitting, yelling, non-compliance, trying to jump in their freezing cold pool, and running out the front door. Re-dosed Sam at 3:30 PM when I got home from work. I gave him a BB sized dose, as I had the previous day. I feared that our experience was an anomaly and that, like all the other meds, it was just false hope. After 30 minute of giving Sam the dose his behavior deescalated to the levels it was the previous night. He was calm, happy, affectionate, more verbal, more compliant, and much more predictable. I noticed that he was open to conversation and even receptive to some short reading instruction. His reduced anxiety level made his behavior manageable and even agreeable. He was perseverating about certain things far less and we were able to redirect him far more quickly and effectively when he did get upset or need correction. January 10th, 2008 Gave him BB sized dose at 7:00 AM. He was staying with his Grandparents again for the day because he was not in school and we had to work. Before 8:00 AM he had a few episodes of acting out. He was becoming agitating and anxious and then around 8:20 my mom noticed that the MC was beginning to take effect. She described it to me as follows. “It was like a wave of calmness just swept over him and he changed from being a monster into a loveable, little boy”. When I got home from work he was still doing great. I didn’t give him an afternoon dose and he was fine for the rest of the day. Slept fine that night. January 11th, 2008 BB sized dose at 7:00 AM. Spent day with his mom. Had one blow out on walk when he wanted to jump in a small creek. No PM dose was necessary. Improved cooperative play with his sister. His sister came to me in disbelief when Sam was playing with her. She said’ “Sam is acting like a regular brother today”. When she told me that I just cried because here was this little girl who had lived in such fear, for so long, finally getting a brother she could love. Sam laughed and played. Again, the results we were getting far exceeded anything we could have imagined. January 12th, 2008 ¾ BB sized dose at 8:00 AM. It is a Saturday. Did Ok up to 2:00 PM and started to get agitated and anxious for an hour or so. Re-dosed him at 3:00 PM with ¾ size BB and within 1 hour he has calm again. That afternoon around 4:00 PM he lay down on our bed and took a nap. He rarely naps but fell asleep for an hour. Woke up happy and had a good evening. January 13th, 2008 8:00 AM dose; 1 BB size; Sunday; plans to go to Boat and RV show. Sam did great at the boat show. No running off, easily redirected, no yelling, and happy. It’s like he is a bit elevated and tipsy. He does look a bit “high” to us but it would never be noticeable to anyone else. His speech is clear (no slurring) and his gross or fine motor coordination are normal. In fact, his speech is moderately improved on the medication (both expressively and receptively). His anxiety level is greatly reduced and it just seems that he can concentrate better for longer stretches of time. This may contribute to the improved language skills we are noticing. If I scaled his anxiety from 1-10, (10 being extreme anxiety and 1 being no anxiety at all) I would place him at a 3 for today. Prior to the MC trial that began Jan. 8th, I would have placed him at a 10. No aggressive behaviors. No hitting, kicking, or threatening to do so. Sam is displaying much greater affection and is more compliant and social. He still has deficits in these social areas but far less pronounced than before the MC trial. January 18th, 2008 The following dosage is what we give Sam. The form of MC is hashish. ¾ BB size dose of MC at 7:00 AM ¾ BB size dose of MC at 3:00-4:00 PM (if necessary) The MC continues to be a very effective medication. Sam aggression has decrease dramatically. Prior to the medication trial, Sam was averaging 4-5 major outbursts per hour at home and an even greater frequency at school (see Functional Analysis Data Summary). An outburst could last minutes or hours. The behaviors included hitting, threatening to hit, kicking, throwing things, knocking things over, destroying property, yelling, crying, running off, and doing other unsafe acts like climbing over fences and leaving the house without supervision at night. Once Sam got into an agitated state it was extremely difficult to redirect him or get him to “move on” to something more positive. I really like the flexibility we have with the MC. There have been afternoons where a dose hasn’t been necessary. We don’t want to give him any medication unless we see symptoms that justify it. The AM dose is consistent because he is going to school but the PM dose can be eliminated. We have been giving him the PM dose 4 out of 5 days on average. Another convenience of the MC is that we can adjust his dose slightly depending on certain variables. If we something special planned, we can adjust the dose. For example, last night our daughter was given a Student of the Month award. There was a ceremony at the school board meeting that lasted 45 minutes or so. Sam was able attend and sit throughout the ceremony without incident. He was able to enjoy it and obviously, for us as parents, it was great that we were both able to be there for our daughter. This is in complete contrast to what usually happened to us when we had to take Sam somewhere like this. Before Christmas and prior to him being on MC, our daughter performed in a school musical. Within 10 minutes, I had to leave with Sam because he would not sit down and he began yelling when we tried to get him to stay and watch. This incident pretty much illustrates what life was like for us before this medication. I am not saying that this wouldn’t happen again but now we feel we have a chance for Sam to be successful in situations where we had little hope before. January 20th, 2008 Since the MC trial began, Sam has not had one act of hitting, kicking or threatening to hit. This includes school and home. SAM HASN’T GONE THIS LONG WITHOUT AGGRESSIVE BEHAVIORS IN YEARS. Additionally, the following improvements have occurred. I have classified these behavioral improvements into the three categories; Reduced Behaviors, Significant Improvements, and Mild Improvements. Reduced Behaviors Reduced aggression Reduced anxiety Reduced mood swings Reduced crying for no reason Reduced negative self talk Reduced obsessive/compulsive behavior Reduced non compliance Reduced running off and escape behaviors Significant Improvements Improved attitude and happier. Shares happiness with others appropriately. (Before the MC trial, the only time Sam laughed was when others were angry, crying or hurt) Increased flexibility to changes in routine or plans Quicker transition from being upset to being OK Improved affection to others Improved concentration and on task behavior at school Improved physical well-being. Far less complaining of stomachaches (probably because of being off other prescriptions) and more typical diet (the pharmaceuticals either made him habitually starving (Respirdol and Abilify) not hungry at all (Adderall, Ritalin) or caused him to have stomach irritation (Paxil, and Celexa). As I’ve stated, we feel much better about giving Sam MC that we did giving him the pharmaceuticals. Mild Improvements Improved language (receptive and expressive) Reduced self stimulation with finger play and fingers to mouth Reduced hyperactivity Increased ability to learn new information Improved sociability with peers February 21st, 2008 Sam continues to do great! He is getting great reports from school. His teachers write daily in a school journal. There has not been one negative entry and they are considering placing him in a more typical setting. Here are a few entries. 2-7-08 “Sam had another great day. He is such a joy to be around. His all day smiles and giggles are contagious.” 2-8-08 “John and I are so proud of Sam. He had a great day! He earned a trip to the barn this afternoon.” 2-20-08 “Sam did great! Today was the “Safety Fair”. Sam was awesome. He participated at each booth.” 2-21-08 “Another great day. We are currently working with Judith to develop a reading program that meets his needs. He always seems so excited to do his work and does great transitioning”. 2-27-08 Sam did great today! He was so awesome at the talent show. We won 3rd place!” Removing the Medical Cannabis After discussing the matter with Sam’s MC doctor, we decided to not give Sam any Medical Cannabis before school for a week or so to see if some of the negative behaviors returned. I concluded there were three main variables that could have accounted for Sam’s major improvement. One was the medical cannabis, two was his new school, and three was that he was no longer on any kind of prescription pharmaceuticals. On February 28th and February 29th (Thursday and Friday) Sam went to his new school for the first time without MC. On both days Sam had acting out behavior that his teachers had not previously seen. He didn’t hit but he did knock things over in his classroom and did a lot of negative self-talk. The staff was able to get him turned around pretty quickly but they were concerned that he was acting out at all. They had not seen any of this behavior since he started there. Conclusions
  14. Curing Addiction With Cannabis Medicines? Addiction is a real target — researchers like Professor Kendall believe the endocannabinoids could be a crucial link to addictive behaviour: “We know that the endocannabinoid system is intimately involved in reward pathways and drug seeking behaviour. So this tends to indicate that that if the link involving endocannabinoids and the reward pathway, using inhibitors, can be interrupted, it could turn down the drive to seek addictive agents like nicotine.” Because cannabinoids have also been shown to bring down blood pressure, it is hoped that related compounds can be used in patients with conditions like hypertension. Dr Michael Randall, a cardiovascular pharmacologist at the University has looked at how endocannabinoids cause blood vessels to relax. “This could have many implications,” Dr Randall said. “The endocannabinoids appear to lower blood pressure under certain conditions; states of shock for example. If the endocannabinoids are of physiological importance, this could have real therapeutic possibilities.” “In terms of getting better medicines the endocannabinoid system has a lot to offer,” said Dr Alexander. “The range of cannabis-related medicines is currently limited, but by increasing our knowledge in this area we can increase our stock.” Short break.. watch this Addiction is generally defined as a physical or psychological dependence on a substance, especially alcohol or other dugs, with use of increasing amounts.[1] For the sake of clarification, physical addiction is covered separately from psychological dependence on this website. (See also the section titled Dependence.) Scientific research on cannabinoid compounds has not demonstrated a strong association with biochemical addiction. In their exhaustive quest for evidence of addiction, federally funded researchers have resorted to relying on questionable data, such as the withdrawal symptoms reported by children who were referred to social service and criminal justice agencies. These researchers may argue that the court-ordered testimony of troubled youths “proves” that marijuana is addictive;[2] however, such questionable data is not scientific evidence of chemical addiction. In another case, an addictions researcher reported on his experiment in which rats displayed withdrawal symptoms upon a sudden discontinuation of THC. Critics point out that the reported withdrawal effects were created with very high doses of THC, and by the introduction of a second drug, a THC-blocking agent used to trigger the withdrawal symptoms. Withdrawal symptoms are not found in rats without using a THC-blocking agent,[3] and even among troubled youths, withdrawal symptoms are relatively mild and of short duration. [4], [5] Dopamine, a neurochemical produced in the central cortex of the brain, is thought to provide the brain’s “reward system.” Interference with dopamine production is considered a major symptom of biochemical addiction. While two studies alleged a minor link between THC and dopamine production in the brains of rats,[6] these were refuted by several subsequent studies showing that cannabis does not radically affect dopamine levels.[7], [8], [9] In assessing the importance of a possible link between cannabis use and dopamine levels, it should be noted that dopamine activity has also been detected in the brains of video game players who were paid money every time they reached a new level of the game.[10] Clearly, minor evidence of dopamine activity is not the sloe indicator of addiction. If it were, than all pleasurable activities would be defined as addictive. Moreover, the scientific evidence that cannabis use produces any amount of increased dopamine activity remains entirely inconclusive. Assessing the scientific literature on marijuana’s addictive potential for the Criminal Justice Commission of Australia, Peter Nelson reported, “… involvement with the ventromedial striatum suggests connections to dopamine circuits. However, the expected reinforcing properties usually associated with these dopamine pathways are difficult to demonstrate in the case of THC.”[11] Cannabinoids bond to anandamide nerve receptors that are primarily concentrated in the frontal lobes of the brain,[12], [13] rather than in the central cortex where dopamine is produced. THC is mild, with effects resembling those of caffeine or chocolate rather than classic addictive drugs such as alcohol, amphetamines, cocaine, opiates, and nicotine. In fact, a 1996 report from Daniele Piomelli of the Neurosciences Institute in San Diego indicated that chocolate contains three compounds that are chemically similar to cannabinoids. Studies involving rats showed that cannabinoid chemicals found in chocolate amplify the effect of natural cannabinoids found in the brain. The article published in Nature concluded that these compounds may, “participate in the subjective feelings of eating chocolate.”[14] In the April 1999 issue of Nature Neuroscience, Piomelli and colleagues at the University of California, Irvine reported that anandamide acts as an inhibitor of dopamine neurons.[15] Far from triggering chemical addiction in the brain, THC, the natural anandamide analogue, may actually help to balance erratic dopamine levels. The common scientific criteria for determining the addictive quality of a drug are examples of animal studies in which subjects self-administer an addictive substance. When given the choice between food and narcotics, for example, animals commonly self-administer the drug to the exclusion of all other activity, often starving themselves to death. Unlike heroin, cocaine, and other substances of abuse, there are no clinical studies showing animals self-administering cannabinoid compounds. In 1993, the Congressional Office of Technology Assessment reached this conclusion: While marijuana produces a feeling of euphoria in humans, in general, animals will not self-administer THC in controlled studies. Also, canabinoids generally do not lower the threshold needed to get animals to self-stimulate the brain reward system as do other drugs of abuse.[16] Clinical studies indicate a very low potential for addiction to cannabinoid drugs. In addition, there is no real-world evidence suggesting that THC is chemically addictive.[17] Epidemiological studies show that the large majority of people who try marijuana do not continue to use it on a regular basis. Moreover, the majority of people who ever use cannabis stop using it entirely before the age of thirty. Of an estimated 65 million “experimenters,”[18] only about 0.8% of Americans use cannabis on a daily basis.[19] The fact that millions of Americans have stopped using marijuana voluntarily and without difficulty is strong epidemiological evidence that cannabis is not chemically addictive. Despite federally funded sociological and scientific findings that marijuana produces only mild dependence in some heavy users,[20], [21] the federal government has officially classified cannabis as a Schedule I substance that has “a high potential for abuse.” Recent research determining that cannabinoids are not chemically addictive and do not have a high potential for abuse forms the basis of a petition filed with the Drug Enforcement Administration. That petition prompted the federal drug agency to enter into a legally binding review of the existing evidence by the US Department of Health and Human Services in 1997.[22] Two years later, investigative authors of the 1999 Institute of Medicine report determined that, “… marijuana was not particularly addictive.”[23] Yet cannabis is still classified as having, “no medical value and a high potential for abuse.” In 1999, Dr. Podrebarac wrote to the White House Office of National Drug Control Policy: “The recently released Institute of Medicine (IOM) study on the medical use of marijuana clearly supports rescheduling it for medical use.” The US Drug Czar’s office refused to comment on the rescheduling issue. Cannabis authority Tod Mikuria wrote extensively on the value of cannabis in treating addiction. Consider the following excerpt: “In 1839, William B. O’Shaughnessy visited cannabis buyers’ centers in India and mingled with the “dissolute and depraved” to learn about the preparations of this social drug for clinical medical trials and found it to be useful in the treatment of tetanus and seizures. In 1843, Clendinning utilized cannabis substitution for the treatment of alcoholism and opium addiction. Potter recommended full-dose Squibb cannabis extract for withdrawal from opium addiction. In 1894, the Indian Hemp Drugs Commission Report recognized the comparative safety of cannabis in its unsurpassed ethnographic studies within different cultures with a concern that if prohibited it would cause the use of more dangerous drugs. McMeens, citing Fronmueller in 1860, found that the use of cannabis in place of, or combined with, opiates reduced harm from increased dose, tolerance, dependance, and side effects of opiates. In 1897, cannabis was confirmed as useful in the treatment of delirium tremens and as an alternative to opium for analgesia. Dutt independently described the comparative safety of cannabis in Materia medica of the Hindus. Yeo and calleagues warned about addiction to morphine in the treatment of neuralgia and suggested cannabis as an alternative.” The connection between dependency on drugs and mood disorders may be caused by unsuccessful attempts to self-medicate uncomfortable feelings with the “cure,” causing more harm and aggravation of the underlying condition. Moreau described cannabis as being useful in the treatment of depression in 1845. Throughout the late nineteenth and early twentieth centuries, the drug was listed in medical texts and pharmaceutical catalogues for treatment f melancholia or mania. Notwithstanding some polysubstance abusers who maladaptively combine cannabis with other psychoactives, there appears to be a significant number of persons who have learned that cannabis can totally substitute for other psychoactive drugs. Following the therapeutic paths of Clendinning, throughout the nineteenth and twentieth century, cannabis was found useful in the treatement of opiate and sedative abuse. Brunton described the use of cannabis for the treatment of opiate dependence or as a substitute when opiates were not tolerated. Shoemaker found cannabis to be used for the cure of opium or chloral habits. Birch advocated for the use of Indian hemp in the treatment of chronic chloral and opium poisoning. Mattison, an early addcition specialist, recommended cannabis as a substitute for morphine and cautioned his fellow physicians about hypodermic use of the opiate. Alcohol abuse, stimulant, sedative, and opioid abuse and dependence are conditions potentially treatable with cannabis substitution. All of these conditions involve management of mood and emotional reactivity. Although there have been numerous synthetic homologues developed, short-acting psychotropic drugs continue to have high potential for dependency and abuse. The quality of immediacy for mood management would appear to be inseparable from abuse potential but cannabis appears to be the exception because of lesser or milder withdrawal symptoms. California cannabis center members and patients in my private practice independently rediscovered and confirmed that cannabis is a safer substitute for many prescribed and most nonmedical psychoactive drugs in the control of depression, anger, and anxiety. Cannabis substitution may be a gateway drug back to sobriety and dealing with the underlying psychopathalogic etiologies.[24] -------------------------------------------------------------------------------- [1] Taber’s Cyclopedic Medical Dictionary. Philedelphia: F.A. Davis Company, 1987 [2] “US Study: Marijuana is addictive.” Reuters, March 31, 1998 [3] “New Scientist special report on marijuana.” New Scientist, February 21, 1998 [4] “US Study: Marijuana is addictive.” op. cit. [5] Institute of Medicine, Marijuana and Medicine: Assessing the Science Base. Washington, DC: National Academy Press, 1999 [6] “Similar effects found in pot, harder drugs.” Maugh, Los Angeles Times, June 27, 1997 [7] Castaneda, et al., “THC does not affect striatal dopamine release: microdialysis in freely moving rats.” 1991 [8] Gifford, Gardner, and Ashby, “The effects of intravenous administration of delta-9-tetrahydrocannabinol on the activity of the A 10 dopamine neurons recorded in vivo in anesthetized rats.” Neuropsychopharmacology Vol. 36, No. 2, pp. 96-99, 1997 [9] “The July 1995 Gettman/High Times petition to repeal marijuana prohibition: An extensive review of relevant legal and scientific findings.” Source: www.hightimes.com/ht/new/petition/jgpetition/index.html [10] "Researchers watch dopamine changes in brain of video game players.” Associated Press, May 21, 1998 [11] Nelson, “A Critical Review of the Research Literature Concerning Some Biological and Psychological Effects of Cannabis.” Advisory Committee on Illicit Drugs, Cannabis and the Law in Queensland, pp. 113-152, Source: Schaffer Library of Drug Policy, www.druglibrary.org [12] Piomelli, “Functional role of high-affinity anamdamide transport, as revealed by selective inhibition.” Science, Vol. 277, No. 5329, p. 1094(4), August 22, 1997 [13] Gettman, op. cit. See also: Gettman, “Marijuana and the human brain.” High Times, March 1995 [14] “Chocolate and Cannabinol.” The Washington Post, August 26, 1996 [15] Stein, “Bits and Pieces.” Geriatric Psychiatry News, Issue 3, No. 7, June/July 1999 [16] U.S. Congress OTA, 1993 [17] Grinspoon, Bakalar, Zimmer, and Morgan, “Marijuana Addiction.” Science, Vol. 277, p. 749, August 8, 1997 [18] Annas, “Reefer Madness—The federal response to California’s medical-marijuana law.” The New England Journal of Medicine, Vol. 337, No. 6, August 7, 1997 [19] Zimmer and Morgan, Marijuana Myths: Marijuana Facts. New York: The Lindesmith Center, 1997 [20] U.S. Code Congressional and Administrative News, 1970 [21] Institute of Medicine, Marijuana and Medicine: Assessing the Science Base. Washington, DC: National Academy Press, 1999 [22] “DEA refers marijuana rescheduling petition to HHS.” The Law Offices of Michael Kennedy, NY, 1998 [23] “Official report backs medical use of marijuana.” Reuters, March 17, 1999 [24] Mikuriya, “Dependency and Cannabis.” Chapter 20, p. 225-227 source: http://www.cannabismd.net/addiction/ Run From The Cure The Rick Simpson Story (Full Version) http://www.youtube.com/watch?v=dvosdIXyjWM Following the therapeutic paths of Clendinning, throughout the nineteenth and twentieth century, cannabis was found useful in the treatment of opiate and sedative abuse. Brunton described the use of cannabis for the treatment of opiate dependence or as a substitute when opiates were not tolerated. Shoemaker found cannabis to be used for the cure of opium or chloral habits. Birch advocated for the use of Indian hemp in the treatment of chronic chloral and opium poisoning. Mattison, an early addcition specialist, recommended cannabis as a substitute for morphine and cautioned his fellow physicians about hypodermic use of the opiate. Alcohol abuse, stimulant, sedative, and opioid abuse and dependence are conditions potentially treatable with cannabis substitution. All of these conditions involve management of mood and emotional reactivity. Although there have been numerous synthetic homologues developed, short-acting psychotropic drugs continue to have high potential for dependency and abuse. The quality of immediacy for mood management would appear to be inseparable from abuse potential but cannabis appears to be the exception because of lesser or milder withdrawal symptoms. Cannabis, also known as marijuana[1] (from the Mexican Spanish marihuana) and by other names,a[›] is a preparation of the Cannabis plant intended for use as a psychoactive drug and as medicine.[2][3][4] Chemically, the major psychoactive compound in cannabis is delta-9-tetrahydrocannabinol (Δ9-THC); it is one of 400 compounds in the plant, including other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), and tetrahydrocannabivarin (THCV), which can produce sensory effects unlike the psychoactive effects of THC.[5] Contemporary uses of cannabis are as a recreational drug, as religious or spiritual rites, or as medicine; the earliest recorded uses date from the 3rd millennium BC.[6] In 2004, the United Nations estimated that global consumption of cannabis indicated that approximately 4.0 percent of the adult world population (162 million people) used cannabis annually, and that approximately 0.6 percent (22.5 million) of people used cannabis daily.[7] Since the early 20th century cannabis has been subject to legal restrictions with the possession, use, and sale of cannabis preparations containing psychoactive cannabinoids currently illegal in most countries of the world; the United Nations has said that cannabis is the most used illicit drug in the world.[8][9] wekipeda Sources: Journal reference: Br J Pharmacol 153 Theme Issue: http://www.nature.co...3/n2/index.html @ommpeddie EddieKirks Blog
  15. 5 Marijuana Compounds That Could Help Combat Cancer, Alzheimers, Parkinsons (If Only They Were Legal) September 14, 2012 | Imagine there existed a natural, non-toxic substance that halted diabetes, fought cancer, and reduced psychotic tendencies in patients with schizophrenia and other psychiatric disorders. You don’t have to imagine; such a substance is already here. It’s called cannabidiol (CBD). The only problem with it is that it’s illegal. Cannabidiol After THC, CBD is by far the most studied plant cannabinoid. First identified in 1940 (though its specific chemical structure was not identified until 1963), many researchers now describe CBD as quite possibly the most single important cannabinoid in the marijuana plant. That is because CBD is the cannabinoid that arguably possesses the greatest therapeutic potential. Cannabinol Cannabinol (CBN) is largely a product of THC degradation. It is typically available in cannabis in minute quantities and it binds relatively weakly with the body’s endogenous cannabinoid receptors. Scientists have an exceptionally long history with CBN, having first isolated the compound in 1896. Yet, a keyword search on PubMed reveals fewer than 500 published papers in the scientific literature specific to cannabinol. Of these, several document the compound’s therapeutic potential – including its ability to induce sleep, ease pain and spasticity, delay ALS (Lou Gehrig’s Disease) symptoms, increase appetite, and halt the spread of certain drug resistant pathogens, like MRSA (aka ‘the Superbug’). In a 2008 study, CBN was one of a handful of cannabinoids found to be “ exceptional” in its ability to reduce the spread MRSA, a skin bacteria that is resistant to standard antibiotic treatment and is responsible for nearly 20,000 hospital-stay related deaths annually in the United States. Cannabichromene Cannabichromene (CBC) was first discovered in 1966. It is typically found in significant quantities in freshly harvested, dry cannabis. To date, the compound has not been subject to rigorous study; fewer than 75 published papers available on PubMed make specific reference to CBC. According to a 2009 review of cannabichromine and other non-psychotropic cannabinoids, “CBC exerts anti-inflammatory, antimicrobial, and modest analgesic activity.” CBC has also been shown to promote anti-cancer activity in malignant cell lines and to possess bone-stimulating properties. More recently, a 2011 preclinical trial reported that CBC influences nerve endings above the spine to modify sensations of pain. “[This] compound might represent [a] useful therapeutic agent with multiple mechanisms of action,” the study concluded. Cannabigerol Similar to CBC, cannabigerol (CBG) also has been subject to relatively few scientific trials since its discovery in 1964. To date, there exist only limited number of papers available referencing the substance – a keyword search on PubMed yields fewer than 55 citations – which has been documented to possess anti-cancer, anti-inflammatory, analgesic, and anti-bacterial properties. Tetrahydrocannabivarin Discovered in 1970, tetrahydrocannabivarin (THCV) is most typically identified in Pakistani hashish and cannabis strains of southern African origin. Depending on the dose, THCV may either antagonize some of the therapeutic effects of THC (e.g., at low doses THCV may repress appetite) or promote them. (Higher doses of THCV exerting beneficial effects on bone formation and fracture healing in preclinical models, for example.) Unlike, CBD, CBN, CBC, CBG, high doses of THCV may also be mildly psychoactive (but far less so than THC). http://www.alternet.org/drugs/5-marijuana-compounds-could-help-combat-cancer-alzheimers-parkinsons-if-only-they-were-legal?page=0%2C0
  16. Nausea / Chemotherapy Is marijuana an effective treatment for reducing nausea and vomiting from chemotherapy? Cancer Monthly, a cancer treatment website, stated in its May 2006 e-newsletter article "Medical Marijuana - The FDA Loses More Credibility": "There are literally hundreds of articles that appear in the peer reviewed medical and scientific literature that discuss marijuana's effects in pain relief, control of nausea and vomiting, and appetite stimulation... Obviously smoking marijuana is not risk-free especially to respiratory organs and tissue. However, compared to the risks of a typical chemotherapy agent such as cytoxan which includes: urinary bladder, myeloproliferative, or lymphoproliferative malignancies, potential sterility, urinary system hemorrhagic cystitis, hematuria, cardiac toxicity, anaphylactic reactions, significant suppression of immune responses, and sometimes fatal, infections; the risks of marijuana pale in comparison. And for cancer patients with advanced cancers who want to improve the quality of their life, a risk versus benefit analysis weighs heavily on the benefit side. More Pro's and Con's How does marijuana help a cancer patient undergoing chemotherapy? Chemotherapy comes with some pretty common, and unpleasant, side effects. Many patients lose their desire to eat and experience nausea and vomiting. Still others develop a condition called cachexia, in which they lose a significant portion of their body weight, both fat and muscle. This condition, especially when combined with the loss of appetite and nausea, can cause those being treated for cancer to feel physically weak and emotionally drained. The National Cancer Institute (NCI) explains that maintaining an adequate weight and absorbing sufficient nutrients can help patients feel, look, and function better, and may even help their bodies tolerate cancer therapy. Traditionally, patients are given drugs called antiemetics in tandem with their chemotherapy in order to reduce nausea and increase appetite. But not all people respond adequately to these medications. That's where marijuana comes in. It has been know for years that THC (delta-9-tetrahydrocannabinol), the main chemical component of marijuana, tends to stimulate one's appetite. In fact, THC has been available since the mid-1980s for cancer patients in a synthetically engineered capsule form. This medication, known as dronabinol in the medical world, has been shown to reduce nausea, increase appetite, and help patients gain weight. Right now there is a study under way, supported by the NCI, which is designed to measure the impact THC therapy, as dronabinol, has on the management of these symptoms in cancer patients. Click here to get more information about this study. There is also research being done on the medical use of THC by people with AIDS and those with glaucoma. More I have a friend who will be going through chemotherapy and radiation. What can she do to build herself up to keep her body in the best condition possible? Chemotherapy and radiation — using drugs and radiation to kill cancer cells — can be tough on both the body and the mind. As you suggest, advance preparation can make the process easier. While it is unclear how much time your friend has before she begins her treatment, the following suggestions may offer some sense of direction in preparing for therapy. Eat right. In order to keep the body working at its best to prepare for treatment, nutrition is important. Typically, a healthy eating plan includes lots of whole grains, fresh fruits and vegetables, and moderate amounts of low-fat meats and dairy products. The nutritional needs of people with cancer, including those who are preparing for chemotherapy or radiation, however, may require high-calorie, high-protein foods, such as milk, cream, cheese, and cooked eggs. Other recommendations may include cooking with more sauces, gravies, butter, margarine, or oil. While the emotional stress of cancer and beginning treatment can affect appetite, these extra nutrients may help to ensure that people with cancer will be able to commence treatment with the energy reserves needed. Your friend needs to consult with her cancer treatment team, which may include a nutritionist, before her sessions begin for specific recommendations tailored to her cancer and the chemotherapy and radiation treatments she will be given. (During treatment, these calorie- and protein-rich food recommendations may change.) More f your friend is having trouble sleeping or relieving stress, or just wants someone to talk with about her treatment, an appointment with a counselor might be helpful. If she's a student at Columbia, she can look at the Counseling and Psychological Services (CPS) web page for info on setting up an appointment, or call x4-2878. To find out more about preparing for cancer treatment, you and your friend can visit the American Cancer Society's site on What to Do Before Treatment Begins. Also, consider a visit to the American Academy of Family Physicians' Cancer: Preparing for Treatment webpage for more ways to make the time and experience during treatment easier. If you or your friend prefers books, pick up The Chemotherapy and Radiation Therapy Survival Guide by Judith McKay and Nancee Hirano. It's great that you're being so supportive before your friend's treatment — she's lucky to have a friend like you! Safety of cannabis Various strains of medical marijuana in front of a vaporizer According to an approved statement from the US Department of Justice in 1988, "Nearly all medicines have toxic, potentially lethal effects. But cannabis is not such a substance. There is no record in the extensive medical literature describing a proven, documented cannabis-induced fatality. In practical terms, cannabis cannot induce a lethal response as a result of drug-related toxicity."[53] From January 1997 to June 2005, the U.S. Food and Drug Administration (FDA) reported zero deaths caused by the primary use of cannabis. In contrast, common FDA-approved drugs which are often prescribed in lieu of cannabis (such as anti-emetics and anti-psychotics), were the primary cause of 10,008 deaths.[54] wiki Cannabidiol Main article: Cannabidiol Cannabidiol has been shown to relieve convulsions, inflammation, anxiety, cough, congestion and nausea, and it inhibits cancer cell growth.[80] Cannabidiol (CBD) is a major constituent of medical cannabis. CBD represents up to 40% of extracts of medical cannabis.[81] Cannabidiol has been shown to relieve convulsion, inflammation, anxiety, cough, congestion and nausea, and it inhibits cancer cell growth.[80] Recent studies have shown cannabidiol to be as effective as atypical antipsychotics in treating schizophrenia.[82] Because cannabidiol relieves the aforementioned symptoms, cannabis strains with a high amount of CBD may benefit people with multiple sclerosis, frequent anxiety attacks and Tourette syndrome.[57][80][83]Source Difference between Cannabis indica and Cannabis sativa Cannabis sativa, Cannabis indica, and Cannabis ruderalis A Cannabis indica plant may have a CBD/THC ratio 4-5 times that of Cannabis sativa. Cannabis with relatively high ratios of CBD:THC is less likely to induce anxiety than vice versa. Indica has more cannabidiol and sativa has more THC.[105] This might partially be due to CBD's antagonist effects at the cannabinoid receptor, compared to THC's partial agonist effect.[106] The relatively large amount of CBD contained in Cannabis indica, means, compared to an Cannabis sativa, the effects are modulated significantly. The effects of sativa are well known for its cerebral high, hence used daytime as medical cannabis, while indica is well known for its sedative effects and preferred night time as medical cannabis. Indica plants are normally shorter and stockier plants than sativas. They have wide, deeply serrated leaves and a compact and dense flower cluster. The effects of indicas are predominantly physical and sedative. Due to the relaxing nature of indicas, they are best used for non-active times of the day, and before bed. Indica strains generally have higher levels of C.B.D and C.B.N and lower levels of T.H.C.[107] Harm reduction Aspergillus fumigatus The harm caused by smoking can be minimized or eliminated by the use of a vaporizer[127] or ingesting the drug in an edible form. Vaporizers are devices that heat the active constituents to a temperature below the ignition point of the cannabis, so that their vapors can be inhaled. Combustion of plant material is avoided, thus preventing the formation of carcinogens such as polyaromatic hydrocarbons, benzene and carbon monoxide. A pilot study led by Donald Abrams of UC San Francisco showed that vaporizers eliminate the release of irritants and toxic compounds, while delivering equivalent amounts of THC into the bloodstream.[128] According to Matthew Seamon and his co-authors “Vaporizers are the optimal route of administration because they allow for rapid and complete absorption with minimal combustible byproducts, often considered the major health risk associated with smoking tobacco.”[129] In order to kill microorganisms, especially the molds A. fumigatus, A. flavus and A. niger, Levitz and Diamond suggested baking marijuana at 150 °C (302 °F) for five minutes. They also found that tetrahydrocannabinol (THC) was not degraded by this process.[130] Marijuana Component Could Ease Pain from Chemotherapy Drugs, Study Suggests ScienceDaily (Oct. 6, 2011) — A chemical component of the marijuana plant could prevent the onset of pain associated with drugs used in chemo therapy, particularly in breast cancer patients, according to researchers at Temple University's School of Pharmacy. The researchers published their findings in the journal Anesthesia and Analgesia. The researchers developed animal models and tested the ability of the compound cannabidiol, which is the second most abundant chemical found in the marijuana plant, to relieve chemo-induced neuropathic pain, said Sara Jane Ward, research assistant professor of pharmaceutical sciences in Temple's School of Pharmacy and the study's lead author. "We found that cannabidiol completely prevented the onset of the neuropathic, or nerve pain caused by the chemo drug Paclitaxel, which is used to treat breast cancer," said Ward, who is also a research associate professor in Temple's Center for Substance Abuse Research More n addition to Ward, Temple researchers involved in the study included Michael David Ramirez, Harshini Neelakantan and Ellen Ann Walker. The study was supported by grants from the National Institutes of Health and the Peter F. McManus Charitable Trust.
  17. Pain / Analgesia Is medical marijuana an effective treatment for patients suffering from severe / chronic pain? The National Institutes of Health (NIH) stated the following in a report to the NIH Director titled "Workshop on the Medical Utility of Marijuana," that was compiled by the self-titled Ad Hoc Group of Experts during a two day meeting held Feb. 19-20, 1997: "A number of studies have been conducted on the antinociceptive [increased pain tolerance] or analgesic [pain reducing] effect of tetrahydrocannabinol (THC) or marijuana in both animals and human subjects; the results have been conflicting...Cannabinoids have been shown to be possibly analgesic in animal models of neuropathic pain... Since oral Delta-9-THC has some analgesic activity, it is highly likely that smoked marijuana has some analgesic activity in some kinds of clinical pain...If marijuana is to be a useful analgesic, healthcare providers need to know how it compares in efficacy and safety to at least a few of the standard analgesics that would be used in managing a particular kind of pain...There appear to be no controlled analgesic studies of smoked marijuana in patients with naturally occurring pain." More on Pro's and Con's Tetrahydrocannabinol (THC) and some other cannabinoids, either from the Cannabis sativa plant or synthetic, have analgesic properties, although the use of cannabis derivatives is currently illegal in many countries. A recent study finds that inhaled cannabis is effective in alleviating neuropathy and pain resulting from e.g. spinal injury and multiple sclerosis.[13] Other psychotropic analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and other a2-adrenoreceptor agonists, and mexiletine and other local anaesthetic analogues. wikipedia "Cananbinoid-induced analgesia appears linked to the same system by which opioids [synthetic narcotics] produce pain relief. But different from opioids, cannabinoids are also effective in a rat model of neuropathic pain, which means pain cased by nerves. For those of us that care for people with HIV—we know about the painful, peripheral neuropathy they get—very painful numb tingling feet. We often start these patients on a trial of drugs that lead ultimately to morphine, because there isn’t anything effective." [26] Dr. Abrams conducted a valuable human study of 50 HIV patients who used smoked marijuana cigarettes three times per day. Subjects showed positive results in daily pain, hyperalgesia, and a 30% reduction in pain. [27] My link A research paper fone at Hammersmith Hospital in London confirmed cannabis’ analgesic effects in the first UK clinical trial. The paper’s abstract began, “Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their clinical use has been restricted by legislation.” That same abstract calling for further studies concluded, “Cannabis naïve patients would tolerate investigations but may generate medicolegal problems.” [28] The use of cannabis for pain relief was widespread in the membership of legitimate medical marijuana groups under attack by the US government. [29] In 1998, federal law enforcers closed San Francisco Bay Area Cannabis Clubs, forcing over 10,000 seriously ill patients to support nefarious “street” sources and pay outrageous black market prices for non-medical grade marijuana. In the following year, the government sponsored Institute of Medicine report elevated pain relief to the top of the list of marijuana’s medical benefits. [30] Due to cannabis prohibition and the bias of research regulation by the National Institutes on Drug Abuse, human studies of the pain relieving qualities of cannabis are limited. Grotenherman writes: " Few clinical studies of cannabinoids in painful conditions exist. In two trials, oral THC proved to be effective against cancer pain in doses of 15 and 20 mg, respectively. However, some patients experienced intolerable side effects. In a single case double-blind study a patient with familial Mediterranean fever clearly reduced his need for opiates while receiving THC (50 mg per day divided in five doses) in comparison to placebo."[31] However, the fascinating new view of the body's endocannabinoid systems provide ample scientific evidence to justify the widespread popularity of cannabis as an analgesic, partivcularly in cases of nerve or neurological pain. Consider the following excerpts from a recent paper titled “Mechanisms of Cannabinoid Analgesia”: “Within the central nervous system, cannabinoids, like opioids, act at both spine (intrathecal) and supraspinal (intracerebroventricular) levels to produce analgesia. Cannabinoid-induced analgesia is not mediated by opioid receptors because it is unaffected by opioid antagonists. However, cannabinoid and opioid agonists have synergistic analgesic affects.” “In vivo electrophysiological studies indicate that, like opioids, cannabinoids suppress the activity of neurons involved in the ascending transmission of nociceptive information. Systemic administration of cannabinoid agonists inhibits noxious stimulus-evoked firing in neurons of the spinal cord dorsal horn and thalamus. Cannabinoids also inhibit windup (a neuronal correlate of hyperalgesia), which is the augmentation of the response of spinal neurons to repetitive noxious electrical stimuli.” “It is now becoming apparent that, like opioids, cannabinoids act via specific receptors within pain pathways to produce analgesia. The distinct anatomical receptors within pain pathways suggests that they may be useful for management of different pain sites. The distinction between cannabinoids and opioids is emphasized by more recent electrophysiological studies and provides a cellular basis for their synergistic analgesic actions. These findings suggest that cannabinoids warrant urgent study as therapeutic agents, particularly with the emergence of novel cannabinoid drugs.”[32] IN 2008, i nvestigators at the University of California at Davis, in conjunction with the University of California Center for Medical Cannabis Research (CMCR), assessed the efficacy of inhaled cannabis on pain intensity among 38 patients with central and/or peripheral neuropathic pain in a randomized, placebo-controlled, crossover trial. Researchers reported that smoking low-grade (3.5 percent THC) and mid-grade (7 percent THC) cannabis equally reduced patients’ perception of spontaneous pain. They concluded: "In the present experiment, cannabis reduced pain intensity and unpleasantness equally. Thus, as with opioids, cannabis does not rely on a relaxing or tranquilizing effect, but rather reduces both the core component of nociception (nerve pain) and the emotional aspect of the pain experience to an equal degree." The study is the second clinical trial conducted by CMCR investigators to conclude that inhaled cannabis significantly reduces chronic neuropathy, a condition that is typically unresponsive to both opioids and non-steroidal anti-inflammatory drugs such as ibuprofen.[33] GW Pharmeceuticals is a company that has isolated canabinoid compounds in arosol sprays for medical use. Another recent study shows that GW's product, Sativex, sowed remarkable value in trating neuropathic pain. Forty-one patients with multiple sclerosis and central neuropathic pain completed the double blind, placebo-controlled "randomized withdrawal" study. Volunteers in the study were administered either Sativex or a placebo daily for four weeks following their long-term use of the cannabis spray. Previous trials of Sativex have reported that patients required fewer daily doses of the drug and reported lower median pain scores the longer they took it.[34] Recent studies have located and determined exact mechanisms of cannabis analgesia through the body's endocannabinoid receptors. The following is an excert from "Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy" from theInperial College of Science in London: "Local administration, peptide release and electrophysiological studies support the concept of spinally mediated endocannabinoid-induced analgesia. Whilst a proportion of the peripheral analgesic effect of endocannabinoids can be attributed to a neuronal mechanism acting through CB(1) receptors expressed by primary afferent neurones, the antiinflammatory actions of endocannabinoids, mediated through CB(2) receptors, also appears to contribute to local analgesic effects." [35] Related sections: Addiction, Arthritis, Neuralgia, Psychoactivity, Replacement of Medications [1] “Doctor urges war on pain, more use of opium-based drugs.” Miami Hearald, January 29, 1998 [2] Stolberg, “Study Finds Elderly Receive Little Pain Treatment in Nursing Homes.” June 17, 1998 [3] “Doctor urges war on pain, more use of opium-based drugs.” Miami Hearald, January 29, 1998 [4] “Researchers say many cancer patients suffer needless pain.” Associated Press, June 17, 1998 [5] Drug Enforcement Administration, “Statement of policy for the use and handling of controlled substances in the treatment of pain.” 1998 [6] Kassirer, “Federal foolishness and marijuana.” Editorial, The New England Journal of Medicine, January 30, 1997 [7] Russo "Cannabinoids in the management of difficult to treat pain" Therapeutics and Clinical Risk Management" 2008-4(1) 245-259 [8] Mikuriya, Marijuana Medical Papers: 1839-1972. Oakland: Medi-comp Press, 1973 [9] Grinspoon, Marijuana Reconsidered. 3rd ed. San Francisco: Quick American Archives, 1971 [10] Russo, "The Role of Cannabis and Cannabinoids in Pain Management" Weiner's Pain Mnagement Guide, 7th ed. American Academy of Pain Management 2006 [11] Noyes and Baram, “Cannabis analgesia.” Comprehensive Psychiatry. Vol. 15, No. 6, 1974 [12] Beltramo and Piomelli, “Functional role of high-affinity anandamide transport, as revealed by selective inhibition.” Science, Vol. 277, No. 5329, p1094(4), 1997 [13] Russo, "The Role of Cannabis and Cannabinoids in Pain Management" Weiner's Pain Mnagement Guide, 7th ed. American Academy of Pain Management 2006 [14] Formukong, Evans, and Evans, “Analgesic and anti-inflammatory activity of constituents of cannabis sativa L.” Inflammation, Vol. 12, No. 4, pp.361-371, 1988 [15] Maurer, Henn, Dittrich, and Hoffman, “Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double blind trial.” European Archive of Psychiatry and Neurological Science. Vol. 240, No. 1, pp. 1-4, 1990 [16] “Cannabidiol, Wonder drug of the 21st century?” Source: Schaffer Library of Drug Policy, www.druglibrary.org [17] “Pre-clinical studies show CT-3 reduces chronic and acute inflammation and reduces destruction of joints.” BW HealthWire, January 1998 [18] "Curative Leaf - Compound in marijuana reduces inflammation without the psychological effects", Amy Maxmen, Science News, June 23rd, 2008, www.sciencenews.com [19] “Medical marijuana: Doing the science.” Synapse, 1998, www.itsa.ucsf.edu/synapse/ [20] Symposium Syllabus, Functional Role of Cannabinoid Receptors. Press Conference, August 26, 1998, Source: Medical Marijuana Magazine, www.marijuanamagazine.com [21] “Study reveals pot chemicals can relieve serious pain.” Los Angeles Times, October 27, 1998 [22] Ibid. [23] Morin, “Research into cannabinoids provides evidence that the use of marijuana to treat pain and nausea should not e so easily dismissed.” May 1998, Source: Morin@Brown.edu [24] Cowen, “Science journal reports that cannabinoid receptors located outside the brain and spine are affected when the skin or flesh is cut or hurt.” July 16, 1998, www.marijuananews.com [25] Widener, “Study: Marijuana, morphine work on same area of brain.” The Seattle Times, September 25, 1998 [26] “Diagnosis: Smoke Pot to Relieve Pain.” The University of Washington Daily, May 1997 [27] Abrams, Lindesmith Center Lecture, San Francisco, May 17, 1999 [28] Holdcroft et al., “Pain relief with oral cannabinoids in familial Mediterranean fever.” Anesthesia, Vol. 52, No. 5, pp. 483-486, May 1997 [29] San Francisco Chronicle, San Francisco Examiner, Associated Press, May 1998 [30] Institute of Medicine: Marijuana and Medicine: Assessing the Science Base. Washington DC: National Academy Press [31] Grotenhermen, “Review of Therapeutic Effects.” Chapter 11, p. 126-128 (see Absracts and Studies section of this website) [32] Vaughn and Christie, “Mechanisms of Cannabinoid Analgesia.” Chapter 8, p. 90-95 [33] Inhaled Cannabis Reduces Central And Peripheral Neuropathic Pain, Study Says, NORML News, May 3rd, 2008 See: www.NORML.org [34] Cannabis Spray Demonstrates Long Term Efficacy In Neuropathic Pain, Study Says, NORML News, 9/11/08, See: www.NORML.org [35] “Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy”, Rice AS, Farquhar-Smith WP, Nagy I., Department of Anaesthetics, Pain Research Group, Inperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital Campus, 369 Fulham Road, London SW10 9NH, UK. a.rice@ic.ac.uk My link Researchers at University of California Davis examined whether marijuana produces analgesia for patients with neuropathic pain. Thirty-eight patients were examined. They were given either high-dose (7%), low-dose (3.5%) or placebo cannabis. The authors reported that identical levels of analgesia were produced at each cumulative dose level by both concentrations of the agent. As with opioids, cannabis does not rely on a relaxing or tranquilizing effect, but reduces the core component of nociception and the emotional aspect of the pain experience to an equal degree. There were undesirable consequences observed from cannabis smoking, such as feeing high or impaired, but they did not inhibit tolerability or cause anyone to withdraw from the study. In general, side effects and mood changes were inconsequential. It was noted by the authors that since high and low dose cannabis produced equal analgesic efficacy, a case could be made for testing lower concentrations to determine if the analgesic profile can be maintained while reducing potential cognitive decline. In addition, the authors said further research could probe whether adding the lowest effective dose of cannabis to another analgesic drug might lead to more effective neuropathic pain treatment for patients who otherwise are treatment-resistant n a randomized, double-blinded, placebo controlled, crossover trial in fifteen healthy volunteers, we evaluated the effects of low, medium, and high dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannibinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 minutes after drug exposure and pain, hyperalgesia, tetrahydrocannibinol plasma levels, and side effects were assessed. Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 minutes after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannibinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests. This study suggests that there is a window of modest analgesia for smoked cannabis with lower doses decreasing pain and higher doses increasing pain. The full results of this study were published in the journal Anesthesiology. ABSTRACT: By every criteria (deterioration in quality of life; loss of work days, and therapy directed dollars) pain is appreciated to be a major medical problem. Recent findings in the molecular biology and the pharmacology of pain transmission have shed light on mechanisms of nociceptive processing and the activity of a variety of "novel therapeutic" modalities that include the cannabinoids. Although the pre-clinical literature suggests that the cannabinoids produce antinociception and anti-hyperalgesic effects, the efficacy of the cannabinoids in the human pain state is unclear. As an experimental variable, clinical pain is a multidimensional phenomenon with few objective physical correlates. Many other factors such as emotional status and coping skills, make "pain" difficult to study in the clinical setting. An important development has been the implementation of well-controlled experimental pain models to investigate the sensory components of pain processing and to use these models in the assessment of analgesic efficacy in normal volunteers. To the degree that human experimental pain models can predict analgesic efficacy of novel agents, the role of mechanisms defined in preclinical studies can be translated to the human experience under well-controlled conditions. Human experimental pain has been used to test a wide range of currently available analgesics. Knowing the effect of these agents on human experimental pain, I now wish to study the effects of cannabis on human experimental pain and how this compares to commonly used analgesics. PUBLICATIONS: Type: Title: Journal Article Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, Gouaux B, Abramson I. Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers. Anesthesiology. 107(5):785-796, November 2007. The most frequent complaint that patients look for medical help with is pain. There are several different types of pain, and unfortunately none of the currently-prescribed pharmacological treatments for pain work completely for certain types. A particular example is that of pain caused by damaged nerves (such as that which causes phantom limb pain), which does not respond well to existing medications. Severe chronic pain is usually treated with opiates, but these are addictive, and tolerance develops so that the dose has to be increased. The risk of severe side effects such as nausea is great, and additionally the user feels drugged, and finds it difficult to function properly. Family life may suffer as patients find it hard to relate to other people, and even reading to children is difficult. Synthetic analgesics are non-addictive but they are not powerful enough. Cannabis has fewer side effects than other analgesics, and users report it "rounds off" the pain quickly after smoking. An Institute of Medicine report contains a minimal list of 5 situations in which cannabis-based medicines are of use in treating pain: There are medical conditions or patients in which they are more effective than any currently available medication. They have a broad clinical spectrum of efficacy and a unique side effect profile that differs from other analgesics. They have synergistic interactions with other analgesics. They exhibit "side effects" which are considered useful in certain clinical situations. Their efficacy is enhanced in patients who have developed tolerance to opioids. Some people have used cannabis to control pain for 20 years or more, and many report that they were able to kick their addiction to opiates with small amounts of cannabis. One strange fact is that more experienced users get a greater pain-relieving effect from cannabis than novices. Experienced users also are able to function normally and ignore the psychoactive effects. Cannabis may be better at controlling the different types of pain. Cannabis has had a long history of use as an analgesic, and was widely used in 19th century Britain, including in the royal household. Dr. J. Russell Reynolds, Fellow of the Royal Society and Physician to Queen Victoria reported in the Lancet in 1890 that he had been prescribing cannabis for 30 years and considered it "one of the most valuable medicines we possess". According to Reynolds indian hemp remained effective as an analgesic for months and even years without an increase in the dose. It seems that cannabis shares some method of action with opioids, but the mechanism with which it accomplishes its analgesic effects differs. This indicates that they may produce an additive effects when used in conjunction with current medicines. In addition they might provide help to patients who do not react satisfactorily to other treatments. Much anecdotal evidence seems to indicate that this is the case. Indeed, the British Medical Association has gone on record as stating that 'the prescription of nabilone, THC and other cannabinoids...should be permitted for patients with intractable pain'. Other official bodies have found similar results. A House of Lords report summed up the situation stating that 'there is scientific evidence that cannabinoids possess painrelieving properties, and some clinical evidence to support their medical use in this indication'. In a press conference on October 26th 1997, the US Society for Neuroscience claimed that 'substances similar to or derived from marijuana...could benefit the more than 97 million Americans who experience some form of pain each year'. Patients' testimonies The medical testimonies database contains 51 testimonies from cannabis users with pain . NameDate Amanda Mon 01 Nov 2010 Annon Mon 01 Nov 2010 Mund Mon 01 Nov 2010 jimmy Mon 01 Nov 2010 Mr Dmoore Mon 02 Nov 2009 Anonymous Mon 02 Nov 2009 Anonymous Sun 06 Dec 2009 Anonymous Wed 02 Dec 2009 Anonymous Wed 02 Dec 2009 Anonymous Sun 02 Nov 2008 Annamarie Grogan Tue 02 Dec 2008 Anonymous Thu 02 Nov 2006 Stephen Livingston Sat 09 Dec 2006 Ian Lunar Module Wed 06 Dec 2006 Anonymous Sat 02 Dec 2006 Roger Pigott Fri 01 Dec 2006 GC Mon 31 Oct 2005 Eleanor Sun 04 Dec 2005 Ronald Roberson Sat 03 Dec 2005 Maggie Froud Fri 02 Dec 2005 Terry Sun 05 Dec 2004 vanessa Fri 03 Dec 2004 gruf Sun 02 Nov 2003 J. Gribbin Sat 01 Nov 2003 Welshstoner Fri 31 Oct 2003 Nicolas Tue 09 Dec 2003 George Lister Sun 07 Dec 2003 Sonia Fri 05 Dec 2003 Bob Mon 01 Dec 2003 John Sat 02 Nov 2002 Anonymous Sat 02 Nov 2002 Winston Matthews Fri 01 Nov 2002 Stacey H Thu 31 Oct 2002 Carl Thu 31 Oct 2002 Steven Mon 09 Dec 2002 Garry Pearson Sat 07 Dec 2002 Missi Fri 06 Dec 2002 Hugh Tue 03 Dec 2002 Russ Points Fri 02 Nov 2001 Puffs Thu 01 Nov 2001 Phil James Thu 01 Nov 2001 Anonymous Sun 09 Dec 2001 Anonymous Mon 03 Dec 2001 Anonymous Sun 02 Dec 2001 Sybil Sun 02 Dec 2001 Anonymous Sun 02 Dec 2001 Anonymous Tue 31 Oct 2000 Anonymous Sat 09 Dec 2000 Nigel Pearson Sat 09 Dec 2000 Anonymous Thu 07 Dec 2000 Anonymous Thu 07 Dec 2000 For the complete collection of testimonies from medical users of cannabis, see our medical testimony database. Do you find that cannabis helps you with this, or any other, medical condition? If so, please tell us about how it benefits you via this form. Anonymous submissions welcome! Scientific evidence Despite the long history of use of cannabis as an analgesic, and the obvious problems with synthetic drugs, the War on Drugs prevented people from reconsidering cannabis until the mid-seventies, when several studies were published. Patients suffering from cancer usually suffer from severe pain. This can be for a number of reasons, such as the invasion of their bones, inflammation or damage caused to nerves. It is a form of pain which is notoriously hard to treat effectively. At the University of Iowa Noyes et al (1975a) gave oral THC or a placebo at random to hospitalised cancer patients who were in severe pain. The THC relieved pain for several hours at very low doses and longer periods at higher doses (15 - 20 mg). It also acted as a sedative at the higher dose. It had fewer physical side effects than other commonly used analgesics. There was no incidence of nausea or vomiting unlike many other analgesics - indeed more than half of the patients had an increased appetite. Then Noyes et al conducted another study (1975b). This time they gave codeine, THC and placebo to 36 patients with advanced cancer. Codeine and cannabis were equally effective, but some patients found the psychoactive effects of THC uncomfortable. However these people did not know they were going to take a psychoactive drug and were obviously frightened. If they had been told beforehand perhaps they would not have been uncomfortable. Many of the patients however felt they generally had a sense of well-being that was absent before. As a result of this experiment, the researchers estimated that 10mg of THC was roughly equivalent to 60mg of codeine. A study revealing potential additive effects of THC on standard medication was done by Holdcroft et al (1997). It centred on a patient who had severe chronic pain of gastrointestinal origin. The patient used morphine as an analgesic.It was found that the patient required a substantially lower amount of morphine when they were treated with oral THC in the form of cannabis oil. The differing mechanism of analgesic action cannabis uses compared to existing (mainly opioid) medications means that not only are additive effects likely, but it could be useful in patients resistant to existing medications, and be useful in treating pain which existing medications fail to deal with adequately. The National Institutes of Health suggested that 'Neuropathic pain represents a treatment problem for which currently available analgesics are, at best, marginally effective. ...THC...may be useful in this inadequately treated type of pain'. The findings of Growing et al (1998) concurred with this conclusion, and suggested that this might be the area of greatest medical potential. Maurer et al (1990) found that a paraplegic patient, who suffered leg pain, gained pain-relief after taking a single dose of THC. Staquet et al (1978) did a trial using a nitrogen analogue of THC. This too showed significant analgesic effects, and was effective as both codeine and secobarbital. A further study using the synthetic THC analogue Levonantradol was done by Jain et al (1981). The trial population was patients who had moderate to severe post-operative pain. They were administered Levonantrodol by injection, and found significant pain relief as a result. In Canada, Milstein et al (1975) studied the analgesic effect of smoked cannabis in normal subjects. Half of them had used cannabis before. The researchers caused pain by pressing onto the subjects thumbnails. The subjects were able to withstand more pressure after they had smoked cannabis. Strangely, the analgesic effect was greater in the experienced users. A article by Noyes and Baram (1974) showed that cannabis relieved the pain of a headache in three patients with an equivalent or better efficacy than aspirin or ergotamine tartrate. Petro (1980) found that two patients suffering pain from a muscle spasticity disorder had a reduction in their discomfort after inhaling cannabis. Recently, it has been found that the body's natural cannabinoid, anandamide is involved in the control of pain. Calignano et al (1998) found that rats release anandamide when cells are damaged. This then causes seemingly pain-relieving effects in the areas of the brain and spinal cord that process pain stimuli. An ACM bulletin in 1998 demonstrated that when anandamide is used with another naturally occuring compound in the body, palmitylethanolamide, pain was reduced by up to 100 times. References Calignano A. et al (1998) Control of pain by endogenous cannabinoids, Nature 394: 277-281. Growing L et al (1998) Therapeutic use of cannabis: clarifying the debate, Drug and Alcohol Review 17: 445-452. Holdcroft A et al (1997) Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia, 52: 483 House of Lords Select Committee on Science and Technology (1998) Science and Technology - Ninth report. Science and Technology Committee Publications, UK. Institute of Medicine (1999) Marijuana and medicine: Assessing the science base. National Academy Press Jain AK, Ryan JR, McMahon FG, Smith G. (1981) Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. Journal of Clinical Pharmacology 21 :320S-326S. Maurer M. et al. (1990) Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. European Archives of Psychiatry and Clinical Neuroscience 240: 1-4. Milstein S.L., MacCannell K., Karr, G. and Clark S. (1975) Marijuana-produced changes in pain tolerance: Experienced and non-experienced subjects. International Pharmacopsychiatry 10: 177-182. National Institutes of Health (1997) Workshop on the Medical Utility of Marijuana: Report to the Director. Washington, D.C. Noyes R., Baram D. (1974) Cannabis analgesia. Compr. Psychiatry 15 : 531. Noyes R., Brunk S.F., Baram D.A. and Canter A. (1975a) Analgesic effect of delta-9-tetrahydrocannabinol. Journal of Clinical Pharmacology 15: 139-143. Noyes R., Brunk S.F., Avery D.H. and Canter A. (1975b) The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapeutics 18: 84-89. Petro D. (1980) Marihuana as a therapeutic agent for muscle spasm and spasticity. Psychosomatics 21: 81-85. Reynolds J.R. (1890) Therapeutic uses and toxic effects of Cannabis indica. Lancet 1: 637 Science: Cannabinoid/anandamide-receptor systems involved in peripheral control of pain, ACM Bulletin, July 26, 1998. Staquet M, Gantt C, Machin D. (1978) Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain. Clinical Pharmacology and Therapeutics 23:397401. For a large collection of research materials, see our research page. Use of Marijuana in Neurological and Movement Disorders Medical Marijuana Use of Marijuana in Neurological and Movement Disorders 1. What research has been done and what is known about the possible medical uses of marijuana? There have been numerous studies both in animals and in various clinical states on the use of cannabinoids on neurological and various movement disorders. These results range from anecdotal reports to surveys and clinical trials. Marijuana or tetrahydrocannabinol (THC) is reported to have some antispasticity, analgesic, antitremor, and antiataxia actions, as well as some activity in multiple sclerosis (MS) and in spinal cord injury patients. The spasticity and nocturnal spasms produced by MS and partial spinal cord injury have been reported to be relieved by smoked marijuana and to some extent by oral THC in numerous anecdotal reports. The effect seems to appear rapidly with smoked marijuana; patients are able to titrate the dose by the amount they smoke. No large-scale controlled studies or studies to compare either smoked or oral THC with other available therapies have been reported. Several relatively good therapeutic alternatives exist. There is no published evidence that the cannabinoid drugs are superior or even equivalent. Substantial experimental animal literature exists showing that various cannabinoids, given primarily by parenteral routes, have a substantial anticonvulsant effect in the control of various models of epilepsy, especially generalized and partial tonic-clonic seizures. Scant information is available about the human experience with the use of marijuana or cannabinoids for the treatment of epilepsy. This is an area of potential value, especially for cannabis therapies by other than the smoked route. Several single case histories have been reported indicating some benefit of smoked marijuana for dystonic states. It must be remembered that dystonia is a clinical syndrome with numerous potential causes, and the information available now does not differentiate which causes are most likely to be improved. Smoked marijuana and oral THC have been tested in the treatment of Parkinson's disease and Huntington's chorea without success. The cannabinoids also have been used as experimental immunologic modifiers to treat such conditions as the animal models of experimental allergic encephalomyelitis (EAE) and neuritis. Parenteral cannabinoids have been successful in modifying EAE in animals, suggesting that cannabinoids may be of value in a more fundamental way by altering the root cause of a disease such as MS rather than simply treating its symptoms. Smoked marijuana would not be acceptable for such a role because of the variability of dose with the smoked route. 2. What are the major unanswered scientific questions? The discovery of dedicated systems of central nervous system (CNS) neurons approximately 8 years ago, which express receptors specific for the cannabinoids, is of major scientific interest and importance. The distribution of these cannabinoid receptor-bearing neurons corresponds well with the clinical effects of smoked marijuana; for instance, their presence in the forebrain may relate to adverse changes in short-term memory, but perhaps positively in the control of epilepsy. Cannabinoid receptors in the brainstem and cerebellum may relate to the recognized incoordination that accompanies smoked marijuana use. The discovery of intrinsic ligands for these receptors in the mammalian brain is also of great importance. This system of cannabinoid receptors and ligands may be analogous to the discovery of opiate receptors and endorphins, which linked various opium derivatives (heroin and morphine) to an intrinsic system of neurons in the CNS. That discovery was of major importance for pain research. The major unanswered scientific questions are: * How useful is smoked marijuana of known specific potency in controlling various neurologic conditions? * In comparative studies, how useful is smoked marijuana in altering objective abnormalities such as spasticity versus current standard therapies that have already been approved for human use? * Can alternative delivery systems (other than the oral route) be developed to provide rapidity of action with more safety than smoked marijuana? * Can available or newly developed synthetic cannabinoids be used more effectively to stimulate or block receptor activity in the cannabinoid system of the CNS? * What are the immune-modulating characteristics of the cannabinoids and can they be used for therapeutic human benefit? * Can the long-term risks of daily smoked marijuana be quantified so that useful risk versus benefit ratios can be determined, especially when considering treatment of long-term conditions such as spasticity or epilepsy? 3. What are the diseases or conditions for which marijuana might have potential as a treatment and which merit further study? Marijuana or the use of other cannabinoids as human therapies might be considered for treating spasticity and nocturnal spasms complicating MS and spinal cord injury, for various active epilepsy states, for some forms of dystonia, and perhaps most interestingly, for treating neuropathic pain (Zeltser et al. 1991). (Also see the chapter titled Analgesia.) Neuropathic pain complicates many CNS diseases. Few available therapies provide even partial relief. Reference Zeltser, R.; Seltzer, Z.; Eisen, A.; Feigenbaum, J.J.; and Mechoulam, R. Suppression of neuropathic pain behavior in rats by a non-psychotropic synthetic cannabinoid with NMDA receptor-blocking properties. Pain 47(1):95-103, October 1991. source: http://www.onlinepot...l/article44.htm
  18. Endocannabinoids potently protect the newborn brain against AMPA-kainate receptor-mediated excitotoxic damage. Abstract Brain lesions induced in newborn mice or rats by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) or S-bromowillardiine (acting on AMPA-kainate receptors) mimic some aspects of white matter cysts and transcortical necrosis observed in human perinatal brain damage associated with cerebral palsy. Exogenous and endogenous cannabinoids have received increasing attention as potential neuroprotective agents in a number of neurodegenerative disorders of the adult. One recent study showed neuroprotection by the cannabinoid agonist WIN-55212 in a newborn rat model of acute severe asphyxia. The present study was designed to assess the neuroprotective effects of the endogenous cannabinoid anandamide using a well-defined rodent model of neonatal excitotoxic brain lesions. In this model, anandamide provided dose-dependent and long-lasting protection of developing white matter and cortical plate reducing the size of lesions induced by S-bromowillardiine. Anandamide had only marginal neuroprotective effect against ibotenate-induced cortical grey matter lesions. Anandamide-induced neuroprotection against AMPA-kainate receptor-mediated brain lesions were blocked by a CB1 antagonist but not by a CB2 antagonist. Furthermore, anandamide effects were mimicked by a CB1 agonist but not by a CB2 agonist. Real-time PCR confirmed the expression of CB1 receptors, but not CB2 receptors, in the untreated newborn neocortex. Finally, neuroprotective effects of anandamide in white matter involved increased survival of preoligodendrocytes and better preservation of myelination. The present study provides experimental support for the role of endocannabinoids as a candidate therapy for excitotoxic perinatal brain lesions. http://www.youtube.com/watch?v=Jd5aoqtNo8Y CEREBRAL PALSY / CANNABIS Statement Before City Council Re: Medical Marijuana Morgan, MD, John P. "Statement Before City Council Re: Medical Marijuana." Feb. 23, 2004. A comparison of cannabis sativa to papaver somniferum, the opium poppy, is apt. Humans found products of both plants useful and pleasurable under certain circumstances, and began to cultivate them. Products of both were used to relieve symptoms (and for other effects), although the use of both also produced fear and attempts to control their production and use. Thirty to forty years ago the appeal of the poppy to humans was elucidated elegantly. The principal constituent of opium, morphine, was found to produce its effects in animals by interacting with a pre-existing structural and functional component of the brain. Morphine binds to a receptor tissue and that binding, changes the function of cells. Further, the receptors were not waiting for morphine, but were ordinarily activated by compounds produced by the brain which provoked effects which we must assume were useful and part of normal brain function. Understanding of this system has lead to pharmacological exploitation of it. We now produce many versions of morphine which bind to the receptor, may be given by various routes and produce variations in effect. We even produce drugs which block the receptor and are useful under certain circumstances. The “marijuana” (perhaps cannabis is a better term) story is similar and in many ways identical. The effects of cannabis are largely due to the presence of a chemical (delta-9-tetrahydrocannabinol, THC) which binds to pre-existing receptors in human calls and that binding alters cellular function. The receptors are part of a structural and functional system. We produce chemicals which bind to the cannabinoid receptors and it is clear that the system is useful and part of normal brain function. There is now active research producing compounds related to THC and products to deliver THC in various ways. There are even cannabinoid receptor blockers which are chiefly used in research to promote understanding of this built-in cannabinoid system in our brains. Activation of the cannabinoid system by delivering THC to receptor sites provokes a variety of effects. Many of those effects, not all, reduce cellular response to stimuli. There is adequate evidence that THC is therapeutic in diminishing pain perception, diminishing nausea and vomiting in response to many stimuli, and reducing muscle tone and spasm secondary to multiple sclerosis, cerebral palsy and spinal cord injury. Interestingly, THC is one of the very few compounds that humans consistently respond to with increased appetite. The development of fuller understanding and exploitation of the effects of cannabis has been delayed by societal and legislative reactions to the widespread use of cannabis by young people in the Western democracies, beginning in the 1960's, for the purpose of having fun. This negative reaction and aversion to cannabis is also fueled by the fact that it is commonly ingested by smoking it using cigarettes and pipes. Many who wish to use cannabis for apparent medical reasons wish to smoke it, and that act remains usually illegal in the United States. In truth, the current federal administration remains committed to continuing and expanding that criminalization of all cannabis use in the USA at incredible costs to taxpayers, patients and truth. Cannabis smoking is always compared to tobacco smoking in terms of health consequences, and some who might support medical cannabis fear tobacco-like consequences. The current federal administration through its ministry of propaganda (The Office of Drug Control Policy), is actively directing a campaign to frighten Americans into believing that smoking of cannabis might even be worse for human health than the smoking of tobacco. This is not even close to true. Despite dire predictions there is no evidence that the smoking of cannabis alone causes lung cancer. It is with real concern that I tell you that the bronchial cells of cannabis smokers show pre-cancerous changes. This has been known for 20 years. Yet there are no reported cases of cancer in marijuana-only smokers. Further, strong evidence indicates that marijuana smoking even in unusually large doses does not produce the most crippling lung disorder, emphysema. The absence of these toxicities reflects the much lower dose of smoke and its irritants inhaled by users of cannabis. Not only do they smoke fewer cigarettes, but they rarely continue their smoking careers for years in the fixed pattern of tobacco use. I agree with those who think the future of cannabinoid medication may not involve smoking; even though There is meaningful and positive research in using vaporizing devices to reduce the irritant load in cannabis smoke. However currently, there are really no alternatives to smoking cigarette and pipe-delivered plant material, for patients who find benefit in cannabis. I believe strongly that the harm in permitting this kind of use approaches zero. Sincerely, John P. Morgan, M.D. source: http://www.lindesmit...yc_comments.cfm Jaqueline Patterson, Cerebal Palsay video included Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance and posture. The disorders appear in the first few years of life. Usually they do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have trouble with tasks such as writing or using scissors. Some have other medical conditions, including seizure disorders or mental impairment. Cerebral palsy happens when the areas of the brain that control movement and posture do not develop correctly or get damaged.There is no cure for cerebral palsy, but treatment can improve the lives of those who have it. Treatment includes medicines, braces, and physical, occupational and speech therapy. - National Institute of Neurological Disorders and Stroke source: http://www.medicalca...documentary.htm Treatment of human spasticity with delta 9-tetrahydrocannabinol. Abstract Spasticity is a common neurologic condition in patients with multiple sclerosis, stroke, cerebral palsy or an injured spinal cord. Animal studies suggest that THC has an inhibitory effect on polysynaptic reflexes. Some spastic patients claim improvement after inhaling cannabis. We tested muscle tone, reflexes, strength and performed EMGs before and after double-blinded oral administration of either 10 or 5 mg THC or placebo. The blinded examiner correctly identified the trials in which the patients received THC in seven of nine cases. For the group, 10 mg THC significantly reduced spasticity by clinical measurement (P less than 0.01). Quadriceps EMG interference pattern was reduced in those four patients with primarily extensor spasticity. THC was administered to eight other patients with spasticity and other CNS lesions. Responses varied, but benefit was seen in three of three patients with "tonic spasms." No benefit was noted in patients with cerebellar disease. Blind Cerebral Palsy Victim Sues City Over Medical Marijuana
  19. Causes, incidence, and risk factors Worldwide, cervical cancer is the third most common type of cancer in women. It is much less common in the United States because of the routine use of Pap smears. Cervical cancers start in the cells on the surface of the cervix. There are two types of cells on the cervix's surface: squamous and columnar. Most cervical cancers are from squamous cells. Cervical cancer usually develops very slowly. It starts as a precancerous condition called dysplasia. This precancerous condition can be detected by a Pap smear and is 100% treatable. It can take years for precancerous changes to turn into cervical cancer. Most women who are diagnosed with cervical cancer today have not had regular Pap smears or they have not followed up on abnormal Pap smear results. Almost all cervical cancers are caused by HPV (human papilloma virus). HPV is a common virus that is spread through sexual intercourse. There are many different types of HPV. Some strains lead to cervical cancer. (Other strains may cause genital warts, while others do not cause any problems at all.) A woman's sexual habits and patterns can increase her risk for cervical cancer. Risky sexual practices include having sex at an early age, having multiple sexual partners, and having multiple partners or partners who participate in high-risk sexual activities. Risk factors for cervical cancer include: Not getting the HPV vaccine Poor economic status Women whose mothers took the drug DES (diethylstilbestrol) during pregnancy in the early 1960s to prevent miscarriage Weakened immune system Symptoms Most of the time, early cervical cancer has no symptoms. Symptoms that may occur can include: Abnormal vaginal bleeding between periods, after intercourse, or after menopause Continuous vaginal discharge, which may be pale, watery, pink, brown, bloody, or foul-smelling Periods become heavier and last longer than usual Cervical cancer may spread to the bladder, intestines, lungs, and liver. Patients with cervical cancer do not usually have problems until the cancer is advanced and has spread. Symptoms of advanced cervical cancer may include: Back pain Bone pain or fractures Fatigue Leaking of urine or feces from the vagina Leg pain Loss of appetite Pelvic pain Single swollen leg Weight loss Signs and tests Precancerous changes of the cervix and cervical cancer cannot be seen with the naked eye. Special tests and tools are needed to spot such conditions. Pap smears screen for precancers and cancer, but do not make a final diagnosis. If abnormal changes are found, the cervix is usually examined under magnification. This is called colposcopy. Pieces of tissue are surgically removed (biopsied) during this procedure and sent to a laboratory for examination. Cone biopsy may also be done. If the woman is diagnosed with cervical cancer, the health care provider will order more tests to determine how far the cancer has spread. This is called staging. Tests may include: Chest x-ray CT scan of the pelvis Cystoscopy Intravenous pyelogram (IVP) MRI of the pelvis Treatment Treatment of cervical cancer depends on: The stage of the cancer The size and shape of the tumor The woman's age and general health Her desire to have children in the future Early cervical cancer can be cured by removing or destroying the precancerous or cancerous tissue. There are various surgical ways to do this without removing the uterus or damaging the cervix, so that a woman can still have children in the future. Types of surgery for early cervical cancer include: Loop electrosurgical excision procedure (LEEP) -- uses electricity to remove abnormal tissue Cryotherapy -- freezes abnormal cells Laser therapy -- uses light to burn abnormal tissue A hysterectomy (removal of the uterus but not the ovaries) is not often performed for cervical cancer that has not spread. It may be done in women who have repeated LEEP procedures. Treatment for more advanced cervical cancer may include: Radical hysterectomy, which removes the uterus and much of the surrounding tissues, including lymph nodes and the upper part of the vagina. Pelvic exenteration, an extreme type of surgery in which all of the organs of the pelvis, including the bladder and rectum, are removed. Radiation may be used to treat cancer that has spread beyond the pelvis, or cancer that has returned. Radiation therapy is either external or internal. Internal radiation therapy uses a device filled with radioactive material, which is placed inside the woman's vagina next to the cervical cancer. The device is removed when she goes home. External radiation therapy beams radiation from a large machine onto the body where the cancer is located. It is similar to an x-ray. Chemotherapy uses drugs to kill cancer. Some of the drugs used for cervical cancer chemotherapy include 5-FU, cisplatin, carboplatin, ifosfamide, paclitaxel, and cyclophosphamide. Sometimes radiation and chemotherapy are used before or after surgery. Support Groups National Cervical Cancer Coalition - http://www.nccc-online.org/ Expectations (prognosis) How well the patient does depends on many things, including: The type of cancer The stage of the disease The woman's age and general physical condition If the cancer comes back after treatment Pre-cancerous conditions are completely curable when followed up and treated properly. The chance of being alive in 5 years (5-year survival rate) for cancer that has spread to the inside of the cervix walls but not outside the cervix area is 92%. The 5-year survival rate falls steadily as the cancer spreads into other areas. Complications Some types of cervical cancer do not respond well to treatment. The cancer may come back (recur) after treatment. Women who have treatment to save the uterus have a high risk of the cancer coming back (recurrence). Surgery and radiation can cause problems with sexual, bowel, and bladder function. Calling your health care provider Call your health care provider if you: Have not had regular Pap smears Have abnormal vaginal bleeding or discharge Prevention A vaccine to prevent cervical cancer is now available. In June 2006, the U.S. Food and Drug Administration approved the vaccine called Gardasil, which prevents infection against the two types of HPV responsible for most cervical cancer cases. Studies have shown that the vaccine appears to prevent early-stage cervical cancer and precancerous lesions. Gardasil is the first approved vaccine targeted specifically to prevent any type of cancer. Practicing safe sex (using condoms) also reduces your risk of HPV and other sexually transmitted diseases. HPV infection causes genital warts. These may be barely visible or several inches wide. If a woman sees warts on her partner's genitals, she should avoid intercourse with that person. To further reduce the risk of cervical cancer, women should limit their number of sexual partners and avoid partners who participate in high-risk sexual activities. Getting regular Pap smears can help detect precancerous changes, which can be treated before they turn into cervical cancer. Pap smears effectively spot such changes, but they must be done regularly. Annual pelvic examinations, including a pap smear, should start when a woman becomes sexually active, or by the age of 20 in a nonsexually active woman. See also: Physical exam frequency If you smoke, quit. Cigarette smoking is associated with an increased risk of cervical cancer. References Noller KL. Intraepithelial neoplasia of the lower genital tract (cervix, vulva): Etiology, screening, diagnostic techniques, management. In: Katz VL, Lentz GM, Lobo RA, Gershenson DM, eds. Comprehensive Gynecology. 5th ed. Philadelphia, Pa: Mosby Elsevier; 2007:chap 28. National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Cervical Cancer Screening. v.1.2011. Smith RA, Cokkinides V, Brooks D, Saslow D, Brawley OW. Cancer screening in the United States, 2010: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin. 2010;60:99-119. Review Date: 12/15/2011. Reviewed by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. Cannabis Slows cervical Cancer in Test Tube Marijuana Ingredients Slow Invasion by Cervical and Lung Cancer Cells By Daniel J. DeNoon WebMD Health NewsReviewed by Louise Chang, MDDec. 26, 2007 -- THC and another marijuana-derived compound slow the spread of cervical and lung cancers, test-tube studies suggest. The new findings add to the fast-growing number of animal and cell-culture studies showing different anticancer effects for cannabinoids, chemical compounds derived from marijuana. Cannabinoids, and sometimes marijuana itself, are currently used to lessen the nausea and pain experienced by many cancer patients. The new findings -- yet to be proven in human studies -- suggest that cannabinoids may have a direct anticancer effect. "Cannabinoids' ... potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials," conclude Robert Ramer, PhD, and Burkhard Hinz, PhD, of the University of Rostock, Germany. Might cannabinoids keep dangerous tumors from spreading throughout the body? Ramer and Hinz set up an experiment in which invasive cervical and lung cancer cells had make their way through a tissue-like gel. Even at very low concentrations, the marijuana compounds THC and methanandamide (MA) significantly slowed the invading cancer cells. Doses of THC that reduce pain in cancer patients yield blood concentrations much higher than the concentrations needed to inhibit cancer invasion. "Thus the effects of THC on cell invasion occurred at therapeutically relevant concentrations," Ramer and Hinz note. The researchers are quick to point out that much more study is needed to find out whether these test-tube results apply to tumor growth in animals and in humans. Ramer and Hinz report the findings in the Jan. 2, 2008 issue of the Journal of the National Cancer Institute. source: http://www.webmd.com...er-in-test-tube Cervical Cancer - Radical Trachelectomy http://www.youtube.com/watch?v=NVsczkyLdOA Medicinal Cannabis Fighting cervical cancer and fibromyalgia, Juliet uses a vaporiser to treat her pain with cannabis. http://natgeotv.com/.../?cmp=user_post Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1 Emmanuel Contassot a, Mirna Tenan a, Valérie Schnüriger a, Marie-Françoise Pelte b and Pierre-Yves Dietrich a, , a Oncology Division, Laboratory of Tumor Immunology, University Hospital, Geneva, Switzerland b Clinical Pathology Department, University Hospital, Geneva, Switzerland Received 9 September 2003. Available online 8 February 2004. References and further reading may be available for this article. To view references and further reading you must purchase this article. Abstract Objective. Δ9-Tetrahydrocannabinol, the active agent of Cannabis sativa, exhibits well-documented antitumor properties, but little is known about the possible effects mediated by endogenous cannabinoids on human tumors. In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines. Methods. To assess the sensitivity of CxCa cells to AEA, we selected three cell lines that were exposed to increasing doses of AEA with or without antagonists to receptors to AEA. DNA fragmentation and caspase-7 activity were used as apoptosis markers. The expression of receptors to AEA were analyzed in CxCa cell lines as well as CxCa biopsies. Results. The major finding was that AEA induced apoptosis of CxCa cell lines via aberrantly expressed vanilloid receptor-1, whereas AEA binding to the classical CB1 and CB2 cannabinoid receptors mediated a protective effect. Furthermore, unexpectedly, a strong expression of the three forms of AEA receptors was observed in ex vivo CxCa biopsies. Conclusion. Overall, these data suggest that the specific targeting of VR1 by endogenous cannabinoids or synthetic molecules offers attractive opportunities for the development of novel potent anticancer drugs. Author Keywords: Author Keywords: Arachidonyl ethanolamide; Cervical cancer; Vanilloid receptor; Apoptosis source: and more info http://www.sciencedi...3a344307d083fe1 Please contact us at info@freemygreenpdx.com to add more to this thread
  20. Crohn's / Gastrointestinal Disorders General Reference (not clearly pro or con) "Inflammatory Bowel Disease - A blanket term covering three serious disorders: ulcerative colitis, proctitis, and Crohn's disease. Ulcerative colitis is an inflammation of the colon that produces ulceration of the inside wall. Its primary symptom is bloody, chronic diarrhea, often containing pus and mucus, and associated with abdominal pain and weight and appetite loss. Crohn's disease is an inflammation of the small and/or large intestine, with accompanying pain, cramping, tenderness, gas, fever, nausea, and diarrhea. Though usually mild, bleeding may occur and may sometimes be massive. Proctitis, an inflammation of the rectum, is characterized by bloody stools, a frequent urge to defecate but inability to do so, and sometimes diarrhea. Ulcerative colitis and Crohn's disease are generally chronic and have no known cures. Irritable Bowel Syndrome - Marked by an abnormally active--even spastic--lower bowel. Its symptoms are similar to a number of other illnesses, including diverticulosis and lactose intolerance. These symptoms include uncomfortable abdominal sensations and periodic diarrhea or constipation, sometimes occurring alternately. Some patients come to depend on laxatives and even enemas to alleviate the constipation. For others, the only symptom is painless diarrhea. Gastroenteritis - Diarrhea, nausea, vomiting, and abdominal cramping brought on by bacteria, amoebas, parasites, toxins, certain drugs, enzymes, or allergens in foods. Ulcers - Can occur in the lower esophagus, stomach, or any part of the small intestine. Can produce heartburn, pain, nausea, indigestion, and, in gastric ulcer, pain after eating a meal. Gastric Cancer - Early signs include indigestion and discomfort, followed by weight and appetite loss, a sensation of fullness after eating, fatigue, and anemia." More on Pro's and Con's
  21. Anandamide Cannabis / Marijuana: THC / Anandamide Anandamide is a natural neurotransmitter found in the brain that binds to the same neuroreceptors as do cannabinoids. [1] [2] Current research suggests that cannabinoids are very similar to anandamide, which regulates mood, memory, pain, movement, and appetite. [3] Although these recent findings are not thoroughly understood, it is clear that cannabis affects the brain in ways completely dissimilar to other drugs, in accordance with natural neurochemical pathways. The 1988 discovery of the CB1 receptor, found abundant in the brain, and the 1992 discovery of the CB2 receptor found throughout the body, clearly distinguish cannabinoid compounds from other substances. [4] Cannabinoids bind to anandamide receptors in the frontal lobes of the brain, according o research published by the American Association for the Advancement of Science. [5] Anadamide is thoguht to be key to the anti-emetic (hunger-inducing) properties of cananbis. Recent studies indicate: “Anandamide induces overeating in rats through a CB1 recptor mediated mechanism. Cannabinoid agonists inhibit the activation of 5-HT3 receptors, a possible mechanism of their anti-emetic effect. Cannabinoid agonists inhibit gastrointestinal motility and gastric emptying in rats. In a recent double-blind study in healthy individuals, an oral dose of delta-9-THC of 10mg/m2 caused a significant delay in gastric emptying compared to placebo. In addition, CB agonists inhibited pentabastrin-induced gastic acid secretion in the rat, presumably by a CB receptor dependent process.”[6] [1] Devane, et al. Science, Vol. 258, pp. 1946-1949, 1992 [2] Axelrod, “Enzymatic synthesis of anandamide, an endogenous ligand for the cannabinoid receptor, by brain membranes.” Laboratory of Cell Biology, National Institute of Mental Health, Bethesda MD, 1997 [3] Fackelman, “Marijuana and the brain: scientists discover the brain’s own THC.” Science News, Vol. 143, No. 6, p. 88, February 6, 1998 [4] Finn, “Cannabinoid Investigations Entering The Mainstream.” The Scientist, Vol. 12, No. 3, pp. 1-8, February 2, 1998 [5] Beltramo and Piomelli, “Functional role of high-affinity anandamide transport, as revealed by selective inhibition,” Science, Vol. 277, No. 5329, p. 1094(4), August 22, 1997 [6] Grotenhermen, Russo. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York: The Hawthorn Integrative Healing Press, 2002, Grotenhermen, “Effects of Cannabis and the Cannabinoids.” Chapter 5, p. 61-62 Cannabis: Professor Raphael Mechoulam - Discovery of THC in 1964, Anandamide in 1992 Dr.'s Mechoulam and Schuel on Anandamides Ron Bain, Boulder Weekly, January 30 - February 6, 2003 You've heard of a "natural high?" Well, it turns out we're all a little bit high all the time, whether or not we smoke dope. In fact, the pleasures derived from marijuana, sex and chocolate are all tied together. by similar chemical reactions in our brains. Right now, there's a naturally occurring molecule in your brain and body that's chemically similar to THC, or delta-9 tetrahydrocannabinol, the stuff in marijuana that gets users high. The scientists who discovered this natural THC-like body chemical in 1992, most notably Raphael Mechoulam of the Hebrew University of Jerusalem, named it "anandamide" after the Sanskrit word for ecstasy, "ananda". THC molecules can plug into the brain's receptors for anandamides quite easily, he found, but THC lasts longer than anandamides, overwhelming the brain's pleasure sites and causing, at least in novice users, feelings of giddiness and ecstasy. For almost 30 years, Jewish researchers have dominated the world's research into marijuana and why it produces a "high" when smoked. Recently, Dr. Mechoulam and his counterpart at the University of Buffalo, Herbert Schuel, explained to Boulder Weekly how and why most people are high most of the time. Mechoulam's and Schuel's ongoing research shows that anandamides appear to be involved in regulating and balancing the body's biochemical systems, influencing or controlling the reproductive, sleep, fight-or-flight and appetite cycles. "It's a quirk of nature that THC works on our receptors," Mechoulam remarked. "We were lucky to be the only group in the world working on this chemical." All mammals, fish, birds and reptiles seem to have anandamide-based regulatory systems; it's even found in cacao nuts, from which chocolate is made. "It is found in substantial quantities in chocolate, and may account for the feelings of pleasure that come from chocolate," Schuel said. Other researchers have found that chocolate seems to prolong the marijuana high, as pot users have long claimed. Street mythology about marijuana has always held that the drug makes girls easier to seduce, that it makes guys impotent or sterile, that it induces drowsiness, and that it prolongs life by easing cumulative stress. Turns out that these two specialized geniuses, Mechoulam and Schuel, no longer view the above as mythology. Experiments with rats, Schuel explains, show that marijuana causes some "enhancement of sexual activities," at least for the female rats "who appear much more eager than the males." Tests of heavy pot-smoking human males show lowered sperm counts to the point that marijuana could be considered an effective contraceptive, Schuel said, although "it's not a cut-and-dried thing. Sometimes when both smoke, they have babies." One of Schuel's studies with sea urchins reveals that anandamides inhibit the process of sperm penetrating and entering the egg cell. When anandamides or THC are present, the sea urchin sperm, which actually has anandamide receptor sites on its surface, cannot break through the egg's tough protein coat. Many people consider marijuana to be a virtual panacea, good for the prevention and treatment of glaucoma and as a digestive aid, or as a treatment for asthma, nausea, insomnia, constipation, menstrual pain, headaches, hangovers, hiccups, eating disorders and lack of appetite. Schuel agrees that, with the discovery of anandamides, "there's an enormous potential for new medicines and home remedies. There are medicinal aspects plus the psychogenic effects." Cannabis-based medicines were common in the 19th century and may become so again in the 21st century, the two scientists speculate. Already, European researchers are testing an anandamide-based stroke treatment that, if used quickly enough, seems to protect and cushion the brain from the worst effects of stroke, Mechoulam said. History of THC Research In the early 1960s, Dr. Mechoulam was fresh from post-doctoral studies at the Rockefeller Institute in New York and working at the Weizmann Institute in Rehovot, Israel. He was looking for a unique field of research in which to work and make his scientific name. "I decided to initiate... a re-examination of the chemistry of hashish," Mechoulam wrote in a 1998 edition of the International Cannabinoid Research Society newsletter. Mechoulam's preliminary research showed that ancient Assyrians used cannabis for mind-expanding and medicinal purposes 4,500 years ago. "Apparently nobody was working on this plant resin, although from a careful perusal of the literature it was quite obvious that, in spite of several claims to the contrary, the active constituent had not been isolated in a pure form and its structure was unknown," he wrote. Mechoulam persuaded an administrator at the Weizmann Institute to contact Israel's top law enforcement commander "and ask for a few kilograms of hashish," he wrote. "Within a week I went to police headquarters and signed a receipt, 'free of charge,' for five kilograms of hashish... still packed in their original cotton bags, with the trademarks of the Lebanese suppliers." Mechoulam thought he had fulfilled all procedural requirements to legally obtain the illicit substance, but later he found out that only the Israeli Ministry of Health could legally dispense "narcotics" and that he had technically broken the law. But he never spent any time in jail and he got to keep his hash stash, Mechoulam explains. In 1964, Mechoulam and a fellow researcher, Prof. Yehiel Gaoni, isolated THC for the first time. Mechoulam applied to the U.S. National Institute of Health (NIH) for a research grant, and was turned down flatly. "The drug was only used by South American natives and was unknown in the United States, I was told." But mid-'60s pot politics turned things around. "A U.S. senator had asked NIH whether they knew anything about marijuana, as his son had been caught smoking it," Mechoulam wrote. "The senator wanted to know whether his son had permanently damaged his brain." Dr. Dani Efron, at that time the head of pharmacology for NIH, contacted Mechoulam immediately. "In order to not look out of touch, they asked for my help. We supplied them with 10 grams of pure delta-9 THC, the entire world supply, and we got a grant," Mechoulam wrote. "Much of the early research on THC in the U.S. was done on our material, although Dr. Efron kept his source of supply a secret." Dr. Mechoulam has held an NIH grant ever since. In the late 1960s, he went on to synthesize most of the other cannabinoids in marijuana, finding that delta-9 THC is the only one that showed measurable laboratory effects on rhesus monkeys. In a 1970 article in Science magazine, Mechoulam speculated that the human body metabolized THC into another chemical that acted on the molecular level to produce the drug's high. Later he found this metabolized substance in mammalian urine, leading to today's urinalysis industry... "and we had neglected to patent it!" he added. In 1988, an American research group that included Bill Devane announced they had found evidence of a cannabinoid receptor in the mammalian brain. Devane joined Mechoulam in Israel to further research this question: Did our brains evolve to receive marijuana? "We assumed that such a receptor does not exist for the sake of a plant compound," they concluded. Other drugs, like opium, had been found to bind at the molecular level to brain receptor sites intended for endorphins, the body's natural pain reliever. Mechoulam and Devane decided to look for the natural version of THC, and in 1992 they announced finding a fatty molecule that bound naturally to the cannabinoid receptor site. "Now, there have been about 12,000 papers published on it," Mechoulam adds proudly. How Anandamides Work Anandamides are produced by our brains and bodies to achieve a sort of yin-yang biochemical balance, and do not produce the extreme "high" of marijuana, Mechoulam says. "They're completely different, from a chemical point of view, from THC," he said. "But they combine in the receptor sites the same way." Anandamides are quickly broken down by the body after they have served their intended purpose, and do not last as long as THC metabolites, which remain in the body for weeks. "The body, the way I see it, is made of compounds which enhance (biochemical) reactions and compounds which reduce reactions," Mechoulam says. "Anandamide is basically a compound that reduces activity; for example, it reduces the formation of many neurotransmitters that are stimulatory." Anandamides play a survival role for young mammals, their instinctive suckling behavior seems integrally tied to the presence of anandamides. "If we block the system (from receiving anandamides), there is no suckling," Mechoulam explains. Scientists today use genetic engineering to create special strains of mice that have no anandamide receptors. "These mice are called 'knock-out' mice... and they survive pretty well," Mechoulam said, but he explained that knock-out mice die at a younger age than their anandamide-receiving counterparts and don't reproduce as well. What would happen if a human were born without the ability to produce or receive anandamides? "I don't think he or she would be born. I don't think they could survive. It would probably be a very difficult life," Mechoulam remarked. But it fits the logic of earlier research into the brain chemical dopamine to assume that there are humans who produce too much or too little anandamide, Mechoulam explained. "There are people with lots of dopamine that are schizophrenics and others who don't have enough dopamine. "Lack of anandamide levels can cause spontaneous abortions" in mammals, Mechoulam said. "And it makes sense that disease would shut down the anandamide system." But testing a human to see if their anandamide levels are correct would require a painful spinal tap to find the specific enzyme produced by the body' s breakdown of anandamides, which is why today's research remains confined to rats, mice and sea urchins. "We can't do that painful procedure (to humans) just for research," Mechoulam said. Across the world, in differing cultures with wildly varying socioeconomic structures, a consistent 10 percent of the population smokes marijuana, studies have shown. Could these be people born with low levels of natural anandamides? Schuel thinks questions like this will be answered soon, now that countries like Canada and Holland are allowing recreational use of marijuana while anandamides research continues in Israel and Ameica. Here, though, "there's a big disconnect between the public policy world and the science of biochemistry," he said, which will prevent America from legalizing marijuana any time soon. But there are already websites selling anandamides and a legal snythetic analog of THC that, Schuel estimates, is 100 to 1,000 times stronger than marijuana. The Israeli Connection Schuel says that the major reason that research into THC and anandamides is based primarily in Israel, rather than some drug Mecca like Holland or Canada. is that Dr. Mechoulam chooses to live and work there. "Raphael is the big mover. I'm just a little fish in the pond," he said, complimenting the elder Mechoulam, who's 72. "There are quite a few people and hundreds of groups working on cannabinoids all over the world now," Mechoulam says, diverting all reverence away from himself. "The world is not just made of small countries anymore. It doesn't matter if my fellow researchers are in Canada, France, Spain, NIH or California, we have these frequent contacts. I am currently refereeing several papers that are up for publication." Schuel thinks the reason it was Jews who broke ground in marijuana research dates back to World War II and has nothing to do with drugs. "Hitler drove all the Jewish physicists out and they came to America and built the bomb," he said, pointing out the tradition of Jewish intellectual inquiry. "Studying for study's sake is a glorious endeavor," Schuel said, noting that today people from an infinite variety of ethnicities work in the cannabinoids research field all over the world. Compared to their percentages in the general population, Jews are more often drawn to careers in science, academic research or writing than other demographic groups, he noted, so it was only natural that Jewish researchers were first drawn to the esoteric field of marijuana research. In the January 2003 issue of High Times magazine, writer Chris Bennett claims that ancient Hebrew royalty and religious leaders used anointing oil containing a large amount of marijuana extracts. Bennett, who referenced his article heavily with scriptural and historical citations, goes on to claim that Jesus might have been called Christ because he was anointed with this oil, called "kaneh-bosem," which was reserved for kings. "Anointing was common among the kings of Israel. It was the sign and symbol of royalty. These kings led their people with the benefits of insights achieved through using the holy anointing oil to become 'possessed with the spirit of the Lord,'" wrote Bennett. "The ministry of Jesus marked the return of the Jewish Messiah-kings, and thus the re-emergence of the holy oil. Jesus was called the Christ because he violated the Old Testament taboo on the cannabis oil and distributed it freely for initiation rites and to heal the sick and wounded," Bennett.s article continues. Maybe the claims of Rastafarians.who say that marijuana is a sacrament, that it allows them to be closer to God and that they are one of the lost tribes of Israel, are not too far from the literal truth. Even Judges Are High Everyone alive, including parents, politicians, judges, police and jailers, is on a natural anandamide high every day. except perhaps for those who lack certain genes to produce or receive the natural THC-like chemical. Thanks to Mechoulam and Schuel, someday soon there will be cannabinoid-based or anandamide-based medical treatments for those who can't sleep, who have no appetite, who develop strokes or heart conditions, who suffer asthma or glaucoma, who are too restless or anxious, or who suffer any number of other maladies. When that day comes, perhaps a memorial will go up for every person who suffered or died in prison for smoking or selling an innocent, medicinal herb and to those who devoted their lifetimes to expand the human race's knowledge of marijuana, cannabinoids and anandamides. Note: Getting stoned is just a matter of degree. Our brains give us all a marijuana-like high every day, like it or not. source: http://cannabismd.or...anandamides.php Anandamide Work As Antidepressant Boosting the amounts of a marijuana-like brain transmitter called anandamide produces antidepressant effects in test rats, according to American and Italian researchers. The researchers, led by Daniele Piomelli, the Louise Turner Arnold Chair in Neurosciences and director of the Center for Drug Discovery at the University of California, Irvine, used a drug they created, called URB597, which blocks anandamide degradation in the brain, thereby increasing the levels of this chemical. “These findings raise the hope that the mood-elevating properties of marijuana can be harnessed to treat depression,” Piomelli said. “Marijuana itself has shown no clinical use for depression. However, specific drugs that amplify the actions of natural marijuana-like transmitters in the brain are showing great promise.” The researchers administered URB597 to chronically-stressed rats that demonstrated behaviors similar to those seen in depressed human patients. The stressed rats treated with the drug, after five weeks of treatment, were behaving similarly to a comparison group of unstressed animals. URB597 works by inhibiting an enzyme in the body FAAH that breaks down anandamide. Anandamide, dubbed as “the bliss molecule” for its similarities to the active ingredient in marijuana is a neurotransmitter that is part of the brain’s endocannabinoid system. In studies by Piomelli and others, anandamide has been shown to play analgesic, anti-anxiety, and antidepressant roles besides being involved in the regulation of feeding and obesity. Inhibiting FAAH activity boosts the effects of anandamide without producing the “high” seen with marijuana. Piomelli and colleagues at the Universities of Urbino and Parma in Italy created URB597. The study appears in an issue of Biological Psychiatry. Reference: University of California Anandamide Written by Mario D. Aceto Thursday, 06 November 2008 17:54 0022-3565/98/2872-0598$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 287, No. 2 Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. JPET 287:598–605, 1998 Anandamide, an Endogenous Cannabinoid, Has a Very Low Physical Dependence Potential1 MARIO D. ACETO, SUSAN M. SCATES, RAJ K. RAZDAN and BILLY R. MARTIN Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University (M.D.A., S.M.S., B.R.M.), Richmond, Virginia and Organix, Inc. (R.K.R.), Woburn, Massachusetts Accepted for publication June 22, 1998 This paper is available online at http://www.jpet.org ABSTRACT Using N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide • HCl (SR 141716A), a cannabinoid antagonist, several investigators (deFonseca et al., 1997; Aceto et al., 1995, 1996; Tsou et al., 1995) demonstrated physical dependence on THC [O9-tetrahydrocannabinol]. This demonstration prompted us to determine whether anandamide, an endogenous cannabinoid agonist, would also produce physical dependence. A low-dose regimen (10, 20, 40 and 40) or a high-dose regimen (25, 50, 100 and 100) expressed as mg/kg/24 hr was infused i.p. on a continuous basis, from days 1 through 4, respectively. During the infusion, especially at the high-dose regimen, the rats became immobile and developed eyelid ptosis. Abrupt discontinuation of anandamide did not elicit rebound behavioral activity. Neither arachidonic acid, a precursor and metabolite of anandamide (50, 100, 200 and 200 mg/kg/24 hr on days 1 through 4, respectively), nor 2-Me-F-AN [2-methylarachidonyl-(2'-fluoroethyl)-amide], a metabolically stable analog of anandamide (5, 10, 20 and 20 mg/kg/24 hr for 4 days, respectively), had remarkable effects. Notably, groups pretreated with anandamide or 2-Me-F-AN and challenged with SR 141716A did not show significantly elevated behavioral scores when compared with SR 141716A controls. On the other hand, nearly all groups receiving SR 141716A showed significant activation of these behaviors compared with vehicle controls, which suggests that this cannabinoid antagonist itself was activating behavior. We concluded that anandamide has little if any capacity for physical dependence. The finding that SR 141716A activated behavior supports the hypothesis that the cannabimimetic system exerts a depressant effect in the CNS. The identification of the major active constituent of Cannabis sativa, THC, by Gaoni and Mechoulam in 1964, followed by the characterization of the cannabinoid receptor (Howlett et al., 1988; Devane et al., 1988; Matsuda et al., 1990), provided a solid foundation and opened new perspectives for the study of this neurochemical system. Additionally, the isolation of an endogenous ligand designated anandamide (Devane et al., 1992), descriptions of its synthetic and metabolic pathways (Deutsch and Chin, 1993; Devane and Axelrod, 1994) and subsequent synthesis of a competitive antagonist, SR 141716A (Rinaldi-Carmona et al., 1994), furnished compelling evidence for the existence of an endocannabinergic system. Anandamide and THC have pharmacological properties in common (see review by Di Marzo and De Petrocellis, 1997). For example, both substances produced hypomotility, hypothermia, antinociception and catalepsy in rodents. Based on the results of studies on chemical structure and biological activity, Martin et al. (1987) showed that THC derivatives Received for publication December 26, 1997. 1 This work was supported by NIDA contract 3-8200 and grant DA 09789. that were active on this tetrad of tests were likely to be psychoactive cannabinoids. Anandamide also produced inhibitory effects on memory (Lichtman et al., 1995), inhibited forskolin-stimulated adenylyl cyclase activity (Felder et al., 1993) and prolactin release (Romero et al., 1994) and stimulated adrenocorticotropic hormone discharge (Weidenfeld et al., 1994). Regulatory effects on dopamine (Schlicker et al., 1996) and GABA neurotransmission (Romero et al., 1995), as well as similar effects on reproductive function (Schuel et al., 1994) and the immune system (Schwarz et al., 1994), were reported. In terms of the pharmacological determinants of dependence, there is evidence that THC causes tolerance and physical dependence in humans and animals (see reviews by Altman et al., 1996; Pertwee, 1991; Jones and Benowitz, 1976; and studies by de Fonseca et al., 1997; Aceto et al., 1995, 1996; Tsou et al., 1995). Other investigators demonstrated cross-tolerance among THC, anandamide and other cannabimimetics for their inhibitory effects on the twitch response in the vas deferens but not for their hypothermic effects (Pertwee et al., 1993). The present study was designed primarily to address the ABBREVIATIONS: SR 141716A, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide • HCl; THC, O9-tetrahydrocannabinol; 2-Me-F-AN, 2-methylarachidonyl-(2'-fluoroethyl)-amide; ANOVA, analysis of variance. 598 Cannabis: The Brain's Other Supplier. by Rosie Mestel New Scientist 31 July 1993 Three years ago, Israeli archaeologists stumbled upon a 1600-year-old tragedy: the remains of a narrow-hipped teenage girl with the skeleton of a full-term fetus still cradled in her abdomen. With her were grey ashes that contained traces of tetra-hydrocannabinol, the active ingredient of marijuana. Could it be that the midwife had administered the plant in a last-ditch effort to bring on labour or to ease her pain? Today, in nearby Jerusalem, another chemical is in the news -- this one extracted not from ancient ashes but from fresh, pulverised pig brain. It is anadamide, a newly christened chemical that might do naturally in our heads what marijuana does when we choose to smoke it. Anandamide's discovery, along with that of the molecule it binds to in the brain, has marijuana researchers buzzing with the best high they have had in years. The findings provide new hope for therapies that draw on the weed's long list of anecdotal medical uses: as a painkiller, appetite stimulant or nausea suppressant, to name a few. They also throw open windows onto the mysterious workings of our brains. More recently came other exciting finds: in 1988, Allyn Howlett of St Louis University Medical School discovered a specific protein receptor for THC in mouse nerve cells -- a protein that only THC and its relatives dock onto. Two years later, Tom Bonner's group at the National Institute of Mental Health pinpointed the DNA that encodes the same receptor in rats. It is now known that humans have the receptor, too. Finding a cannabinoid receptor implies that THC -- unlike alcohol -- has a quite precise modus operandi that taps into a specific brain function. Presumably the drug binds to nerves that have the receptor, and the nerves respond in turn by altering their behaviour. The classic effects of marijuana smoking are the consequences: changes in mood, memory, appetite, movement and perception, including pain. Researchers think THC affects so many mental processes because receptors are found in many brain regions, especially in those that perform tasks known to be disturbed during THC intoxication: in the banana-shaped hippocampus, crucial for proper memory; in the crumpled cerebral cortex, home of higher thinking; and in the primitive basal ganglion, controller of movement. Once a specially tailored receptor was found, the next step was simple -- in theory, anyway. "The receptor had to be there for a purpose -- presumably it didn't evolve so that people could smoke cannabis and get high," says Roger Pertwee, a pharmacologist at Aberdeen University. Instead, there had to be a natural chemical inside of us that fitted onto the receptor and sent some biochemical signal cascading through the nerve cell to do who knows what. But plucking that one chemical out of a brain stuffed with millions of others was never going to be easy. Several laboratories set to work on the problem and, fittingly, Mechoulam's was the first to come up with an answer, in the form of a greasy, hairpin-shaped chemical. The researchers dubbed it anandamide, from "ananda", the Sanskrit word for bliss. "The guy discovers the active ingredient of marijuana back in the 1960s, and now, almost 30 years later to the day, he discovers anandamide," says Paul Consroe, a neuropharmacologist at the University of Arizona. "Isn't that great?" Mechoulam's strategy was to chase after chemicals that, like THC, are soluble in fat. By teasing these substances away from those that are water soluble, his group extracted a substance from pig brain that did indeed bind to the cannabinoid receptor. But did it act like THC? To find out they sent their specimen to Pertwee who had devised a sensitive test for cannabinoids that involved monitoring a substance's ability to stop muscle-twitching in mouse tissue, when dropped on certain nerves. "When it arrived, there was so little of it in the phial I couldn't even see it," Pertwee recalls. "We didn't know what it was - just that it was a greasy substance." But the tests went well: anandamide depressed the twitch just like THC, and last December the researchers published their results in "Science". The mouse result gave Mechoulam and his group the encouragement they needed to extract more anandamide from pig brains and then analyse and synthesis the chemical in the lab. They also wanted more evidence that anandamide docked specifically onto the cannabinoid receptor and acted like THC, which has a very different molecular structure. And so, with Zvi Vogel and colleagues at the Weizmann Institute near Tel Aviv, they came up with a plan. They would add the DNA encoding the cannabinoid receptor to hamster or monkey cells growing in dishes. The cells equipped with this DNA would then produce masses of receptor, which would sit in the cell membrane ready and available for any chemical "key" that should happen along. Vogel's researchers would add anandamide to the cells and watch what happened. The results, published in July's issue of the "Journal of Neurochemistry," were clear: anandamide acted as a key, and a precise one at that, sticking only to the cells containing the receptor, and not to others. What's more, when anandamide stuck to the cells, it triggered biochemical changes similar to those associated with THC and related chemicals. Not only did anandamide fit the same lock as THC, but it appeared to open similar doors in the brain. More tests followed in a number of laboratories, and those researchers found that in every way that has been tested so far, anandamide acts very much like THC. But why would we want such a mind-altering substance in our brains? Studies on another class of drugs provide a useful parallel. Opiates such as morphine and heroin act upon the body's nervous system to cause euphoria and block pain. In 1973, natural opioids, which behave in the same way as opiates, but have a different structure, were pulled out of the body. It appears that when the body is under serious assault, nerve cells spit out these opioids, which promptly bind to other nerve cells to stop pain signals dead in their tracks. At the same time, they fasten onto sites in the brain to induce a feeling of wellbeing. Anandamide, like the natural opioids, will probably have its own specific set of jobs to perform in the brain and body. The effects of THC give a rough guide to what these might be: involvement in mood, memory and pain are obvious examples. But what would the brain be like without anandamide? Researchers intend to find out. Bonner is gearing up to produce a genetically engineered mouse that has no cannabinoid receptors: no receptors, no anandamide function. Others want to tinker with anandamide to make a version that binds to the receptor but doesn't trigger any change in the nerve's behaviour. Added to a mouse, it would stop the body's real, internal anandamide from doing its job. Researchers are also excited by anandamide's possible role in mental and neurological disease. There are also other questions to be asked. If anandamide, like THC, hampers memory, could a drug with the opposite effects -- a "memory pill" -- be made? "It's all speculation for now," says Steven Childers, a pharmacologist at Bowman Gray School of Medicine, North Carolina, "but we like to think about these things." It will take more time before anandamide is firmly established as the bona fide partner to the cannabinoid receptor. Meanwhile, Mechoulam's lab has two other anandamide-like chemicals waiting in the wings. And in the US, Howlett and Childers both have chemicals of an entirely different kind that bind to the receptor: they are water soluble, not fat soluble. The importance of each remains to be seen. Whatever anandamide turns out to be, it provides pharmacologists with a fresh plan of attack in their hunt for drugs that act like the cannabinoids. Such drugs could be valuable to help keep at bay the nausea of cancer chemotherapy; to stimulate appetite in AIDS patients; to dampen tremors in neurological disorders; to reduce eye pressure in patients with glaucoma; and to dull pain in those for whom other painkillers do not work. Cannabinoids can do at least some of these things, with one small drawback [sic.]: they also make the recipient high. The holy grail of cannabinoid therapeutics has been to separate what causes the high from the source of the desired effects, by chemical tinkering with THC or its relations -- shortening a side group on one part of the molecule, lengthening a carbon chain in another -- in the hope that the "undesirable" effects will be lost in the reshuffle. Despite the drug's dubious reputation, several US pharmaceuticals spent several years trying to make this work, but without success. Nor did they reach another equally sought after goal: an antagonist that will block the effects of THC and similar substances when taken. Until marijuana researchers succeed in doing something along these lines, it is unlikely that drugs companies will pay much attention. "There is a real stigma with working with drugs of abuse," says Billy Martin, a pharmacologist at the Medical College of Virginia. "If drugs companies had three choices of classes of drugs to work on and one was a drug of abuse, they're just not going to work on the drug of abuse." This view is shared by Larry Melvin, who worked on the Pfizer pharmaceuticals company's now defunct cannabinoid therapeutics programme. "What will ultimately legitimise the field in a big way is if researchers can come up with a really good therapeutic ability. Then you'll see the companies turn around." But Gabriel Nahas, an anaesthetist from Columbia University in New York, who has spoken out against marijuana use for many years, maintains that THC's effects on the brain are too general and too toxic for this route ever to work. The discovery of anandamide and its receptor have not changed his mind. "The brain is a computer," he says. "To put THC in the brain is akin to putting a bug in the computer. I'm sticking to my guns about its harmful effects -- not only to man but to society." Only time will reveal the value of anandamide and its receptor to drug therapy. But the importance of these discoveries to brain research is not in doubt. "We're no longer just dealing with the pharmacology of a recreational drug," says Pertwee. "We're dealing with the physiology of a newly discovered system in the brain. And that's an enormously bigger field." source: http://nepenthes.lyc...anandamide.html Anandamides & Glaucoma, David Pate, PhD, MSc http://www.youtube.com/watch?v=aBCDZ-czKuM Addressing 2002 Clinical Cannabis Therapeutics Conference in Portland, OR, Dr. Pate demonstrates that Anandamide, the "Bliss Molecule" naturally occuring in the body, has potential as an isolated compound to lower inter-ocular pressures. Also, Anandamide has neuronal protection properties: 1. NMDA hyper-excitability blockade 2. Microcirculatory stimulation 3. Apoptosis suppression 4. Free-Radical scavenging 5. TNF - alpha inhibition http://video.google....160958789588720
  22. Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects A A Izzo1, M Camilleri2 1 Department of Experimental Pharmacology, University of Naples Federico II and Endocannabinoid Research Group, Naples, Italy 2 Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA Correspondence to: Professor A A Izzo, Department of Experimental Pharmacology, University of Naples Federico II, via D Montesano 49, 80131, Naples, Italy; aaizzo@unina.it ABSTRACT A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas. These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion. Cannabinoids have the potential for therapeutic application in gut and liver diseases. Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases. This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases. Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans. We anticipate that, in addition to the approval in several countries of the CB1 antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia. SOURCE: http://gut.bmj.com/c...tract/57/8/1140 Cannabinoid 1 and Ulcerative Colitis and the Phenotype in Crohn's Disease The Cannabinoid 1 Receptor (CNR1) 1359 G/A Polymorphism Modulates Susceptibility to Ulcerative Colitis and the Phenotype in Crohn's Disease Martin Storr,1* Dominik Emmerdinger,2 Julia Diegelmann,2 Simone Pfennig,2 Thomas Ochsenkühn,2 Burkhard Göke,2 Peter Lohse,3 and Stephan Brand2 1Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada 2Department of Medicine II – Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany 3Department of Clinical Chemistry – Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany Syed A. Aziz, Editor Health Canada, Canada * E-mail: mstorr@ucalgary.ca Conceived and designed the experiments: MS JD TO BG PL SB. Performed the experiments: DE. Analyzed the data: MS DE JD SP PL SB. Contributed reagents/materials/analysis tools: MS TO BG PL. Wrote the paper: MS SB. Received January 15, 2010; Accepted January 27, 2010. This article has been cited by other articles in PMC. Abstract Background Recent evidence suggests a crucial role of the endocannabinoid system, including the cannabinoid 1 receptor (CNR1), in intestinal inflammation. We therefore investigated the influence of the CNR1 1359 G/A (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) on disease susceptibility and phenotype in patients with ulcerative colitis (UC) and Crohn's disease (CD). Methods Genomic DNA from 579 phenotypically well-characterized individuals was analyzed for the CNR1 1359 G/A SNP. Amongst these were 166 patients with UC, 216 patients with CD, and 197 healthy controls. Results Compared to healthy controls, subjects A/A homozygous for the CNR1 1359 G/A SNP had a reduced risk to develop UC (p=0.01, OR 0.30, 95% CI 0.12–0.78). The polymorphism did not modulate CD susceptibility, but carriers of the minor A allele had a lower body mass index than G/G wildtype carriers (p=0.0005). In addition, homozygous carriers of the G allele were more likely to develop CD before 40 years of age (p=5.9×10−7) than carriers of the A allele. Conclusion The CNR1 p.Thr453Thr polymorphism appears to modulate UC susceptibility and the CD phenotype. The endocannabinoid system may influence the manifestation of inflammatory bowel diseases, suggesting endocannabinoids as potential target for future therapies. http://www.youtube.com/watch?v=hak-eMev-T0 Introduction Anecdotal reports suggest that marijuana- or tetrahydrocannabinol-containing products may be effective in alleviating symptoms in patients with ulcerative colitis (UC) and Crohn's disease (CD). [1], [2] This is supported by recent studies of our group and others suggesting that pharmacological activation of the cannabinoid 1 (CB1) receptor with selective receptor agonists decreases the inflammatory response in various murine models of colonic inflammation including dinitrobenzene sulphonic acid (DNBS)-, trinitrobenzene sulphonic acid (TNBS)- and dextran sodium sulfate (DSS)-induced colitis. [3]–[7] Interestingly, pharmacological blockade of CB1 receptors or genetic ablation of CB1 receptors (CNR1−/− mice) aggravates intestinal inflammation in these models, [3], [7] emphasizing the physiological relevance of the CB1 receptor in the protection against intestinal inflammation. Increased mucosal levels of the endocannabinoid anandamide during intestinal inflammation in humans further stress the role of the CB1 receptor and the endocannabinoid system in intestinal inflammation. [4] Thus, present knowledge suggests up-regulation of endocannabinoids as an important protective mechanism in intestinal inflammation. The endocannabinoid system and the CB1 and CB2 receptors seem to be crucially involved in the regulation of multiple physiological functions, e.g. in the heart, where they relax coronary arteries and decrease cardiac work, [8] in organ perfusion, [9] in metabolic homeostasis, [10], [11] and in the regulation of bone mass by osteoclasts, [12] as well as in the protection against stress responses, inflammation, and associated repair mechanisms. [13], [14] Although recent evidence suggests that the endocannabinoid system is involved in many physiological and pathophysiological functions of the gastrointestinal tract such as intestinal motility, secretion, and intestinal inflammation [3], [15]–[20], the exact mechanisms underlying these findings are not yet known. It was recently suggested that CB1 signaling may be up-regulated during colitis, [3] but it is unknown whether this is a specific feature of the colitis model or a general response to intestinal inflammation. Moreover, the role of the CB1 receptor in human inflammatory bowel disease (IBD) has not been clarified. Increased anandamide levels were found in mucosal biopsies from UC patients, suggesting a role of the endocannabinoid system in UC. [4] In contrast, the colonic expression of the endocannabinoid 2-acyl-glycerol (2-AG) is not increased in UC. [4] So far, however, no other studies analyzing the endocannabinoid system or the pharmacological effects of cannabinoids in human IBD have been published. Gastrointestinal inflammation is likely the result of multiple factors, e.g., increased pro-inflammatory stimuli and reduced protective capability. The overall balance between pro- and anti-inflammatory mechanisms may determine the progression and severity of intestinal inflammation. [21], [22] Given the results of recent genome-wide association studies, [23] genetic susceptibility is an important factor contributing to IBD development. Moreover, knowledge of genetic susceptibility factors could provide important pathophysiologic insights for the generation of novel IBD therapeutics. Considering our previous work on the endocannabinoid system in murine intestinal inflammation, [3], [6], [7], [24] we hypothesized that genetic variants in the CNR1 gene, which may modulate CB1 receptor function, could be associated with an increased susceptibility to IBD. To test our hypothesis, we genotyped a cohort of more than 550 individuals including 382 IBD patients and analyzed whether the 1359 G/A (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) within the CNR1 gene encoding the CB1 receptor modulates the susceptibility to CD and UC or results in a certain IBD phenotype. The selection of the CNR1 1359 G/A SNP was based on previous studies reporting that this polymorphism is associated with other disorders modulated by the endocannabinoid system such as alcohol dependence and hebephrenic schizophrenia. [25], [26] Methods Cannabinoids ameliorate cerebral dysfunction following liver failure via AMP-activated protein kinase Abstract Hepatic encephalopathy (HE) is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We studied the etiology of cerebral dysfunction in a murine model of HE induced by either bile duct ligation or thioacetamide administration. We report that stimulation of cerebral AMP-activated protein kinase (AMPK), a major intracellular energy sensor, is a compensatory response to liver failure. This function of AMPK is regulated by endocannabinoids. The cannabinoid system controls systemic energy balance via the cannabinoid receptors CB-1 and CB-2. Under normal circumstances, AMPK activity is mediated by CB-1 while CB-2 is barely detected. However, CB-2 is strongly stimulated in response to liver failure. Administration of Δ9-tetrahydrocannabinol (THC) augmented AMPK activity and restored brain function in WT mice but not in their CB-2 KO littermates. These results suggest that HE is a disease of energy flux. CB-2 signaling is a cerebral stress response mechanism and makes AMPK a promising target for its treatment by modulating the cannabinoid system.—Dagon, Y., Avraham, Y., Ilan, Y., Mechoulam, R., Berry, E. M. Cannabinoids ameliorate cerebral dysfunction following liver failure via AMP-activated protein kinase. My link
  23. Cannabis compound benefits blood vessels Dr. Dave Allen, a heart surgeon explains marijuana may help avoidance of diseases and conditions. http://www.youtube.com/watch?v=xHfE9hNJyLI This computer rendition shows how fatty deposits can narrow blood vessels Roxanne Khamsi A compound derived from the cannabis plant protects blood vessels from dangerous clogging, a study of mice has shown. The discovery could lead to new drugs to ward off heart disease and stroke. The compound, called delta-9-tetrahydrocannabinol (THC), combats the blood-vessel disease atherosclerosis in mice. This disease occurs when damage to blood vessels, by nicotine from cigarettes, for example, causes an immune response that leads to the formation of fatty deposits in arteries. These deposits form because the immune cells can linger too long, recruiting others and leading to an inflamed blockage that snares fatty molecules. The disease is the leading cause of heart disease and stroke in the developed world. Science: Cannabinoids prevented the development of heart failure in animal study Heart failure is a serious possible consequence of a heart attack or other diseases that damage the heart. It occurs when the heart loses its ability to pump enough blood through the body. Often it develops slowly over years, as the heart gradually loses its pumping ability. In rats heart failure develops within 12 weeks after a big cardiac infarction. Scientists of the University of Wurzburg in Germany found out that daily application of the synthetic cannabinoid HU-210 after the infarction prevented the drop of blood pressure (left-ventricular systolic pressure) and dysfunction of the arteries (endothelial dysfunction). However, the cannabinoid also increased the filling pressure in the left chamber of the heart (left-ventricular end-diastolic pressure), which may be negative in the long run. HU-210 activates CB1 receptors as does THC. CB1 receptors are not only found in the brain where they cause the characteristic psychic effects, but also in the heart and many other organs. Dr. Jens Wagner and colleagues treated another group of rats with a selective blocker of the CB1 receptor which reduced the pumping ability of the heart after cardiac infarction. Researchers concluded that taken together with other results their studies show that endocannabinoids produced by the body itsself excert a protective effect after a heart attack. A commentary by the British Journal of Pharmacology says that "cannabinoids and endocannabinoid systems may therefore present useful targets for therapy following myocardial infarction." (Sources: Wagner JA, et a. Br J Pharmacol 2003 Apr;138(7):1251-8; Hiley CR, Ford WR. Br J Pharmacol 2003 Apr;138(7):1183-4; press release of the University of Wurzburg of 11 April 2003) source: http://www.cannabis-...el.php?id=145#2 DIABETES, CARDIOVASCULAR DISEASE | Pot? Future drugs THC could be deployed alongside currently used cholesterol-controlling drugs called statins to fight atherosclerosis, Mach suggests. "I don't think this will replace statins. But we may add another compound that will fight against inflammation," he explains. Because THC might suppress the immune system in a general way, there is a danger that it may harm the body's ability to fight infection. To avoid this, Mach says, it may be necessary to identify similar compounds that specifically target the CB2 protein. Still, the discovery adds to the range of potential medicinal benefits of cannabis compounds. Besides its well-publicized use for pain relief, the drug is also given to anorexics to stimulate appetite, and cancer patients to combat the nauseating side-effects of chemotherapy Anatomy & Physiology Online - Cardiac conduction system and its relationship with ECG ECG FOR DUMMIES. HEART RATE DETERMINATION TUTORIAL Heart Anatomy and How it Works Science: THC protects heart cells in the case of lowered oxygen supply Israelian researchers at the Bar-Ilan University in Ramat-Gan demonstrated that THC protects heart cells (cardiomyocytes) against the damage caused by hypoxia (reduced oxygen concentration in the blood) in experimental studies. Pre-treatment of cultures of cardiomyocytes with THC for 24 hours prevented leakage of LDH induced by hypoxia. Leakage of LDH (lactate dehydrogenase) from cells is a sign of cell damage. This protective effects of THC was mediated by the CB2 receptor. CB2 receptor activation by THC induced the production of nitric oxide (NO). Nitric oxide signals the smooth muscles of blood vessels to relax, thus dilating the artery and increasing blood flow. This underlies the action of nitroglycerin and other drugs used in the treatment of heart disease, since these compounds are converted to nitric oxide in the body. Researchers noted that THC also "probably pre-trains the cardiomyocytes to hypoxic conditions." They concluded that their research "demonstrates that THC has beneficial effects on cardiac cells and supports the consideration of marijuana for specific medical uses." (Source: Shmist YA, Goncharov I, Eichler M, Shneyvays V, Isaac A, Vogel Z, Shainberg A. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production. Mol Cell Biochem 2006;283(1-2):75-83)
  24. CB2 Receptor Mutations Linked to Bone Health September 7th, 2009 | by J.Marcu | Genetic variations, polymorphisms, or mutations on the gene for the Cannabinoid Type 2 (CB2) Receptor have been linked to osteoporosis, low Bone Mineral Density (BMD), and hand bone strength in case controlled Studies (Yamada 2007, Karsak 2005, and Karsak 2009). Most cannabinoid research on bone has been conducted in rats and mice. These recent case controlled studies in humans have established a significant association between CB2 gene polymorphisms/mutations to certain bone phenotypes; Mutant CB2 receptors lead to bad bones. The first study (Karsak 2005) looked at CB1 and CB2 receptor DNA in a sample of French post-menopausal patients and female controls. The authors report that certain changes in CB2 receptor, but not the CB1 receptor, were strongly associated with osteoporosis. The authors claim this is the first study to find a link between the CB2 receptor and a disease in human patients. A study published out of Japan replicated these findings in 2007, in a group of pre and post menopausal women. Furthermore, it has been speculated that CB2 receptor activation can inhibit atherosclerotic plaques. Atherosclerosis is a late onset disorder, that is inversely correlated to bone mineral density. If your bone density or strength starts decreasing, atherosclerosis progresses. So, CB2 receptor variations could explain the association between the two disorders. THC has already been shown to reduce atherosclerosis in mice by activating the CB2 receptor. The third study on CB2 genes in humans, examined the role of CB2 DNA or genes on hand bone strength. The author took radio-graphic images and DNA samples from a Chevashian population, an ethnically homogeneous population of people of Bulgaric ancestry that live along the Volga river. The authors found several recurring, small mutations or SNPs (Small Nucleotide Polymorphisms) were significantly associated certain bone phenotypes. Basically, a less functional form of the CB2 receptor leads to weak hand bone strength. These studies have showed that the effects of CB2 receptor gene variations have been observed in three different genetic/ethnic backgrounds. Thus supporting a link between the CB2 receptors in humans and bone health. Drugs that activate this receptor are of medical value and importance. While it appears that cannabinod receptor activation may be positively associated with bone health, no studies have been approved for observing the long term effects of cannabis use/ receptor activation on bone health. An anecdotal answer could be easily derived by comparing different measurements of bone health in long term cannabis users vs. non-users. source: http://cannabination...to-bone-health/ Cannabinoids, Oleoyl serine & Osteoporosis - Raphael Mechoulam, PhD The original version of this article first appeared in the Lab Bench Science Column of the West Coast LeafNewsPaper on June 4th 2010. The Lab Bench By Jahan Marcu A research team from the School of Medicine at Temple University, Philadelphia, presented their preliminary cannabinoid and bone data at a scientific meeting in Anaheim, CA in April. Our results add to a growing body of scientific evidence, suggesting a prominent role for the endocannabinoid system in bone development. For the last year, researchers have been trying to reproduce and build upon previous work on cannabinoids and bone, specifically, by characterizing the effects of removing the CB1 and CB2 receptors from mice. Few labs have published new discoveries regarding cannabis and bone. However, those that have are surprising so far. Some findings are so profound that the upcoming International Cannabinoid Research Society (ICRS) meeting will have a special symposium to discuss the bone data produced by just a few laboratories. Research shows that bone cells have cannabinoid receptors and produce endocannabinoids. Bone cells express a lot of CB2 receptors and nerves that traverse our bones produce CB1 receptors. The `anti-cannabinoid’ receptor, GPR55, is also expressed in bone. These receptors appear to work together to regulate bone health. Some clinical evidence supports the role of cannabinoids in various diseases. The Clinical Endocannabinoid Deficiency (Russo 2004) is thought to underlie many treatment- resistant conditions such as irritable bowel syndrome, fibromyalgia, and chronic pain. Recently, CB1 receptor mutations were linked to migraines, bi-polar disorder, and major depression (Monteleone 2010). Now CB2 receptor mutations may be linked to lower human bone density and hand-bone strength. Research from Japan and France shows that mutations correlate to osteoporosis in post-menopausal women. The two studies looked at 2,626 elderly adults with and without osteoporosis. A study out in Russia analyzed the hand-bone strength of 574 adults and found that those with CB2 receptor muta- tions had weaker hand-bone strength (Yamada 2007, Karsak 2005, 2009). These all suggest that a less functional receptor is related to poor bone health. MORE Impact Of Cannabis On Bones Changes With Age, Study Finds As reported in ScienceDaily, scientists investigating the effects of cannabis on bone health have found that its impact varies dramatically with age. The study has found that although cannabis could reduce bone strength in young people, it may protect against osteoporosis, a weakening of the bones, in later life. The team at the University of Edinburgh has shown that a molecule found naturally in the body, which can be activated by cannabis -- called the type 1 cannabinoid receptor (CB1) -- is key to the development of osteoporosis. It is known that when CB1 comes into contact with cannabis it has an impact on bone regeneration, but until now it was not clear whether the drug had a positive or negative effect. Researchers, funded by the Arthritis Research Campaign, investigated this by studying mice that lacked the CB1 receptor. The scientists then used compounds ñ similar to those in cannabis ñ that activated the CB1 receptor. They found that compounds increased the rate at which bone tissue was destroyed in the young. The study also showed, however, that the same compounds decreased bone loss in older mice and prevented the accumulation of fat in the bones, which is known to occur in humans with osteoporosis. The results are published in Cell Metabolism. Osteoporosis affects up to 30 per cent of women and 12 per cent of men at some point in life. Stuart Ralston, the Arthritis Research Campaign Professor of Rheumatology at the University of Edinburgh, who led the study, said: "This is an exciting step forward, but we must recognise that these are early results and more tests are needed on the effects of cannabis in humans to determine how the effects differ with age in people. "We plan to conduct further trials soon and hope the results will help to deliver new treatments that will be of value in the fight against osteoporosis."