Oregon Medical Marijuana Act
Debilitating Medical Conditions Advisory Panel
Anxiety with Depression Research Review
NOTE: This review considers one petition relating to depression as stated
above. This petition appears to also have anxiety as underlying symptom.
Research relating to cannabis dependence issues has been included only if
it represents significant new information which has not been covered
within the Psychotic Disorders Research Review. Depressive issues may
more properly fall into the category of Mood Disorders, i.e. bipolar disorder
but will be considered here to maintain consistency. Anxiety and agitation
including PTSD will be considered in a subsequent review.
1. CONSIDERATION OF EVIDENCE
Description of Evidence Considered:
1. Cannabis Indica in 19th-Century Psychiatry [Carlson, American Journal
of Psychiatry, 131: 9, 1974, pp. 1004-1007.]
A study of the history and usage of cannabis indica. The article makes frequent
reports that indicate cannabis was widely prescribed by physicians in Europe and
America for depressive and anxious symptoms. The...” review of the drug’s
physiological and psychological effects reveals that most of the effects reported
in the 1960’s were known to writers of the 19th century, when the drug was
alternately considered a cure for and a cause of insanity.” “Frequently cited as a
sedative, a hypnotic, or a soporific, cannabis was widely prescribed for
insomnia.” “With the widespread reports of the pleasant and cheerful stimulating
effects of the drug and its reduction of horrible feelings and fears, it was
inevitable that cannabis was to be subjected to extensive trial in the treatment of
GRADE: Good historical evidence that cannabis was widely appreciated as an
antidepressant and anxiolytic in the 19th century, prior to the pharmaceutical era.
2. [Delta-9] Tetrahydrocannabinol in Depressed Patients [ Kotin, et. al.,
Archives of General Psychiatry, Vol. 28: 1973, pp. 345-348.]
Double-blind clinical trial of THC in 8 patients suffering from depression over a
period of 7 days failed to produce significant euphoria or anti-depressant effect. 2
patients experienced severe anxiety reactions.
GRADE: Good evidence that THC does not produce an anti-depressant effect.
3. Haschish in Melancholia [ Polli, Medical Times, Vol. 100, No. 7, 1972, pp.
A single case study in the 1860’s of a physician using a cannabis preparation to
successfully treat a woman with severe, incapacitating depression with what
appeared to be psychotic features. According to the author the treatment lasted
10 days with steadily increasing doses. The cure was permanent.
GRADE: Fair evidence of a single case-report of incapacitating depression
being successfully treated with cannabis.
4. The Management of Treatment Resistance in Depressed Patients with
Substance Use Disorders [ Nunes, et. al., The Psychiatric Clinics of North
America, Vol. 19, No. 2: 1996, pp. 311-327.]
Discusses depression and comorbid substance use with evaluation of depression
and comorbid substance use and treatment recommendations. Case studies are
described. It recommends a “harm reduction” approach and emphasizes the
debilitating effects of ETOH and cocaine. One reference to cannabis as being
perceived by patients as being harmless
GRADE: Good evidence that cannabis is not a significant etiological factor in
depressed patients who self-medicate to relieve symptoms.
5. The Management of Treatment-Resistant Depression in Disorders on the
Interface of Psychiatry and Medicine [ Gruber, et. al., The Psychiatric
Clinics of North America, Vol. 19, No. 2:1996, pp. 351-368.]
No mention of Cannabis, no relevance to inquiry.
GRADE: No relevance to inquiry
6. Advertisement for cannabis U.S.P. (American Cannabis) fluid extract
Parke, Davis & Company 1929-1930 physicians’ catalog of the
pharmaceutical and biological products pp. 82.]
This is an advertisement for a cannabis-based fluid extract of 80% alcohol which
was distributed to physicians. “Extensive pharmacological and clinical tests have
shown that its medicinal action cannot be distinguished from that of the fluid
made from imported East Indian cannabis.” “Narcotic, analgesic, sedative.”
GRADE: Excellent evidence that cannabis preparations were produced and
advertised to physicians and were indicated as a sedative.
7. Do patients use marijuana as an antidepressant? [Gruber et.al.,
Depression 4(2): 1996, pp. 77-80.]
The authors “present 5 cases in which the evidence seems particularly clear that
marijuana produced a direct antidepressant effect. If true, these observations
argue that many patients may use marijuana to “self-treat” depressive
GRADE: Good case study evidence that some patients use cannabis to treat
7. Petitioner application and information submitted with application
The petitioner and her husband submitted documents including a letter to the
State Health Officer describing her diagnosis by two doctors of “Clinical
Depression and High Anxiety.” She also testified by telephone at the March 20th
“The depression/anxiety is nothing new for me as I have struggled with this for
most [of] my life with relief only from smoked Marijuana.”
She repeatedly emphasizes less than acceptable results form medications. Her
petition is attached to 11 pages of chart notes from her physician, which indicates
a gradual decrease of functioning over the 2-3 years of treatment. Chart notes
indicate treatment with Paxil, Buspar, Prozac, Lithium, Xanax, Luvox, and
Thorazine. The notes indicate some psychotic symptoms of varying frequency
and duration as well as fluctuating weight. The doctors’ notes state:
“ I feel that the patient may benefit from medical marijuana to help control her
anxiety, but I told her that I would not prescribe this because it does not fall within
the guidelines for treatment with medical marijuana.”
The petitioner appears also to be prescribed long-term benzodiazepines.
“Marijuana eliminates the need for Xanax. It does not produce withdrawal as with
Xanax. I can smoke Marijuana without a problem.”
The petitioner relays by telephone that she doesn't get “high” and smokes every
few hours. Her partner states that legal drugs haven’t helped. “Legal drugs make
her dysfunctional.” “Marijuana seems to work for her.”
GRADE: Good evidence that this severely incapacitated individual benefits from
using cannabis and that cannabis is a drug of last resort after trials of many
drugs have failed and she has been on long-term benzodiazepines.
Clinical Effectiveness (and comparison with established alternatives)
This research base describes significant although slim empirical evidence of
cannabis’ usefulness for depression. There is good evidence that cannabis falls
well within established safety parameters especially when compared with
commonly used anti-depressant and mood-stabilizing drugs. Clinical trials are
scant and tend to indicate minimal if any anti-depressant effect.
Health Benefits and Risks:
Health benefits appear to be related to increased medication toleration by
minimizing side effects, and possibly exerting some anti-anxiety effect, which lifts
the cloud of despondency, and hopelessness, which is common with, depressed
persons. Risks include the potential for dependence associated with long-term
heavy use and the possibility that cannabis may mask or cover symptoms
depressive symptoms rather than actually relieve them.
Factors Affecting Safety, Effectiveness, and Related Considerations for All
Patients and for Specific Patient Types.
Safety factors appear to favor cannabis. There is no clear evidence that
cannabis use exacerbates suicidal ideation in depressed patients without
psychotic symptoms. Factors related to effectiveness are not clear other than
underlying substance dependence or perhaps liver disease, which may alter
cannabinoid metabolism or interact with other medications.
What is clearer is that depression carries with it high mortality rates due to
suicide. Additionally, depression interferes with energy and enjoyment. Factors,
which affect safety, include the side effects of commonly used medications.
These side effects may cause significant harm or death, as with MAOIs. The
relative harm associated with cannabis appears minimal when compared with
side-effect profiles of many drugs used to treat depression-most notably Lithium.
Cannabis appears effective in a small but unknown percentage of depressed
persons who do not suffer from underlying substance use disorders.
Net Health and Overall Impact of Medical Marijuana Use for This Condition:
Please see above
As is the case with all psychiatric conditions evaluated, the legal status of
cannabis remains the single biggest detriment to ill persons through contact with
law-enforcement or illegal drug networks. Depressed patients sometimes act in
a suicidal manner in response to hopelessness and despair. The trauma of
arrest and prosecution may be considered a potential risk factor for suicide.
II. Performance On Assessment Criteria
1. Quality and Sufficiency of Available Evidence: There is sufficient available
evidence of sufficient quality to permit reaching a sound determination relating to
the use of medical marijuana for the treatment of this condition.
Comments: Few if any carefully controlled clinical trials have been done to
measure cannabis’ antidepressant effect. The case histories and “N of 1” studies
which have been done indicate that cannabis’ anxiolytic properties may actually
represent the underlying mechanism of it’s anti-depressant effect, rather than a
primary anti- depressant effect.
2. [A] Clinical Effectiveness: The use of medical marijuana for this condition is
Comments: For some percentage of patients suffering from depression
cannabis is effective.
Relative Clinical Effectiveness: The use of medical marijuana for this
condition is clinically effective relative to established alternative treatments for
Comments: Insufficient data is available to evaluate relative clinical
effectiveness due to a lack of randomized clinical comparison trials with
commonly used antidepressants.
3. Health Benefit/ Risk Ratio: The health benefits of medical marijuana use for
this condition outweigh the health risks.
Comments: For those who do not suffer from comorbid substance use disorders,
and have exhausted their medical alternatives the benefits of cannabis use under
medical supervision outweigh the risks-especially when compared with the
statistical likelihood of suicide.
4. Net Health Impact: The use of medical marijuana for this condition improves
net health outcomes (functional status and/or ability to perform activities of daily
living) for those individuals with this condition who use medical marijuana.
Comment: The extent to which cannabis use creates a net health impact is
unknown at this time.
5. Net Overall Impact: The use of medical marijuana for this condition improves
net overall outcomes (quality of life and/or perceived satisfaction with condition
improvement) for those individuals with this condition who use medical
Comments: Net overall impact is difficult to assess until randomized clinical trials
have been conducted. For the petitioner, at least, there appears to be a net
overall benefit in her quality of life as perceived by her, her physician, and
6. Safety, Effectiveness, or Related Issues: There are no such compelling or
overriding issues that alter any of the determinations regarding the use of
medical marijuana for the treatment of this condition that would have been
reached absent these issues.
Comments: The potential danger to the petitioner as well as other depressed
patients who use cannabis by contact with the legal system cannot be
overstated. These potentially violent confrontations with police and/or illegal drug
networks may result in death directly, or through suicide.
III. Overall Findings and Recommendations
Summary of Findings:
One (1) petitioner’s written and oral comments appear to support therapeutic use
of cannabis for depression;
Two (2) surveys detailing the history of cannabis for treating depression and
treatment guidelines for depressed people;
One (1) pharmaceutical advertisement indicating that cannabis was prescribed
by physicians for insomnia in this century;
One (1) clinical trial indicating no anti-depressant effect from THC in clinical
One (1) clinical trial indicating efficacy of THC in treating insomnia;
One (1) survey of no relevance.
Recommendation Regarding Adding this Condition to the list of
“Debilitating Medical Conditions” for Purposes of the Oregon Medical
Add disease to list of disease conditions pursuant to ORS 475.302(2)(a)
COMMENTS: This “yes” recommendation is based upon the following rationale:
It is medically indefensible and contrary to the ethics of the nursing profession for
me to advocate that ill people be arrested and jailed for their use of cannabis.
This situation has arisen because of Federal abdication of research protocols,
which would have long-since clarified cannabis’ relative value. Ill Oregonians
should not bear the weight of this governmental negligence. Furthermore, the
taxpayers of Oregon should not be saddled with the costs of processing ill people
through the criminal justice system. This represents an unfair burden to patients
and taxpayers and will further alienate depressed people from accessing the
I would make the following recommendations for depressed patients and their
doctors wishing to avail themselves of cannabis, should depression be approved
for inclusion on the list of debilitating medical conditions:
1. The patient should be refractory to more efficacious treatments like SSRIs,
2. The patient should have no history of significant dependence issues with
alcohol, tobacco, or psychoactive drugs.
3. The patient should be, and remain under the care of a physician or nurse
4. The patient should have periodic assessments to determine the presence or
severity of suicidal ideation.
5. The patient should be willing to trial new anti-depressants providing they have
the financial means to do it.
6. The patient should be educated about the potential side effects of cannabis
including cognitive, pulmonary, and dysphoric.
RATIONALE Re: this recommendation
The rationale for this decision is related to the unavoidable political climate in
which elected leaders support laws which are in direct opposition to the safety
and benefit of ill Oregonians. This was clearly articulated by Oregon voters in
November of 1998 by the simultaneous passage of the Oregon Medical
Marijuana Act, while at the same time rejecting an increase in criminal penalties
for all cannabis use. The sentiments of Oregonians appear to favor removing ill
Oregonians from the criminal justice system. Thus, in spite of the meager amount
of evidence demonstrating efficacy for the treatment of depression with cannabis,
I recommend including it within the protections of the OMMA. Since depression
may also be thought of as a symptom as well as a disease entity, the inclusion of
the symptom of “severe depression” may fulfill patient need adequately and allow
this decision to be made in a physician’s office instead of a District Attorney’s
Cannabis may produce directly an acute panic reaction, a toxic delirium, an acute paranoid state, or acute mania. Whether it can directly evoke depressive or schizophrenic states, or whether it can lead to sociopathy or even to "amotivational syndrome" is much less certain. The existence of specific cannabis psychosis, postulated for many years, is still not established. The fact that users of cannabis may have higher levels of various types of psychopathology does not infer a casual relationship. Indeed, the evidence rather suggests that virtually every diagnosable psychiatric illness among cannabis users began before the first use of the drug. Use of alcohol and tobacco, as well as sexual experience and "acting-out" behavior, usually antedated the use of cannabis. When the contributions of childhood misbehavior, school behavioral problems, and associated use of other illicit drugs were taken into account, it was difficult to make a case for a deleterious effect of regular cannabis use. Thus, it seems likely that psychopathology may predispose to cannabis use rather than the other way around.
1. ACUTE PANIC REACTION
This adverse psychological consequence of cannabis use is probably the most frequent. About one in three users in high school reported having anxiety, confusion, or other unpleasant effects from cannabis use. These unpleasant experiences were not always associated with unfamiliarity with the drug; some subjects experienced these adverse reactions after repeated use. The conventional wisdom, however, is that such acute panic reactions occur more commonly in relatively inexperienced users of cannabis, more commonly when the dose is larger than that to which users may have become accustomed, and more commonly in older users who may enter the drug state with a higher level of initial apprehension.
The acute panic reactions associated with cannabis are similar to those previously reported to be caused by hallucinogens. The subject is most concerned about losing control or even of losing his or her mind. Reactions are usually self-limited and may respond to reassurance or "talking down"; in the case of cannabis use, sedatives are rarely required as the inherent sedative effect of the drug, following initial stimulation, often is adequate. Occasionally one may see a dissociative reaction, but this complication is readily reversible. Depersonalization may be more long lasting and recurrent, somewhat akin to "flashbacks" reported following hallucinogens; the electroencephalogram shows no abnormality.
2. TOXIC DELIRIUM
Very high doses of cannabis may evoke a toxic delirium, manifested by marked memory impairment, confusion, and disorientation. This nonspecific adverse psychological effect is seen with many drugs, but the exact mechanism is not clear in the case of cannabis as it is in the case of datura stramonium smoking, for instance, which produces potent anti-cholinergic actions. As high doses of any drug tend to prolong its action, delirium is self-limited and requires no specific treatment. Highly potent preparations of cannabis are not as readily available in North America as in other parts of the world, so these reactions are less commonly observed in the United States and Canada.
3. ACUTE PARANOID STATES
It is difficult to gauge the frequency of these reactions. In a laboratory setting, they are frequently encountered. Quite possibly the experimental setting creates a paranoid frame of reference to begin with. That this reaction is not peculiar to the laboratory is evident from reports in which it has been experienced in social settings. The illegal status of the drug might contribute in such instances, for while intoxicated, one might be more fearful of the consequences of being caught. Undoubtedly, the degree of paranoia of the individual is also an important determinant, so that this reaction may represent interplay between the setting in which the drug is taken as well as the personality traits of the user.
A variety of psychotic reactions has been ascribed to cannabis use. Many are difficult to fit into the usual diagnostic classifications. Two cases of manic reaction were reported in children who were repeatedly exposed to cannabis by elders. Both required treatment with antipsychotic drugs but ultimately showed a full recovery. Hypomania, with persecutory delusions, auditory hallucinations, withdrawal, and thought disorder, was observed in four Jamaican subjects who had increased their use of cannabis. Twenty psychotic patients admitted to a mental hospital with high urinary cannabinoid levels were compared with twenty such patients with no evidence of exposure to cannabis. The former group was more agitated and hypomanic but showed less affective flattening, auditory hallucinations, incoherence of speech, and hysteria than the twenty matched control patients. The cannabis patients improved considerably after a week, while the control patients were essentially unchanged. Thus, a self-limiting hypomanic-schizophrenic-like psychoses following cannabis has been documented.
This curious phenomenon, in which [b]events associated with drug use are suddenly thrust into consciousness in the non-drugged state, has never been satisfactorily explained. It is most common with LSD and other similar hallucinogens but has been reported fairly often with cannabis use. At first, it was thought that the phenomenon occurred only in subjects who had used LSD as well as cannabis, but recent experience indicates that it occurs in those whose sole drug use is cannabis. One possibility is that flashbacks represent a kind of déjà vu phenomenon. Another is that they are associated with recurrent paroxysmal seizure-like activity in the brain. The most unlikely possibility is that they are related to a persistent drug effect. They may occur many months removed from the last use of either LSD or cannabis, so that it is highly unlikely that any active drug could still be present in the body. Further, the interval between last drug use and the flashback is one in which the subject is perfectly lucid. For the most part, the reactions are mild and require no specific treatment.
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