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***EDDIEKIRK*** · 07-07-2012, 07:37 PM

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 drugs

physiological and psychological effects reveals that most of the effects reported

in the 1960s 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

melancholia.

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.

236-238.]

A single case study in the 1860s 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

symptoms.

GRADE: Good case study evidence that some patients use cannabis to treat

depressive symptoms.

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

meeting.

Petitioner states:

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.

Petitioner states:

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 havent 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

Other Considerations

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.

NO

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 its anti-depressant effect, rather than a

primary anti- depressant effect.

2. [A] Clinical Effectiveness: The use of medical marijuana for this condition is

clinically effective.

POSSIBLY

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

this condition.

NAD

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.

POSSIBLY

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.

NAD

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

marijuana.

NAD

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

partner.



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.

YES

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) petitioners 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

surroundings.

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

Marijuana Act

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

medical system.

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

practitioner.

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 physicians office instead of a District Attorneys






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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.

4. PSYCHOSES

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.

5. FLASHBACKS

This curious phenomenon, in which 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 dj 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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