Medical Marijuana 1

Medical Marijuana: An Advocacy for its therapeutic Use?

Medical Marijuana 2

OUTLINE


I. Introduction

A. Medical marijuana
1. History of use
2. Therapeutic uses
B. Legislation of medical marijuana
1. Court cases that paved the way towards legalization of medical marijuana
2. Marijuana Medical Access Regulations (MMAR)
3. Marijuana for Medical Purposes Regulations (MMPR)
C. Depression
1. Prevalence of the disease
2. Burden

II. Body

A. Therapeutic use of marijuana in depression
1. Pharmacology of marijuana as an anti-depressant
2. As self-medication
3. Motivation for self-medication of individuals
4. Studies in favor of using marijuana as an adjunct to treat depressive symptoms
B. Marijuana use has been linked to depression.
1. Twin study
2. Causal relationship of marijuana use and depression
3. Link to suicidal ideations
C. Other psychiatric effects linked to marijuana use
1. Psychosis
2. Anxiety disorders
D. Other side-effects of marijuana use
E. Limitations of current available researches on depression and marijuana
1. Confounding factors
2. Clinical significance
3. Measures of outcome

III. Conclusion

A. Scientific consensus
1. Information provided by Health Canada on marijuana
2. Marijuana as a double-edged sword
B. Issues for health care professionals
1. Lack of established prescription guidelines
2. Liability
C. Prescription of marijuana for depression


Medical Marijuana 3

Introduction
Cultivated as early as ten thousand years ago primarily for food and hemp, marijuana is
recognized as one of the oldest medicinal plants. In Central Asia, where varieties have more
bioactive compounds, it has been utilized as such in tinctures or teas. The use of medicinal
marijuana was introduced in Europe by the Irish doctor William OShaughnessy in 1840, and by
the early 20
th
century, it was a key ingredient in most medicines recommended for a variety of
conditions, such as asthma, insomnia, migraine, throat infection and menstrual cramps (NCSM,
2011).
Logistical difficulties, however, such as taxes, acquisition, dosage and quality control,
prevented continued use of medicinal marijuana. It disappeared from the scene in the late 1930s,
only to be pushed back into the spotlight in the 1960s due to its popularity as a recreational drug.
The World Health Organization (WHO) reported that marijuana no longer served any medicinal
purpose and labeled it as a dangerous narcotic with a high potential for abuse (NCSM, 2011).
Marijuana remains to be the most common illicit drug use worldwide despite legal
prohibitions. Nevertheless, in the last decade, scientific research on how marijuana exerts its
pharmacologic effects on the body has broken ground for reconsideration of its therapeutic
purpose. Indications in which evidence has shown marijuana to be of some benefit include:
neuropathic pain; nausea, loss of appetite and vomiting in patients with chronic, debilitating
diseases or undergoing chemotherapy; therapy-resistant glaucoma; and in some psychiatric
disorders (IACM, 2013).
Not only on the medical front does marijuana seem to be winning; it has overcome legal
obstacles as well. After the court cases R v Parker in 2000 and R v Mernargh in 2011, in which
decisions ruled the prohibition and the difficult access to medicinal marijuana unconstitutional
Medical Marijuana 4

(CanLII, 2011), the old Marijuana Medical Access Regulations (MMAR) in place since 2001
have been replaced by the Marijuana for Medical Purposes Regulations (MMPR) earlier this
year. The MMAR had previously allowed the small-scale growing of marijuana by approved
agents, with Health Canada subsidizing the costs for its production and distribution. Under the
new policy, marijuana will be regarded as a pharmaceutical drug. Licensed production by
commercial growers will be permitted on a wider scale, and quality of the dried plant will be
strictly monitored and controlled. Instead of individuals having to apply directly to Health
Canada for permission to use marijuana, physicians have been designated to decide on the
necessity of its consumption (Aglukkaq, 2013).
Both programs are currently in place to smooth transition, and the MMPR is expected to
be fully enforced by April 2014. Meanwhile, new provincial regulations in British Columbia are
expected to authorize nurse practitioners to prescribe marijuana for medicinal purposes
(CRNBC, 2013). With this development, there rings the loud question any healthcare
professional would be hard-pressed to answer.
Should I advocate the use of medicinal marijuana?
Amidst the plethora of scientific research both favoring and disproving the use of
medicinal marijuana, there is probably no greater confusion than there is in the field of
psychiatry, especially in mood disorders. Depression is one of the most common psychiatric
illnesses in the Canadian population and worldwide, with a national prevalence of 5.3%. Work-
related productivity losses alone have been estimated to be at $4.5 billion (PHAC, 2006), hence
the tremendous government effort to support the mentally-ill.
The spotlight is on marijuana, and its fledgling industry has been set in motion. Given the
burden of depression in this country and with the possible use of marijuana as pharmacologic
Medical Marijuana 5

treatment for depression dependent on the judgment of health professionals, it becomes
imperative to review and evaluate the available evidence on scientific and ethical grounds so as
to provide a sound consensus, if not a definite answer, to that difficult, looming question.

Cannabinoids and Psychiatric Illness
The active ingredient in marijuana responsible for most of its effects is the cannabinoids,
particularly tetrahydrocannabinol (THC). It acts upon endogenous cannabinoid receptors in the
body and interacts with many neurotransmitters, including dopamine, gamma-amino butyric acid
(GABA), opioid systems and serotonin, thereby affecting psychomotor systems. The increased
release of serotonin, specifically, is most favored as the mechanism by which marijuana elevates
the mood and induces a transient state of euphoria (Ashton, 2001). Other psychiatric effects
linked to the use of cannabis include panic attacks, anxiety, dependence and psychosis leading to
the development of schizophrenia (Johns, 2001). In fact, a prevalence study that recruited self-
reported marijuana users seeking treatment and rehabilitation as subjects revealed a co-morbidity
of marijuana dependence with primarily depression and schizophrenia (Arendt and Munk-
Jorgensen, 2004).

Cannabinoids as Cure
People with psychiatric disorders have been reported to self-medicate with marijuana, as
in a study of forty-nine (49) patients diagnosed with psychosis (Schofield, 2006). Primary
motives for use of cannabis included boredom, social motives, improvement of sleep, anxiety,
and improvement of negative symptoms associated with either psychosis or depression were
cited. Another study on teens involved with recreational marijuana use differentiated themselves
Medical Marijuana 6

from those with addiction by stating that marijuana use helped them cope with their health and
emotional problems, which allegedly could not be adequately managed by standard medical
treatment or when they have lacked access to care. Conditions reported relieved including
anxiety, depression, difficulty concentrating and even physical pain (Bottorff, 2009).
A study that utilized an online survey sent to drug policy organizations, designed for
marijuana users, compared depression scores based on the Center for Epidemiologic Studies
scale among groups that took the drug daily, less than once a week and never. Interpersonal
symptoms among three groups varied little. Nevertheless, those who used marijuana, regardless
of frequency, were noted to report a less depressed mood, a more positive affect and less
physical symptoms than non-users. Medical users, however, in contrast to recreational users,
reported increased feelings of depression and more somatic complaints; this suggests that
medical and psychiatric conditions do contribute to depression scores and may be a confounding
factor when assessing the effect of marijuana use (Denson and Earleywine, 2005).
A report of two case studies by an Austrian physician (Blaas, 2008) reiterated the clamor
for an alternative drug for depression that can be used in the event of failure with standard
medical practice. He stated that from 2003 to 2006, 75 of his patients suffering from depression,
stress and burnout syndrome were treated successfully with dronabinol, a cannabinoid, either
alone or in conjunction with other medications. He further stated that only 20% of his treated
patients did not experience any significant improvement in mood, and that even when dronabinol
was given with selective serotonin reuptake inhibitors (SSRIs), there were little noted side-
effects. He therefore recommended that dronabinol should remain an anti-depressive option,
especially when patients are not responding to the usual treatment.

Medical Marijuana 7

The Other Way Around: Cannabinoids as Cause
Despite positive reports from marijuana users, there is a paucity of literature supporting
positive outcomes of depression with marijuana given as intervention. Most of the available
studies have shown marijuana use to be associated with depression or with depressive symptoms.
Earlier systematic reviews of literature have shown moderate to heavy use of marijuana to be
associated with depression and little use of the drug in those already diagnosed with depression,
thus contradicting the hypothesis of self-medication (Degenhardt et al., 2002). Another study
that aimed to determine the relative contribution of marijuana use to depression, including other
factors such as methampethamine use and sex, invited psychiatrists to screen the study
population for depression. This study later concluded that females and cannabis use were major
risk factors for the development of depression (Durdle et al., 2008).
There are generally two kinds of depression: independent depression and drug-dependent
depression. The latter typically resolves upon withdrawal of the offending agent. A case-control
study (Dakwar et al., 2011) showed that unlike with cocaine or opioids, those with dependence
on marijuana showed significantly higher rate of independent depression. But despite the strong
association between depression and marijuana, no study has yet established irrefutable causality.
This case-control study (Dakwar et al., 2011), however, was able to show a temporal association
between marijuana use and onset of depressive symptoms. It was also able to correlate marijuana
use at a younger age with an earlier onset of mood disorders. This corroborated an earlier study
by Green and Ritter (2000), which also put forth the finding that the development of depression
in marijuana users is also mediated by social factors such as educational attainment, employment
and marital status.
Medical Marijuana 8

If not an outright depression, cannabinoid use has also been linked with depressive
symptoms, the most alarming of which are suicidal ideations and attempts. This has been shown
in a population-based longitudinal study, with young adult users as the subjects (Pederson,
2008). There is also one case report of a patient, diagnosed previously with major depressive
disorder (MDD) and also used marijuana, who attempted suicide via ingestion of ethylene glycol
(Nussbaum, 2011). It could certainly be argued that it might have been the psychiatric illness and
not the drug use that triggered these suicidal thoughts and ideas. However, there is another report
of two individuals, who had never been diagnosed with depression and had never previously
used marijuana, succumb to suicide attempts after episodic use (Raja and Azzoni, 2009).
Perhaps the most compelling evidence that exists, linking marijuana use to suicide and
depression, is the study on discordant identical and fraternal twins (Zickler, 2005). This study
showed that twins dependent on marijuana were 2.9 times more likely to have suicidal ideations
and 2.5 times more likely to make an attempt, compared to their non-dependent co-twins. Pairs
discordant for early marijuana use also showed that the twins who started marijuana younger
were 3.5 times more likely to have suicidal ideas, but were no more likely to develop MDD.
Interestingly, the reverse was also true for discordant fraternal twins. Twins who were diagnosed
with MDD earlier and who had suicidal ideations at a younger age also showed an increased risk
of marijuana dependence (Zickler, 2005). This study most clearly eliminates the effect of genetic
influences on the development of psychiatric illness and therefore seems most reliable.

Other Effects Linked to Marijuana Use
Aside from isolated psychiatric symptoms, psychosis, schziophrenia, mood and anxiety
disorders, marijuana use has also been linked to cognitive defects, detectable as soon as
Medical Marijuana 9

immediately after its first use. These cognitive defects, among others, include memory loss and
poor concentration. These changes, however, appear to resolve after a week within the last drug
use (Pope et al., 2001).
Marijuana use also affects the other body systems. It affects the respiratory system and is
associated with the development of chronic bronchitis, emphysema and even lung cancer. It also
has significant effects on the cardiovascular and cerebrovascular system, resulting in systemic
vasodilation and compensatory tachycardia. There have also been reports of spontaneous
myocardial infarcts and cerebral vasospasms in marijuana users, as well as a predilection to
developing arrhythmias. Because endocannabinoid receptors are also present on bone, marijuana
use has also been linked with massive bone loss, with the jaw becoming the most common site of
bone loss, leading to erosive periodontitis. Marijuana has been identified as a teratogen and as a
carcinogen (Reece, 2009).

Limitations of Studies on Marijuana and Depression
In the midst of the wealth of studies done on marijuana use and depression, limitations of
previous researches have been identified, and these are many. The primary issue is the
classification of marijuana usethe definition of dependency, a standardized hierarchy of use
frequency, and the realization that dependence does not necessarily equate to harmful or
problematic effects in users. It has also been quite difficult to isolate confounding factors, which
are pivotal in the development of psychiatric disorders, such as personal experiences, general
medical conditions, genetic predisposition to illness and undiagnosed illness. Concerns have also
been raised about the prism with which marijuana users have been viewed by scientists: there has
been more focus and more expectations on marijuana use as pathology, possibly preventing
Medical Marijuana 10

neutrality in the treatment of the subjects. Lastly, there is a lack of standardization on the kind of
marijuana used and the actual dose of the active cannabinoids present per use in a test subject.
Smoke is difficult to quantify after all, and there are different types of cannabis; as well, the
frequency with which users take to their marijuana do not necessarily correlate with dose,
potency and toxicity levels.
The many limitations in the study designs and methods of previous experiments largely
contribute to the discrepancies in research findings and make meta-analysis of existing data.

Consensus
The results of a study conducted on mice in 2007 suggested a unifying explanation for
the contradictory data available: it is that at low doses, marijuana increases serotonin expression,
causing mood elevation, but at high doses, reverses its mechanism (McGill University, 2007).
Nevertheless, the lack of unassailable conclusions make consensus difficult. Health
Canada has increased an information booklet (Health Canada, 2013) reviewing the literature for
marijuana; while this booklet is informative and detailed, it fails to advise healthcare
professionals on the prescription of the drug. As the College of Family Physicians of Canada
declared in their position statement (CFPC, 2013), it would be unfair for the law to require
physicians to prescribe marijuana, thereby making them liable should the patient suffer an
adverse reaction to the drug. The CFPC recommended instead a declaration, which will state
simply that a patient is eligible to use marijuana, but will not necessarily mean that this has been
advised by the physician and so will not indicate dose, duration or frequency. The CFPC also
recommended that Health Canada come up with a set of guidelines on the use of the drug,
bearing in mind the following factors: first, that marijuana is delivered via smoke, which is
Medical Marijuana 11

difficult to quantitate and in itself posits danger; second, that the active ingredient of marijuana is
readily available as a drug; and that the evidence of its affectivity is lacking, and that thus far, the
evidence shows that the risks of using this drug outweigh any benefits it may incur (CFPC,
2013).
The CFPC raises reasonable concerns that must be adequately resolved. Their reluctance
to promote the use of marijuana, except in more extreme circumstances, mirror the results of an
online poll conducted by the New England Journal of Medicine (NEJM) (Adler and Colbert,
2013). The publication posted a case of a woman suffering from severe metastatic bone pain
from breast cancer, pain that cannot be alleviated by use of recommended medications and asked
its readers to vote whether or not they would allow marijuana to be prescribed. The poll finished
with 76% advocating marijuana use. Readers who recommended marijuana use cited the
following reasons: to alleviate the suffering of the patient, patient choice, prior positive
experience with prescribing the drug and as a safer alternative to the known toxicity of the more
commonly used opioids. Those who did not, however, cited the lack of evidence for its
effectively, the many possible side-effects and problems with its consistent dosing (Adler and
Colbert, 2013).

Conclusion
Regardless of popular opinion among health professionals and in the midst of conflicting
evidence both for and against marijuana use, there is very little ground for a blanket
recommendation in using marijuana to treat depression. Given that the available data shows the
many risks associated with use and unless a safe pharmacologic regimen has been determined,
consideration should be done on a case-to-case basis. Only when the benefits outweigh the risks,
Medical Marijuana 12

and only when more the last line of treatment and therapy have failed should marijuana be
advocated for a clientand even then with caution and vigilance.


Medical Marijuana 13

REFERENCES

Arendt, M. and P. Munk-Jorgensen. 2004. Heavy cannabis users seeking treatment: Prevalence
of psychiatric disorders. Soc Psychiatry Psychiatr Epidemiol. 39 : 97105. DOI
10.1007/s00127-004-0719-7.
Aglukkaq, Leona. 2013. Canadas medical marijuana policy provides access while protecting
safety. The Globe and Mail. Retrieved 05 December 2013 from
http://www.theglobeandmail.com/globe-debate/canadas-medical-marijuana-policy-
provides-access-while-protecting- -safety/article1294 5016
Ashton, C. 2001. Pharmacology and effects of cannabis: a brief review. The British Journal of
Psychiatry. 178: 101-106.
Blaas, K. 2008. Treating depression with cannabinoids. Cannabinoids 3(2):8-10.
Bottorff, J., Johnson, J., Moffat, B. and T. Mulvogue. 2009. Relief-oriented use of marijuana by
teens. Substance Abuse Treatment, Prevention, and Policy. 4:7 doi:10.1186/1747-597X-4-
7.
Bricker, J., Russo, J., Stein, M., Sherbourne, C., Craske, M., Schraufnagel, B. and P. Roy-Byrne.
2007. Does occasional cannabis use impact anxiety and depression treatment outcomes?:
Results from a randomized effectiveness trial. Depression and Anxiety 24:392-398.
Canadian Legal Information Institute. 2011. R. v. Mernagh, 2011 ONSC 2121. Retreived 05
December 2013 from
http://www.canlii.org/en/on/onsc/doc/2011/2011onsc2121/2011onsc2121.html#_
Toc289892665.
Medical Marijuana 14

College of Family Physicians of Canada. 2013. The College of Family Physicians of Canada
Statement on Health Canadas Proposed Changes to Medical Marijuana Regulations.
Retrieved 05 December from
http://www.cfpc.ca/uploadedFiles/Health_Policy/CFPC_Policy_Papers_and_Endorsements
/ CFPC_Policy_Papers/Medical%20Marijuana%20Position%20Statement%20CFPC.pdf.
College of Registered Nurses in British Columbia (CRNBC). 2013. New regulations to change
how Canadians access medical marijuana. Retrieved 05 December 2013 from
https://crnbc.ca/crnbc/ Announcements/2013/Pages/PrescribingMarijuana.aspx
Copeland, Jane. 2006. Cannabis use, depression and public health. Addiction 101: 1380.
Dakwar, E., Nunes, E., et al. 2011. A Comparison of Independent Depression andSubstance-
Induced Depression in Cannabis-, Cocaine- and Opioid-Dependent Treatment Seekers. The
American Journal on Addictions. 20: 441446.
Degenhardt, L., Hall, W. and M. Lynskey. Exploring the association between cannabis use and
depression. Addiction 98: 14931504.
Denson, T. and M. Earleywine. 2005. Decreased depression in marijuana users.
doi:10.1016/j.addbeh. 2005.05.052.
Dragt, S. et al. 2012. Cannabis use and age at onset of symptoms in subjects at high clinical risk
for psychosis. Acta Psychiatr Scand 2012: 125: 4553.
Durdle, J., Lundahl, L., Johanson, C. and M. Tancer. 2008. Major Depression: The Relative
Contribution of Gender, MDMA and Cannabis Use. Depression and Anxiety 25:241247.
Green, B. 2000. Marijuana use and depression. Journal of Health and Social Behavior. 41: 40-
49.
Medical Marijuana 15

Harder, V., Morral, A. and J. Arkes. Marijuana use and depression among adults: testing for
casual associations. Addiction 101: 14631472.
Health Canada. 2013. Information for Health Care Professionals: Cannabis and the cannabinoids.
Retrieved 05 December from http://www.hc-sc.gc.ca/dhp-
mps/alt_formats/pdf/marihuana/med /infoprof-eng.pdf.
International Association for Cannabinoid Medicines (IACM). 2013. Medical Uses. Retrieved 05
December 2013 from http://cannabis-
med.org/index.php?tpl=page&id=21&lng=en&sid=e2623
74922d43f421d5b64e4ebeb0e37.
McGill University. 2007. Cannabis: Potent anti-depressant in low doses, worsens depression at
high doses. Science Daily. Retrieved 05 December from
http://www.sciencedaily.com/releases/ 2007/10/071023183937.htm.
Nederlandse Associatie voor legale Cannabis en haar Stoffen als Medicatie (NCSM), translated
into the Dutch Association for Legal Cannabis and its Constituents as Medicine. 2011. A
short history of medical cannabis. Retrieved 05 December 2013 from http://www.ncsm.nl.
Pedersen, W. 2008. Does cannabis use lead to depression and suicidal behaviors? A population-
based longitudinal study. Acta Psychiatr Scand 2008: 118: 395403.
Public Health Agency of Canada (PHAC). 2006. The Human Face and Mental Health and
Mental Illness in Canada: Mood Disorders. pp. 59-64. Retrieved 05 December from
http://www.phac-aspc.gc.ca/publicat/human-humain06/pdf/human_face_e.pdf.
Raja, M. and Azzoni, A. 2009. Suicide Ideation Induced by Episodic Cannabis Use. Case
Reports in Medicine. Volume 2009. doi:10.1155/2009/321456.
Reece, A. 2009. Chronic toxicology of cannabis. Clinical Toxicology. 47: 517-524.
Medical Marijuana 16

Schofield, D., Tennant, C., Nash, L., Degenhardt, L., Cornish, A., Hobbs, C. and G. Brennan.
2005. Reasons for cannabis use in psychosis. Australian and New Zealand Journal of
Psychiatry. 40: 570-574.
Temple, E., Brown, R. and D. Hine. 2011. The grass ceiling: limitations in the literature hinder
our understanding of cannabis use and its consequences. Addiction. 106: 238244.
Zickler, P. 2005. Twin study links marijuana abuse, suicide and depression. NIDA Notes. 20(2):
12.