Medical Marijuana: An Advocacy for its therapeutic Use?
Virginia F. Lasiste, SN: T00059107 Thompson Rivers University HLTH 3611
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.