Marijuana Reform: At Long Last
In March of 2017, the Parliament of Canada is anticipated to release a proposal for the legalization and strict regulation of marijuana.1 This change comes after decades of research concluding that there are fewer deleterious effects than previously imagined when marijuana was criminalized in 1923.2 Although medical marijuana use is currently legal, there is a significant amount of bureaucracy and stigma that impede the cultivation of specialized marijuana strains and research on the therapeutic potential of these cultivations. Such is the case for cannabidiol-rich (CBD) marijuana strains, which are artificially selected to have a higher concentration of the active medical ingredients with anti-seizure and anxiety-reducing properties that are effective as an adjuvant therapy for diseases like multiple sclerosis and Parkinson’s disease dementia. The March 2017 marijuana legislation is set to make it easier for scientists to research and publish data on some of the 80 active ingredients in marijuana to treat symptoms associated with rare diseases.3
Currently, marijuana is listed as a Schedule II Drug under the Controlled Drugs and Substances Act in Canada, meaning that its possession and redistribution is illegal for nonmedical purposes. However, in the spring of 2017, a legislative framework will be proposed for the legalization of marijuana with three key objectives:
- Better regulation of recreational marijuana use;
- Reduce profit for illicit drug dealers and organized crime groups in the marijuana trafficking business;
- Keep it out of the hands of youths.4
In addition to these objectives, easier access to marijuana would allow for more preclinical and clinical trials on the effectiveness of marijuana active ingredients like CBD and tetrahydrocannabinol (THC) as a superior or equivalent treatment for various diseases. Marijuana criminalization in the past had made it extremely difficult for researchers to access marijuana for research purposes because the marijuana used in these trials needed to be obtained from one of a few specialized growth centers across the country. To predict that potential impact of this legislation, we can take a look at the United States where there are similar barriers to marijuana access, but these barriers are better studied. In the United States, researchers studying marijuana would also need to obtain a license issued by the National Institute on Drug Abuse, which has a mission to study drug abuse as opposed to potential benefits.5 A combination of these factors has created a skewed picture of the effects of marijuana. In fact, only 6% of current US marijuana studies investigate the benefits of medical marijuana.5 Legalization is anticipated to work to restore this imbalance and promote experimental procedures, especially n-of-1 trials. Specifically, n-of-1 trials look at the effect of different interventions on a single patient, allowing subjects to serve as their own control. It is an adaptive design that allows researchers to modify the sequential design and duration of the treatment to minimize the amount of time a subject is exposed to an inferior intervention. It has been found to be extremely effective for rare diseases, where it may be difficult to recruit enough subjects for a randomized controlled trial.6 Legalization would increase the efficiency of clinical trials for medical marijuana by giving researchers easier and cheaper access to medical marijuana and by increasing National Institute on Drug Abuse approval of trials.
N-of-1 trials has proven to be extremely beneficial for patients such as Charlotte Figi, an eleven-year-old girl who had suffered from 300 seizures a week, some of which lasted two to four hours. She suffered from a rare disease called Dravet Syndrome, which produces myoclonic epilepsy starting from infancy.5 Charlotte’s seizures led to both physiological and mental developmental delays that significantly impacted her quality of life. Her doctor prescribed a concoction of drugs, including an anti-seizure medication being tested on dogs in France.5 While these drugs did alleviate some of her symptoms, they also produced side effects such as loss of bone density, immunodeficiency, and behavioural problems. As part of an n-of-1 trial, Charlotte was placed on different medications during different intervals to assess their effectiveness. Charlotte’s doctor prescribed her a marijuana derivative known as hash oil. It has not only been more effective at reducing her seizure frequency to only several times a month but also has minimal side effects.5
Specifically, Charlotte was prescribed hash oil that was high in CBD, an active ingredient in marijuana that is at the center of medical marijuana research. Unlike THC, which causes the euphoria and intoxication by binding to CB1 receptors on neurons and glial cells in the brain, CBD has poor affinity to these receptors.3 While the specific sites of CBD binding have not yet been elucidated, pre-clinical trials have shown promising results of CBD acting on the brain’s signaling system to produce anti-seizure, anti-tumour, and neuroprotective effects in animal models. There is a significant interest in the use of purified CBD oils for intractable pediatric seizure disorders such as Dravet Syndrome and Lennox-Gastaut Syndrome.3 Research has shown that CBD has anticonvulsant effects for the treatment of major seizure disorders, but has minimal impact on minor seizure disorders. CBD can also be combined with THC to lower muscle spasm frequency and increase mobility in patients with multiple sclerosis.7 Additionally, CDB has been shown to be effective as a palliative treatment for cancer. It helps improve patient comfort by reducing pain and nausea and increasing appetite. It also inhibits metastasis through reducing cell viability and increasing cancer cell death, which is an extension of CBD’s various antioxidant and anti-inflammatory effects.3
In addition to treatment of physical disorders, CBD has also been shown to be effective in treating symptoms associated with rare psychological disorders such as the psychosis associated with schizophrenia and Parkinson’s disease dementia.1 It also seems to reduce behavioural and physiological measures of stress and anxiety through mediating changes in serotonin receptor 1a signaling.7 Although the exact mechanism is not clear, it is known that serotonin is an important neurotransmitter for maintaining mood balance. Furthermore, CBD can also be used to treat substance use disorders by reducing the rewarding effects of morphine and the drug-seeking behaviour for heroin.3 CBD has not only therapeutic potential for psychosis, anxiety, and substance abuse, but also boasts minimal side effects. However, it is important to remain cautiously optimistic because 95% of medications that are promising in pre-clinical trials never enter the pharmaceutical market.3 This is because early trials are often based on individual cases rather than a large cohort of patients. As a result, the drastic effects are often diminished when the drug undergoes rigorous testing through a number of randomized controlled trials and follow-ups that are mandatory prior to becoming approved as a treatment for a disease.
The therapeutic potential of marijuana has been known since the 1840s when early journal articles described marijuana as a treatment for “neuralgia, convulsive disorders, and emaciation.”5 Prior to the criminalization of marijuana, it was commonly prescribed for neuropathic pain, which is currently treated with much more addictive poppy plant derivatives such as morphine and oxycodone.5 As of July 2015, the College of Family Physicians of Canada only recommend that physicians prescribe marijuana if conventional therapies were unsuccessful and that it should only be considered for patients suffering from neuropathic pain and not anxiety and insomnia.8 It is anticipated that a new body of recommendations will accompany the government’s commitment to legalize, strictly regulate, and restrict access to marijuana. It is anticipated that these reforms will allow marijuana to be prescribed as an alternative treatment as opposed to the last resort.
Medical marijuana holds tremendous potential for treating symptoms associated with a plethora of rare diseases. It shows promising effects for the treatment of seizures, anxiety, and even cancer without the extreme side effects of certain pharmaceutical, some of which are so severe that the drugs aren’t even deemed fit for human consumption. With the legalization of marijuana coming in early 2017 in Canada, it will become easier and less stigmatizing to explore these therapeutic potentials and test for the safety and efficacy of different strains of marijuana for the treatment of different conditions. The increased research opportunities will pave the path for evidence-based care with medical marijuana.
1. Legalization and Regulation of Cannabis. Government of Canada Web site. https://www.canada.ca/en/services/policing/justice/legalization-regulation-marijuana.html. Published December 13, 2016.
2. Fischer B, Kuganesan S, Room R. Medical Marijuana programs: Implications for cannabis control policy – Observations from Canada. Int J Drug Policy. 2015; 26(1):15-19. Doi:10.1016/j.drugpo.2014.09.007.
3. The Biology and Potential Therapeutic Effects of Cannabidiol. National Institute on Drug Abuse Web site. https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2016/biology-potential-therapeutic-effects-cannabidiol. Published June 24, 2015.
4. Changing Marijuana Laws. Government of Canada Web site. http://www.justice.gc.ca/eng/cj-jp/marijuana/lawc-loic.html. Published December 13, 2016.
5. Gupta S. Why I changed my mind on weed. CNN News. August 8, 2013. http://www.cnn.com/2013/08/08/health/gupta-changed-mind-marijuana/.
6. Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate strategy for individualizing medicine?. Per med. 2011; 8(2):161-173. doi:10.2217/pme.11.7.
7. Kogan NM, Mechoulam R. Cannabinoids in health and disease. Dialogues Clin Neurosci. 2007; 9(4):413-430.
8. Medical Marijuana: Considerations for Canadian Doctors. The Canadian Medical Protective Association Web site. https://www.cmpa-acpm.ca/-/medical-marijuana-new-regulations-new-college-guidance-for-canadian-doctors. Published May 2014. Updated August 2016.
Cite This Article:
Zhang B., Zheng K., Chan G., Ho J. Marijuana Reform: At Long Last. Illustrated by C. Scavuzzo. Rare Disease Review. February 2017. DOI:10.13140/RG.2.2.19229.31207.