I am asked almost daily about medical marijuana for PD. For the purposes of this essay, I will call marijuana “MJ.” I am not alone in being asked this question; my movement disorder colleagues around the state have had similar experiences. The National Parkinson Foundation (NPF) states that, among physicians surveyed at their 40 NPF Centers of Excellence, 95% of neurologists reported PD patients had asked for a medical MJ prescription, and 80% of patients with PD had used MJ, whereas only 10% of physicians had recommended it, and 75% of physicians felt that MJ would have a negative effect on short term memory (1).
MJ in PD is a complex subject, and to be clear, under Federal law, is not legal, though a couple of drugs derived from MJ are: dronabinol (Marinol) and nabilone (Cesamet). Since President Nixon signed the Controlled Substances Act in 1970, MJ has been classified by the FDA as a Schedule I drug, defined as a drug with a “high potential for abuse … no currently accepted medical use.” Schedule I designation is an impedance to scientific study for potential medical use. In other words, it is hard to conduct trials with this designation. However, trials or not, in Maine medical MJ has been approved since 1999. Under the Rules Governing the Maine Medical Use of Marijuana Program (MMMP), there are certain indications for the use of medical MJ, but PD is not one of them (2). Regardless of medical law, the recent citizen initiative to legalize recreational MJ passed. Access is legal (within certain limits) for adults under State law. Many people with PD tell me they will be, or have already been, trying MJ. I have heard from people who report improved tremors and dyskinesia, some who have better sleep, some who say it does nothing, and some who do not tolerate it due to side effects. This is all anecdotal. What does science show?
The pharmacology of MJ is complicated. Most MJ strains come from two species of plant: Cannabis sativa, and Cannabis indica. Over 60 neuroactive compounds have been identified in MJ. Many of these work on the brain’s endocannabinoid system, which is known to affect neurotransmission in the motor system of the brain, and there are many receptors in the basal ganglia – the main region dopamine is used. Endocannabinoids also are implicated in the control of mood, cognition, and pain. THC is found in a higher concentration in sativa plants, and is thought to be the primary psychotropic compound in MJ, the cause of paranoia, and other psychotic features. Cannabidiol (CBD) is a non-psychoactive substance, and is in higher concentration in indica strains. CBD has sedating, anti-emetic (helps with nausea and vomiting), and analgesic (pain) properties.
There is a lot of data about MJ in the basic science, and some in the medical literature about people taking MJ as an intervention. The type of study is important. Case reports may describe the experience of only one, or of very few patients with an intervention. An open label study is one in which there is no placebo, and the concern is that there may be bias, whether conscious or unconscious, on the part of the participant or the evaluator. In other words, if you know you are taking an intervention, you may believe you are changed by that intervention. Belief is important in the mind-body connection, and is the basis of the “placebo effect.” This is not to say that open label trials are useless, just that they must be interpreted with caution.
In one open label observational study at an academic movement disorder center, 22 PD patients were tested at baseline and at 30 min after smoking MJ (3). The group showed improvements of tremor, rigidity, and bradykinesia in the UPDRSIII motor score used to evaluate PD patients, improving on average from 33.1 to 23.2 after consumption. If the score means nothing to you, know that the UPDRSIII score ranges from 0, with no PD, to 108, the worst PD imaginable. Therefore, the lower the UPDRSIII score, the better, sort of like golf.
The scientific approach to prove the effectiveness of any drug or intervention would be to progress through trials which demonstrate safety with a few patients (phase I), a larger group (phase II), and efficacy (phase III). In all phases, side effects are noted. In the phase III trial, the gold standard is the well-designed, randomized, double-blinded, controlled trial (RDBCT). In this trial participants must meet certain criteria for entry, and take either the trial intervention (for example, MJ), or a placebo. When people participate in studies, they are evaluated periodically to measure effect. A study is double-blinded when neither the study participant nor the evaluator know who is taking the intervention, and who is taking placebo. All data is eventually collected, interpreted, described and discussed in peer-reviewed medical journals. Doctors then read these articles and use their own skills of critical analysis to interpret the study. There are many variables at play, and a study may raise many questions. A single study may need additional support. A study that shows unique results should ideally be repeated by a separate group of researchers and study participants.
Larger study groups tend to provide more valid information about how people may respond generally because researchers are able to average a lot of data. Unfortunately, there is very little study data with MJ in large groups of PD patients or the RDBCT. Some authors have tried to go through the available data and produce a conclusion from several case reports and studies. For example, researchers looked at a collection of papers and showed that oral cannabis extract (OCE) is probably ineffective for treating levodopa-induced dyskinesias (4).
Papers such as this led a subcommittee of the American Academy of Neurology to review multiple studies involving the use of MJ in the treatment of neurologic diseases (5). These studies showed that, in PD, treatment with the compound 9-tetrahydocannabiol (THC) or with OCE are probably ineffective in treating tremor. OCE is probably ineffective for treating levodopa-induced dyskinesias in PD. They noted that among 34 studies the risk of serious adverse psychopathologic effects was about 1%. The authors reported that comparative effectiveness of medical MJ vs. other therapies is unknown for these indications.
In 2015, researchers published in the journal of the Movement Disorders Society another summary of study data, which concluded that MJ is probably not helpful for the treatment of tremors or dyskinesias (6).
There are concerns about MJ in PD beyond paranoia and psychotic features. While MJ might help with pain, insomnia, nausea, and weight loss, it might cause side effects. MJ use decreases reaction time, has negative effects on cognitive and executive function, may lead to risky behaviors, create apathy or a lack of motivation, cause dizziness and blurred vision, cause mood or behavioral changes, affect balance, or just make a person sleepy. All of these are already potential problems in PD, which may be exacerbated. Chronic use of MJ has been shown to unmask underlying psychiatric disorders. Finally, smoking MJ is associated with increased risk of lung cancer and stroke. Vaporizing MJ is also probably not a healthy option.
In conclusion, there is not much data to support the use of MJ in PD, but there is a huge political will to legalize it, and a growing feeling among patients that it is safe to try. This may not be true. As with any neuroactive substance, large RDBCTs are needed to demonstrate benefit and safety. In addition, if effective, MJ, which is a very potent compound, would ideally go through approval process with the FDA. MJ has not, and physicians do not have label or dose recommendations, timing instructions, or adequate description of all potential side effects.
References
- http://www.parkinson.org/understanding-parkinsons/treatment/complementary-treatment/medical-marijuana-and-parkinsons-disease
- http://www.maine.gov/dhhs/mecdc/public-health-systems/mmm/documents/MMMP-Rules-144c122.pdf
- Lotan et al. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clin Neuropharmacol. 2014;37(2):41-4
- Koppel et al. Systematic review of medical marijuana 1948-2013. Neurology. 2014;82(17):1556-63
- Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Apr 29;82(17):1556-63.
- Kluger et al, The therapeutic potential of cannabinoids for movement disorders. Mov Disord. 2015;30(3):313-327
