Research on Cannabinoids and Parkinson’s disease to Date Is Inconclusive

New York’s first medical marijuana dispensary opened in January, over a year after the state became the 23rd to legalize the drug for medical use and the fifth to approve Parkinson’s disease (PD) as a condition for its use. This news understandably led the patient and physician communities to ask a number of research and clinical questions about marijuana and Parkinson’s.

Marijuana is derived from the plant Cannabis sativa, which contains more than 60 different compounds referred to as cannabinoids. One of these is the major “psychoactive” component — Delta-9-tetrahydrocannabinol (THC) — which causes alterations in perception, mood and behavior. The ratio of THC to the other cannabinoid compounds, which do not have these psychoactive effects, varies from plant to plant and among the various formulations of medical marijuana.

We naturally make our own cannabinoids that bind to receptors found throughout the body and brain — this is called the “endocannabinoid system.” When these cannabinoids bind to receptors, they can impact brain chemicals, including dopamine, which decreases in Parkinson’s. One area of the brain that contains a high number of these receptors is the basal ganglia — the complex of cells that controls movement and is affected in PD. Because the cannabinoids in marijuana work in some of the same sites and ways as those made by the body, researchers have looked into what role they could play in modifying PD and in treating motor and non-motor symptoms.

Research on Cannabinoids and Parkinson’s to Date Is Inconclusive
Pre-clinical research (including work supported by MJFF in 2007 and 2012) has concentrated on learning about the structure and function of the endocannabinoid system, while determining if cannabinoids could help in Parkinson’s. Early data suggests that cannabinoids have antioxidant, anti-inflammatory and other properties that could be neuroprotective. Pre-clinical studies evaluating symptomatic effects, though — improvement in motor symptoms and levodopa-induced dyskinesia — have produced varied results.

Clinical studies have demonstrated similarly inconsistent outcomes. Several cannabinoid trials have reported benefit on Parkinson’s motor and non-motor symptoms including pain, sleep dysfunction, rapid eye movement sleep behavior disorder and psychosis. (Of course, numerous anecdotal accounts exist of marijuana aiding with these and a variety of other symptoms as well.) Complicating matters, four controlled clinical trials concluded that cannabinoids did not lessen motor symptoms but had mixed results regarding levodopa-induced dyskinesia.

The positive results should be read cautiously for several reasons:

  • small numbers of patients were enrolled,
  • many of the studies were observational (patients self-reported results through questionnaires) or uncontrolled and open-label (all participants took the study drug and were aware of this), and
  • different formulations (smoked cannabis, oral cannabinoids, etc.) and doses of marijuana and its derivatives were utilized.

The trials with negative results should also be interpreted carefully since they too included small numbers of volunteers and used varied doses and formulations of cannabinoids. However, they were placebo-controlled and therefore provide stronger evidence in support of the current prevailing clinical viewpoint, which is that cannabinoids are probably ineffective for Parkinson’s motor symptoms and levodopa-induced dyskinesia.

Medical Marijuana Is Approved for Parkinson’s in a Few States
The District of Columbia and 23 states have passed legislation allowing the use of marijuana-based products for medical purposes. The approved medical conditions, cannabinoid formulations (Minnesota and New York do not permit smoked cannabis, for example), and patient and physician requirements are different for each state. Typically patients must register in order to possess and use cannabinoids, and physician documentation of an approved condition is required for patient registration. Under federal law, doctors cannot prescribe cannabinoids, but state guidelines authorize qualified doctors to issue “certifications” that allow patients to obtain medical marijuana.

In five states (Connecticut, Illinois, Massachusetts, New Mexico and New York), Parkinson’s disease is an approved condition for use of medical marijuana. In some states, however, this diagnosis alone does not make a person eligible for the drug. In New York, for instance, one must have PD plus at least one approved associated condition — extreme malnutrition, severe or chronic pain, severe nausea, seizures, or severe or persistent muscle spasms. With regard to the latter, it’s worth pointing out that if people with Parkinson’s experience muscle problems they are more often cramps rather than spasms.

Medical Marijuana Has Potential Risks
In considering whether cannabinoids are a suitable therapy for Parkinson’s symptoms, the potential benefits must be weighed against the possible side effects. Used in moderation, cannabinoids appear to be relatively well tolerated. Even so, a review of clinical trials involving cannabinoids showed that nearly seven percent of participants discontinued them due to issues such as nausea, dizziness, weakness, mood and behavioral changes, hallucinations and impairment of cognitive (memory/thinking) abilities. Of particular concern are potential influences on cognition, motivation and balance — Parkinson’s impacts these areas in many people and it’s unclear to what degree marijuana could exacerbate this. Furthermore, the risk of prescription drug interactions with medical marijuana is not known. No definite interactions have been found, but people with Parkinson’s can be on complex medication regimens and caution always should be exercised when adding to them.

Potential harm of long-term use has not yet been established. Outside of clinical trials, though, chronic use of marijuana has been correlated with an increased risk of mood disorders and lung cancer.

Concerns about addiction and abuse are frequently raised, but these are controversial and focus mostly on marijuana acting as a “gateway” drug.

Further Research on Cannabinoids and Parkinson’s Is Necessary
Review of the research to date on cannabinoids and PD stresses the need for additional work at both the pre-clinical and clinical levels. The goals include gaining a better understanding of the endocannabinoid system, clarifying conflicting data (specifically the mixed results regarding motor symptoms and levodopa-induced dyskinesia), and determining the tolerability, safety and efficacy of cannabinoids on individual motor and non-motor symptoms in Parkinson’s. The only route to solid clinical data is through well-designed trials that include larger numbers of people with Parkinson’s, make use of formal objective outcomes measures (i.e., tools other than patient surveys where able) and employ standardized cannabinoid formulations to allow better comparison of results across trials.

The “Ask the MD” series is supported by Acorda Therapeutics. While our generous sponsors make the “Ask the MD” program possible, their support does not influence MJFF’s content or perspective.


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