With medical marijuana now legalized in 28 states and Washington, D.C., it is obvious that there is strong interest in its therapeutic properties. Researchers are testing marijuana, which is also called cannabis, as a treatment for many illnesses and diseases, including neurological conditions, with Parkinson's disease (PD) high on the list. But despite several clinical studies, it has not been demonstrated that cannabis can directly benefit people with Parkinson's. What is the science and pharmacology behind marijuana, and can it be used to treat Parkinson's symptoms?
The Science Behind Marijuana
The endocannabinoid system is located in the brain and made up of cannabinoid receptors (a receptor is molecular switch on the outside of a cell that makes something happen inside a cell when activated) that are linked to neurons (brain cells) that regulate thinking and some body functions.
Researchers began to show enthusiasm to study cannabis in relation to Parkinson's after people with PD gave anecdotal reports and posted on social media as to how cannabis allegedly reduced their tremors. Some researchers think that cannabis might be neuroprotective — saving neurons from damage caused by Parkinson's. Cannabinoids (the drug molecules in marijuana) have also been studied for use in treating other symptoms, like bradykinesia (slowness caused by PD) and dyskinesia (excess movement caused by levodopa). Despite some promising preclinical findings, researchers have not found any meaningful or conclusive cannabis benefits for people with Parkinson's.
Researchers issue caution for people with PD who use cannabis because of its effect on thinking. Parkinson's can impair the executive function — the ability to make plans and limit risky behavior. People with a medical condition that impairs executive function should be cautious about using any medication that can compound this effect.
The Pharmacology of Cannabis
Marijuana contains more than 100 neuroactive chemicals that work with two types of cannabinoid receptors, type 1 (CB1) located in the brain and type 2 (CB2) located in the brain and peripheral immune system. Cannabinoids have powerful, indirect effects on these receptors, but researchers are unsure how. People with PD have less CB1 receptors than people who do not have PD. A boost to the CB1 receptor through an agonist, like marijuana, can improve tremors and may alleviate dyskinesia. Similarly, the other receptor, CB2, is also being studied to determine if it can modify the disease or provide neuroprotective benefits. However, a unified hypothesis does not currently exist for either receptor because there is too much conflicting data on the effectiveness of cannabinoids and these receptors.
Cannabis can contain two different types of molecules that interact with cannabinoid receptors: agonists and antagonists. An agonist is a drug that attaches to the same receptor as a natural chemical and causes the same effect. A dopamine agonist is a drug that is not dopamine, but attaches to the dopamine receptor. An antagonist is different as it attaches to the receptor, but blocks the action of the natural chemical. Medical marijuana can contain both cannabinoid agonists and antagonists. Recreational marijuana use is derived from its effects on agonists.
The varying amounts of cannabinoid agonists and antagonists in different marijuana plants makes cannabis studies difficult to conduct. When researchers study the effects of a medication, dosages are controlled and often set to a specific number of milligrams. When testing medical marijuana, the dosage administered can vary dramatically depending on the plant and method of administration.
THC is a primary component of marijuana. Cannabidiol is the other primary component.THC has a long latency of onset and cannot be easily measured for a therapeutic or medicinal dose. Medical marijuana studies primarily provide participants with THC and/or cannabidiol in the form of a capsule, nasal spray or liquid.
PD-Related Medicinal Marijuana Trials
The use of cannabinoids has been suggested to help with managing neurological and non-neurological conditions. Literature on medical marijuana is incredibly varied. Studies have not clearly supported the use of marijuana for Parkinson's. The clinical studies of cannabis as a PD treatment that have been conducted did not use the clinical trial gold standard of a double blind, placebo controlled trial design. Some studies had as few as five subjects. While some results have been positive, the effects of medical marijuana are probably not completely understood, which is why more studies, especially those with a greater number of subjects, are needed. Most doctors do not support study results because these studies do not meet the minimum research standard.
Below are several PD-related medical marijuana studies that have been conducted to evaluate the use of cannabinoids in Parkinson's:
- The Therapeutic Potential of Cannabinoids for Movement Disorders: clinical observations and trials of cannabinoid-based therapies suggest a possible benefit to tics and probably no benefit for tremor in dyskinesias or PD motor symptoms. Further preclinical and clinical research is needed to better characterize the pharmacological, physiological and therapeutic effects of this class of drugs in movement disorders.
- Cannabinoids Reduce Levodopa-induced Dyskinesia in Parkinson's Disease: A Pilot Study: the authors demonstrate that nabilone, the cannabinoid receptor agonist, significantly reduces levodopa-induced dyskinesia in PD.
- Neurokinin B, Neurotensin, and Cannabinoid Receptor Antagonists and Parkinson Disease: evaluation of the effects of three antagonists on the NK3, neurotensin and cannabinoid receptors on the severity of motor symptoms and levodopa-induced dyskinesias after administration of a single dose of levodopa in 24 patients with Parkinson's. The study concluded that the drugs tested were safe, but did not improve parkinsonian motor disability.
- The Endocannabinoid System as an Emerging Target of Pharmacotherapy: reviews the endocannabinoid system and its regulatory functions in health and disease.
Risks and Benefits for People with Parkinson's
There are risks and benefits associated with the use of cannabis for people with PD. Benefits include a possible improvement in: pain management, sleep dysfunction, weight loss and nausea. Potential adverse effects include: impaired cognition (impairment in executive function), dizziness, blurring of vision, mood and behavioral changes, loss of balance and hallucinations. Chronic use of marijuana can increase risk of mood disorders and lung cancer.
Medical Marijuana and Legislation by State
Washington, D.C., and 28 states passed legislation allowing the use of marijuana-based products for medical purposes. Three of those states (Minnesota, New York and Ohio) do not allow it to be smoked. In some states patients must register in order to possess and use cannabis. Other states require patients to acquire a document from a physician stating that the patient has an approved condition. Under federal law doctors cannot prescribe cannabis, but many states authorize them to issue certifications that allow patients to obtain medical marijuana.
Parkinson’s is a qualifying condition for medical marijuana in: Arizona, Connecticut, Florida, Illinois, Maine, New Mexico, New York, Pennsylvania and Rhode Island.
Medical marijuana is legal in: Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Hawaii, Illinois, Maine, Maryland, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, Washington and Washington, D.C. In Texas, medical marijuana is only approved for people with epilepsy.
NPF Centers of Excellence and Medicinal Marijuana
NPF in partnership with Northwestern University researchers studied attitudes about cannabis at 40 NPF Centers of Excellence. To the best of our knowledge, this is the first study to provide data on the practices, beliefs and attitudes of expert PD physicians in regards to cannabis use.
The results were interesting: most experts said they knew what cannabis did, but disagreed on the details. While there is no general agreement on what the benefits might be for people with PD, the survey confirmed that cannabis is a popular subject within NPF centers as 95 percent of neurologists reported patients have asked them to prescribe it.
Cannabis study results also included:
- Only 23% of physicians had any formal education on the subject of cannabis (such as a course or lecture), thus 93% of physicians want cannabis to start being taught in medical school.
- Physicians reported that 80% of their patients with PD have used cannabis.
- Only 10% of physicians have recommended the use of cannabis to patients with PD.
- In terms of memory: 75% of physicians felt that cannabis would have negative effects on short-term memory and 55% felt that cannabis could have negative effects on long-term memory
- Only 11% of physicians have recommended use of cannabis in the last year
Graph caption: This graph shows how physicians expect cannabis would improve, worsen, or show no effect to PD-related symptoms given their expertise and observations of patients with PD.
The study emphasized that physicians would be more apt to the use of medical marijuana as a treatment if the drug was approved through regulation instead of legislation. Nearly all medications are only approved after passing a science-based evaluation proving their effectiveness in a process overseen by the U.S. Food and Drug Administration. Since cannabis has been approved through legislation rather than regulation, there are no labels, dosage recommendations or timing instructions that physicians can reference.
Is Medical Marijuana an Option for Me?
What's next for a person with Parkinson's who wants to know if medical marijuana is an option? "Marijuana should never be thought of as a replacement for dopaminergic and other approved therapies for Parkinson's disease," said Dr. Michael S. Okun, the Parkinson's Foundation National Medical Director. Research is still needed to determine how medical marijuana should be administered and how its long-term usage can effect Parkinson's disease symptoms. To keep patients safe, states that legalize medical marijuana will eventually need to develop training programs for doctors and medical teams that prescribe medical marijuana. Consult your doctor to see if medical marijuana is an option for you.
Joseph Jankovic, MD, is the Director of the Parkinson’s disease Center and Movement Disorders Clinic Baylor College of Medicine, a Parkinson’s Foundation Center of Excellence. Information from this article is attributed to Dr. Jankovic’s data and presentation at the Foundation’s 2016 Center of Leadership Conference.