Parkinson’s Foundation: Better Lives. Together.

With medical marijuana now legalized in 33states 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 PD.

What is the science and pharmacology behind marijuana, and can it be used to treat Parkinson's symptoms?

Theendocannabinoid systemis located in the brain and made up ofcannabinoid receptors(a receptor is molecular switch on the outside of a cell that makes something happen inside a cell when activated) that are linked toneurons(brain cells) that regulate thinking and some body functions.

Researchers began to show enthusiasm to study cannabis in relation to PD after people with PD gave anecdotal reports and posted on social media as to how cannabis allegedly reduced their tremors Involuntary shaking of the hands, arms, legs, jaw or tongue. The typical Parkinsons tremor is pill-rolling it looks like holding a pill between thumb and forefinger and continuously rolling it around. Some people report an internal tremor, a shaking sensation inside the chest, abdomen or limbs that cannot be seen. Most Parkinsons tremor is resting tremor, which lessens during sleep and when the body part is actively in use.. Some researchers think that cannabis might be neuroprotective Something that protects neurons against damage, degeneration or apoptosis (programmed cell death). saving neurons from damage caused by PD.

Cannabinoids(the drug molecules in marijuana) have also been studied for use in treating other symptoms, like bradykinesia Slowness of movement. (slowness caused by PD) and dyskinesiaAbnormal, involuntary body movements that can appear as jerking, fidgeting, twisting and turning movements; frequently caused by dopaminergic medications to treat Parkinsons. (excess movement caused by levodopaThe medication most commonly given to control the movement symptoms of Parkinsons, usually with carbidopa. It is converted in the brain into dopamine.). Despite some promising preclinical findings, researchers have not found any meaningful or conclusive benefits of cannabis for people with PD.

Researchers issue caution for people with PD who use cannabis because of its effect on thinking. PD 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.

Marijuana contains more than 100 neuroactive chemicals that work with two types of cannabinoid receptors,type 1 (CB1)located in the brain andtype 2 (CB2)located in the brain and peripheral immune system. Cannabinoidshave 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 cannabinoidsand these receptors.

Cannabis can contain two different types of molecules that interact with cannabinoid receptors: agonists and antagonists. Anagonistis a drug that attaches to the same receptor as a natural chemical and causes the same effect. Adopamine agonist A class of medications used to treat Parkinson's disease. Agonists enhance the activity of a neurotransmitter in this case, dopamine. Ropinirole (Requip), pramipexole (Mirapex), rotigotine (Neupro) and apomorphine (Apokyn) are common dopamine agonists.is a drug that is not dopamine A chemical messenger (neurotransmitter) that regulates movement and emotions., but attaches to the dopamine receptor. Anantagonistis different as it attaches to the receptor, but blocks the action of the natural chemical. Medical marijuana can contain both cannabinoid agonistsandantagonists. 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 aprimary 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 as a capsule, nasal spray or liquid formulation.

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 PD. The clinical studies of cannabis as a PD treatment that have been conducted did not use the clinical trial A research study in humans that aims to test a new intervention this could be a drug, surgery or therapy like exercise or diet guidelines to make sure it is effective and safe. 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 more subjects, are needed. Most doctors dont support study results because these studies do not meet minimum research standards.

Below are several PD-related medical marijuana studies that have been conducted to evaluate the use of cannabinoids:

There are risks and benefits associated with the use of cannabis for people with PD. Benefits include a possible improvement in anxiety A feeling of nervousness, worried thoughts and physical distress., pain management, sleep dysfunction, weight loss and nausea. Potential adverse effects include: impaired cognition (impairment in executive function), dizziness, blurred vision, mood and behavioral changes, loss of balance and hallucinations. Chronic use of marijuana can increase risk of mood disorders and lung cancer.

Washington, D.C., and 33states 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 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.

PD is a qualifying condition for medical marijuana in: Arizona, Connecticut, Florida, Illinois, Maine, New Mexico, New York, Pennsylvania and Rhode Island.

Medicalmarijuanais legal in: Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Hawaii, Illinois, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, Utah, Vermont, Washington, West Virginia, and Washington,D.C.

The Parkinsons Foundation, in partnership with Northwestern University researchers, studied attitudes about cannabis at 40Centers 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 concerning 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 Parkinsons Foundation centers as 95 percent of neurologists reported patients have asked them to prescribe it.

Cannabis study results also included:

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 touse medical marijuana as a treatment if it 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.

What's next for a person with PD 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 PD," 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 use can affect symptoms of PD. 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.

Page reviewed by Dr. Bhavana Patel, Movement Disorders Fellow at the University of Florida, a Parkinsons Foundation Center of Excellence.

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