Dr. Gilbert discusses the basics of Cannabidiol (CBD) and how it is being researched as a possible treatment for symptoms of Parkinson's disease. Medical Marijuana With medical marijuana now legalized in 38 states and the District of Columbia, there is strong interest in its therapeutic properties. Researchers are testing marijuana, which
Use of Cannabidiol (CBD) for PD symptoms
People with PD are eager to find alternative methods to help their symptoms, leading many of these patients to look into whether other therapies, such as medical marijuana, also known as medical cannabis, can be useful. Previously, I wrote a blog on medical marijuana and PD which you may find interesting.
More recently, I have received many inquiries specifically about the use of cannabidiol or CBD, for symptoms of PD. So today I’ll take a more in-depth look at CBD to help you better understand what it is and its possible use for symptoms of PD.
(Of note, the acronym for CBD is confusing in the context of PD, since the acronym is also used to refer to cortico-basal degeneration, a neurodegenerative disease that shares some clinical properties with PD. In this article, CBD refers to cannabidiol).
What is CBD?
Cannabidiol, or CBD, is one of the two main components of medical marijuana. (The other one is tetrahydrocannabinol or THC.) Pure CBD does not cause a “high” and does not pose a risk of abuse or dependence. THC on the other hand, can cause these effects.
Pre-clinical evidence that CBD has anti-inflammatory and antioxidant properties
CBD has been studied extensively in the laboratory and has been shown to have anti-inflammatory and antioxidant properties. Inflammation in the nervous system has been linked to neurodegeneration and therefore it has been hypothesized that CBD might even be beneficial as a neuroprotective agent. Although this is interesting and potentially exciting information, there are numerous other chemicals that have been studied in the laboratory with these properties that did not result in clinical benefit when tried in humans. Therefore, clinical trials become essential to support any claims that CBD should be used for medical purposes. Bottom line, don’t get too excited until there is scientific data to back it up.
Is CBD legal?
There is a lot of confusion around this question, related to the fact that the law distinguishes between CBD extracted from hemp and CBD extracted from marijuana. In reality, hemp and marijuana are two different names for the cannabis plant, with hemp defined as cannabis containing less than 0.3% THC. CBD products derived from hemp are federally legal. On the other hand, CBD derived from a cannabis plant containing more than 0.3% THC is federally illegal – even if the CBD is purified and the product itself contains less than 0.3% THC. To add to the confusion, is the fact that each state has its own laws that govern the use of CBD products which often contradict federal law.
The increased interest in CBD products as supplemental treatment
There is also a very confusing array of CBD products that are available for purchase. These vary in:
- What the manufacturers state is in the product. That is, some formulations of CBD will state on their label that they also contain a small amount of THC or that they contain other cannabis-derived compounds, but not THC. Others state that they are pure CBD.
- The formulation. CBD is available in oils, creams, pills, inhalants and more.
It is not just the Parkinson’s disease community that has taken an interest in CBD. There are countless health claims that CBD is helpful for a whole host of conditions. Clinical trial evidence to support the use of CBD however, is minimal. The only FDA-approved indication for CBD is to reduce seizure frequency in certain rare and severe forms of childhood epilepsy. A purified form of CBD, sold under the brand name Epidiolex® was tested in a well-designed clinical trial in order to gain this approval. (Three other cannabis related drug products that are not CBD, but rather synthetic THC, also have FDA approval and are used to treat loss of appetite and weight loss in patients with HIV, and severe nausea and vomiting due to chemotherapy).
For all the other health claims, there is not enough clinical trial data to allow the FDA to state whether or not CBD is effective. And there definitely is not enough data to support the use of one type or formulation of CBD over another.
This has not dimmed the enthusiasm of millions of CBD users for a wide range of medical conditions.
The challenge of regulating CBD products
Practically, CBD products can be obtained relatively easily at health food stores and online. They are not considered drugs (except for Epidiolex®), and therefore are not regulated by the Food and Drug Administration (FDA). This can be very problematic because without FDA oversight:
- There is no assurance that what is stated on the package is what is being sold. For example, even if the bottle says it is pure CBD, the product may contain other chemicals from the cannabis plant, or a higher amount of THC than advertised
- The manufacturing process, which is also not regulated, may introduce contaminants
- There is no assurance that the dosage written on the bottle is correct
- Medication interactions between CBD products and other drugs are not clear to consumers
The FDA is aware of the health claims that are made by manufacturers about various products and issues warnings to companies who market CBD products with unsubstantiated health claims.
CBD and Parkinson’s Disease
What evidence is available for the use of CBD for PD?
The FDA is aware that patients are frustrated that our understanding of how best to use CBD remains minimal because of the lack of clinical trials. In 2015, the FDA changed some of their regulations to make it easier to study CBD in clinical trials.
There have been a few studies of CBD for various symptoms of PD which have generally involved a small number of patients. Many have been open-label trials, in which the doctor and patient are both aware that the patient is receiving treatment and there is no control group that received a placebo.
- In one, an open label study of CBD was conducted on six patients with psychosis. Psychotic symptoms decreased.
- In a second trial, an open-label study of CBD was conducted on four patients with REM behavior sleep disorder. Symptoms decreased.
- A third trial was conducted on 21 patients with PD and was double blinded, meaning neither patient nor doctor knew who received treatment and who received a placebo. Motor scores did not improve, but quality of life scores did.
Additionally, three more recent trials of CBD for PD were conducted.
of 13 patients studied the tolerability and efficacy of CBD on tremor in PD. The trial is completed but results have not yet been published.
- Epidiolex®, the CBD formulation approved by the FDA for certain intractable childhood epilepsies, was trialed in 10 people with PD in an open-label study. Results were published and showed improvements in motor scores, nighttime sleep and emotional dysregulation scores.
- Finally, a double blinded study for motor symptoms of PD is currently underway. This trial aims to enroll 60 people with 30 patients receiving CBD and 30 receiving placebo.
Using CBD for treating Parkinson’s disease symptoms
People with PD are already using CBD in various forms for all sorts of symptoms of PD including insomnia, anxiety, tremor, dystonia and pain.
Without clinical trial data however, we do not know whether CBD is safe and effective for a particular symptom, and if it is, what CBD formulation and dosage is best to be used for a particular symptom.
We also don’t know the side effect profile of CBD in people with PD. At baseline, people with PD may have various non-motor symptoms that may make them more prone to side effects from CBD, including fatigue and nausea.
If you would like to try CBD for one of your PD symptoms, have a conversation with your movement disorders specialist about it. Your doctor may be willing to oversee your trying it, or may feel that it is too risky for you without evidence that it will help. At the very least, he/she can make sure that there are no drug interactions between CBD and anything else that you take and discuss with you any potential side effects that you need to be aware of.
With medical marijuana now legalized in 38 states and the District of Columbia, 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 Parkinson’s disease (PD). However, despite this interest, there isn’t conclusive scientific evidence that marijuana is beneficial in PD.
The Science Behind Marijuana
What is the science and pharmacology behind marijuana, and can it be used to treat Parkinson’s symptoms?
The endocannabinoid system is located in the brain and made up of the endocannabinoids (molecules in our body that act on the cannabinoid receptors) and cannabinoid receptors (a molecular switch on the outside of a cell that makes something happen inside a cell when activated) on neurons (brain cells). The endocannabinoid system helps regulate many functions, including memory, pleasure, concentration, movement, appetite, and pain.
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. Some researchers think that cannabis might be neuroprotective (ie, that it saves neurons from damage caused by PD), though there have not yet been studies in humans that demonstrate this effect.
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 benefits of cannabis for people with PD.
The Pharmacology of Cannabis
The two primary components (ie, cannabinoids) of marijuana are delta-9-tetrahydrocannibinol (THC) and cannabidiol (CBD). THC and CBD act on the cannabinoid receptors type 1 (CB1) and type 2 (CB2), which are primarily found throughout the nervous system and on cells of the immune system. The way that THC and CBD acts on these two receptors is different and may help explain the different effects mediated by each of these compounds. For example, THC is the psychoactive component of marijuana and causes alterations in perception and mood. CBD, on the other hand, can reduce anxiety and may have anti-inflammatory properties.
The various compounds present in different marijuana plants and their variable effects on the CB1 and CB2 receptors make 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.
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 PD. The clinical studies of cannabis as a PD treatment that have been conducted are generally small studies that are predisposed to biases. Most of studies have not followed 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. This is why more studies, especially those with more subjects, are needed.
PD-related Medical Marijuana Studies
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.
The authors demonstrate that nabilone, the cannabinoid receptor agonist, significantly reduces levodopa-induced dyskinesia in PD.
This study is an 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 people with PD. The study concluded that the drugs tested were safe, but did not improve Parkinsonian motor disability.
This study reviews the endocannabinoid system and its regulatory functions in health and disease.
Risks and Benefits for People with PD
There are risks and benefits associated with the use of cannabis for people with PD. Benefits include a possible improvement in anxiety, pain, sleep dysfunction, weight loss and nausea. Potential adverse effects include impaired cognition (specifically in executive function, or planning and judgement), dizziness, blurred vision, mood and behavioral changes, loss of balance and hallucinations. Chronic use of marijuana can increase the risk of mood disorders, particularly among young users, and lung cancer.
Researchers issue caution for people with PD who use cannabis particularly 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.
Medical Marijuana and Legislation by State
Thirty-eight states and Washington, DC have passed legislation allowing the use of marijuana-based products as a medical intervention.
In some states where medical marijuana is legalized, consumers must register to possess and use cannabis. Other states require consumers to acquire a document from a physician stating that the person has an approved condition. Under federal law doctors cannot prescribe cannabis, but many states authorize them to issue certifications that allow people to obtain medical marijuana.
PD is listed as a qualifying condition for medical marijuana in California, Connecticut, Florida, Hawaii, Illinois, Louisiana, Maine, Massachusetts, Michigan, Mississippi, Missouri, New Hampshire, New Mexico, New York, Ohio, Oklahoma, Pennsylvania, Vermont and West Virginia.
Medical marijuana is legal in Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Hawaii, Illinois, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Dakota, Utah, Vermont, Virginia, Washington, West Virginia and Washington, DC.
Eighteen states and the District of Columbia have legalized the recreational use of marijuana, making it legal for adults over the age of 21 to legally consume marijuana without a doctor’s recommendation. Many of these states still differentiate recreational from medical marijuana. In some states, medical marijuana consumers may have access to specialized dispensaries, strains of marijuana and sales tax exemptions.
Recreational marijuana is legal in Alaska, Arizona, Connecticut, California, Colorado, Illinois, Maine, Massachusetts, Michigan, Montana, New Jersey, New Mexico, New York, Nevada, Oregon, Virginia, Vermont, Washington and Washington, DC.
Multiple states, counties or cities have decriminalized certain marijuana-related offenses. In these areas, the possession of marijuana can be met with a citation — forgoing an arrest or criminal record — or no penalty at all.
For state-by-state guidance on marijuana legalization, medical laws and discrimination visit Norml.org/laws.
Parkinson’s Foundation Centers of Excellence and Medicinal Marijuana
The Parkinson’s Foundation, in partnership with Northwestern University researchers, studied attitudes about cannabis at 40 Centers of Excellence — members of our Global Care Network. 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 Parkinson’s Foundation centers, as 95 percent of neurologists reported people have asked them to prescribe it.
These 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 taught in medical school.
- Physicians reported that 80% of their people with PD have used cannabis.
- Only 10% of physicians have recommended the use of cannabis to people 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.
This graph shows how physicians expect cannabis would improve, worsen or show no effect to PD-related symptoms given their expertise and observations of people with PD.
The study emphasized that physicians would be more apt to use 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 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 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 Advisor.
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 people 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.
The Parkinson’s Foundation Consensus Statement on the Use of Medical Cannabis for Parkinson’s Disease is designed to help guide the PD community in making informed decisions about using cannabis for Parkinson’s. The statement is based on the input from 46 experts who attended the Foundation’s first-ever medical marijuana convening. Read it now.
Page reviewed by Dr. Chauncey Spears, Clinical Assistant Professor and Dr. Sydney M. Spagna, Clinical Fellow at the University of Michigan.