Cannabidiol in Parkinson’s disease
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Parkinson’s disease (PD) is a common and complex neurological disorder that encompasses a range of clinical, epidemiological, and genetic subtypes. Loss of dopaminergic neurons in the substantia nigra leading to striatal dopamine depletion is the core mechanism underlying the cardinal motor features of PD. Although depletion of dopamine is the most notable neurotransmitter change in PD, other neurochemical changes occur and contribute to PD symptomatology. Many regions of the nervous system outside the basal ganglia are also involved in PD. The underlying molecular pathogenesis involves multiple pathways and mechanisms, such as α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation.
Although clinical diagnosis relies on the presence of cardinal motor features, PD is also associated with numerous non-motor symptoms that can be equally disabling than the motor symptoms or even more so. Drugs that enhance intracerebral dopamine concentrations or stimulate dopamine receptors remain the main treatment for motor symptoms. None of available treatments have proven to be neuroprotective or disease-modifying. Dopaminergic drugs are particularly effective during the early stages of the disease. However, PD invariably progresses, and long-term use of these medications may lead to reduced drug efficacy and the development of complications such as motor fluctuations and dyskinesias.
Unlike most of the motor features of PD, many non-motor symptoms do not respond to dopaminergic therapy, and some are indeed aggravated by them, with great impact on patient quality of life. The refractoriness of these symptoms to dopaminergic therapy implicates non-dopaminergic mechanisms. Therefore, current needs in the management of symptomatic patients with PD include dopamine-unresponsive axial motor impairments and non-motor symptoms, such as dementia, depression, anxiety, psychosis, and pain.
There is a clear need for therapies that target other pharmacological systems. A multimodal approach combining activity on dopaminergic as well as non-dopaminergic system would be very helpful and needs to be explored.
There has been interest in cannabidiol (CBD) as a treatment option for PD because of the identification of multiple potential targets of action in the CNS. CBD is one of the many cannabinoids identified in Cannabis sativa, being the second most abundant constituent after Δ9-tetrahydrocannabinol (THC). Unlike THC, CBD is non-psychoactive, and has been ascribed many potential medical benefits.
In this issue of the Brazilian Journal of Psychiatry, a research group from Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil, addressed animal and human clinical studies involving the use of CBD for PD.1 The authors discussed the biological bases for a potential effect of CBD in this setting, as well as preclinical and clinical studies of CBD in PD. The latter, all conducted by their group, are an open-label study,2 a case series,3 and a randomized controlled trial.4 The open-label pilot study was conducted with six PD patients with psychotic symptoms, lasting at least 3 months before study entry, that could not be controlled by reduction of antiparkinsonian medications.2 Oral CBD doses ranging from 150-400 mg/day, combined with classic antiparkinsonian agents, reduced psychotic symptoms evaluated by different scales (the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire), with no influence on cognitive and motor signs and no severe side effects. The second study was a case series of four PD patients with REM sleep behavior disorder (RBD).3 All had prompt, substantial, and persistent reductions in he frequency of RBD after CBD treatment. After drug discontinuation, the complex movements of RBD returned with baseline frequency and intensity. The third study was an exploratory double-blind trial of CBD versus placebo.4 Twenty-one PD patients without dementia or comorbid psychiatric conditions were assigned to three groups of seven subjects each who were treated with placebo, CBD 75 mg/day, or CBD 300 mg/day. Participants were assessed with respect to motor and general symptoms score (Unified Parkinson’s Disease Rating Scale [UPDRS]) and well-being and quality of life (Parkinson’s Disease Questionnaire [PDQ-39]). There were no differences across groups in motor score. However, the groups treated with CBD 300 mg/day had significantly different mean total scores in the PDQ-39. The authors point to a possible effect of CBD in improving measures related to quality of life in PD patients without psychiatric comorbidities.
All of these studies showed interesting results, but sample sizes were very small and the duration of follow-up was very short. The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD published in 2018 concluded that there was insufficient evidence to support the use of CBD for the treatment of PD at the time.5
It is vital to note that no conclusions can be drawn on the efficacy of CBD in this setting, as larger phase III and conclusive efficacy trials have not been conducted in PD. Double-blind, placebo-controlled, randomized trials with larger samples of patients with PD are needed to elucidate the possible effectiveness and mechanisms involved in the therapeutic potential of CBD in PD. Additionally, studies conducted specifically to evaluate the safety profile of CBD in patients with PD (including long-term safety), possible interactions with antiparkinsonian drugs, and possible side effects, as well as the therapeutic window for motor and non-motor PD symptoms, are also required.
CRR has been on the speakers’ bureau/advisory board and/or has acted as a consultant for UCB Biopharma S.A., Teva Farmacêutica, Roche Farmacêutica, and Medtronic.
What to Know About Marijuana and Parkinson’s Disease as CAM Therapy
Sarah Jividen, RN, BSN, is a freelance healthcare journalist and content marketing writer at Health Writing Solutions, LLC. She has over a decade of direct patient care experience working as a registered nurse specializing in neurotrauma, stroke, and the emergency room.
Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.
Nicholas R. Metrus, MD, is a board-certified neurologist and neuro-oncologist. He currently serves at the Glasser Brain Tumor Center in Summit, New Jersey.
People with Parkinson’s disease are becoming more interested in learning how medical marijuana and cannabidiol (CBD) can relieve symptoms associated with the disease. Medical marijuana is a type of complementary and alternative medicine (CAM) that has not traditionally been used in the medical community.
But in recent years, more states have authorized the use of marijuana for both recreational and medicinal use. As a result, Parkinson’s patients are asking their physicians if medical cannabis is an effective treatment for their disease.
Parkinson’s disease is a neurodegenerative disease with no cure, but some studies have shown that medical marijuana helps relieve symptoms. Learn more about the benefits and considerations that come with using marijuana as a therapy for Parkinson’s disease.
Verywell / Michela Buttignol
What Is Medical Marijuana?
Medical marijuana is cannabis that’s prescribed by a physician to treat or provide relief for a medical condition.
There are around 400 chemicals in the cannabis plant, and more than 60 of them are referred to as “cannabinoids.” The “high” marijuana users get is primarily due to the most psychoactive cannabinoid in the plant called tetrahydrocannabinol, or THC.
Cannabinol, or CBD, is the other cannabinoid, which is used in medical marijuana. CBD does not cause a “high” when taken alone and, in fact, moderates the psychoactive effects. Research is being done to determine how medical marijuana can help treat or relieve symptoms of various diseases, including Parkinson’s disease.
How Does Medical Marijuana Affect the Body?
Marijuana affects the body through neurotransmitters, which are the chemical messengers of the nervous system.
Various factors can stimulate neurotransmitter activity, initiating a set of physiological responses. In cannabis, it is mainly THC or CBD binding to endocannabinoid receptors that produce new physiological reactions in the body.
The endocannabinoid system (ECS) is one of the most important neurotransmitter systems in the body. It utilizes cannabinoid receptors located throughout the central nervous system (CNS) and peripheral nervous system (PNS). Cannabis works to “turn on” endocannabinoid neurotransmitters through activity at these receptors.
The Endocannabinoid System
The endocannabinoid system is not fully understood. However, experts know that it helps to regulate various body functions such as mood, sleep, memory, appetite, and fertility. While everyone has an ECS, medical cannabis’s direct interactions with it may affect individuals differently.
There are two types of cannabinoids involved in cannabis use:
- Endocannabinoids are chemical messengers that affect the cannabinoid receptors in humans and animals. “Endo” means produced in the body system.
- Phytocannabinoids are chemical messengers found in cannabis and hemp plants. “Phyto” refers to plants.
Cannabis and hemp are legally classified based on THC content. Hemp is a plant that contains 0.3% or less THC. Cannabis plants contain more than 0.3% THC.
How THC and CBD Work
Cannabinoids from cannabis activate the ECS by binding to endocannabinoid receptors throughout the brain and body. The two most affected by cannabis are:
- CB1 receptors: Found in the brain in high levels, they are responsible for marijuana’s psychoactive properties, or the “high” effect.
- CB2 receptors: Found throughout the body, they affect pain levels and inflammation.
THC strongly activates CB1 receptors, triggering a feeling of euphoria. This activation also increases blood flow to the prefrontal cortex of the brain, which is the area that controls the ability to focus, as well as our motor skills, attention, memory, and decision-making abilities.
THC also interacts with CB2 receptors, providing added analgesic (pain relieving), muscle relaxing, and antiemetic effects (helping with nausea and vomiting).
CBD activates both CB1 and CB2 receptors, although less strongly than THC. Although its CB1 and CB2 receptor activation does not produce a “high,” it has been shown to interact with additional receptors in the body and have calming and anti-inflammatory effects. For this reason, CBD has been used to treat pain, anxiety, and seizures.
Medical Marijuana as a Treatment for Parkinson’s Symptoms
Parkinson’s disease is a disorder of the central nervous system that causes tremors, slow movement, stiffness, and loss of balance. Because marijuana directly affects the central and peripheral nervous systems, scientists have studied the effect of marijuana as a treatment for Parkinson’s symptoms.
A 2020 review of 14 different studies acknowledged evidence that medical marijuana provides a reduction in anxiety, tremors, and involuntary or erratic movements. However, the researchers concluded that there is insufficient evidence to recommend medical marijuana use as part of Parkinson’s treatment.
A 2017 study with patients who used medical marijuana over three months to manage Parkinson’s symptoms found that the treatment improved their symptoms and did not cause major adverse effects.
Other research has shown that medical marijuana may be able to help with some Parkinson’s disease symptoms, including:
(decreased movement ability)
- Sleep problems
Cannabis use for patients with Parkinson’s has also been shown to help improve mood, memory, and fatigue.
Talk to Your Physician
The use of medical marijuana remains controversial, and there is no official guidance on its use at present. Though there are studies suggesting potential benefits of medical marijuana for Parkinson’s disease, patients should discuss their treatment options with their physicians and whether medical marijuana is appropriate for them.
Medical marijuana use can provide additional benefits for patients with Parkinson’s, including symptom relief for:
- Poor sleep
Possible Side Effects
As with any medication, there are potential side effects of medical marijuana. Negative effects of medical marijuana use for Parkinson’s can include:
- Cognitive impairment, such as issues with attention, focus, and memory
- Increased appetite and weight gain
- Lung damage (if smoking)
- Increased heart rate or potential withdrawal symptoms
There may also be potential negative interactions that medical marijuana may have with other medications. Check with your physician before taking a medical marijuana product.
How to Use Cannabis for Parkinson’s
There are many ways to use medical marijuana. If you are considering using medical marijuana to treat Parkinson’s symptoms, speak with your physician about the best products and applications for your specific case.
Forms of medical marijuana include:
- Dermal patches
- Dermal sprays
There is no universal marijuana or CBD dosage. Studies are being done to determine how patients respond to the effects of marijuana differently. Longer clinical trials with more patient involvement are needed to establish dosage parameters, so speak to your physician about the right dosing options for you.
Medical marijuana is legal in 36 states and four territories as of May 2021. There are some restrictions regarding THC content in many states.
Recreational marijuana is legal in 18 states, two territories, and the District of Columbia as of July 2021.
Although CBD does not produce a psychedelic effect, it is not legal in all 50 states, even if it’s sourced from hemp containing less than 0.3% THC. The reason is that each state has its own Controlled Substances Act (CSA) that considers CBD to be marijuana in some states.
Considerations Before Buying Marijuana Products
Marijuana is a Schedule 1 drug, meaning that it is a drug with a high potential for abuse and no currently accepted medical use. For that reason, it is still illegal to use in much of the country.
If you are considering using marijuana for medical purposes, there are a few things you need to consider, such as:
- THC and CBD content levels
- Published and accessible Certificates of Analysis (CoA), which certify the test results of the product from the manufacturer
- Organic vs. not
- Where it’s sourced
- Methods of consumption
A Word From Verywell
Living with Parkinson’s disease can be challenging and stressful. While there are treatments available to help you manage your symptoms, you may want to discuss the possibility of medical marijuana as part of your treatment plan. Before taking any medication for symptom management, discuss your options with your physician, and whether medical marijuana is appropriate for your disease case.
Frequently Asked Questions
Every state has its own rules and regulations for getting a medical marijuana card. If you live in areas where medical marijuana is legal, you may want to consider the following options:
- Talk to your primary care physician
- Find a certified medical marijuana professional in your state
- Register with your state department if required in your state
Some studies show that CBD can help with tremors and other Parkinson’s disease symptoms. However, more studies are needed. Speak with your physician if you are considering medical cannabis for tremor relief.
Many companies produce CBD oil, and there are no studies available that favor one brand over another. If you are taking CBD oil, it is essential that you follow your physician’s prescription. CBD oil is most commonly taken as a sublingual drop (under the tongue). CBD oil is an alternative for patients who don’t like taking medication in a pill form.
The THC in medical marijuana stimulates neurons that signal the release of dopamine neurotransmitters at higher levels than usual.