Trial of Cannabis for Essential Tremor
This is a pilot trial to evaluate the safety and efficacy of a combined oral formulation of THC and CBD in patients with Essential Tremor.
|Condition or disease||Intervention/treatment||Phase|
|Essential Tremor||Drug: CBD/THC Drug: Placebo oral capsule||Phase 1 Phase 2|
Essential tremor (ET) is the most common neurological movement disorder, affecting up to 1% of the population and up to 5% of individuals over the age of 65. ET is characterized by often disabling tremors that occur when an individual moves. The tremors most commonly affect the hands, head, voice, and legs in order of frequency, leading to impairment in activities of daily living and morbidity. No pharmacological agent has been developed for ET, though existing agents such as propranolol and primidone are used off-label to reduce tremor amplitude. Deep brain stimulation surgery is often reserved for only individuals with the most severe tremors. Patients with ET have long reported tremor benefits with the use of cannabis, though no controlled trials have been conducted. The investigators plan to conduct the first double-blind, placebo-control clinical trial of cannabis in an oral capsule. Various validated tremor rating methods will be used to quantify tremor severity, while looking at tolerability and safety.
Essential Tremor Research Program: Cannabidiol Anti-Tremor Action and Mechanisms
“People tend to think of medical marijuana as a single substance; a substance that may have beneficial effects but also causes mood- and mind-altering effects,” explains Dr. Adrian Handforth, Assistant Chief of Neurology at VA Greater Los Angeles Healthcare System in California, “But that is not the case at all. Actually, marijuana is made up of many related chemicals, called cannabinoids.”
Dr. Handforth is the lead researcher of an upcoming IETF funded study that will explore the effects of a particular cannabinoid known as “CBD” (cannabidiol) on essential tremor. Unlike the well-known cannabinoid “THC” (tetrahydrocannabinol), which has mind- and mood-altering effects, CBD does not alter the mind, the emotions, or one’s judgment. Although its long-term safety remains to be thoroughly studied, CBD has already shown some promising initial results in the treatment of epilepsy, pain, anxiety, and other disorders. Dr. Handforth and his team will try to find out whether CBD can suppress essential tremor in an animal model. And if it does, he will take the next step and try to understand how it works.
This is exactly why the IETF is so pleased to support Dr. Handforth and this cutting-edge research with a nearly $20,000 grant. “The significance of this work is two-fold,” says Dr. Handforth. “First, finding that CBD suppresses tremor in an animal model may provide justification for a clinical trial of CBD for essential tremor in humans. Second and more importantly, if we can understand how CBD stops the tremor, what mechanisms are at work, then an ET-specific medication could be developed that would be better-tolerated and more effective than what it available today.”
An ET-specific medication would impact millions of people around the world who have this life-altering condition but who don’t respond to the medications that are currently available. An ET-specific medication would be a life-changer for millions of men, women and children today and for generations to come.
Cannabidiol Anti-Tremor Action & Mechanisms – Conclusion
Principle Investigator: Adrian Handforth, MD
Cannabis, also known as marijuana, has been used for medicinal purposes for thousands of years. However, by federal law, the possession of cannabis is illegal in the United States, except within approved research settings; however, a growing number of states, territories, and the District of Columbia have enacted laws to legalize its medical use.
The U.S. Food and Drug Administration (FDA) has not approved cannabis as a treatment for any medical condition. However, the chemical components in cannabis are being studied. It is well known that certain chemicals in cannabis activate specific receptors throughout the body and these chemicals may be useful in treating neurological conditions, like ET. In this study, Dr. Handforth is looking at a specific chemical called Cannabidiol. Cannabidiol (CBD) is one of at least 113 active chemicals (also known as cannabinoids) identified in cannabis. However, CBD does not produce any intoxicating effects or alteration in mood. For years it was thought to be a benign and unimportant part of the plant. Now it is being investigated as a possible treatment option for ET.
In this study, Dr. Handforth aimed to show CBD can suppress tremor in animal models. If successful, it would offer justification for further study of CBD in humans. First, the study had to determine what effects CBD would have on mice impacted with harmaline–induced tremor. Then, if reduced, the team had to discover how CBD suppressed the tremor.
Testing a variety of doses, Dr. Handforth was able to note a robust suppression of tremor in the mice given CBD, without the animals showing any signs of impairment or sedation. Next, the team worked to discover what receptors in the brain might be involved in the noted effects. After looking at several options the information suggests that CBD activates the 5HT1a receptors to suppress tremor by activating the TRPV1 receptor.
Although the finding is clear with this model in mice, the extrapolation to human ET is tentative and would ultimately require validation in trials with the suggested therapies. So the findings are only suggestive at this time.