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Friday, October 6, 2017

Cannabinoids in Movement Disorders


Date: October 2017

Authors: Nestor Galvez-Jimenez, MD, MSc, MHA; Camilo Garcia, MD; Ramon Rodriguez, MD; Connie Marras, MD
Blog Editor: Stella Papa, MD




The use of cannabis for medical disorders is a global issue, whether or not the drug is legalized for general use, only for use in some medical disorders or not legal in any setting.  Where not legal, there is black market selling and purchasing and large scale use in many countries.  Social media has popularized the use of cannabis for many medical disorders, including pain, anxiety, wasting and appetite loss, all issues faced by our patients with movement disorders.  Laws in many countries are changing regarding the use of cannabis, prompting an influx of questions from many patients about its usefulness for them. Unfortunately, there is little evidence-based or even expert guidance for physicians.  Several American physicians offered thoughts on this controversial topic.  

Discussion

The use of cannabis for medical disorders is a global issue, whether or not the drug is legalized for general use, only for use in some medical disorders or not legal in any setting.  Where not legal, there is black market selling and purchasing and large scale use in many countries.  Social media has popularized the use of cannabis for many medical disorders, including pain, anxiety, wasting and appetite loss, all issues faced by our patients with movement disorders.  Laws in many countries are changing regarding the use of cannabis, prompting an influx of questions from many patients about its usefulness for them. Unfortunately, there is little evidence-based or even expert guidance for physicians.  Several American physicians offered thoughts on this controversial topic.
Have patients asked you about the use of marijuana for the treatment of movement disorders?

Dr. Galvez-Jimenez:
To date, 29 states have approved the use of medical marijuana in the United States, Since its approval in my state, not a day goes by without having to answer the question about the therapeutic role of cannabis in Parkinson’s disease (PD). Surprisingly, it is not the children but rather the elderly patient who comes inquiring about the therapeutic virtues of cannabis.  Can it help me with tremor? What should I expect? Should I try it? Answers can only be provided with a very honest, non-judgmental and open mind approach coupled with the realities of evidence-based medicine. This insatiable thirst is compounded by the misconceptions many do have on the benefits of cannabis. The AAN and MDS members, and expert opinion papers on the subject matter made the point that there may be a role, albeit limited in the treatment of neurological conditions, and at present, there is no conclusive evidence for the use of marijuana in PD.  However, patients continue to show an interest in using these compounds.
Dr. Rodriguez:
As Dr. Galvez Jimenez mentioned, the widespread legalization of marijuana in many states have both raised the curiosity and provided hope to many suffering from intractable medical disorders. The issue of using cannabis has become a daily question in my medical practice as well. Patients with PD, parkinsonian syndromes and dystonia, in particular, have been inquiring about the potential role of cannabis in the treatment of their particular conditions.  In my experience, patients with PD have been very interested and eager to try the therapy.  However, I make it very clear to them that there is no conclusive research or recommendations from the major medical organizations about the use of medical marijuana for the treatment of PD and other movement disorders.  More interestingly, patients are not inquiring about using medical marijuana for the disease itself but rather to control particular symptoms. And most patients became interested in using medical marijuana with a suggestion made by one of their children or younger family members. My impression is that most patients with PD nowadays are baby boomers, which may have seen marijuana as a common thing during their youth and do not seem skeptical about it. I also inquire how they became more informed about medical marijuana, and the most common answer is “I googled information about medical marijuana for PD”, alerting about the important role of the doctor providing current and unbiased information to patients.  
Once the patient asked you about marijuana, how do you approach the topic?

Dr. Galvez-Jimenez:
I begin the discussion by providing a simple neurobiological explanation on the existence of cannabinoid receptors and internal or endogenous production of such compounds in the central nervous system, particularly the presence of such receptors in abundance in the basal ganglia, one of the areas we focus on patients who have PD. I further explain the influences of the endocannabinoid system on multiple brain functions such as cognition, mood, memory, pain, motor behavior, and others. I do emphasize this is not a new discovery since the endocannabinoid system has been under study for decades, and the use of marijuana has been associated with several neuropsychiatric symptoms.  Furthermore, I do state that cannabinoids based drugs such as nabilone and dronabinol have been used extensively to treat nausea and vomiting in the context of chemotherapy.  And importantly, I mention the conditions that have been recommended by the AAN and Expert consensus review by MDS members. I also emphasize that notwithstanding the societal approval in Florida and other states for the use of medical marijuana, authorities continue to work on deciding how to regulate its medical use, what conditions will be “approved” for use, and physicians must decide if they want to be involved and certified in such care.
Dr. Rodriguez:
The first thing I tried to explain to them is that the use of medical marijuana is not currently approved for the treatment of PD. I also make the comment that nowadays it is very easy to create a “fancy and glossy brochure” about anything, and it is important to discuss this issue with their doctor. I follow this with letting them know that I personally do not have any opposition for them to try medical marijuana. However, we need to have an open discussion about the real benefits of medical marijuana, the actual medical recommendations from experts, and at times how it can be accessed.  Regarding the access to marijuana, there are important points to discuss. Products that can be purchased in some health food stores containing CBD, one of the neuroactive substances in marijuana, are reported by patients to produce mild improvement of symptoms, in particular tremor and anxiety. The problem is that all these products are different, there is no way to standardize the dosages, and we truly do not know how much patients are ingesting. Some patients also decide to travel to states where the use of medical marijuana has been present longer, looking for other alternatives on how to consume the substance. Unfortunately, they end up in “street clinics” with no licensed certified healthcare providers recommending products (“brownies” and other candies with marijuana). All these products create the same problems of non-standardized treatments. 
In which conditions or symptoms have cannabinoids been reported to have some use, according to the American Academy of Neurology?

Dr. Galvez Jimenez:
According to the AAN Guideline Development Subcommittee, cannabinoids may be effective in Multiple Sclerosis, central pain and spasms. However there is insufficient evidence for the use for dyskinesias in PD, HD, tics or dystonia.  I do emphasize this latter point. However, many patients, despite the evidence, still prefer to try. It is important to keep in mind the local, state or national rules and consensus, if any, on the approved use of these medications when addressing or answering some of these questions. In some states, there is a long list of conditions for approved used of cannabinoids, but in many conditions there is insufficient evidence to support its use. Also it is important to clearly understand the rules and regulations. In most states where the program exists, neurologists must have a certification to dispense such drugs. Importantly, not all institutions will be willing to allow their employed or affiliated physicians to prescribe such compounds.
What are the common complaints that patients with PD hope cannabis alleviates and what do you tell patients who insist on using these medications?

Dr. Galvez-Jimenez:
In my experience, tremor is by far the symptom that patients with PD most often hope that cannabis will improve. I emphasize to patients that the role of cannabis for PD has not been conclusively established. I educate them explaining that at the moment the two compounds most commonly used are CBD (cannabinoid) and less so THC (tetrahydrocannabinol). The latter with its psycho-affective effects usually control symptoms not by direct motor control but rather by “providing a calming or psychological effect”.  It is also important to make clear to the patients wishing to do so, the need to find a reputable and reliable company or distributor who can guarantee what the product is. Eatables, chewable, skin oil lotions and vaporizers are not suitable for a reliable delivery of the compound, and more importantly what compound and dose is actually provided is variable.  Most studies were based on the use of CBD and in doses of up to 300 mg a day avoiding using THC. Most providers or distributors may be able to isolate the active chemicals from the marijuana leaf; however, the quantity of such elements may be quite variable, and there is no regulation by an independent agency on the quality of the products. Some dispensaries do provide combinations of CBD with THC, with CBD in higher concentrations or doses than THC. Some of these are used or recommended by those who have been providing these substances in the past for both the psycho-affective effect and the motor component, for example.
Dr. Rodriguez:
Probably the most common symptom patients inquire about is the treatment of medication refractory resting tremor. Another symptom that triggers the question is the presence of levodopa induced dyskinesias.  I believe the reason for this is the viral spread of videos of patients with PD and severe dyskinesias demonstrating a significant improvement after using what seems to be the oil form of CBD.  Frequent motor fluctuations are another cause.
Do you think there will be a role for medical marijuana in PD and movement disorders?

Dr. Rodriguez:
The use of marijuana for medical purposes is not new, and there seems to be evidence for the use of marijuana as a medical treatment in ancient civilizations.  Judging by the anecdotal experience of some of my patients, I believe that medical marijuana may play a role in those patients suffering from severe anxiety and having symptoms easily exacerbated by anxiety, such as tremors and dyskinesias, a common occurrence in movement disorders.  Also, the drug may provide a sense of “well-being” to some of them, which can be of benefit especially to those suffering from severe motor fluctuations or dyskinesias. Research suggests that the ratio of THC to CBD can be important in the effect that people will obtain from the therapy, and these are issues that still need to be addressed.  In the meantime, efforts should be directed toward performing more research to answer key questions about the effects of marijuana in PD and other movement disorders.
Is marijuana, CBD or THC useful for epilepsy or movement disorders related to epilepsy?

Dr. Garcia:
Several epileptic disorders have been initially interpreted as possible movement disorders. This is the case of facio-brachial dystonic seizures that have been described in the movement disorders and epilepsy literature. Myoclonic abnormal movements could be initially diagnosed as movement disorders and the etiology may be epileptic in nature as well. In fact, antiepileptic medications are used for different movement disorders. Therefore, there is an overlap of manifestations of movement disorders and epilepsy conditions. The compounds CBD and THC have already been studied in animal models and are currently under research in humans. Thus far there is no strong evidence supporting these new therapies as effective for adult patients with epilepsy.  In contrast, in the pediatric population, there is some evidence of improvement of the seizure frequency in patients with Dravet and Lennox Gastaut syndromes.
The American Epilepsy Society is committed to supporting research in this field, and given the uncertainty of the available knowledge, it “urges all people touched by epilepsy to consult with an epilepsy specialist to explore the existing treatment options, so that they can make informed decisions with their specialist that weighs the risks and benefits of the different treatment options”. Currently there is a great interest in the professional community to explore these new possible treatments, and new CBD compounds are being studied. CBD may show better results than expected as it has been proven in pediatric patients; however, until better evidence shows clear results physicians should be informed and share information with patients in order to make the best decision for and with the patient. 

http://www.movementdisorders.org/MDS/Scientific-Issues-Committee-Blog/Cannabinoids-in-Movements-Disorders.htm

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