Roughly one million Americans are living with this incurable disease. Today’s treatments are masking some of the symptoms, but are overall proving to be ineffective in preventing the progression of Parkinson’s Disease (PD). Over the past few years, cannabis has become a drug target to ameliorate some of the symptoms of this disease.
With the rise in legalization of both medical and recreational marijuana, its effects are becoming better understood. Cannabis has protective properties for many diseases and conditions, and its potential benefits for PD are gaining a lot of attention.
Although the people most affected by PD, the elderly, are stereotyped as anti-marijuana, its popularity and acceptance is growing. Components of cannabis can directly target receptors to elicit a positive response, and bypass the high-inducing effects.
While there are many side effects of PD, tremors may be one of the most debilitating. In extreme conditions, tremors limit autonomy and disrupt the daily activities of individuals. Fortunately, there is hope for cannabinoids, a component of cannabis, as a treatment to reduce these involuntary motor symptoms in PD.
PD is one of the most progressive neurological disorders today. It results from the loss of dopaminergic neurons in the basal ganglia, a region of the brain. The loss of dopamine attributes to the motor disabilities in patients with PD; without this neurotransmitter, the brain has a harder time regulating smooth movement within the limbs7. The connection between the substantia nigra and the striatum, which can be seen in Figure 1., is responsible for this motor control.
It was estimated in 2015 that 1-2% of the worldwide population older than 65 have the disease. Its prevalence in the U.S. has increased over the last decade in males and females of all races, although males are 1.5-2 times more likely to get the disease7,9. Of the one million Americans living with PD, only 5-10% stem from familial-inheritance13.The rest of the cases, 90-95%, have an unknown cause of origin.
The most common symptoms and side effects of PD are tremors, bradykinesia, rigidity, dyskinesia, slurring words and inflammation. Currently, treatments for PD include deep brain stimulation and a variety of drugs featuring levodopa, the most effective medication for PD on the market. However, chronic use of levodopa can lead to dyskinesia (involuntary movements) or resistance to the drug9. Because of this discouraging reality, scientists and doctors have begun looking to medical marijuana and cannabinoids as a potential treatment.
Cannabinoids are compounds found in marijuana (Cannabis sativa). In addition to psychoactive components, cannabinoids also exhibit central nervous system and immune system benefits. The two main active components of cannabinoids are cannabidiol (CBD), which provides treatment without a “high”, and delta-9-tetrahydrocannabinol (THC), which does cause a “high” effect in large doses10. By blocking one of the cannabinoid receptors, THC shows promising signs of delaying the progression of PD and ameliorating some of the symptoms4. Cannabinoids have also been proven to show numerous neuroprotective properties in a few studies13. This leads scientists to believe they have the potential to alleviate the motor symptoms of PD.
PD causes detrimental effects in the areas of the brain responsible for movement, such as the basal ganglia. This can be seen in Figure 2. Endocannabinoids and cannabinoid receptors are found in these movement regions, which suggests the consumption of cannabis may target these damaged regions to alleviate PD symptoms5 and modulate motor function11.
With the increasing legalization of medicinal cannabis throughout the U.S., more studies and research will be done to see all the possibilities this drug has. PubMed, a database for scientific studies and publications relating to physiology, yields a handful of PD studies focusing on cannabis. We know that cannabis can elicit a relaxation response in the body– but how it does it do this?
Examining the scientific evidence
Trials done in mice have shown high success with alleviating tremor2 and delaying the progression of PD. However, there are not many published human trials out there yet. Human trials are slowly rising in participation rates, but the preclinical literature is robust.
Although there have been few controlled studies on the treatment of PD tremors with cannabinoids, some reports are promising. These trials are based on the idea that cannabinoids may protect cells in a region of the brain known as the basal ganglia, which is progressively destroyed over time in PD. For example, one small study evaluated 22 subjects with PD at baseline and 30 minutes after smoking cannabis. Using several questionnaires, surveys, and scales, the researchers were able to determine that the cannabis significantly improved not only tremor, but also rigidity and bradykinesia by 30.6%. These findings give researchers a reason to explore this possible treatment for PD. By manipulating CB1 and CB2 receptor functions and increasing endocannabinoids, PD management is possible1.
In another successful trial, 54 people who had been using cannabis for at least 3 months reported a mild or substantial alleviation of their parkinsonian tremor, among other symptoms. Interestingly, patients who had been using cannabis for less than 3 months felt less of a benefit. This suggests a correlation with time and effectiveness of treatment17.
On the contrary, some studies have found that cannabinoids binding to the CB1 receptor might actually worsen bradykinesia. However, blocking this receptor has a chance of reducing akinesia, the lack of voluntary movement3. These particular studies are done in mice, and in some trials in fruit flies. Therefore, more research is needed in humans.
What to think
Overall, it is evident that further clinical research is needed, specifically within randomized controlled trials. Within the few successful trials, a more concrete conclusion in the near future is promising. The current treatments for PD are not effective, and in some cases are somewhat detrimental. Treating PD symptoms such as tremor, bradykinesia, and rigidity with cannabinoids is therefore something that needs more focus.
The majority of the trials and research discussed here all come to the conclusion that cannabinoids do alleviate tremor, among other symptoms, in PD. While improvements might not be overwhelmingly significant, they point to possible future research and treatments.
The negative side effects of cannabis are few and far between, though some subjects complained of dizziness, drowsiness, palpitations, and bad taste12. For the most part, the improvements in tremor, bradykinesia, and rigidity heavily outweigh these negative side effects.
Patients that are suffering from PD should consult their doctor about the potential of cannabis as medicine to alleviate some of the symptoms.
- Arjmand, Shokouh, et al. “Cannabinoids and tremor induced by motor-related disorders: friend or foe?.” Neurotherapeutics4 (2015): 778-787.
- Baker, David, et al. “Cannabinoids control spasticity and tremor in a multiple sclerosis model.”Nature 6773 (2000): 84-87.
- Fernández-Ruiz, Javier, María A. Moro, and José Martínez-Orgado. “Cannabinoids in neurodegenerative disorders and stroke/brain trauma: from preclinical models to clinical applications.” Neurotherapeutics4 (2015): 793-806.
- Garcia, C., et al. “Symptom‐relieving and neuroprotective effects of the phytocannabinoid Δ9‐THCV in animal models of Parkinson’s disease.” British journal of pharmacology7 (2011): 1495-1506.
- Gómez-Gálvez, Yolanda, et al. “Potential of the cannabinoid CB 2 receptor as a pharmacological target against inflammation in Parkinson’s disease.”Progress in Neuro-Psychopharmacology and Biological Psychiatry 64 (2016): 200-208.
- Kluger, Benzi, et al. “The therapeutic potential of cannabinoids for movement disorders.” Movement Disorders3 (2015): 313-327.
- Lotan, Itay, et al. “Cannabis (Medical Marijuana) Treatment for Motor and Non–Motor Symptoms of Parkinson Disease: An Open-Label Observational Study.” Clinical neuropharmacology2 (2014): 41-44.
- More, Sandeep Vasant, and Dong-Kug Choi. “Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection.” Molecular neurodegeneration1 (2015): 17.
- Venderová, Kateřina, et al. “Survey on cannabis use in Parkinson’s disease: subjective improvement of motor symptoms.” Movement Disorders9 (2004): 1102-1106.