Medical Cannabis and Parkinson’s Disease

Medical Cannabis and Parkinson’s Disease

Dopamine is a powerful neurotransmitter in the brain responsible for transmitting signals between neurons, and also aids in smooth muscle movement. While healthy bodies produce sufficient levels of dopamine deep in the brain, people with Parkinson’s Disease (PD) have decreased dopamine production, making it harder for their body to execute intentional muscle movements. Currently, levodopa-containing drugs are prescribed long-term to patients with PD, because it reduces motor symptoms by being converted to dopamine in the central nervous system and acting as a neurotransmitter. However, the chronic use of levodopa can cause levodopa-induced dyskinesia or involuntary and jerky movements. In order to combat those unwanted side effects, researchers have been tasked with the challenge of finding a suitable alternative that has an antidyskinetic effect while maintaining serum levels of dopamine in the brain. This is where medical cannabis comes into play. Research shows that cannabis increases dopamine levels in the body and therefore eases muscle tremors and dyskinesia. This phenomenon has been highlighted in research studies as an alternative to drugs containing levodopa that are currently used to manage symptoms of PD. These findings come with huge benefits for those suffering from levodopa-induced dyskinesia who are looking for something new. In this paper, the research question “In patients with Parkinson’s Disease, does the use of cannabinoids improve motor function better than levodopa containing drugs” will be explored.

Clinical Practice Past and Present

In Parkinson’s Disease, levels of dopamine are decreased from the progressive destruction of brain cells that are responsible for production of dopamine. One medication currently used to correct this imbalance is Levodopa. In the brain, Levodopa is converted into dopamine and acts as a neurotransmitter allowing for improved function of the movement control centers in the brain. More specifically, this drug is indicated as a therapy for slowness, stiffness and tremor. Upon diagnosis of Parkinson’s disease and evaluation of motor fluctuations, patients are prescribed a levodopa containing drug. Current recommendations include prescribing Carbidopa/Levodopa 25/100 (tablet), ½ tablet three times a day for one week and then 1 tab three times a day (Parkinson’s toolkit, 2011). Since this drug has to be taken several times per day, many individuals experience a rise and fall in their dopamine levels. This, combined with gradual loss of dopamine producing brain cells makes it extremely difficult to maintain a therapeutic level of dopamine in the brain. These fluctuations are believed to contribute to dyskinesia.

When it comes to medical intervention, one therapy has garnered a great amount of national attention in recent years; medical cannabis. Although many states have legalized the use of medical cannabis, the federal government is still hesitant in accepting their use. This leaves cannabis in the Schedule I substance category with other illegal drugs like cocaine and methamphetamine, despite the positive effects noted in clinical trials (Hanson & Garcia, 2018). Because of this, the amount of research related to medical cannabis and PD is limited, but the quality of research is not. If given time for more research to develop, there will be more information available for those looking to develop clinical practice guidelines for Parkinson’s disease and the use of medical cannabis in primary care. That being said, the research provided in this report may provide a preclinical platform for future research on this topic.

Research Process

Multiple search engines were used in order to collect research data directly related to cannabinoid therapy for patients with PD. These search engines included PubMed, EBSCOhost and ProQuest. Keywords used when searching these databases included: cannabinoids, cannabidiol, cannabis, Parkinson’s disease, dyskinesia and motor function. The John Hopkins Nursing Evidence-Based Practice Research Evidence Appraisal Tool was used to determine the type of research, level of evidence, quality rating and strength of research. The impact of this research and its relation to the research will be discussed in detail below. For each articles sample, sample size, setting, findings related to the topic, observable measures and limitations, please see the evaluation table in the appendix A.

Article One

This article summarizes the effects of cannabis and cannabinoids on motor dysfunction in basal ganglia movement disorders based on current clinical and experimental data. One of the authors main goals in this study was to provide research showing the different types of cannabis, their different routes of administration and the effects seen in human and nonhuman subjects diagnosed with PD.

This article looks at how cannabis can alleviate PD symptoms by consuming fresh or dried cannabis leaves by mouth, once a day. It also shows improvement in patients with levodopa-induced dyskinesia by 14.1%. When discussing a more specific drug, nabilone, researchers have seen decreased levodopa-induced dyskinesia and an increase in the duration of anti-parkinsonian action of levodopa by 76% in nonhuman primates.

This article provides relevant data that supports the use of cannabis related alternatives for those diagnosed with PD. Limitations for this article include the fact that the authors only reported on studies completed by other researchers, rather than completing their own research. If their own research was conducted, they would have been able to focus more on the effect of cannabis on motor function in patients with PD (Abdel-Salam, 2017).

Article Two

This article explores the potential for cannabis to enhance the quality of life in Parkinson’s patients in relation to motor and nonmotor symptoms. The authors reviewed any scientific evidence that specifies the potential use of cannabis (or related compounds) for the treatment of PD without adverse effects like dyskinesia, seen in those taking levodopa.

In a study of 339 participants using smoked cannabis, significant improvement of general PD symptoms were seen in 46% of the patients. Within this 46%, 31% of them reported improvement in resting tremor, 38% reported relief from rigidity, 45% defined reduced bradykinesia, and 14% reported improved dyskinesias. These symptoms were relieved for up to three hours following one dose of smoked cannabis. This review also elaborates on the benefit of cannabidiol and nabilone, both having the ability to improve dyskinesia.

Strengths of this article include the significant findings related to improved motor function for patients with PD while also describing the specific route of administration. Limitations found in this article include the authors ability to provide data on safety, pharmacokinetics and different drug interactions of cannabinoids. If this information was added, there would be less concerns with future dosing and adverse effects. In addition, it would be helpful to see a comparison of PD patients utilizing cannabis treatments to those taking levodopa on a less time restricted scale (Babayeva, Assefa, Basu, Chumki, & Loewy, 2016).

Article Three

 This article focuses on the role of cannabidiol and the neuroprotective effects seen in patients with PD. Many studies focus on the results seen in animal models of PD, however this study focuses on the effects of cannabidiol in humans. The researchers designed a double-blind clinical trial to assess the effects of cannabidiol in PD globally, including neurological assessments of motor and functional symptoms.

 Significant improvement in overall functioning and well-being was seen in patients treated with cannabidiol 300 mg/day compared to a group that received a placebo. In relations to effects on quality of life, patients experienced an improvement in daily life activities with a statistically significant improvement in emotional well-being and mobility.

Strengths of this article include the use of a double-blind study design, which increases the study’s reliability. Although significant results are seen in this study, the sample used was small which does not allow for definitive conclusions. Studies with larger samples with more specific PD symptoms studied would be beneficial. Other limitations include the absence of studying neurotransmitters other than dopamine that are affected by individuals with PD and how they are affected by cannabidiol. There also needs to be further research and understanding of the neuroprotective effects in individuals with PD who are on a regular cannabidiol regimen (Chagas et al., 2014).

Article Four

 This article investigates the measures of disability between PD and Multiple Sclerosis cannabis users and non-users by using a web-based survey hosted on the Michael J. Fox Foundation website. Because the positive and negative effects of cannabis use in PD are not fully known, the authors look to better clarify the positive effects of cannabis for individuals with PD. Here, the authors compared results of the web-based survey, looking specifically at the effects of cannabis on neurological disability.

 The authors found that about 44% of respondents with PD and Multiple Sclerosis currently use cannabis. These individuals self-report lower levels of disability compared to non-users. More than half of the current users (59%) reported reducing prescription medication since beginning cannabis use. When using the Nottingham Health profile, PD users reported an increase in physical abilities when compared to non-users. When using the Guy’s Neurological Disability Scale, PD users had a slightly better score for arm and hand function and improved mobility compared to non-users. The survey was viewed a total of 801 times. After eliminating those who did not have a PD or Multiple Sclerosis medical diagnosis, did not have accurate demographical information, did not provide consent, those who submitted the survey multiple times, and those who did not complete the entire survey, the final dataset came out to 538 surveys.

 Strengths of this article include the use of different assessment tests when determining the effectiveness of cannabis on patients with PD. Because different tests were used, the researchers were able to further clarify which therapies were more beneficial. Limitations of this study include the authors broad definition of cannabis. In future studies, cannabis use should be further categorized into either cannabidiol or tetrahydrocannabinol (THC). Another limitation is method of data collection, in that an open web-based survey allows anyone with access to the internet to participate but also limits participants to those who are somewhat familiar with the use of online tools (Kindred et al., 2017).

Article Five

 In this article, the authors conducted a systematic review aimed to provide a more in depth description on the effectiveness of cannabis on movement disorders in humans. Randomized controlled trials were included in this review if they compared and examined the use of cannabis for pharmacological therapy. Within this review were three studies (49 participants) on PD, all being double-blind study designs.

 Of the three studies reviewed, one found a significant 22% reduction in the Rush dyskinesia disability scale in the treatment group taking 0.03 mg/kg of nabilone. In the more recent Chagas et al. study, significant difference was found between the placebo and treatment groups using the Unified Parkinson’s Disease Rating Scale. This study randomized 21 patients with PD to receive 75 mg/day of cannabidiol, 300 mg/day of cannabidiol or a placebo and saw a significant improvement in activities of daily living for the 300 mg/day cannabidiol group.

        Strengths of this article include the different types of cannabis studied, and being able to compare an approved drug (nabilone) with one current seeking approval (cannabidiol). Limitations of this study include the limited knowledge of the specific mechanism of cannabis on the cellular level. If a more precise background is known, researchers could better understand the therapeutic benefits of cannabis for motor function in patients with PD. There is also a limited number of clinical trials studied and a lack of quantitative data which may reduce the reliability (Lim, Mei See, & Lee, 2017).

Conclusion

 Research shows that the use of medical cannabis for PD outshines the current levodopa therapy in eliminating dyskinesia. Dyskinesia is often a painful, bothersome side effect that often interferes with the individuals personal and social life. By implementing medical cannabis as an alternative for Levodopa, these individuals could reunite with activities and hobbies they used to love. This improve their quality of live, overall well-being and most importantly will improve individuals motor symptoms.

Appendix A

Appendix A

References

• Abdel-Salam, O. (2017). Chapter 95. Cannabis for basal ganglia disorders (Parkinson Disease and Huntington Disease). In Handbook of cannabis and related pathologies: Biology, pharmacology, diagnosis, and treatment. http://dx.doi.org/10.1016/B978-0-12-800756-3.00110-1
• Arizona Medical Marijuana Question. (2010). Retrieved from https://ballotpedia.org/Arizona_Medical_Marijuana_Question,_Proposition_203_(2010)
• Babayeva, M., Assefa, H., Basu, P., Chumki, S., & Loewy, Z. (2016, October 10). Cannabis compounds: A nonconventional approach to Parkinson’s Disease therapy. PD, 2016(), 1-19. http://dx.doi.org/10.1155/2016/1279042
• Chagas, M. N., Zuardi, A. W., Tumas, V., Pena-Pereira, M. A., Sobreira, E. T., Bergamaschi, M. M., … S Crippa, J. A. (2014). Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial. Journal of Psychopharmacology, 1-5. http://dx.doi.org/10.1177/0269881114550355
• Damlo, S. (2007, March 15). AAN Releases Recommendations on Treatment of Parkinson’s Disease. Retrieved from https://www.aafp.org/afp/2007/0315/p922.html
• Hanson, K., & Garcia, A. (2018, June 27). State Medical Marijuana Laws. Retrieved from http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx
• Kindred, J. H., Li, K., Ketelhut, N. B., Proessl, F., Fling, B. W., Honce, J. M., … Rudroff, T. (2017, July 7). Cannabis use in people with Parkinson’s disease and Multiple Sclerosis: A web-based investigation. Complementary Therapies in Medicine, 33, 99-104. http://dx.doi.org/10.1016/j.ctim.2017.07.002
• Lim, K., Mei See, Y., & Lee, J. (2017, July 6). A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clinical Psychopharmacology and Neuroscience, 15, 301-312. http://dx.doi.org/10.9758/cpn.2017.15.4.301
• Parkinson’s Toolkit. (2011, May). Retrieved from http://toolkit.parkinson.org/node/138