Prized Fighter Turned Parkinson’s Patient: Muhammad Ali’s Last Fight
“I shook up the world. Me! Whee!” — Muhammad Ali (1942-2016)
Indeed, Ali was and still is considered the G.O.A.T. (Greatest of All Time) in heavyweight boxing. In his prime, he turned the game upside down and continued to shake things up throughout his career. However, when the world saw their once invincible legend with progressively shakier hands, worsening motor control and crippling spirit, the world realized he was fighting a losing battle and the grim reality of Parkinson’s disease (PD) started making headlines around the world. While a cure for PD continues to elude scientists, treatment can significantly improve quality of life and manage symptoms of the disease—especially with cannabis.
What Is Parkinson’s disease?
Parkinson’s disease is a progressive illness characterized by a loss of 50-70% of dopamine neurons—primarily in the substantia nigra (SN), the part of the brain dealing with movement and motor functions.1 Loss of dopamine signaling “leads to a functional change in the complex circuitry of the basal ganglia, which results in an excessive inhibition of motor systems”.1,2 This eventually causes the classic signs of Parkinson’s, such as the tremors (also known as the “shakes”) witnessed in patients such as Muhammad Ali. Cannabis and the endocannabinoid system have been implicated in a wide range of disorders. The same is true for Parkinson’s Disease, as there is promise in cannabinoid treatment for these patients.
High Levels of Endocannabinoid Receptors in Brain Region Affecting Movement
The rapidly expanding field of endocannabinoid and cannabis science has revealed much about its extensive role in just about every major biological function, from mood and memory to motor control, as in the case of Parkinson’s disease. 3 CB1 receptors in the brain are, among other things, often associated with the psychoactive effects of cannabis (the high). 4 However, they are also present in high levels in the parts of the brain, such as the basal ganglia, where these dopamine neurons are dying as a result of the disease. Because of this high density of CB1 receptors and endocannabinoids found in the basal ganglia, there is promise that cannabinoid targets may be useful in treating PD.1
The Complexity of Endocannabinoid Pharmacology Extends Beyond the eCS
One of the most intriguing things about cannabinoid and endocannabinoid pharmacology is that the signaling systems also entail multiple other, non-cannabinoid pathways in the body. In the instance of the endocannabinoid signaling in the basal ganglia, a 2008 study investigating the endocannabinoid system in Parkinson’s Disease made the following observation:
“The components of the endocannabinoid (ECB) system are highly expressed at different levels in the basal ganglia neural circuit where they bidirectionally interact with dopaminergic, glutamatergic and GABAergic signaling systems.” 5
The Pieces Are There, Now We Must Put Them Together
To simplify, the body’s very own cannabis-like compounds it intrinsically and naturally creates does not solely act upon its respected endocannabinoid receptors. In this case alone, it has modulating effects all the way from GABAergic to dopaminergic and glutamatergic signaling systems (all three of which are distinct receptor systems from the ECB system). Additionally, endocannabinoid signaling is one of the only neurotransmitter systems that is “lipid-based” or “fat-based”; interestingly enough, studies have shown “lipids as central players in this disease.” 6 Thus, there is concrete evidence that our body’s own cannabinoids play a role in this deadly and progressive neurodegenerative disease. It is only with further scientific research and clinical testing that we can truly begin to piece together effective treatments and therapies.
The Good News: We Already Have a Head Start on Completing This Puzzle
It was briefly mentioned that endocannabinoids have a “bidirectional” effect on multiple receptor systems in Parkinson’s disease. While this certainly complicates the process of understanding, we also have some brilliant scientists working to figure out how all this works!
A groundbreaking 2007 study in Nature, the most prestigious and highly acclaimed scientific journal today, found the following to be true: “endocannabinoid-mediated depression of indirect-pathway synapses has a critical role in the control of movement.” 7 This means that endocannabinoid signaling in the form of suppressing other types of cell signaling has a critical role in the control of movement and motor function.
Digging deeper into the study, we realize that: “In models of Parkinson’s disease, indirect-pathway eCB-LTD is absent but is rescued by a D2 receptor agonist or inhibitors of endocannabinoid degradation.” 7 In English: Parkinson’s patients can benefit by using a dopamine receptor agonist or a compound that prevents the degradation of the body’s own cannabis-like molecules, endocannabinoids.
Personalized & Preventative Medicine in the Context of Parkinson’s Disease
Since Parkinson’s is genetic, it’s quite possible the future of personalized medicine will include the use of supplementing with certain cannabinoids from an early age to prevent something like Parkinson’s later in life, should such a patient be genetically predisposed to the illness as per certain genetic markers discovered at birth. I personally lost my grandfather to Parkinson’s, and could benefit from genetic testing that examines markers for dopamine and cannabinoid genetic markers to develop an effective prophylactic therapy. In the future, patients with family history of genetic illness can supplement their bodies with compounds they may be predisposed to be deficient in; cannabinoids are poised to be major players in the future of preventative care.8,9
To learn more about the future of personalized medicine and the role of medical cannabis, click here.
Promising Studies Warrant Further Research and Clinical Trials
After years of research, many signs have pointed to a clear role between the body’s intrinsic cannabis-like signaling system and the development and progression of Parkinson’s disease.3,5,7,10 The results suggest a wide range of possible therapeutic targets, some of which include using CBD to help treat the condition, as well as for its “neuroprotective” effects against this vicious, neurodegenerative disorder.10,11 At the moment, research in the US is stalled due to federally prohibitive regulations regarding cannabis. However, other countries are not bound by such archaic policies, and it is this author’s hope that breakthroughs in cannabis and cannabinoid therapy may indeed sprout up more quickly as more progressive policies are enacted around the world, allowing cannabis research to progress, unencumbered, and provide the medicines and treatments we all have the right to.
Special Thanks to Time Magazine for the featured image of Muhammad Ali in this article!
About the Author: Gaurav Dubey holds his Master’s in Biotechnology, and has publications in the field of stem cell research and transplant medicine. Combining his experience as a scientist with his passion for creative writing and medical cannabis, he actively contributes for several clients in the cannabis industry, including: The Medical Cannabis Community, Green Flower Media, Midwest Compassion Care, and Bloom Medicinals. Recently, he launched his first company, Karmik, LLC, which provides high-quality, evidence-based content marketing solutions. Karmik aims to restore credibility to the internet by publishing resourceful and trustworthy content that empowers the reader with enlightening, science-based information.
- Chaves-Kirsten, G. P. et al. Temporal Changes of CB1 Cannabinoid Receptor in the Basal Ganglia as a Possible Structure-Specific Plasticity Process in 6-OHDA Lesioned Rats. PLoS ONE 8, (2013).
- Alexander, G. E. & Crutcher, M. D. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 13, 266–271 (1990).
- Lotan, I., Treves, T. A., Roditi, Y. & Djaldetti, R. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clin. Neuropharmacol. 37, 41–44 (2014).
- Russo, E. B. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol. 163, 1344–1364 (2011).
- Di Filippo, M. et al. The endocannabinoid system in Parkinson’s disease. Curr. Pharm. Des. 14, 2337–2347 (2008).
- Xicoy, H., Wieringa, B. & Martens, G. J. M. The Role of Lipids in Parkinson’s Disease. Cells 8, (2019).
- Kreitzer, A. C. & Malenka, R. C. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s disease models. Nature 445, 643–647 (2007).
- Chan, I. S. & Ginsburg, G. S. Personalized medicine: progress and promise. Annu. Rev. Genomics Hum. Genet. 12, 217–244 (2011).
- Flores, M., Glusman, G., Brogaard, K., Price, N. D. & Hood, L. P4 medicine: how systems medicine will transform the healthcare sector and society. Pers. Med. 10, 565–576 (2013).
- Chagas, M. H. N. et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J. Psychopharmacol. Oxf. Engl. 28, 1088–1098 (2014).
- Iuvone, T., Esposito, G., De Filippis, D., Scuderi, C. & Steardo, L. Cannabidiol: a promising drug for neurodegenerative disorders? CNS Neurosci. Ther. 15, 65–75 (2009).