The National Hockey League Alumni Association (herein “NHLAA”) recently entered into a partnership with Canopy Growth Company (“CGC” or “Canopy”). The Canopy-NHLAA collaboration will focus on exploring cannabis-based neurological treatments for athletes. The collaboration also seeks to “reduce reliance on highly-addictive opioids and other pharmaceutical painkillers.”
According to Canopy, their collaboration with the NHLAA represents “a transformative clinical research partnership that will investigate the efficacy of cannabinoids as an integral part of a novel treatment for post-concussion neurological diseases in former NHL players.” The study, led by Dr. Amin Kassam, a neurosurgeon at NEEKA Healthcare, will focus on studying (1) how certain compounds from the cannabis plant can treat illnesses associated with concussions and (2) the medicinal value of cannabis when combined with other proven treatments.
In particular, the Canopy-NHLAA collaboration will investigate Cannabidiol (CBD) (Figure 1), which is a compound from the cannabis plant that is believed to provide substantial medicinal benefits without the intoxicating effects or “high” often associated with cannabis.
NHL Alumni Association Director Glenn Healy reacted to the Canopy-NHLAA partnership, saying “To me this is hope and this is help for players.” Mr. Healy explained that the hardest part of his job has been receiving calls from players’ families as they cope with the neurological consequences of years on the ice. “As of today, with this partnership,” he promised, “We are going to have science to back those answers.”
Canopy Growth founder and co-chief executive Bruce Linton hopes that the star-power of the NHL players will build better awareness for what medical cannabis has to offer: “This is something you couldn’t believe even six months ago,” said Mr. Linton, “These are real players, the main guys, who are here because they want answers about their health. This is a pretty big deal.”
According to an article written by Jeff Lagerquist of Yahoo Finance, the Canopy-NHLAA partnership will begin with a double-blind clinical trial involving about 100 former hockey stars and is aimed to reduce reliance on highly-addictive opioids and other pharmaceutical painkillers. Canopy has not made any statements explaining how an initial focus on reducing opioid dependence supports their goal of “exploring cannabis-based neurological treatments for athletes.”
New Appreciation for Brain Damage in Athletes
Canopy’s collaboration with the NHLAA comes shortly after several groundbreaking studies demonstrating a disturbingly high incidence of brain damage amongst athletes in certain sports. These studies highlight the strong correlation between (A) participation in sports with a high incidence of head trauma, such as hockey or football and (B) a high risk of developing brain damage.
In 2017, Boston University scientists published a study in the Journal of the American Medical Association showing that 99% of NFL players studied exhibited features of chronic traumatic encephalopathy (CTE, see below).1 The authors of that study opined that the high incidence of CTE in former football players “may be related to prior participation in football.” Other evidence indicates that athletes in other sports are also at risk for CTE. For example, professional hockey players are at risk for CTE as a result of the high incidence of head trauma amidst players in the NHL.
In late 2018, three hundred NHL players settled a lawsuit with the NHL, in which the players asserted that the NHL did little to warn them about the risks and the long-term effects of repeat concussions.
CTE is a degenerative brain disease found in athletes, military veterans, and others with a history of repetitive brain trauma. Some symptoms of CTE include impulse control problems, aggression, depression, and paranoia. As the disease progresses, some CTE patients may experience problems with thinking and memory, including memory loss, confusion, impaired judgment, and eventually progressive dementia. Researchers estimate that between 1.6 and 3.8 million athletes suffer a sports-related concussion each year, and 10 to 15 percent go on to develop symptoms that can affect their ability to function.
Cannabis Appears to Mitigate Damage Caused by Traumatic Brain Injury
A 2014 study found that traumatic brain injury (TBI) patients who tested positive for THC were more likely to survive with less impairment than TBI patients who abstained from marijuana.2 Mounting experimental evidence suggests cannabis, compounds thereof, or both may work to mitigate brain damage by reducing inflammation and vasoconstriction via modulation of a variety of receptors.3-11 One way cannabinoids may be accomplishing this by interrupting or decreasing the cascade of damaging secondary compounds that are triggered after a TBI.
Cannabinoid receptors type 1 and 2 (also known as CB1R and CB2R) are of particular interest to researchers. This interest stems from the ubiquitous presence of these receptors in the central nervous system (CB1) and the tissues of the immune system (CB2) and their implication in multiple pathophysiological states.11
In 2011, researchers studied how modulation of the CB1R in a mouse model affected aspects of neuroinflammation from TBI.6 The results showed that selectively activating CB1R had neuroprotective effects and was associated with “recovery of acute motor and exploratory deficits.” In another mouse TBI study, researchers used a CB2R agonist to examine the role of the receptor in blood-brain barrier damage and neurodegeneration.7 Stimulation of the CB2R receptor with the agonist reduced the number of degenerated neurons in the brains of the mice compared to the controls. Also, the treated mice had less disruption of the blood-brain barrier in their brains (as indicated by the uptake of sodium fluorescein) and reduced numbers of immune system inflammation indicators in their neural tissues. Additional research in 2015 confirmed the involvement of CB1R and CB2R in the neurological deficit and brain edema resulting from TBI in mice.8
In sum, consuming cannabis appears to mitigate the adverse effects of traumatic brain injury. In other words, a cannabis user sustaining head trauma would be less likely to develop lasting brain damage compared to an equally situated person who does not use cannabis. While the cannabis plant contains hundreds of different molecules, the scientific community appears to attribute some of the beneficial effects to the cannabinoid CBD. It is unclear whether CBD is solely responsible for mitigating brain damage or whether its benefits arise from synergy with other components of the cannabis plant. See Entourage Effect.
While the molecules in cannabis (e.g., CBD) have been identified as potential agents for preventing brain damage following head trauma, there is no evidence that these molecules repair damage after it has occurred. Accordingly, preventing long term brain damage would probably require administering cannabis-based medicine shortly after the head trauma occurs.
The Future of Canopy’s “Medical Cannabis” and “Cannabis-based” Treatments
What should we expect from Canopy’s development of “cannabis-based” neurological treatments? All publicly available information point to Canopy developing cannabinoid formulations. In other words, Canopy will probably develop formulated products that combine specific amounts of particular cannabinoids. Rolling Stone recently highlighted the advantages of formulated cannabis products. Specifically, formulated cannabis products provide the patient with advantages over naturally occurring cannabis. Additionally, from Canopy’s perspective, these compositions could be patented whereas the cannabis plant cannot.
Advantages of Cannabis Formulations Versus Natural Cannabis
Consuming cannabis is already a known treatment for head trauma and CTE. Canopy’s Chief Medical Officer Dr. Mark Ware notes “We know that many athletes are already self-medicating with cannabis and its derivatives in an attempt to reduce both the physical and emotional consequences of head injury.” Many professional athletes are outspoken about their medicinal use of cannabis. Aside from providing scientific support for an existing treatment, why is Canopy interested in researching “cannabis-based” treatments for head trauma?
Canopy’s “Focus on Intellectual Property” Suggests Cannabis Formulations
Canopy’s previous investments in intellectual property indicate that their development of “cannabis-based” neurological treatments for athletes will focus on creating proprietary cannabinoid formulations. Unlike natural cannabis, cannabis formulations are products of human engineering. Accordingly, these new formulations could be distinguished from natural cannabis and patented as new compositions of matter. The following facts suggest that Canopy is pursuing proprietary cannabis formulations:
- Canopy’s wholly owned subsidiary, Canopy Health Innovations, has devoted millions of dollars toward cutting edge research and IP development that can be commercialized.
- “Canopy Growth works with the Beckley Foundation and has launched Beckley Canopy Therapeutics to research and develop clinically validated cannabis-based medicines, with a strong focus on intellectual property protection.”
- In a deal described as creating “Canopy’s mote: Powered by ebbu,” Canopy Growth acquired ebbu Inc’s assets, including its patent portfolio.
- According to Canopy “ebbu’s IP portfolio will contribute to the clinical formulations program executed by Canopy Health Innovation.”
Given that Canopy is focused on creating “cannabis-based medicines, with a strong focus on intellectual property protection,” it stands to reason that their future R&D will focus on creating patentable formulations having particular “cannabinoids” and “certain compounds from the cannabis plant.”
Preventing Neurological Damage vs Regenerating Damaged Neurons
While some molecules in cannabis (e.g., CBD) have been identified as potential agents for preventing brain damage following head trauma, there is no evidence that these molecules repair damage after it has occurred. Accordingly, preventing long term brain damage would probably require administering cannabis-based medicine shortly after the subject sustains the head trauma. This is good news for today’s athletes. But it does not offer much hope to the athletes already suffering from brain damage. What can we do for those athletes?
Although further research is needed, the answer to repairing the damaged brain may come from another infamous naturally occurring organism: magic mushrooms. World-renowned mycologist Paul Stamets has invented “Compositions and methods for enhancing neuroregeneration and cognition by combining mushroom extracts containing active ingredients psilocin or psilocybin with erinacines or hericenones enhanced with niacin.” See US Patent Application Publication No. 20180021326. According to Mr. Stamets’ patent, combinations of various mushroom extracts “can synergistically repair and improve neurological function,” which he describes as “an important step in helping cognitive and motor skills, in particular, as humans age and/or when exposed to neurotoxins, stress or head trauma.” (emphasis added).
Conclusions – Today, Cannabis Formulations & Tomorrow Magic Mushroom Formulations?
Many athletes assume a substantial risk of brain damage because they experience frequent head trauma. Some of the molecules in cannabis (especially CBD) appear to have tremendous potential for reducing the risk of brain damage following head trauma. Canopy has recently collaborated with the NHL Alumni Association to explore cannabis-based medicines for athletes exposed to head trauma. For a variety of reasons, Canopy will probably focus on formulations having particular “cannabinoids” and “certain compounds from the cannabis plant.”
Based on the scientific evidence, cannabis-based medicines will probably provide the greatest benefit when administered shortly before and/or after the trauma. In other words, these medicines will focus on preventing brain damage for athletes suffering from head trauma. Treating the damaged brain would likely require an additional approach, such as using compositions comprising psilocybin derivatives. Given the near perfect analogy between cannabis and magic mushrooms, making formulated psilocybin products (not mushroom extracts) seems like a reasonable approach.
- Mez J, Daneshvar DH, Kiernan PT, et al. Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA. 2017;318(4):360-370. doi:10.1001/jama.2017.8334
- Nguyen BM, Kim D, Bricker S, et al. Effect of Marijuana Use on Outcomes in Traumatic Brain Injury. https://www.ingentaconnect.com/content/sesc/tas/2014/00000080/00000010/art00015. Published October 2014.
- Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury: therapeutic implications. Trends in Molecular Medicine. 2002;8(2):58-61. doi:10.1016/S1471-4914(02)02276-1
- van der Stelt M, Di Marzo V. Cannabinoid receptors and their role in neuroprotection. Neuromol Med. 2005;7(1):37-50. doi:10.1385/NMM:7:1-2:037
- Mechoulam R, Shohami E. Endocannabinoids and Traumatic Brain Injury. Mol Neurobiol. 2007;36(1):68-74. doi:10.1007/s12035-007-8008-6
- Elliott MB, Tuma RF, Amenta PS, Barbe MF, Jallo JI. Acute Effects of a Selective Cannabinoid-2 Receptor Agonist on Neuroinflammation in a Model of Traumatic Brain Injury. Journal of Neurotrauma. 2011;28(6):973-981. doi:10.1089/neu.2010.1672
- Amenta PS, Jallo JI, Tuma RF, Elliott MB. A cannabinoid type 2 receptor agonist attenuates blood-brain barrier damage and neurodegeneration in a murine model of traumatic brain injury. Journal of Neuroscience Research. 2012;90(12):2293-2305. doi:10.1002/jnr.23114
- Lopez-Rodriguez AB, Acaz-Fonseca E, Viveros M-P, Garcia-Segura LM. Changes in Cannabinoid Receptors, Aquaporin 4 and Vimentin Expression after Traumatic Brain Injury in Adolescent Male Mice. Association with Edema and Neurological Deficit. PLOS ONE. 2015;10(6):e0128782. doi:10.1371/journal.pone.0128782
- Lopez-Rodriguez AB, Mela V, Acaz-Fonseca E, Garcia-Segura LM, Viveros M-P. CB2 cannabinoid receptor is involved in the anti-inflammatory effects of leptin in a model of traumatic brain injury. Experimental Neurology. 2016;279:274-282. doi:10.1016/j.expneurol.2016.03.018
- Bisogno T, Oddi S, Piccoli A, Fazio D, Maccarrone M. Type-2 cannabinoid receptors in neurodegeneration. Pharmacological Research. 2016;111:721-730. doi:10.1016/j.phrs.2016.07.021
- Kendall DA, Yudowski GA. Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Front Cell Neurosci. 2017;10. doi:10.3389/fncel.2016.00294