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Previously published on: civilized.life.com

Cannabis could be the key to treating traumatic brain injuries (TBI) that are taking their toll on the lives of professional athletes and Americans in general. TBI is a public health issue that’s not going to go away no matter how much the NFL wishes it would. Football is the most popular sport in the US, but in the last few years, it’s been hard to watch games and not consider the damage done to the players’ brains.

But sport-related TBI doesn’t just affect NFL players. Estimates suggest that each year, between 1.6 and 3.8 million individuals suffer a sport-related TBI in the United States alone. And since many instances of TBI go unreported due to patients failing to seek medical care, the exact number of cases is unknown, but experts estimate that 42 million people suffer from TBI every year.

Individuals serving in the military are especially vulnerable. Roughly 17% of deployed troops in Operation Iraqi Freedom and Operation Enduring Freedom reported a TBI during deployment, and 59% had multiple TBIs. That’s a huge problem because TBI carries a massive $76.5 billion economic burden with unaccountable emotional costs.

But scientists are learning that the brain’s cannabinoid system is a powerful tool for handling TBIs, which means cannabis could become a promising treatment strategy for treating the debilitating condition.

How the damage occurs

The damage done to the brain by physical trauma doesn’t end with the initial impact. In fact, much of the damage occurs in the minutes and hours following the physical injury. The physical trauma itself triggers a series of harmful molecular and cellular events that lead to a damaging secondary injury. Dampening the delayed response to the physical trauma improves cognitive and behavioral outcomes after a TBI (Hint: that’s where cannabis comes in).

The secondary injuries occur in an active process that involves many cellular pathways that fall into three main categories.

1) Increase in excitatory neurotransmitter release: There’s a massive increase in the release of excitatory brain-signaling chemicals called neurotransmitters. In an uninjured brain, the release of excitatory neurotransmitters, called glutamate, is highly regulated because too much glutamate kills brain cells. In TBI, the increase in glutamate can lead to braincell death.

2) Increase in reactive oxygen species: After TBI, there’s an increase in chemicals called reactive oxygen species, which can wreak havoc on brain cells by damaging your DNA, impairing protein function, and even causing cell death. You’ve undoubtedly heard of antioxidants which can neutralize reactive oxygen species. But after a TBI, the brain becomes so overwhelmed with reactive oxygen species that wolfing down blueberries won’t be sufficient.

3) Increase in brain inflammation: TBI increases inflammatory proteins called cytokines. These cytokines have wide-ranging effects and can have long-term impacts on how braincells behave. Research is revealing that activating the body’s endogenous cannabinoid system can reduce the damaging effects of each of these three consequences of TBI, and thereby improve functional outcomes.

A role for the endocannabinoid system

The two primary endocannabinoid receptors in the brain, Type I and Type II (CB1 and CB2), both play roles in reducing the extent of injury after head trauma. Normally, there are far more CB1 receptors than CB2 receptors in the brain. However, after injury the number of CB2 receptors jumps. A recent report revealed that activating these CB2 receptors reduces brain inflammation largely by both preventing the activity of pro-inflammatory cells (i.e., M1 macrophages) and enhancing the activity of anti-inflammatory cells (i.e., M2 macrophages). Further, activating CB2 receptors reduces the amount of braincell death following injury. So it’s not surprising that activating these CB2 receptors improves many behavioral outcomes after TBI, such as balance, coordination and managing anxiety.

CB2 receptors’ protective effects are largely reached via reducing brain inflammation. CB1 receptor activation also protects the brain from further injury by reducing the amount of excitatory neurotransmitter release, thus preventing the cascade of events that lead to cell death. Activating the CB1 receptor also blocks the expression of pro-inflammatory genes and reduces reactive-oxygen species. Together, these effects make braincells more resilient in the face of a myriad of post-trauma cellular events.

How cannabis could help

In a healthy brain, the body’s endogenous cannabinoid signaling mechanisms generally function in an on-demand manner; they’re used when they’re needed. In an injured brain, however, things can get out of whack.

Supplementing endogenous cannabinoid signaling with exogenous cannabinoids, such as those found in cannabis, could help protect the brain from injury by activating CB1 and CB2 receptions. Numerous retired NFL players have already come forward to describe the benefits of medicinal cannabis with regards to brain injury and pain. Although more research is needed to substantiate such anecdotal evidence, the accounts from athletes are promising.

They also raise the question of whether cannabis could be used as a neuroprotectant prior to injury. This is a largely unexplored area of research but there’s evidence that low amounts of THC have a neuroprotective effect against brain injury caused by the toxicity of excessive excitatory neurotransmitter release. So THC could protect the brain if consumed one week prior to the injury or within three days afterward.

One of the challenges faced by those using THC-rich cannabis to treat or protect against brain injury is the issue of drug tolerance. Tolerance to THC means that it will no longer work as effectively as a neuroprotectant in brain injury. However, tolerance is less of an issue when low levels of the drug are used, and as stated above, low THC levels may be more effective than higher levels.

Cannabidiol (CBD), a prevalent non-psychoactive cannabinoid in cannabis, may also have protective benefits without inducing tolerance. One study looking at the protective benefits of CBD and THC found that CBD had a stronger protective effect without inducing the tolerance associated with THC use. Further, they found that CBD was a potent antioxidant, which reduced the amount of damaging reactive oxygen species.

The long-term consequences of traumatic brain injury

The damage to the brain caused by TBI continues long after the physical injury. TBI increases risk for a number of devastating conditions such as stroke, early-onset dementia, and Alzheimer’s disease — conditions that cannabis (especially CBD) could treat, according to recent studies. CBD has been shown to reduce inflammation and damage to braincells that provide nourishment, support, and maintain homeostasis in the brain. CBD can also promote neuron growth and development (a process called neurogenesis) in the hippocampus, an important brain region for learning and memory. The hippocampus is one of the first regions to show impairment in Alzheimer’s disease and is often impaired in dementia, thus indicating an additional mechanism in which CBD may provide beneficial effects.

Scientists are continuing to unravel the mechanisms by which TBI leads to neurodegenerative diseases later in life. But given the prevalence of TBI in sports and other walks of life, and considering there are few effective neuroprotective treatments available right now, don’t be surprised if cannabis gets an increasing amount of attention in 2018 and beyond.

Josh Kaplan, Ph.D. is a neuroscientist at the University of Washington and freelance science writer specializing in the science of cannabis. Visit neurokaplan.com to learn more.