Cannabis was considered medicine for thousands of years and only over the last eighty years has it been stigmatised as a ‘drug of abuse’. Thanks to countless scientists and their curiosity we now understand that the compounds in cannabis interact directly with a widespread and complex system named the Endocannabinoid System (ECS), which works to maintain homoeostasis (equilibrium) within our brains and bodies. Almost every physiologic process in the human body is affected by the ECS including our natural protective response to injury and inflammation.
The ECS was discovered as a result of scientists searching for the mechanism of action of tetrahydrocannabinol (THC). Working as a ‘key and lock’ mechanism, cannabinoid receptors (the ‘locks’) that sit in the cell membrane are activated by ‘key’ chemical compounds. The keys include endocannabinoids, compounds that we make internally, phytocannabinoids, compounds made by the cannabis plant and laboratory-derived synthetic cannabinoids, used mostly in research. When the cannabinoid activates the receptor by binding to it, a chemical reaction takes place in the cell, telling the cell to change its message. For instance, if a person suffering from pain uses cannabis medicine, pain is often minimised or eliminated. This happens because the brain cell alters the perception of pain in response to the activation of the cannabinoid receptor by the cannabinoids, which in turn tells the cell to stop sending the message of pain. Knowing where cannabinoid receptors are located allows us to understand the conditions that cannabis medicine can affect. In the brain the receptors are located in areas that control pain, nausea, vomiting, learning, stress, memory, appetite, motor coordination and higher cognitive function. In the body, cannabinoid receptors are mostly located in the gut, immune system and liver and are largely involved in regulation of inflammation.
When there is a traumatic brain injury (TBI), damage from the initial insult occurs followed by a number of secondary damage mechanisms. Injured brain cells release a neurotransmitter called glutamate, which is toxic to cells when it accumulates. This over-abundance of glutamate leads to a cascade of chemical reactions that produce even more compounds that further damage the brain. Brain injury also causes the release of chemicals that cause blood vessels to constrict, decreasing blood flow that leads to cell energy loss and cell death. Brain inflammation is triggered within hours of injury and adds to the massive destruction of brain cells. These multiple mechanisms that harm brain cells are the reasons why TBI is so difficult to treat. We need treatment that will address all of the different mechanisms, glutamate accumulation, decreased blood flow and inflammation, taking place in the injured brain.
Cannabis’ two major cannabinoids, THC (tetrahydrocannabinol) and CBD (cannabidiol) are responsible for the beneficial effects following TBI’s. Cannabinoids have been shown to act on the CB1 and CB2 receptors of the ECS, which in turn prevents release of pro-inflammatory cytokines after brain trauma. Activating the CB1 and CB2 receptors has been shown to stimulate the release of minocycline, which reduces brain swelling and neurological impairment and diffuses further injuries to the brain’s axons. Research shows that the ECS is activated immediately after injury. Endocannabinoids block the release of compounds that cause secondary damage to brain cells.
Endocannabinoids have been found to decrease intensity and duration of toxicity to brain cells and enhance brain cell survival after injury. Endocannabinoids are anti-inflammatory and antioxidant, so simply put, your brain makes self-protective endocannabinoids in response to injury with the goal of minimising cell damage and death in a multitude of ways. As both synthetic and plant cannabinoids mimic our endocannabinoids, researchers have investigated them to see if they can provide neuroprotection for TBI with promising results. From the 2004 study, Cannabinoids as neuroprotective agents in traumatic brain injury;
“Cannabinoids of all classes have the ability to protect neurons from a variety of insults that are believed to underlie delayed neuronal death after traumatic brain injury (TBI), including excitotoxicity, calcium influx, free radical formation and neuro-inflammation. The pathways and experimental models supporting a neuroprotective role for the various classes of cannabinoids are critically reviewed vis a vis their potential to support the development of a clinically viable neuroprotective agent for human TBI”.
This flow chart outlines the pathway of secondary damage from brain injury and the modulation of the resulting outcome via endocannabinoids. Negative signs correspond to a decrease in the respective effect, whereas positive signs correspond to an increase.
In a three-year retrospective review, Effect of Marijuana* Use on Outcomes in Traumatic Brain Injury (2014), adult patients presenting with TBI to a trauma centre with a positive THC screen at the time of TBI had decreased risk of death; 2.4% versus 11.5% for those who tested negative for THC. The three-year retrospective review of 446 separate cases of similarly injured patients highlighted to researchers that TBI patients who had a history of cannabis consumption possessed increased survival rates compared to non-consumers (97.6% survived surgery, versus 88.5% of those who didn’t consume cannabis).
“Our data suggest an important link between the presence of a positive THC screen and improved survival after TBI”, the researchers concluded. “With continued research, more information will be uncovered regarding the therapeutic potential of THC and further therapeutic interventions may be established”.
Many studies highlight the incredible neuroprotective role of cannabinoids. While effective therapies to treat ongoing TBI symptoms have been difficult to come by, thanks to researchers like Professor Yosef Sarne of Tel Aviv University, we’ve discovered Cannabis may prevent long-term brain damage by administering THC before or shortly after injury. Sarne and his team published their results in 2013, demonstrating that administering just a fraction of the amount of THC that would be found in a typical cannabis joint anywhere from one to seven days prior to, or one to three days after an injury, induces the biochemical processes necessary to protect critical brain cells while preserving long-term cognitive function.
Clinicians in jurisdictions where cannabis medicine is recognised and appreciated, see many patients struggling to recover from TBI and can attest that cannabis medicine has profound positive effects. Patients report restorative sleep, emotional balance and an overall sense of well-being with cannabis. Many report discontinuation of ineffective pharmaceutical medications that cause a multitude of unwanted and sometimes dangerous side effects. That being said, clinical trials using plant cannabinoids during the acute phase of injury are warranted. TBI patients should not have to suffer for months or years after the injury to reap the neuroprotective, antioxidant and anti-inflammatory benefits of cannabis. Researchers and clinicians need to be free to study cannabis compounds and dosing in humans so that with early treatment, we can minimise and likely prevent the devastating consequences of TBI.