Cannabis was considered medicine for thousands of years and only over the last eighty years has it been stigmatized 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 homeostasis 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 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 minimized 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 overabundance 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.
Fortunately we have natural protective mechanisms that are triggered to try to save the brain and restore balance after TBI. Research shows that the endocannabinoid system is activated immediately after injury. Endocannabinoids block the release of the compounds that cause secondary damage to brain cells. Endocannabinoids have been found to decrease the intensity and duration of toxicity to brain cells and they also enhance brain cell survival after injury. Also endocannabinoids are anti-inflammatory and antioxidant. Simply put, your brain makes self-protective endocannabinoids in response to injury with the goal of minimizing cell damage and death in a multitude of ways.
Since both synthetic and plant cannabinoids mimic our endocannabinoids, researchers have investigated them to see if they can provide neuroprotection for TBI and have found promising results. Numerous studies have shown that synthetic cannabinoids given to animals with brain injury protected against cell damage and death. Cannabidiol (CBD) given immediately to animals after interruption of oxygen and blood flow helped to reduce brain cell injury, brain swelling and seizures, and significantly restored motor and behavioral performance in the first 72 hours after the insult. Cannabidiol also inhibits the breakdown of our endocannabinoids, thereby enhancing our own self-neuroprotective mechanisms. THC was found to significantly reduce the release of glutamate in animals with brain cell injury due to stroke. In a three-year retrospective review of patients presenting with TBI to a trauma center, a positive THC screen at the time of TBI was associated with decreased risk of death in adult patients; in this review, TBI patients who tested positive for THC has a risk of death of 2.4% versus 11.5% for those who tested negative for THC. These are only a few of the many studies that highlight the incredible neuroprotective role of cannabinoids.
As a clinician, I have seen many patients struggling to recover from TBI and I 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 that they can discontinue pharmaceutical medications that are ineffective and causing unwanted 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 minimize, and likely prevent, the devastating consequences of TBI.
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Cover photo courtesy of Allie Beckett
Originally published in Culture Magazine on Aug. 8, 2016.