Use of marijuana for recreational or medicinal purposes has become a significant topic of discussion over the past decade. While the push for legalization has become increasingly ‘trendy’, as some would say, the physiological systems this drug affects have been helping our bodies thrive throughout our entire lifetime. The endocannabinoid system (ECS) in particular is a direct recipient of THC, the compound in marijuana responsible for its psychoactive, and possibly medicinal effects. Given the ECS’s wide variety of roles in the brain, impaired signaling to this system may contribute to development of several neurological diseases.
Although THC does bind to endocannabinoid receptors, our body produces endogenous endocannabinoids (eCBs) that bind to these receptors as part of our body’s normal functioning. These receptors, the CB1 receptor and CB2 receptor, are located in many areas of the brain, and one of the unique things about the ECS signaling process is the fact that endocannabinoid receptors on neurons are located presynaptically or on the axonal segments, instead of postsynaptically like many receptors. This allows for retrograde signaling, where communication between neurons occurs in the opposite direction that it normally does.
The binding of eCBs to these receptors through this retrograde signaling is now understood to regulate several everyday processes in the brain, including mood regulation, synaptic plasticity (involved with learning an memory), and pain perception. There’s a decent chance you’ve heard about cannabinoid receptors in the brain prior to reading this blog, but did you know that in addition to their CNS locations, cannabinoid receptors are also found within the rest of the body? Researchers have discovered these receptors in a plethora of PNS locations such as the spleen, heart, liver, male and female reproductive systems, sympathetic nerve terminals and immune cells, where they serve many diverse functions.
Dysregulation of the ECS has been implicated in several neurological diseases and conditions. In Huntington’s disease, for example, expression of the CB1 receptor is reduced, and impaired ECS signaling has also been implicated for Alzheimer’s disease and Multiple Sclerosis. Conversely, enhancement of ECS signaling has been shown to improve symptoms of these diseases, as well as symptoms of Traumatic Brain Injury. These improvements are thought to be through the ECS’s mechanisms of neuroprotection against the cytotoxic factors such as nitric oxide seen in Multiple Sclerosis, the degeneration of the striatum seen in Huntington’s disease, AB toxicity seen in Alzheimer’s disease, and excitotoxicity and inflammation seen in Traumatic Brain injury.
While marijuana use is linked to some side effects, evidence seems to suggest that the potential benefits of THC, through interaction with the eCB system, outweigh the risks. And yet, marijuana continues to be labelled a schedule 1 drug (the most restricted level of controlled substances), while cocaine and methamphetamine are less restricted as schedule 2 drugs. The order of these drugs’ rankings don’t make logical sense in the context of their respective addictive and lethal properties, but they do reflect the stigma toward marijuana (and groups of people that have been associated with its use) throughout the decades.
This high level of restriction can additionally create difficulties for conducting research with marijuana. On the bright side, however, the recent election does offer insight into how benefits of marijuana are slowly becoming more valued; all 5 states that held a vote to either legalize marijuana either medically or recreationally, overwhelmingly passed it. There is still much to discover surrounding marijuana and the ECS, but with the rising interest and support, I feel confident that we will.
