Endocannabinoid breakdown post traumatic brain injury

Endocannabinoid breakdown post Traumatic Brain Injury causes damage

Trauma leads to hyper-metabolism of 2-AG, the most prominent endocannabinoid in the human brain. Fortunately, CBG can stop the excessive breakdown of the endocannabinoid which might have positive outcomes on TBI (Traumatic Brain Injury.)

Brain injury causes cannabis seeking but a previously discussed study on veterans missed a potential cause — endocannabinoid deficiency.

Inflammation is a major aftershock after the primary injury. Excessive endocannabinoid degradation then follows the neuroinflammatory assault. Accordingly, 2-AG deficiency was specifically identified as a symptom of trauma in a study by researchers from the University of Texas’s Health Science Center. However, secondary injuries such as inflammation can, unfortunately, last anywhere from days to years after a TBI.

Immunity of an Injured Mind

Injuries to the brain shift an individual’s behaviour and sense of character. Less noticeably, though, neurological damage from trauma can alter the immune system and cause chronic neuroinflammation. Cells within the brain react to blunt impact and release inflammatory cytokines. From here, enzymes that degrade 2-AG are affected by a constellation of inflammatory events.

Specifically, Traumatic Brain Injury can lead to the excitation of an inflammatory agent known as COX-2. Albeit a less common metabolic process, COX-2 does break the endocannabinoid, 2-AG down into further metabolites during an injury.

Cannabinoids that stop endocannabinoid degradation are promising for treating Traumatic Brain Injury.
Trauma leads to degradation of the endocannabinoid, 2-AG, causing a vicious cycle. The breakdown cycle is promoted by enzymes such as COX-2, for example, but more so by MAG-lipase. Optimistically, MAG-l and COX-2 are both blocked by CBG, which should prevent 2-AG degradation.

Stop Endocannabinoid Breakdown Post TBI, CBG Versus THC

2-AG is an endocannabinoid found everywhere in the body that facilitates incredible neuroprotection. And THC, the intoxicating cannabinoid in cannabis, helps release 2-AG. Therefore, doses of THC will provide some relief but effectively act as a bandaid. Treating TBI with THC is like continuing to bail water out of a boat without patching the hole. Whereas both, the active leak and current flood, must be actioned to successfully save the boat.

Rather than continuing to promote 2-AG production with doses of THC. A better solution for traumatic brain injury is to stop 2-AG from rapidly degrading. To do this, one can use specific phytocannabinoids to block enzymes that degrade 2-AG, particularly CBG and THCa.

Depleting Endocannabinoid Tone

Different enzymes break down 2-AG, but degradation typically depends on endocannabinoid location. 85% of the endocannabinoid is degraded in neurons by the enzyme, MAG-lipase. Substances that block endocannabinoid breakdown should ultimately stop damaging neuroinflammation after a TBI.

Endocannabinoid breakdown
The endocannabinoid, 2-AG, activates CB1 and CB2 receptors as well as PPARs.

2-AG is an endocannabinoid that, like THC, agonizes the two cannabinoid receptors, CB1 and CB2. But it activates the cannabinoid receptors without causing intoxication. To better regulate neuroinflammatory cytokines, though, 2-AG targets an additional receptor — PPARy.

Regulating inflammation is vital considering that traumatic brain injury also leads to cognitive decline and dementia in severe cases. Neurological symptoms occur due to the clumping or breaking down of certain proteins, like beta-amyloid and tao. Thankfully, CBG prevents the endocannabinoid, 2-AG from rapidly breaking down which might treat secondary injury after a TBI. Keep in mind that further research is required to guarentee the benefits of CBG in a clinical setting.

Leave a comment if you had success treating any ailment with CBG. And don’t forget to check out this story to read about a root cause behind a genetic endocannabinoid system deficiency.

Show your Work

  • MAG-lipase operates within the presynaptic region of the CB1 receptor, and 2-AG transmits pre to post. Increased presynaptic 2-AG is known to therefore desensitize CB1 receptors. Thus, MAG-l inhibitors cause some dependency and tolerance concerns.

Sources for Researching Endocannabinoid Breakdown Post TMI

  1. D.; Gao, F.; Chen, C. Endocannabinoid Metabolism and Traumatic Brain Injury. Cells 2021, 10,