How Cannabinoid Receptors Treat Spinal Cord Injury

The increase in cannabinoid (CB) 2 receptor likely occurs to protect cellular systems. CB2 receptors in the brain and gut adapt to specific cells after the loss of CB1 receptors. And a recent study evaluated cannabinoid two receptors, which treat spinal cord injury and recycle a critical inflammasome.

Inflammatory injuries and diseases

Earlier this year, Harvard Medical School published a pivotal study on Covid-19. The virus attacks an inflammasome, resulting in fiery cell death. I hypothesized that endocannabinoid deficiency, a major loss of 2-AG to be precise, is a key factor in viral disease.

2-AG is a CB1 and CB2 receptor agonist. However, cannabinoid-2 receptors are drug targets that treat diseases and injuries caused by an inflammatory storm, including spinal cord injury.

Spinal Cord Injury and Cannabinoid Receptors

According to a recent study, CB2 receptors help recycle the inflammatory protein known as NLRP3. The inflammasome remains dormant under homeostasis, a function of the endocannabinoid system. But when macrophage cells are unable to clear toxins from the body, they alert the immune system, which releases NLRP3 proteins.

The process occurs in numerous diseases and leads to an excess of cryopyrin. However, proteins must be broken down and properly recycled to avoid inflammation and pyroptosis. During spinal cord injury, CB2 receptor activation recycles inflammatory proteins via a unique enzymatic process – ubiquitination.

CB2 receptors partially amplify a nutrient sensory axis (AMPK/ULK1) to recycle proteins. And the reduction of the NLPR3 inflammasome in turn regulates the polarity of neurons and epithelial cells. CB2 receptor agonists can therefore regulate autophagy, prevent cell death and attenuate neuroinflammation.

“Structure of the NLRP3 inflammasome. The NLRP3 inflammasome is a complex composed of NLRP3, ASC and procaspase-1. NLRP3 consists of three regions: the pyrine domain (PYD) in the amino terminus, the NIGHT domain, and the leucine-rich repeat domain (LRR) in the carboxy terminus.” — Seok et al. 2021

A drug or a terpene?

Beta-caryophyllene and delta-9-THC agonize CB2 receptors, but THC also targets the cannabinoid-1 receptor. Pharmaceutical companies have failed to synthesize a selective CB2 agonist in the last decade.

The value of a functional and selective CB2 receptor agonist is in the billions, despite the ubiquitous presence of caryophyllene in our food supply. Drugs or terpenes that selectively target cannabinoid two receptors can treat various conditions including Covid-19 and spinal cord injuries by recycling inflammatory proteins.

Sources

1. Jiang F, Xia M, Zhang Y, et al. Cannabinoid receptor-2 dampens neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome following spinal cord injury. front immunol. 2022;13:993168. Published September 26, 2022. doi:10.3389/fimmu.2022.993168
2. E. Sefik, R. Qu, C. Junqueira et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature. 2022;606(7914):585-593. doi:10.1038/s41586-022-04802-1
3. Seok, Jin & Kang, Han Chang & Cho, Yong-Yeon & Lee, Hye & Lee, Joo. (2021). Therapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases. Pharmaceutical Research Archives. 44. 10.1007/s12272-021-01307-9.

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