Cannabinoid (CB) 2 receptor uptick likely occurs to protect cellular systems. CB2 receptors in the brain and gut adapt to specific cells following the loss of CB1 receptors. And a recent study assessed cannabinoid two receptors treat spinal cord injury recycling a critical inflammasome.
Inflammatory injury and illness
Earlier this year, Harvard Medical School released a pivotal study on Covid-19. The virus upticks an inflammasome, leading to a fiery cell death. I hypothesized an endocannabinoid deficiency, a major loss of 2-AG to be exact, as a crucial factor in the viral disease.
2-AG is a CB1 and CB2 receptor agonist. But cannabinoid two receptors are druggable targets that treat disease and injury caused by an inflammasome storm, including a 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 inactive under homeostasis, a function of the endocannabinoid system. But if macrophage cells fail to clear toxins from the body, they warn the immune system, which releases NLRP3 proteins.
The process occurs in numerous diseases and leads to excessive cryopyrin. Proteins must degrade and properly recycle to avoid inflammation and pyroptosis, though. During spinal cord injury, CB2 receptor activation recycles inflammatory proteins via a unique enzymatic process — ubiquitination.
CB2 receptors, in part, boost a nutrient sensor axis (AMPK/ULK1) to recycle proteins. And NLPR3 inflammasome reduction, in turn, regulates neuron and epithelial cell polarity. CB2 receptor agonists can, therefore, regulate autophagy, prevent cell death, and attenuate neuroinflammation.
A drug or a terpene?
Beta-caryophyllene and delta-9 THC agonize CB2 receptors, but THC also targets the cannabinoid one receptor. Pharmaceutical companies failed to synthesize a selective CB2 agonist over the last decade.
The value of a functional and selective CB2 receptor agonist is in the billions, despite caryophyllene’s ubiquitous presence in our food supply. Drugs or terpenes that selectively target cannabinoid two receptors can treat various conditions, including Covid-19 and spinal cord injury, by recycling inflammatory proteins.
- Jiang F, Xia M, Zhang Y, et al. Cannabinoid receptor-2 attenuates neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome post spinal cord injury. Front Immunol. 2022;13:993168. Published 2022 Sep 26. doi:10.3389/fimmu.2022.993168
- Sefik E, Qu R, Junqueira C, et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature. 2022;606(7914):585-593. doi:10.1038/s41586-022-04802-1
- Seok, Jin & Kang, Han Chang & Cho, Yong-Yeon & Lee, Hye & Lee, Joo. (2021). Therapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases. Archives of Pharmacal Research. 44. 10.1007/s12272-021-01307-9.