Themed Issue in: Molecules

Extracts of cannabis plants (Cannabis sativa and Cannabis indica) have been used for centuries because of their recreational and therapeutic effects. However, it has only been around 50 years that we have known the identity of their most active principle [Δ⁹-tetrahydrocannabinol (THC)], and of the >110 compounds collectively termed “phytocannabinoids”. Shortly after the discovery of THC, it was recognized that endogenous ligands of the same targets activated by phytocannabinoids had to be present in our body, a concept that boosted active research leading to the discovery of N-arachidonoylethanolamine, 2-arachidonoylglycerol and other lipids as “endocannabinoids” (eCBs). Then, many more derivatives of ω-6 or ω-3 fatty acids were found to be biologically active eCBs, along with a multitude of compounds that were better considered “eCB-like” substances.

It seems now time to review the manifold actions of phytocannabinoids and eCBs in the central nervous system and at the periphery of our body, and to discuss hot topics and open questions of (endo)cannabinoid signalling that could represent an opportunity to discover new biomarkers and new therapeutic targets for disease treatment.