Cannabinoid and Endocannabinoid Research Timeline

From;

Early Phytocannabinoid Chemistry to Endocannabinoids and Beyond

Almost all early research was devoted to clarification of cannabinoid chemistry^{3, 4, 104, 105}, and pharmacology was mainly done using synthetic compounds⁵. Following the isolation and structure elucidation of the plant cannabinoids, particularly of cannabidiol¹⁰⁶ and of Δ9-tetrahydrocannabinol (Δ⁹-THC)⁶, pharmacological and physiological work was initiated^8, 9, 15. The identification of cannabinoid receptors^24, 29, 31, of endogenous cannabinoids^{30, 32, 107} and of receptor antagonists^50, 66 made possible extensive pharmacological and neurobiological research leading to cloning of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH)¹⁰⁸, the discovery of retrograde signaling by 2-arachidonoyl glycerol (2-AG)⁴⁵, the discovery of allosteric sites on cannabinoid receptor 1 (CB1)³³, the discovery that endocannabinoids bind to receptors other than CB1 and CB2 (Refs ^{109, 110, 111}), the discovery and evaluation of endocannabinoid-like molecules in the brain^95, 96 and the discovery and function of inhibitors of the endocannabinoid-degrading enzymes^112, 113. Cell biology¹¹⁴and neuroscience^115, 116 investigations were also carried out, and clinical trials were initiated^{101, 117, 118}. Cloning of DAG lipase was also reported¹¹⁹.