21 August 2015
Cannabinoid and Endocannabinoid Research Timeline
Almost all early research was devoted to clarification of cannabinoid chemistry3, 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 initiated8, 9, 15. The identification of cannabinoid receptors24, 29, 31, of endogenous cannabinoids30, 32, 107 and of receptor antagonists50, 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 brain95, 96 and the discovery and function of inhibitors of the endocannabinoid-degrading enzymes112, 113. Cell biology114and neuroscience115, 116 investigations were also carried out, and clinical trials were initiated101, 117, 118. Cloning of DAG lipase was also reported119.