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Phyto and Endocannabinoid research

Early phytocannabinoid chemistry to endocannabinoids and beyond

Abstract | Isolation and structure elucidation of most of the major cannabinoid constituents — including Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive molecule in Cannabis sativa — was achieved in the 1960s and 1970s. It was followed by the identification of two cannabinoid receptors in the 1980s and the early 1990s and by the identification of the endocannabinoids shortly thereafter. There have since been considerable advances in our understanding of the endocannabinoid system and its function in the brain, which reveal potential therapeutic targets for a range of brain disorders.

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Almost all early research was devoted to clarification of cannabinoid chemistry and pharmacology was mainly done using synthetic compounds. Following the isolation and structure elucidation of the plant cannabinoids, particularly of cannabidiol and of Δ9-tetrahydrocannabinol (Δ9-THC) pharmacological and physiological work was initiated. The identification of cannabinoid receptors of endogenous cannabinoids and of receptor antagonists, made possible extensive pharmacological and neurobiological research leading to cloning of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH) the discovery of retrograde signaling by 2-arachidonoyl glycerol (2-AG) the discovery of allosteric sites on cannabinoid receptor 1 (CB1) the discovery that endocannabinoids bind to receptors other than CB1 and CB2 , the discovery and evaluation of endocannabinoid-like molecules in the brain and the discovery and function of inhibitors of the endocannabinoid-degrading enzymes.  Cell biology and neuroscience  investigations were also carried out, and clinical trials were initiated. Cloning of DAG lipase was also reported.

Cannabinoid and endocannabinoid research — a timeline. Almost all early research was devoted to clarification of cannabinoid chemistry and pharmacology was mainly done using synthetic compounds. Following the isolation and structure elucidation of the plant cannabinoids, particularly of cannabidiol and of Δ9-tetrahydrocannabinol (Δ9-THC) pharmacological and physiological work was initiated. The identification of cannabinoid receptors of endogenous cannabinoids and of receptor antagonists made possible extensive pharmacological and neurobiological research leading to cloning of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH) the discovery of retrograde signaling by 2-arachidonoyl glycerol (2-AG) the discovery of allosteric sites on cannabinoid receptor 1 (CB1), the discovery that endocannabinoids bind to receptors other than CB1 and CB2, the discovery and evaluation of endocannabinoid-like molecules in the brain and the discovery and function of inhibitors of the endocannabinoid-degrading enzymes. Cell biology and neuroscience, investigations were also carried out, and clinical trials were initiated. Cloning of DAG lipase was also reported.”

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