Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.

Cannabis (Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally. The main psychoactive component of cannabis is (-)-trans-Δ⁹-tetrahydrocannabinol (Δ⁹-THC), a molecule with a diverse range of pharmacological actions. The unique and distinctive intoxication caused by Δ⁹-THC primarily reflects partial agonist action at central cannabinoid type 1 (CB₁) receptors. Δ⁹-THC is an approved therapeutic treatment for a range of conditions, including chronic pain, chemotherapy-induced nausea and vomiting, and is being investigated in indications such as anorexia nervosa, agitation in dementia, and Tourette’s syndrome. It is available as a regulated pharmaceutical in products such as Marinol®, Sativex®, and Namisol®, as well as in an ever-increasing range of unregistered medicinal and recreational cannabis products. While cannabis is an ancient medicament, contemporary use is embroiled in legal, scientific, and social controversy, much of which relates to the potential hazards and benefits of Δ⁹-THC itself. Robust contemporary debate surrounds the therapeutic value of Δ⁹-THC in different diseases, its capacity to produce psychosis and cognitive impairment, and the addictive and “gateway” potential of the drug. This review will provide a profile of the chemistry, pharmacology, toxicology, and recreational and therapeutic uses of Δ⁹-THC, as well as the historical and societal importance of this unique, distinctive, and ubiquitous psychoactive substance.