Histoire de la kétamine et du psychédélisme

Ketamine's history begins in the fifties in Detroit, at Parke-Davis laboratories. In 1956, Maddox synthetized phencyclidine or PCP. Domino studied PCP effects in animals and in 1958, Greifenstein made the first trials of PCP in humans under the name of Sernyl. Sernyl elicited severe excitation with a prolonged postoperative recovery. Because of its psychedelic effects, it became a street-drug under the name of “angel dust”. Calvin Stevens synthesized ketamine in 1962. The drug was studied in humans in 1964, by Domino and Corssen who described the so-called “dissociative anesthesia”. Ketamine was patented in 1966 under the name of Ketalar for human use and was administered to soldiers during the Vietnam war. The psychedelic effects and the arrival of propofol prompted the shelving of ketamine. However, the discovery of the NMDA-receptor and its non-competitive inhibition by ketamine revolutionized the pathophysiology of hyperalgesia and mental functioning. In early 1990s, the discovery of opioid-induced hyperalgesia elicited a paradigm shift in the management of pain, and a comeback of ketamine, as an anti-hyperalgesic drug. Ketamine is nowadays under the spotlight in the field of treatment-resistant depression and has been proposed as a potential fast antidepressant in patients with high suicidal risk.