SP56 Psychedelic drugs and pain

Abstract

<h3></h3> Ketamine, a non-competitive NMDA inhibitor with significant psychedelic properties, is widely used in the management of acute and chronic pain. Ketamine is used intraoperatively to spare opioids and prevent acute and chronic postoperative pain; it is also used in patients with complex pain syndromes and patients with opioid tolerance. Medical cannabis is already used widely in many countries to control pain and other conditions. Recently, psychedelic drugs like lysergic acid diethylamide (LSD), psilocybin, ecstasy (3, 4-methylenedioxy-N-methamphetamine or MDMA), ayahuasca, DMT (dimethyltryptamine) and others have regained a significant place among research and medical scientific talks for their therapeutic potential in pain management. Historically, there has been interest in using psychedelics to treat chronic pain since 1960s where it was suggested that psychedelic drugs may be therapeutically useful in cancer and phantom limb pain, but due to lack of the methodological rigor of modern trials they haven’t gained much attention. Recent studies suggest that psychedelics may be therapeutically useful in treating intractable headaches such as migraine and cluster headaches, and few recent reviews hypothesize potential mechanisms and applications for psychedelics in chronic pain. Pharmacologically, this concept is plausible. The primary mechanism of action of classic psychedelics is via the 5-HT_2A serotonin receptor, which is integral to descending inhibitory pain pathway. The acute effects of psychedelics may also contribute toward an analgesic response by reorienting attention away from unpleasant sensations toward altered perceptions, e.g., visual hallucinations. Despite the great interest and possibilities, the current legal status of many psychedelic drugs imposes a hinder to obtaining robust research evidence regarding their effectiveness and safety profile. Whelan A, Johnson MI. Lysergic acid diethylamide and psilocybin for the management of patients with persistent pain: a potential role?. Pain Manag. 2018;8(3):217–229. doi:10.2217/pmt-2017-0068 Kadriu B, Greenwald M, Henter ID, et al. Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants. Int J Neuropsychopharmacol. 2021;24(1):8–21. doi:10.1093/ijnp/pyaa087 Alexander, John C, and Girish P Joshi. ‘A review of the anesthetic implications of marijuana use.’ Proceedings (Baylor University. Medical Center) vol. 32,3 364–371. 21 May. 2019, doi:10.1080/08998280.2019.1603034 Castellanos JP, Woolley C, Bruno KA, Zeidan F, Halberstadt A, Furnish T. Chronic pain and psychedelics: a review and proposed mechanism of action. Reg Anesth Pain Med. 2020;45(7):486–494. doi:10.1136/rapm-2020-101273 Bornemann J, Close JB, Spriggs MJ, Carhart-Harris R and Roseman L. Self-Medication for Chronic Pain Using Classic Psychedelics: A Qualitative Investigation to Inform Future Research. Front. Psychiatry <b>2021; </b>; <b>12</b>:735427. doi: 10.3389/fpsyt.2021.735427