Classic Psychedelics in Pain Modulation: Mechanisms, Clinical Evidence, and Future Perspectives
ACS Chemical Neuroscience June 6, 2025 Anna Czopek, Jakub Jończyk, Monika Fryc et al. 9 citations
Classic psychedelics such as psilocybin, LSD, and DMT, which primarily act on serotonin 5-HT2A receptors, may offer an alternative to conventional pain medications like opioids and NSAIDs for chronic pain—a condition often accompanied by depression and anxiety. Evidence from case studies, preclinical research, and early clinical trials suggests these substances can alleviate pain in cluster headaches, migraines, fibromyalgia, and other chronic pain syndromes by influencing neuroplasticity, descending pain modulation pathways, and inflammatory processes. However, the exact mechanisms remain unclear, and rigorous randomized controlled trials are needed to establish safety, efficacy, and optimal dosing.