Chronic pain affects about 1.5 billion people worldwide. Current treatments like opioids and non-opioid drugs can cause side effects, addiction, or fail to relieve pain. Psychedelics such as LSD and psilocybin may alter pain perception through serotonin receptor activation, anti-inflammatory effects, and synaptic remodeling. This scoping review identified 21 human studies on psychedelics for pain. Few clinical trials exist, and sample sizes are small, limiting clinical use. Overall, psychedelics show promise for analgesia in certain headache disorders and cancer pain. Future research should examine combining psychotherapy with psychedelics for chronic pain.
Ketamine-assisted psychotherapy (KAP) can, in specific circumstances, initiate and prolong clinically significant reductions in pain, anxiety, and depressive symptoms, while encouraging rapport and treatment engagement, and promoting abstinence in patients addicted to other substances. A systematic review of seventeen articles including 603 participants found that combining ketamine with psychotherapy, provided before, during, and after ketamine sessions, can maximize and prolong benefits despite much variance in how KAP is applied. Additional large-scale randomized controlled trials are warranted to understand better the mutually influential relationships between psychotherapy and ketamine in optimizing responsiveness and sustaining long-term benefits in patients with chronic pain.