Chronic pain and psychedelics: a review and proposed mechanism of action
Regional Anesthesia & Pain Medicine May 4, 2020 Joel Castellanos, C. Leonard Woolley, Kelly Bruno et al. 118 citations
Chronic pain develops through complex mechanisms involving strengthened neural circuitry from repeated pain signals, leading to peripheral and central sensitization. Psychedelics, through serotonin 2A receptor agonism, may 'reset' brain functional connectivity involved in central neuropathic pain. They have a favorable safety profile compared to opioid analgesics. Clinical evidence for chronic pain is limited, but studies over 50 years show potential benefit for cancer pain, phantom limb pain, and cluster headache. The mechanisms are unclear but may involve similarities between psychedelic activation pathways and nociceptive modulation. Functional connectivity changes from psychedelics could help reverse neural changes in chronic pain. Further research is needed given the opioid epidemic and limited non-opioid options.