Pain and Perception: Exploring Psychedelics as Novel Therapeutic Agents in Chronic Pain Management

Curr Pain Headache Rep. 2025 Jan 7;29(1):15. doi: 10.1007/s11916-024-01353-0.

Abstract

Purpose of review: Chronic pain affects approximately 1.5 billion people worldwide, representing the leading cause of disability and a significant financial burden on healthcare systems. Conventional treatments, such as opioids and non-steroidal anti-inflammatory drugs, are frequently linked to adverse effects, including dependency and gastrointestinal issues, and often offer limited long-term relief. This review explores the potential of psychedelics, including psilocybin, LSD, and ketamine, as alternative therapeutic agents in chronic pain management.

Recent findings: These substances modulate pain perception through actions on serotonergic and glutamatergic systems and may promote neuroplasticity, offering novel pathways for pain relief. Specifically, the review details the pharmacologic actions of psychedelics, their effects on chronic pain syndromes such as cancer pain, migraines, and neuropathic pain, and their clinical implications. The safety profiles, patient responses, and analgesic properties of these compounds are examined, highlighting the need for further research to validate their efficacy and optimize their therapeutic use in pain management.

Keywords: Analgesic effects; Chronic pain; Cluster headaches; Ketamine; LSD (lysergic acid diethylamide); Neuropathic pain; Pain modulation; Phantom limb pain; Psilocybin; Psychedelics; Psychotherapy.

Publication types

  • Review

MeSH terms

  • Analgesics / therapeutic use
  • Chronic Pain* / drug therapy
  • Chronic Pain* / physiopathology
  • Hallucinogens* / pharmacology
  • Hallucinogens* / therapeutic use
  • Humans
  • Pain Management* / methods
  • Pain Perception* / drug effects
  • Pain Perception* / physiology

Substances

  • Analgesics
  • Hallucinogens