• Natalie H Strand, Madeline Whitney, Brooks Johnson, Tyler Dunn, Sumedha Attanti, Jillian Maloney, Lopa Misra, Diego Gomez, Omar Viswanath, Eric Emami, and James Leathem.
• Division of Pain Medicine, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA. strand.natalie@mayo.edu.
• Curr Pain Headache Rep. 2025 Jan 7; 29 (1): 1515.

Purpose Of ReviewChronic 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 FindingsThese 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.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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