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Chronic pain and psychedelics: a review and proposed mechanism of action
  1. Joel P Castellanos1,
  2. Chris Woolley1,
  3. Kelly Amanda Bruno1,
  4. Fadel Zeidan1,
  5. Adam Halberstadt2 and
  6. Timothy Furnish1
  1. 1Anesthesia Pain, UC San Diego, La Jolla, California, USA
  2. 2Department of Psychiatry, UC San Diego, La Jolla, California, USA
  1. Correspondence to Dr Joel P Castellanos, Anesthesia Pain, UC San Diego, La Jolla, CA 92037, USA; jcastellanos{at}


The development of chronic pain is a complex mechanism that is still not fully understood. Multiple somatic and visceral afferent pain signals, when experienced over time, cause a strengthening of certain neural circuitry through peripheral and central sensitization, resulting in the physical and emotional perceptual chronic pain experience. The mind-altering qualities of psychedelics have been attributed, through serotonin 2A (5-HT2A) receptor agonism, to ‘reset’ areas of functional connectivity (FC) in the brain that play prominent roles in many central neuropathic states. Psychedelic substances have a generally favorable safety profile, especially when compared with opioid analgesics. Clinical evidence to date for their use for chronic pain is limited; however, several studies and reports over the past 50 years have shown potential analgesic benefit in cancer pain, phantom limb pain and cluster headache. While the mechanisms by which the classic psychedelics may provide analgesia are not clear, several possibilities exist given the similarity between 5-HT2A activation pathways of psychedelics and the nociceptive modulation pathways in humans. Additionally, the alterations in FC seen with psychedelic use suggest a way that these agents could help reverse the changes in neural connections seen in chronic pain states. Given the current state of the opioid epidemic and limited efficacy of non-opioid analgesics, it is time to consider further research on psychedelics as analgesics in order to improve the lives of patients with chronic pain conditions.

  • chronic pain: central pain syndromes, fibromyalgia
  • chronic pain: neuropathic pain
  • alternative therapies
  • pharmacology: other
  • pain medicine

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All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article.

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  • Correction notice This article has been corrected since it published Online First and in print. This article has been corrected due to multiple referencing errors. Some references had become misordered while the authors were finalising the paper and others were inaccurate. The correctly ordered and comprehensive references are now included and published. Some minor clarifications have been made to the text to ensure that the evidence is clear. The main messages of the paper are unchanged by the corrections and clarifications. The journal considered that these were honest errors and the authors apologise for these oversights in the original version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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