Chronic pain and psychedelics: a review and proposed mechanism of action
This review synthesises clinical and mechanistic evidence suggesting classic psychedelics — via 5‑HT2A receptor agonism and resultant changes in brain functional connectivity — may reverse neural alterations underlying chronic pain and produce analgesic effects, with limited but promising reports in cancer pain, phantom limb pain and cluster headache. Given their comparatively favourable safety profile versus opioids, the authors propose further clinical research into psychedelics as non‑opioid analgesics.
Authors
- Castellanos, J. P.
- Woolley, C.
- Bruno, K. A.
Published
Abstract
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.
Research Summary of 'Chronic pain and psychedelics: a review and proposed mechanism of action'
Introduction
Psychedelics are psychoactive compounds that alter perception and consciousness and have a long history of ceremonial and medicinal use across cultures. Recent decades have seen a resurgence of clinical interest, driven by improved research methods and promising findings for psychiatric indications such as depression, anxiety and addiction. There is also growing, though limited, evidence that classic serotonergic psychedelics may produce antinociceptive effects in certain chronic pain conditions. Chronic pain development is described as a multifactorial process in which prolonged somatic and visceral nociceptive input produces peripheral and central sensitization and consequent durable changes in pain perception. This review sets out to examine the historical context, safety profile and pharmacologic classification of psychedelic compounds and to discuss potential mechanisms by which they might affect chronic pain. Castellanos and colleagues frame the review around molecular actions (especially at the serotonin-2A, 5-HT2A, receptor), downstream effects on gene expression and inflammation, and alterations in brain functional connectivity (FC) that could plausibly reverse or remodel the neural changes seen in chronic pain states. The authors aim to synthesise clinical reports and basic science to motivate focused future research on psychedelics as analgesics.
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Study Details
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- APA Citation
Castellanos, J. P., Woolley, C., Bruno, K. A., Zeidan, F., Halberstadt, A., & Furnish, T. (2020). Chronic pain and psychedelics: a review and proposed mechanism of action. Regional Anesthesia & Pain Medicine, 45(7), 486-494. https://doi.org/10.1136/rapm-2020-101273
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