Analgesic potential of macrodoses and microdoses of classical psychedelics in chronic pain sufferers: a population survey
An online survey of 250 chronic pain sufferers with psychedelic experience found that macrodoses produced greater self‑reported analgesia than microdoses and conventional pain treatments (including opioids and cannabis), while microdoses showed weaker but suggestive benefits. Reported pain relief appeared independent of mood improvements or advocacy, indicating potential analgesic applications that warrant controlled clinical trials.
Authors
- Kim Kuypers
- Johannes Ramaekers
- Amanda Feilding
Published
Abstract
Although several studies and reports have shown the potential analgesic use of serotonergic psychedelics in cancer pain, phantom limb pain and cluster headache, evidence supporting their use for chronic pain is still limited. The past years have seen a considerable renewal of interest toward the therapeutic use of these compounds for mood disorders, resulting in a marked increase in the number of people turning to psychedelics in an attempt to self-medicate a health condition or improve their wellbeing. In western countries particularly, this population of users overlaps substantially with chronic pain sufferers, representing a unique opportunity to evaluate the effects these compounds have on pain and wellbeing. Here, we report results from an online survey conducted between August 2020 and July 2021 in a population of 250 chronic pain sufferers who had experience with psychedelics, either in microdoses (small sub-hallucinogenic doses), macrodoses (hallucinogenic doses), or both. Macrodoses, while less often used for analgesic purposes than microdoses, were reported to induce a higher level of pain relief than both microdoses and conventional pain medications (including opioids and cannabis). Although the effects were weaker and potentially more prone to expectation bias than with macrodoses, our results also suggested some benefits of psychedelics in microdoses for pain management. The reported analgesic effect appeared unrelated to mood improvements associated with psychedelic use, or the advocacy of psychedelic use. Taken together, our findings indicate interesting potential analgesic applications for psychedelics that warrant further clinical research.
Research Summary of 'Analgesic potential of macrodoses and microdoses of classical psychedelics in chronic pain sufferers: a population survey'
Introduction
Bonnelle and colleagues situate their study in the context of a rising global burden of chronic pain and growing concern about harms associated with conventional analgesics such as opioids and long-term NSAID use. They note that interest in alternative treatments has expanded alongside a renaissance in clinical research on serotonergic psychedelics (for example LSD and psilocybin), which act primarily via 5-HT2A receptor agonism and have shown promise for mood disorders as well as some pain conditions (cancer pain, phantom limb pain, cluster headache). Proposed mechanisms for psychedelic analgesia include modulation of descending serotonergic inhibitory pathways, anti-inflammatory effects (inhibition of TNFα signalling), promotion of neuroplasticity via glutamatergic pathways, and facilitation of affective regulation through amygdala modulation. The study aimed to evaluate self-reported analgesic effects of classic serotonergic psychedelics in a population of chronic pain sufferers who had used these substances. Specifically, the investigators sought to compare perceived pain relief from macrodoses (hallucinogenic doses producing marked changes in consciousness) versus microdoses (sub-hallucinogenic doses that do not impair normal functioning), and to compare both to conventional pain medications. The analysis also explored whether reported analgesia was mediated by mood or driven by expectancy or advocacy for psychedelic use.
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Study Details
- Study Typeindividual
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- APA Citation
Bonnelle, V., Smith, W. J., Mason, N. L., Cavarra, M., Kryskow, P., Kuypers, K. P., Ramaekers, J. G., & Feilding, A. (2022). Analgesic potential of macrodoses and microdoses of classical psychedelics in chronic pain sufferers: a population survey. British Journal of Pain, 16(6), 619-631. https://doi.org/10.1177/20494637221114962
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Syed, O. A., Petranker, R., Fewster, E. C. et al. · Journal of Psychoactive Drugs (2024)
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