Potential analgesic effects of psychedelics on select chronic pain conditions: A survey study

Chronic pain (CP) affects about 20% of the population, is a leading cause of disability and frequently co-occurs with psychiatric symptoms such as depression and anxiety. Standard pharmacological treatments (NSAIDs, opioids, anticonvulsants, antidepressants) and psychological therapies provide incomplete relief for many people living with chronic pain (PLCP), and some options—most notably opioids—carry substantial risks including dependence and opioid-induced hyperalgesia. Against this backdrop, classic serotonergic psychedelics (for example LSD and psilocybin) have re-emerged in research and anecdotal reports as candidate treatments for pain, with historical clinical data, experimental work in healthy volunteers and observational reports suggesting possible analgesic and prophylactic effects at both full (psychoactive) doses and low or ‘‘micro’’ doses. Cavarra and colleagues set up an online survey to capture self-reported analgesic effects of psychedelic use in people who have experienced CP and who had used psychedelics. The present paper focuses on five pain conditions chosen for within-category diagnostic homogeneity: fibromyalgia (FM), arthritis, migraine, tension-type headache (TTH) and sciatica. The study aimed to compare perceived pain relief from conventional treatments, psychedelic microdoses and psychedelic full doses, and to explore whether mood changes or expectations explained any reported analgesia. The authors frame this naturalistic work as a first step to inform controlled investigation of dose, frequency, condition specificity and mechanisms.

Recruitment was via an online Qualtrics survey advertised on the Beckley Foundation website and social media from August 2020 to July 2021. Eligible respondents were aged 18 or older, had experience with psychedelics and were currently or previously suffering from chronic pain. Ethics approval was granted by Maastricht University's Ethics Review Committee of Psychology and Neuroscience. The test battery collected demographics, history of psychedelic use (compound most experienced with, frequency and duration for microdosing and full dosing), current and past pain complaints, and ratings of pain relief from conventional medication, cannabis, psychedelic microdoses and psychedelic full doses. Pain severity was recorded on a 0–10 Visual Analogue Scale (VAS) and pain frequency on a four-point Likert scale. Participants also reported whether they had used psychedelics intentionally to treat pain, whether their mood changed after use, and how long any benefit lasted (same day only; following day; 2–3 days after; beyond 3 days). The authors selected five complaint categories for analysis (FM, arthritis, migraine, TTH and sciatica) on the basis of presumed diagnostic homogeneity. Responses naming non-classical psychedelics (for example ketamine, MDMA or THC) were excluded from analyses comparing classical psychedelic relief. Statistical analysis used SPSS v26.0. Non-normality of relief scores led to nonparametric tests: Kruskal-Wallis tests compared relief between classes of conventional medication; Friedman's two-way ANOVA for related samples compared relief across three treatment types (conventional medication, microdoses, full doses), with pairwise Wilcoxon signed-rank tests and Bonferroni correction for contrasts. Effect sizes reported included Kendall's W for Friedman's ANOVAs and eta-squared for Kruskal-Wallis tests. Pearson correlations tested associations between mood change and relief, and Mann-Whitney U tests compared relief by intentional self-treatment (expectation) status.

Sample and general characteristics: Of 976 initial respondents, 170 completed the survey and met inclusion criteria. The sample comprised 93 females, 70 males and 7 who preferred not to say; the modal age group was 31–40 years. Participants reported a mean of approximately 5–8 concurrent pain complaints depending on the subgroup. Across condition subsamples, psilocybin and LSD were the most commonly reported psychedelics. Fibromyalgia (n = 47): For conventional medications most used were opioids, cannabis and OTC/NSAIDs; no significant differences were found between conventional treatment classes. Psilocybin (n = 26) and LSD (n = 15) were the common psychedelics. Most FM participants used both microdoses and full doses. Friedman's test indicated a significant effect of treatment type (F r (2) = 19.042, p < 0.001; W = 0.50). Mean reported relief was 5.32 for conventional medication, 6.51 for microdoses and 8.25 for full doses. Pairwise comparisons showed full doses provided significantly greater relief than both conventional medication (p < 0.001) and microdoses (p < 0.001). Duration of benefit for full doses varied: 31.6% same-day only, 21.1% next day, 21.1% 2–3 days, 26.3% beyond 3 days. No significant correlations were found between mood change and relief for either full doses (r = 0.025; p = 0.919) or microdoses (r = 0.180; p = 0.461). Arthritis (n = 67): Conventional treatments reported included opioids, cannabis and OTC/NSAIDs; no significant differences across conventional classes (H(3) = 8.08, p = 0.044, η2 = 0.098, reported as nonsignificant in interpretation). Psilocybin and LSD were common. Most participants alternated microdosing and full dosing. Friedman's analysis showed a significant treatment-type effect (F r (2) = 12.873, p = 0.002; W = 0.31). Mean relief scores were 5.79 for conventional medication, 7.76 for microdoses and 8.23 for full doses. Full doses produced significantly greater relief than both conventional medication (p < 0.001) and microdoses (p < 0.001). Reported benefit duration for full doses included 33.3% same-day only and 28.6% beyond 3 days. Mood-change–relief correlations were non-significant. Migraine (n = 63): The most used conventional options included OTC/NSAIDs, opioids and cannabis; no significant differences between conventional classes. Psilocybin (n = 33) and LSD (n = 18) were most common. Treatment-type effect was significant (F r (2) = 19.973, p < 0.001; W = 0.48). Mean relief was 5.25 for conventional medication, 7.05 for microdoses and 8.07 for full doses. Full doses gave significantly greater relief than both conventional medication and microdoses (p < 0.001), and microdoses gave significantly greater relief than conventional medication (p < 0.005). Benefit-duration responses for full doses included 19% same-day only and 28.6% beyond 3 days. No significant correlations with mood change were found. Tension-type headache (TTH; n = 47): Conventional medication relief means were similar across drug classes. Psilocybin and LSD predominated. A significant treatment effect was observed (F r (2) = 13.16, p < 0.005; W = 0.13). Mean relief was 5.23 for conventional medication, 6.93 for microdoses and 7.97 for full doses. Full doses exceeded both microdoses (p < 0.01) and conventional medication (p < 0.001), and microdoses exceeded conventional medication (p < 0.01). Benefit-duration estimates again showed a mix of same-day and multi-day effects. Correlations between mood change and relief were not significant; one microdose correlation approached significance (r = 0.467, p = 0.051) but did not reach conventional thresholds. Sciatica (n = 65): Conventional medication use included opioids, cannabis and OTC/NSAIDs; no significant differences across conventional classes. Psilocybin and LSD were commonly reported. Mean relief values were 7.00 for conventional medication, 7.05 for microdoses and 8.05 for full doses; however, the main effect of treatment type did not reach statistical significance (F r (2) = 5.4, p = 0.067). Benefit-duration distributions were similar to other conditions. No significant correlations between mood change and relief were observed. Expectations: Comparing participants who intentionally used psychedelics to self-treat pain with those who did not showed no significant difference in reported relief for either microdoses (U = 882; p = 0.328) or full doses (U = 1455; p = 0.325). Across conditions, the authors excluded responses where the reported ‘‘psychedelic’’ was not a classical serotonergic psychedelic. Overall, the main pattern was that full-dose psychedelics received higher self-reported analgesia than conventional medication in FM, arthritis, migraine and TTH, with microdoses sometimes performing comparably to or better than conventional medication (notably in migraine and TTH). Sciatica was the exception, with no statistically significant superiority of psychedelics over conventional treatments.

Cavarra and colleagues interpret their findings as indicating that, in naturalistic self-administration, classical psychedelics are perceived to provide greater pain relief than conventional pharmacological treatments for several chronic pain conditions (FM, arthritis, migraine and TTH), whereas no such advantage was detected for sciatica. Full doses tended to be rated as more effective than microdoses, though microdosing produced relief comparable to conventional medication for some conditions and surpassed it for migraine and TTH. The authors note that some respondents reported benefits that extended beyond the dosing day, suggesting potential both for acute relief and for prophylactic effects in paroxysmal disorders such as migraine; they caution that establishing a preventive effect would require measurement of baseline and post-treatment episode frequency. The investigators consider biological mechanisms that might account for analgesic effects, including serotonergic 5-HT2A receptor agonism, modulation of nociceptive signalling, anti-inflammatory actions and promotion of neuroplasticity. They also report that correlations between mood change and pain relief were non-significant, and that intentionality (expectation) did not differentiate relief scores, suggesting the observed analgesic reports cannot be fully attributed to mood improvement or to simple expectancy effects. Still, the authors acknowledge that other psychological mediators (for example psychological flexibility or personality) could play a role. Key limitations are emphasised: the study's naturalistic, retrospective and self-selected survey design limits generalisability and is vulnerable to bias; dosage and dosing schedules—especially for microdosing—were not captured; contextual factors (set and setting) and many potentially relevant individual variables (such as personality) were not assessed; diagnostic heterogeneity remained within some categories (for example different forms of arthritis were not distinguished); abortive and preventive medications were not separated in the conventional-medication listing; important comparators (gabapentinoids for sciatica) were not explicitly listed; frequency measures for paroxysmal pain (attacks per month) were not collected; and sample sizes for each condition were limited. The authors therefore caution that causal inference is not possible from these data. For future work, the paper recommends controlled clinical studies that can specify doses and schedules, monitor biological and psychological mediators, separate acute from preventive effects, and target condition-specific mechanisms or categories that share causal pathways (for example nociplastic pain irrespective of anatomical location). The authors suggest pairing psychedelics with established treatments (such as physical therapy for sciatica) may be worth exploring.

The study provides naturalistic survey evidence that people with certain chronic pain conditions report greater perceived pain relief from psychedelic full doses than from conventional pharmacological treatments, with microdoses showing comparable or intermediate effects depending on the condition. Cavarra and colleagues conclude that psychedelics may hold therapeutic value for selected chronic pain disorders, but they underline that controlled clinical trials are needed to determine causality, establish optimal doses and schedules, and investigate underlying biological and psychological mechanisms while monitoring safety.