The epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects

Mescaline (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic phenethylamine found primarily in cacti such as Peyote (Lophophora williamsii) and San Pedro (Trichocereus pachanoi). The introduction summarises pharmacology (primarily 5-HT2A receptor modulation), typical oral dosing (synthetic mescaline ~200–400 mg), duration (peak ~2 h, total 8–12 h), rapid tolerance and low dependence liability, and a long history of ceremonial use among Indigenous peoples. Despite preclinical work and case reports describing visual, emotional and occasionally challenging effects, the authors note a lack of epidemiological data on patterns of use, subjective acute and enduring effects, and harms or benefits of mescaline in broader populations. Vedøy Uthaug and colleagues set out to fill this gap by conducting an international, web-based epidemiological survey of English-speaking adults who had used mescaline at least once. The primary aim was to characterise patterns and motivations for mescaline use, the acute subjective experience and enduring effects, and perceived harms or benefits. Secondary aims included assessing whether medical or psychological functioning changed after use and whether subjective effects or use patterns differed by mescaline type (synthetic, extracted, Peyote, or San Pedro).

Data were collected via an anonymous online survey (Qualtrics) advertised on multiple internet platforms and shared through personal networks between January and October 2019. Eligibility criteria were age 18 or older, ability to read English, and lifetime mescaline use. The local ethics committee at Maastricht University approved the procedures. The survey was introduced with descriptions of mescaline types and asked respondents to report in detail about their single "most memorable" mescaline experience and about lifetime use more broadly. The study duration estimate shown in recruitment materials was 45–60 minutes. The survey captured administration route, source of mescaline, dose characterisation, session characteristics (location, presence of others, number of doses, duration), preparation, lifetime frequency, and items assessing abuse potential (craving, attempts to quit or change use, legal or medical consequences). Medical and psychiatric history and perceived changes following the most memorable experience were queried. Standardised psychometric instruments were used to assess acute and enduring subjective effects: the Psychological Insight Questionnaire (PIQ; 23 items, Cronbach's alpha = 0.95), the MEQ-30 mystical experience questionnaire (alpha = 0.96; a "complete mystical experience" defined as >=60% of maximum on all subscales), the Challenging Experience Questionnaire (CEQ; alpha = 0.92), the Ego-Dissolution Inventory (EDI; eight items, alpha = 0.91; authors altered its response scale), and the Persisting Effects Questionnaire (PEQ) for longer-term changes. Analyses proceeded from descriptive statistics to subgroup comparisons by mescaline type. The researchers used chi-square tests (with post-hoc z-tests and Bonferroni corrections) to examine categorical differences across synthetic, San Pedro, Peyote, and extracted subgroups, and one-way ANOVA (with Bonferroni-corrected post-hoc tests) for continuous variables. IBM SPSS Statistics v25 and v26 were used for analyses. The extracted text does not report a primary outcome a priori, nor any power calculation.

Recruitment yielded 2,025 clicks on advertisements; 788 individuals consented and began the survey, 477 completed the main questionnaires and reported valid responses, and after excluding respondents with unidentified mescaline type (n = 22) and those under 18 (n = 3), the final sample comprised 452 respondents. The sample was predominantly White/Caucasian (83%), male (76%), heterosexual (82%), with a mean age of 38 years (SD = 14.4), and 60% residing in North America. Subgroup comparisons showed the San Pedro group was younger (mean 35.6 years) than the Peyote (mean 47.0) and synthetic (mean 42.9) groups; a larger proportion of Peyote respondents lived in North America (75% vs 53% in San Pedro), and the Peyote group had a higher proportion reporting an advanced degree (37% vs 23% in San Pedro). Lifetime and recent use patterns indicated 66% had used San Pedro, 36% Peyote, and 31% synthetic mescaline; most respondents reported their most memorable experience involved San Pedro (48%), Peyote (22%), synthetic (15%), or extracted (15%). Oral ingestion was the dominant route (97%). First use typically occurred between 18 and 30 years (65%), and 46% reported lifetime use of mescaline one to three times; 23% reported >11 lifetime occasions. Frequency of use was low for most: 60% used mescaline less than once per year, 23% more than once per year but less than monthly, and only 3% monthly. Most last consumed mescaline at least six months before the survey (67%). Motivations and context were largely spiritual/personal: 74% reported spirituality or connecting with nature as their main reason for use, and high proportions believed mescaline had potential applications for personal growth (90%), spiritual growth (87%), psychotherapy (81%), creative enhancement (76%), and cognitive enhancement (61%). Sessions were commonly self-administered (78%) and often took place outdoors (47%). Abuse-potential indicators were low: 55% never took more than one dose in a session, 32% reported using mescaline with other substances on one or two occasions, craving/desire was reported by 9%, legal problems by 1%, engagement with therapy/psychiatric treatment related to mescaline by <1%, and none reported seeking medical attention due to mescaline use. Characteristics of the most memorable experience showed most respondents rated dose for that session as moderately high to very high and duration as 8–13 hours or longer. The sample averaged three prior uses and four subsequent uses relative to that memorable experience. Across mescaline types, there were no significant differences in ratings of acute subjective effects: average ratings were "moderate" for mystical-type effects, "very slight" for challenging effects, and "slight" for psychological insight and ego-dissolution. Around 28%–35% of respondents rated the experience among the top five or the single most personally meaningful, spiritually significant, or psychologically insightful experiences of their lives; 11% rated it among the top five or single most psychologically challenging. No significant subgroup differences were found for these enduring-effect proportions. Psychiatric history was common: 49% reported prior anxiety and 44% prior depression, with smaller proportions reporting prior drug misuse (20%), PTSD (17%), or alcohol misuse (17%). Among respondents reporting a prior condition, large proportions reported perceived improvement after their most memorable mescaline experience: depression improved for 86%, anxiety for 80%, PTSD for 76%, drug misuse for 68%, and alcohol misuse for 67%. These improvement rates did not differ significantly across mescaline-type subgroups. Subgroup-specific findings included that Peyote users reported ingesting more doses in their most memorable session (mean 2.9 doses) and a larger proportion of Peyote sessions were reported as provided in a ceremony (43%) compared to other subgroups. The synthetic subgroup reported higher rates of purchasing mescaline (69%) while San Pedro users were more likely to report being gifted it (6% less likely than other groups), and both San Pedro (27%) and Peyote (31%) users more often reported administration by a shamanic practitioner compared to synthetic or extracted users. A larger proportion of Peyote respondents reported total session duration less than 7 hours compared with the San Pedro subgroup. The extracted text does not provide exact p-values or confidence intervals for all comparisons; it reports that many comparisons showed no significant differences.

Vedøy Uthaug and colleagues interpret these data as the first international epidemiological characterisation of mescaline use in an English-speaking convenience sample. They emphasise that mescaline use in this sample was typically infrequent, oral, self-administered, and motivated by spiritual exploration or connection with nature. The low frequency of use, low reported craving, and very rare reports of legal, psychological or medical problems lead the investigators to suggest a low abuse potential and a relatively favourable psychological safety profile in naturalistic settings, consistent with prior survey work on other psychedelics. The researchers note that average ratings of acute mystical, ego-dissolution, psychological insight and challenging experiences were modest compared with reports for other psychedelics such as ayahuasca and psilocybin, and they attribute this in part to mescaline's lower potency and to many respondents reporting low-to-moderate doses. A notable finding is the high proportion of respondents with prior psychiatric conditions who reported improvements following their most memorable mescaline experience; the authors align this observation with earlier clinical and observational reports suggesting psychedelics may yield mental health benefits, while also acknowledging that mechanisms are likely multifactorial (set and setting, acute subjective effects, neurobiological changes). Several limitations are acknowledged. The cross-sectional, retrospective design and the focus on the "most memorable" experience introduce recall bias and selection bias; individuals with negative experiences may have been less likely to participate. The online recruitment strategy yielded a sample skewed towards White, heterosexual men, limiting generalisability, and the survey reached few Native American or Indigenous respondents (<10), despite outreach efforts. The investigators also note the altered response scaling for the EDI, lack of physiological safety data (vital signs, ECG), and inability to control for concurrent use of other substances. They stress that observed similarities or differences between mescaline types could be confounded by demographics or contextual factors (set and setting) and that controlled laboratory studies are required to establish causality, safety parameters, and any true pharmacological differences between synthetic and plant-derived mescaline. Finally, the authors call for broader, more representative research including Spanish-speaking and Indigenous populations, and for clinical trials and naturalistic studies to better characterise therapeutic potential, mechanisms of action, and safety.

The authors conclude that, in this self-selected English-speaking sample, mescaline in any form was associated with meaningful and spiritually significant experiences, perceived improvements in mental health for many respondents with prior psychiatric conditions, and low indicators of misuse or acute medical harm. They recommend further research among Native American and other Indigenous populations to better understand ceremonial use, and advocate for additional naturalistic and controlled clinical studies to confirm and extend these findings.