The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring, fast-acting indolealkylamine found in several plants and in particularly high concentrations in Bufo alvarius toad venom. Earlier pharmacological work and case reports indicate that 5-MeO-DMT acts as a serotonergic agonist (notably at 5-HT1A and 5-HT2A receptors), produces intense but short-lived perceptual and emotional effects, and has been used in spiritual and recreational contexts; nevertheless, prevalence, patterns of use, subjective effects, and potential harms or therapeutic benefits are poorly characterised because most national surveys do not query this substance specifically. Legal restrictions (for example, Schedule I status in the USA) further complicate systematic study, and available information has largely been limited to self-experiments, anecdotal reports, and animal data. Davis and colleagues set out to fill that gap by conducting an epidemiological survey of English-speaking adults who have used 5-MeO-DMT at least once. The primary aim was to describe patterns of use, motivations, and subjective effects; secondary aims were to document perceived changes in medical and psychiatric functioning following use, and to compare patterns and effects across reported source types (synthetic, toad venom, and plant extracts/yopo). The investigators framed the study as an initial descriptive effort to inform safety understanding and guide future clinical research.

Recruitment occurred online from April to August 2017 using forum and social media advertisements (for example, 5meodmt.org, Reddit, Bluelight, Erowid, and Facebook). Advertisements described the study purpose, estimated completion time (~20 minutes), anonymity, and offered a charitable donation incentive (US$2 per respondent, up to US$250 total) rather than direct payment. Eligible participants had to be at least 18 years old, English-speaking, and to have used 5-MeO-DMT at least once. The survey was hosted on a secure platform, did not collect identifying information, and procedures received institutional review board approval at Bowling Green State University. The online questionnaire collected demographic data and a detailed 5-MeO-DMT history including type of product used (synthetic, toad venom, plant extracts/yopo), route of administration, frequency and typical dose, age at first use, setting and source of the substance, who administered it, and motives for use (e.g., spiritual exploration, recreation, healing). Addiction-related items covered re-dosing in the same session, craving/desire, attempts to quit or reduce, and any legal, medical, or psychiatric consequences attributed to use. The researchers also asked about lifetime diagnoses of medical and psychiatric conditions and whether symptoms improved, stayed the same, or worsened after 5-MeO-DMT use. Two validated psychometric scales were embedded for retrospective reporting about the first 5-MeO-DMT episode: the Mystical Experiences Questionnaire (MEQ30), which yields four subscales and a total score and allows classification of a "complete mystical experience" (mean score ≥ 60% across subscales), and the Challenging Experiences Questionnaire (CEQ), which assesses aversive psychological and somatic reactions across seven subscales. Internal consistencies (Cronbach's alpha) for these scales in the sample were high. The survey also collected past-3-month use frequencies for other substances. For analysis, the team conducted descriptive statistics, chi-square tests, and one-way ANOVAs to examine differences by 5-MeO-DMT subtype, using an alpha of 0.05 and SPSS v.24. The authors noted reasons for not applying a Bonferroni correction in this context.

After online recruitment, the final analytic sample comprised 515 respondents. The sample was predominantly male (79%) and White/Caucasian (86%), with a mean age of 35.4 years (SD = 11.7); 58% resided outside the USA. Recent substance use in the prior 3 months was common for cannabis (mean days = 34.22, SD = 37.43), tobacco (mean days = 25.12, SD = 36.99), and alcohol (mean days = 16.22, SD = 23.59). Regarding 5-MeO-DMT characteristics and patterns, 55% reported most experience with synthetic 5-MeO-DMT, 29% with toad venom, and 16% with plant extract/yopo. Most respondents (60%) had used 5-MeO-DMT in the past year and 81% reported smoking/vapourising as the common route of administration. Lifetime use tended to be infrequent: 59% had used the substance 1–4 times, and only 21% reported more than 10 lifetime occasions. Among repeat users, 54% reported a frequency of about once per year or less. Typical use settings were private residences (own or friend's home) for 64% of respondents. Sources of the substance included a guide/session leader (30%), a friend (29%), and the Internet (26%). Spiritual exploration was the top stated motive for 68% of participants, with recreation reported by 18% and healing/psychological treatment by 14%. Measures of addiction potential and harms were low: 61% reported never re-dosing immediately after the initial dose, 28% sometimes re-dosed, and 11% frequently/always re-dosed. Only 8% endorsed craving/desire for 5-MeO-DMT, and 1% reported legal, medical, or psychiatric problems attributed to use. Most (86%) reported that their recent use had decreased or stayed the same, and roughly 95% had never attempted to reduce or quit use. Subjective acute effects were dominated by mystical-type experiences. On the MEQ30 the sample mean intensity was 3.64 (SD = 1.11) on a 0–5 scale, and large proportions endorsed individual mystical items (typically 84–97%). A "complete mystical experience" (≥ 60% on each MEQ subscale) was reported by 57% of respondents. Challenging experiences were less intense on average: the CEQ mean was 0.95 (SD = 0.91) and about 37% reported some challenging psychological or somatic items, though intensities were generally rated as very slight. When asked to compare intensity with other psychedelics they had used, 60% judged 5-MeO-DMT to be more intense than LSD, psilocybin mushrooms, or ayahuasca/DMT. Self-reported effects on medical and psychiatric functioning varied. Few respondents reported medical conditions, and most with such conditions (73–78%) reported no change after 5-MeO-DMT; 15–24% reported improvement and 4–7% reported worsening for select medical issues. Lifetime prevalence of self-reported psychiatric diagnoses in the sample included anxiety (63%), depression (61%), drug use disorder (33%), alcoholism/hazardous drinking (22%), ADHD (22%), and PTSD (21%). Across psychiatric conditions, only about 4% on average reported worsening following 5-MeO-DMT, whereas larger proportions reported improvements: depression improved in 77% of those with a diagnosis, PTSD in 79%, anxiety in 69%, substance use problems in approximately 63%, and OCD in 53%. Improvements of 35–50% were reported for ADHD, autism, bipolar disorder, and eating disorders in affected respondents, although these were smaller subsamples. Comparisons by reported subtype revealed several group differences. The Synthetic and Plant Extract/Yopo groups were younger and included fewer females than the Toad group. Synthetic users reported higher recent use of some other substances (e.g., cannabis, benzodiazepines, research chemicals) than Toad users. Nearly all Toad users consumed by smoking/vapourising, whereas Synthetic and Plant groups had higher proportions using oral or insufflation routes. Synthetic and Plant groups reported higher total lifetime counts but synthetic users reported lower frequency of recent consumption compared with Toad and Plant groups. Re-dosing frequency also differed, with more Toad users reporting that they never re-dosed. There were no significant group differences in indices of addiction potential or safety outcomes such as craving, legal problems, medical treatment, or psychiatric treatment related to 5-MeO-DMT. On subjective scales, Toad users tended to endorse more intense mystical effects than Synthetic users, while Synthetic users endorsed slightly more intense challenging experiences; however, mean magnitudes across groups remained in the strong-mystical and very-slight-challenging ranges respectively.

Davis and colleagues interpret these findings as the first descriptive epidemiological portrait of people who report lifetime 5-MeO-DMT use. The principal observations are that, in this convenience sample, most users reported infrequent consumption, predominant use of synthetic product and inhalation routes, and motivation centred on spiritual exploration. Subjective effects were characterised by high rates of moderate-to-strong mystical-type experiences and relatively low intensity of challenging experiences. Markers of addiction liability and acute adverse medical, psychiatric, or legal consequences were uncommon in the sample. Many respondents with prior psychiatric diagnoses reported perceived symptom improvements after 5-MeO-DMT use, notably for depression, PTSD, anxiety, and substance use problems, which the authors suggest is consistent with anecdotal reports, animal pharmacology, and therapeutic findings for related tryptamines. The investigators emphasise that these associations are observational and cannot establish causality: the cross-sectional design, reliance on retrospective self-report (including unvalidated symptom measures and unverified diagnoses), and a high prevalence of polysubstance use limit causal inference. Selection bias is another key limitation because recruitment was online and the sample skewed towards white, heterosexual men; the donation-based incentive may have introduced additional volunteer bias. The authors note the absence of laboratory studies on synthetic 5-MeO-DMT pharmacokinetics and safety in humans and acknowledge at least one published fatality involving ayahuasca preparations containing 5-MeO-DMT plus other substances, underlining incomplete knowledge of risk. In terms of implications, the study team suggests that 5-MeO-DMT's short duration of action compared with longer-acting tryptamines might make it a pragmatic candidate for controlled clinical investigation as an adjunct to psychotherapy, potentially improving scalability and reducing session costs if therapeutic effects are demonstrated. They recommend that future research employ rigorous experimental designs to assess safety, pharmacokinetics, and therapeutic efficacy in humans, and that studies attempt to recruit more diverse and clinically characterised samples to address the limitations observed here.