Dimethyltryptamine (DMT): Prevalence, user characteristics and abuse liability in a large global sample

DMT (N,N-dimethyltryptamine) is a naturally occurring tryptamine found in mammals and plants worldwide and produces rapid, short-lived but profound alterations of perception and consciousness. Earlier clinical work from the mid-20th century and renewed investigations since the 1990s characterised its subjective effects using structured scales and described pharmacology implicating serotonergic (especially 5-HT2a) mechanisms, some activity at sigma-1 receptors, and marked first-pass metabolism by monoamine oxidase (necessitating MAO inhibitors for oral activity, as in ayahuasca). Smoking emerged ethnographically and pharmacologically as a route that avoids first-pass metabolism, producing an onset within minutes and a brief peak and overall duration much shorter than most other classic psychedelics. Winstock and colleagues note that, despite prior characterisations of subjective experiences, large-scale contemporary data on the prevalence of DMT use and how its effect and risk profile compare with other commonly used psychedelics are lacking. The study therefore set out to estimate the prevalence of DMT use in a large global sample, describe user characteristics, and compare the subjective effect profile and perceived harms of DMT with those of LSD, psilocybin (magic mushrooms) and ketamine, with particular attention to the implications of the smoking route of administration.

The investigators used data from the Global Drug Survey, an annual anonymous online survey promoted through media partners (including The Guardian, Mixmag and Fairfax Media in 2012) and via social networks. Data were collected between November and December 2012. The survey tool and recruitment strategy target a large sentinel population of people who use or have experimented with drugs; the paper notes prior work by the group establishing this methodology and its utility for rapidly assessing emerging drug trends. Respondents reported lifetime and recent use of various drugs. For detailed comparative profiling, a subset was selected consisting of participants who identified DMT as the last new drug they had tried for the first time; the sample size for that subgroup was 472 (2.1% of the total survey respondents). Participants completed ‘‘foot-printing’’ questions adapted from earlier risk-profiling work, rating each drug on seven effect domains (pleasurable effect when high; strength of effect; negative effect when high; comedown; risk of harm when high; value for money; urge to use more) on a 0–10 scale. The survey also asked about route of administration, time to onset, duration of peak effect, and the predominant intoxicating effect category (e.g. psychedelic, stimulant). The paper presents descriptive comparisons between DMT and the three other psychedelics (LSD, magic mushrooms, ketamine) using these self-reported metrics. The extracted text does not specify inferential statistical models or adjustment strategies in detail, nor does it report inclusion/exclusion criteria beyond self-selection into the survey.

A total of 22,289 responses were received worldwide in the November–December 2012 wave. Respondents were predominantly from the UK (33.0%), Australia (34.9%), the USA (16.9%) and the Euro zone (9.7%) using local currency as a proxy for country. Of the whole sample, 2.1% (n=472) reported that DMT was the last new drug they had tried for the first time and comprised the subgroup used for detailed effect profiling. Lifetime prevalence of DMT use is reported in the Conclusion as about 9% in this sample; past-year prevalence is reported elsewhere in the text. Within the subgroup analysed for effect profiling, DMT was almost exclusively reported to be smoked (reported as 92% of users for whom DMT was the last new drug tried), whereas ketamine was the only substance reported as injected among the comparators. Time-to-peak onset for DMT was rapid: 93% of users reported a peak effect within 5 minutes. The mean reported duration of effect for DMT was 23.8 minutes (SD 33.9), the shortest among the four substances examined. The vast majority of respondents characterised DMT’s predominant intoxicating effect as psychedelic. On the 0–10 ‘‘foot-printing’’ ratings, DMT scored highly on strength of effect and pleasurable effect, and relatively low on negative effects when high and on comedown, compared with the other substances. DMT, magic mushrooms and LSD had very similar proportions of users reporting strong urges to use more; ketamine (especially intranasal) had higher urge-to-use scores. The authors state that DMT was rated equally pleasurable as LSD and more pleasurable than magic mushrooms and ketamine. Fourteen per cent of respondents considered the effects of DMT to be different from other drug classes. Regarding perceived safety, among an experienced user subgroup 55% rated DMT as "very safe" and 38% as "quite safe"; the most commonly perceived risks were a ‘‘bad trip’’ (51%), psychospiritual problems (39%) and physiological risks such as respiratory irritation and burns (26%). Demographically, the new-user subpopulation was more likely to be younger, male and currently in education compared with lifetime DMT users and non-users; 72% of new DMT users had tried at least one other commonly used psychedelic. The extracted text does not provide detailed inferential statistics (confidence intervals or p-values) for the comparisons, nor dose or contextual data for episodes of use.

Winstock and colleagues interpret their findings as demonstrating that contemporary users regard DMT as a potent, short-acting psychedelic with a largely desirable subjective profile. They emphasise the apparent increase in interest in DMT: the proportion of respondents for whom DMT was the most recently tried new drug was higher than for ketamine, LSD and psilocybin, suggesting growing popularity among those seeking alternatives to traditional hallucinogens. The short duration of effect, attributed to the smoking route, is proposed as a factor that may limit negative effects and permit dose titration, contributing to high pleasurability but a relatively low urge to reuse, in contrast to substances such as intranasal ketamine which showed higher urge scores. The authors place their results alongside prior work showing that classic hallucinogens often generate only modest urges to use and mild comedowns, and they highlight route-specific considerations: smoking reduces first-pass MAO metabolism and the need for MAO inhibitors, which lowers the (theoretical) risk of severe serotonin syndrome associated with combined MAOI/DMT oral preparations. They note an estimated human LD50 extrapolated from animal data (560 mg) and a safety margin when compared to typical ayahuasca oral doses, but stress that human lethality data are limited. Several limitations are acknowledged. The survey sample was self-nominating and recruited via media likely to reach recreational and dance-music audiences, so it may not represent the broader population of DMT users. Comparisons across drugs were drawn from different respondent groups rather than within-subject contrasts, which limits the robustness of direct comparisons. Self-report introduces potential recall bias, lack of dose/contextual details, inability to verify the chemical identity of consumed substances, and confounding from poly-drug use. The investigators also note that the survey did not capture setting or ceremonial context, and that media exposure (film, documentaries, magazine features) may have influenced awareness and uptake among younger users. Despite these caveats, the authors consider sentinel self-report surveys a useful tool for mapping emerging drug trends and guiding further research. They advise caution for novice users because the rapid and intense onset of smoked DMT may be unpleasant and warrants harm-reduction advice.

In this large, self-selected online sample, DMT was reported by the subgroup of new users as producing a short, intense and pleasurable psychedelic experience with few negative after-effects. Lifetime prevalence in the surveyed population was about 9%, making DMT an uncommon but globally notable substance. The drug was typically smoked, which the authors suggest contributes to its rapid onset and strong effect. While DMT displays characteristics that could imply high abuse liability from a subjective-effect perspective, the reported low urge to reuse indicates a low potential for habitual use outside of religious or ceremonial contexts, and overall its potential for abuse appears limited in this sample.