Use of Benefit Enhancement Strategies among 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) Users: Associations with Mystical, Challenging, and Enduring Effects

Psychedelic tryptamines are a class of substances that alter perception, thought, and affect; examples include psilocybin, DMT, and 5-MeO-DMT. Earlier research has reported both potential therapeutic benefits (for example reductions in depression, anxiety and substance use) and rare but serious adverse events associated with tryptamine exposure. 5-MeO-DMT has gained recent popularity because of its rapid onset, short duration, and reports of intense, reliably produced mystical-type experiences, yet population prevalence appears low and the drug has a steep dose–response curve that could increase risk. Lancelotta and colleagues note that anecdotal reports suggest users intentionally employ cognitive, behavioural and contextual tactics to increase positive effects and reduce challenging effects, but no empirical study had systematically examined such strategies among 5-MeO-DMT users. This study therefore aimed primarily to document the prevalence of 14 benefit enhancement (BE) strategies in a large survey of lifetime 5-MeO-DMT users (N = 515). As a secondary aim, the investigators examined, in a subset of respondents who reported using 5-MeO-DMT only once (n = 116), whether use of individual BE strategies was associated with the intensity of acute mystical-type and challenging experiences and with enduring appraisals of personal meaning, spiritual significance, and changes in well-being attributed to that single experience. The authors framed the concept as "benefit enhancement" rather than "harm reduction" because their primary outcomes of interest were positive acute and lasting effects; they drew BE items from clinical psychedelic practice, online reports, and neoshamanic ceremonial practices to capture psychological, environmental and physiological tactics employed before, during or after sessions.

This paper reports a secondary analysis of data collected in an international online survey conducted April–August 2017. Recruitment used electronic advertisements linking to an anonymous web survey hosted on SurveyGizmo. Eligibility required being at least 18 years old, reading English, and reporting lifetime use of 5-MeO-DMT. The study protocol and procedures were approved by Bowling Green State University's institutional review board; participants were informed of anonymity and offered a small charitable donation paid by the investigators. The survey asked respondents about the type and frequency of 5-MeO-DMT use and included 14 investigator-developed yes/no items assessing whether participants had used specified BE strategies (examples: preparing a comfortable/safe space, focusing on intentions, using ceremonial techniques, using with a guide). An open-ended item allowed reporting of other strategies. Acute subjective effects of respondents' first 5-MeO-DMT episode were measured with the 30-item Mystical Experiences Questionnaire (MEQ; 0–5 scale; total mean score used) and the 26-item Challenging Experiences Questionnaire (CEQ; 0–5 scale; total mean score used); internal consistencies were excellent (MEQ alpha = .97, CEQ alpha = .94). Persisting effects were assessed with three items from the Persisting Effects Questionnaire probing personal meaningfulness (0–7), spiritual significance (0–5), and change in well-being/life satisfaction (-3 to 3). Demographic and recent substance use items were also included. Analyses proceeded in two stages. For the full sample (N = 515) the investigators reported frequencies and descriptive statistics for BE strategy endorsement, demographics, and substance use. For the subsample of participants who reported having used 5-MeO-DMT on only one occasion (n = 116), the study used a series of independent-samples t-tests to compare mean MEQ, CEQ and persisting-effect scores between those who did and did not endorse each BE strategy. The conventional alpha of .05 was applied; the authors justified this choice by citing limitations of significance tests and the exploratory nature of the analyses, and they reported effect sizes (Cohen's d and Phi) alongside p-values. All analyses were performed in SPSS v.24. The extracted text does not report adjustment for multiple comparisons beyond the authors' stated approach.

Respondent characteristics for the full sample (N = 515) showed a predominance of White/Caucasian participants (86%), males (79%), and heterosexual respondents (82%). Mean age was 35.4 years (SD = 11.7). Many respondents also reported recent use of other substances in the prior three months, particularly marijuana/cannabis (78%), alcohol (77%), and tobacco (56%). BE strategy endorsement was common. In the entire sample more than one-half to three-quarters of respondents reported using several strategies: preparing a comfortable place for the session (85%), preparing a safe space (82%), ensuring there would be no distractions (76%), obtaining 5-MeO-DMT from a trusted source (74%), focusing on intentions immediately before using (67%), and using with friends or familiar people (51%). Strategies used by roughly one-third to one-half of respondents included abstaining from alcohol or other intoxicants prior to the session (50%), preparing music (49%), having someone to talk to after the session for integration (45%), meditating prior to session (43%), utilising ceremonial/shamanic techniques (38%), and using with a guide for challenging experiences (35%). Less commonly endorsed strategies included writing about the session afterwards (32%) and abstaining from sex in the days leading up to the session (14%). Open-ended responses (79 total) were themed into categories after excluding duplicates and irrelevant entries; themes included Meditative/Mindfulness practices (15 responses), Spiritual Rituals/Practices (6), Environmental/Bodily Preparations (25), Pharmacological/Medical Preparations (12), and Social Preparations/Support (10). There were 18 miscellaneous/not-applicable responses and 8 duplicate strategy reports. In the single-use subsample (n = 116), several BE strategies were associated with differential acute and enduring outcomes. Four strategies were associated with higher intensity of mystical-type experiences (MEQ): meditating prior to the session (d = 0.77), utilising ceremonial/shamanic techniques (d = 0.78), focusing on intentions immediately before use (d = 0.60), and using with a guide (d = 0.45). One strategy—preparing music for the session—was associated with lower intensity of challenging experiences (CEQ; d = 0.49) compared with non-users of that strategy. Regarding enduring appraisals, three strategies were associated with greater personal meaningfulness attributed to the session: ceremonial/shamanic techniques (d = 0.64), abstaining from alcohol and other substances prior to the session (d = 0.57), and meditating prior to the session (d = 0.51). Four strategies were associated with higher ratings of spiritual significance: ceremonial/shamanic techniques (d = 0.63), using with a guide (d = 0.53), meditating prior to the session (d = 0.54), and writing about the session afterwards (d = 0.41). By contrast, using with friends was associated with lower ratings of personal meaning (d = 0.45) and spiritual significance (d = 0.58) compared with not using with friends. Finally, three strategies were associated with greater self-reported improvement in well-being/life satisfaction: meditating prior to the session (d = 1.00), ceremonial/shamanic techniques (d = 0.66), and using with a guide (d = 0.53). The extracted text provides effect sizes for these comparisons but does not include the full set of p-values, confidence intervals, or the detailed table referenced; it also does not report dose information or frequency of BE-strategy usage for repeat users.

Lancelotta and colleagues interpret their findings to indicate that BE strategies are commonly used by 5-MeO-DMT consumers and that certain strategies are associated with more intense acute mystical-type experiences, reduced acute challenging experiences, and greater enduring appraisals of personal meaning, spiritual significance, and improved well-being. They note that many of the BE strategies observed overlap with protective behaviours reported by users of alcohol, MDMA and cannabis (for example, obtaining substances from a trusted source, using with familiar people, abstaining from other substances), which may reflect shared concerns about purity, social consumption contexts, or the tendency of polysubstance users to transfer strategies across substances. The authors highlight particular practices that appear salient for psychedelic contexts—such as preparing music, using a guide, meditating, and setting aside time for integration—and they point out that these are consistent with procedures recommended in laboratory psychedelic research. Lancelotta and colleagues emphasise that the associations found in this cross-sectional, retrospective survey are consistent with the concept that "set and setting" influence psychedelic experiences, but they explicitly caution that causality cannot be inferred from their data. They acknowledge several limitations: reliance on retrospective self-report subject to recall bias, a binary yes/no measurement of BE strategies that precludes frequency assessment, lack of dose information, potential selection bias from internet-based recruitment, and a demographically homogenous sample (predominantly white, heterosexual men) which limits generalisability. Implications discussed by the authors include the need for longitudinal and controlled research to test causal effects of BE strategies on acute and lasting outcomes, and the possible utility of incorporating selected BE practices into human laboratory protocols for 5-MeO-DMT. They also suggest that harm reduction workers, peer-support volunteers and community educators might disseminate information about BE strategies to help people prepare for, navigate, and integrate 5-MeO-DMT experiences. The investigators recommend future studies recruit more diverse samples and adopt more rigorous designs to clarify the role of BE strategies in shaping 5-MeO-DMT outcomes.