Reported effects of psychedelic use on those with low well-being given various emotional contexts

Mason and colleagues frame the study within renewed clinical interest in psychedelics (classic psychedelics such as LSD, psilocybin, and DMT-containing ayahuasca, and empathogens such as MDMA) and the long-standing idea that non-pharmacological factors—"set" (internal state, mood, expectations, personality) and "setting" (physical and social environment)—substantially influence acute and longer-term outcomes. Earlier work indicates that trait factors (for example, neuroticism) and pre-administration mood may shape the acute experience, but clinical trials typically enrol highly screened participants and thus may not capture how substances perform across the range of psychological states found in real-world or clinical populations. The study therefore aimed to characterise when and where recreational users take specific psychedelic substances, and to examine mood outcomes after use in relation to two clinical characteristics: low psychological well-being (measured with the WHO-5 index) and personality, with a focus on neuroticism. The researchers sought to determine (1) common settings and pre-use mood states for LSD, psilocybin, MDMA and ayahuasca, and (2) whether people with low well-being and/or higher neuroticism report different acute mood changes or rates of unwanted effects after use. The authors position this work as complementary to clinical trials by drawing on a larger, naturalistic sample of users.

An online, retrospective questionnaire was administered between May and July 2017 via websites and forums; respondents had to be aged 18 or older and provide informed consent. Ethics approval was obtained from Maastricht University's committee. From 4,892 survey starts, 1,967 respondents (40%) completed the questionnaire; average completion time was about 96 minutes. The extracted text does not provide a full breakdown of recruitment sites or screening beyond these points. Measures included demographics (age, gender, education, continent of origin, history of mental health disorder), lifetime use of four substances (MDMA/ecstasy, psilocybin, LSD, ayahuasca), typical setting of use (party, festival, home, work, ceremonial/spiritual, other; multiple selections allowed), and typical mood state at time of use (positive, negative, neutral, other) plus whether mood usually changed during use and to what valence. A "positive mood change" was defined as initial negative or neutral mood changing to positive after use; conversely, a "negative mood change" was defined as initial positive or neutral mood changing to negative. Neutral-to-neutral or valence-preserving changes were excluded from the primary mood-change analyses. Psychological measures comprised the WHO-5 Well-being Index (scores 0–100; scores ≤50 classified as 'low' well-being) and the 10-item Big Five Inventory (yielding scores for Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness). For analysis, respondents were split into normal (WHO-5 > 50) and low (WHO-5 ≤ 50) well-being groups. Descriptive statistics (frequencies, proportions) were reported for settings, mood states, and reports of unwanted effects. Group differences in continuous variables (age, personality scores) were tested with independent-samples t-tests; categorical differences (gender, education, mental health history, substance use) used chi-squared tests. Primary inferential analyses used binary logistic regression to predict positive mood change and negative mood change separately, with group (low versus normal well-being) and the five continuous personality trait scores entered as predictors. Exploratory logistic regressions assessed whether well-being and personality predicted reports of unwanted effects for each substance. Odds ratios (ORs) and 95% confidence intervals were reported; statistical significance was set at p < 0.05. The paper notes the scale-dependent interpretation of ORs for continuous predictors.

Sample and group allocation. Of 1,967 respondents, 1,324 (67.3%) were categorised as having normal well-being (mean WHO-5 67.9, SD 10.8) and 643 (32.7%) as having low well-being (mean WHO-5 35.47, SD 10.88). The extracted text indicates differences in demographics between groups: the low well-being group contained a higher proportion of females, fewer individuals with an advanced degree, a higher reported frequency of mental health disorders, and lower reported lifetime use of MDMA and psilocybin compared with the normal well-being group. Setting (environment). Regardless of well-being group, most respondents reported typically using LSD (N = 1313; 83.9% of LSD users) and psilocybin (N = 1159; 80.6% of psilocybin users) at home. MDMA was most commonly used in party (N = 800; 71.0%) or festival (N = 692; 61.4%) contexts. Ayahuasca was most often used in ceremonial or spiritual ritual settings (N = 80; 52.6%) or in an "other" category (N = 102; 67.1%). These values come from reported frequencies in the extracted text; full tables and figures referenced in the paper are not present in the extraction. Set (pre-use mood) and acute mood change. Across substances and well-being groups, respondents most commonly reported using substances when in a positive mood. Substance-independent analyses showed that roughly 60% of respondents did not report a mood-state change after LSD and MDMA; for psilocybin and ayahuasca the proportion reporting no mood change was around 50%. When mood did change, the extracted text reports percentages for positive versus negative changes in a table that is not included here. Well-being-related effects. Logistic regression found that individuals with low well-being were more likely than those with normal well-being to report a positive mood change after use of LSD, psilocybin, or MDMA. There were no significant differences between well-being groups in likelihood of negative mood change (all p > 0.20). The extraction includes an incomplete sentence fragment about a well-being-dependent negative mood-state change and does not supply full statistics for the well-being predictors; therefore exact ORs for the well-being group variable are not clearly reported in the provided text. Personality-related effects. The low well-being group had higher neuroticism scores (the extracted methods and discussion consistently report this finding). Further analyses showed that higher neuroticism was associated with greater likelihood of experiencing a positive mood change when mood did change: for example, for LSD the logistic model gave b = 0.01, OR = 1.01, p = 0.04 (95% CI 1.00–1.01). The psilocybin result is truncated in the extraction but is reported in the same direction. In exploratory analyses, higher neuroticism was also associated with greater likelihood of reporting unwanted or negative side effects across substances. Well-being score itself was not predictive of experiencing unwanted effects (all p > 0.21). Additional points. The authors note that some statistically significant associations for continuous predictors may represent small effects that reached significance due to the relatively large sample size. Several referenced tables and figures that would provide fuller numerical detail are not present in the extracted text.

Mason and colleagues interpret the findings as indicating user awareness of the importance of set and setting: classic psychedelics (LSD, psilocybin) were most commonly used at home, ayahuasca in ceremonial or ritual contexts, and MDMA in party or festival environments, aligning with historical and contemporary patterns of use and motives (for example, MDMA for social/hedonic reasons; classic psychedelics for introspection or spiritual aims). The authors suggest the predominance of home settings for classic psychedelics mirrors the comfortable, living-room-style environments emphasised in therapeutic research. Regarding mood outcomes, the researchers report that most respondents used substances when already in a positive mood and that most did not experience a mood change; when changes did occur, people with low well-being were more likely to report positive mood shifts after LSD, psilocybin, or MDMA but less likely after ayahuasca. The higher propensity for positive change among those with low well-being is interpreted as potentially reflecting a larger room-for-improvement (starting from a more neutral or negative baseline) and is consonant with clinical reports of positive effects in depressed and anxious patients. At the same time, nearly all respondents who took psychedelics while in a negative mood reported some mood change, leading the authors to conclude that pre-use low mood does not invariably produce a negative acute experience; other state factors such as preparedness, openness, intentions and expectations also appear important. Personality (neuroticism) is discussed as a double-edged factor: higher neuroticism was associated with greater likelihood of positive mood change after classic psychedelics, suggesting that people high in this trait need not be automatically excluded from research, but it was also associated with increased reports of unwanted effects. The authors therefore recommend that participants with higher neuroticism might benefit from additional preparation and integration time and that trials could consider including personality assessment in screening. Key limitations acknowledged by the authors include the cross-sectional, retrospective and self-report design, potential recall inaccuracies, inability to validate responses, selection bias from recruiting on psychedelic-focused forums (which may under-represent people with predominantly negative experiences), and the inability to infer causality (for example, whether low well-being predisposes to greater mood change or vice versa). The extraction also notes that respondents were asked about their average experience, and the authors highlight that single negative experiences can have disproportionately large lasting effects, so future work should differentiate between specific episodes. Despite these caveats, the authors conclude that recreational users appear mindful of set and setting and that individuals with low psychological well-being and higher neuroticism report predominantly positive acute outcomes, a finding the authors suggest supports continued investigation of psychedelics in clinical populations.