Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study

Psychedelic substances produce marked alterations in perception, mood and cognition and are increasingly investigated for therapeutic uses across a range of psychiatric and neurological conditions. Earlier research has reported promising outcomes for substances such as psilocybin, LSD, DMT, MDMA and ketamine in disorders including treatment-resistant depression, PTSD, addiction and anxiety associated with life‑threatening illness, and has noted improvements in wellbeing and prosocial behaviour. Despite the growing evidence base, the longstanding clinical assumption that 'set' (the individual's mindset, personality and intentions) and 'setting' (the physical, social and cultural environment of use) shape the nature and therapeutic value of psychedelic experiences has received limited quantitative scrutiny, particularly with respect to how specific motivations, locations and companions relate to psychopathology, wellbeing and the meaningfulness of experiences. Borkel and colleagues set out to address this gap by examining associations between set and setting variables and outcome measures in a large Spanish‑language sample. The study aimed to determine whether distinct motives for use, locations where psychedelics were taken and types of companion present predict self‑reported meaningfulness of experiences, various wellbeing indices and measures of psychopathology, and to generate experimental hypotheses for future clinical and longitudinal studies.

This correlational study collected data via an online Spanish‑language survey distributed through social media (Facebook, Reddit, LinkedIn) between September and November 2022. The final sample comprised 1,022 respondents from Spanish‑speaking countries and the United States; 63.3% lived in Europe, 30.7% in South America and the remainder in North America or other continents. The sample was 52.2% male and 47.8% female, with reported mean ages of 41.3 years (±13.7) for males and 36.7 years (±13.7) for females. Most participants lived in urban areas (79%), and 68% reported university education. Ethical approval and informed consent were obtained. To measure substance use patterns and set/setting variables the investigators developed the 39‑item Psychedelic Use Scale (PUS). The PUS gathered sociodemographics, lifetime and recent use of a range of substances (LSD, psilocybin, DMT, mescaline, MDMA, ketamine, Salvia, ibogaine, 5‑MeO‑DMT), motivations for use (including self‑knowledge, fun seeking, therapeutic, spiritual, creativity, escapism, group acceptance, and 'not knowing'), locations of use (home, nature, street, parties, retreats, clinic, research centre, religious space) and types of companion (therapist, shaman, friends, partner, family, religious community, strangers, alone). The PUS intentionally did not attempt to quantify dose. Outcome measures included standardised Spanish‑language instruments: the Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), the International Positive and Negative Affect Schedule short form (I‑SPANAS‑SF), the Philadelphia Mindfulness Scale (PHLMS), the Satisfaction With Life Scale (SWLS), the IPIP Big Five inventory, and the SA‑45 symptom checklist for psychopathology. Internal consistencies for these scales in Spanish validations were reported in the paper. Data analysis was performed in R using nonparametric methods because normality assumptions were violated. The MRCV package was used to compute phi coefficients and odds ratios for associations among categorical PUS items. Spearman correlations assessed relationships among continuous or ordinal variables. Stepwise regression with Akaike information criterion (AIC) was employed for variable selection to examine how set and setting predictors related to wellbeing, personality and psychopathology outcomes. Substances were analysed in aggregate rather than separately.

Sample composition and substance use: Of 1,022 respondents, 750 (73.4%) reported lifetime psychedelic use and 272 (26.6%) were psychedelic‑naive. Among users, 78.5% continued to use psychedelics while 21.5% reported they no longer consumed them. Psilocybin, LSD and MDMA were the most commonly used substances. Lifetime overall use was most frequently estimated between 1 and 30 times, and annual use typically fell between two and 11 times. Microdosing had been attempted by 348 users (46%). Cannabis, alcohol and caffeine were the most commonly combined substances. Set and setting distributions and associations: The principal motivations ranked (in descending order) as self‑knowledge, fun seeking, therapeutic purposes, creativity enhancement and spiritual/religious purposes. Locations most commonly reported were natural settings and home; companions most frequently were friends, partner, alone or a shaman/spiritual guide. Contingency analyses showed plausible patterns: home was positively associated with being alone or with a partner and with therapeutic, self‑knowledge and creativity motivations; nature was associated with self‑knowledge, spiritual/religious, creativity and therapeutic motives; parties and street use were linked to fun seeking and escapism; retreats and therapy settings were positively associated with shamans/therapists and therapeutic or spiritual motivations. These detailed associations were reported in supplementary tables. Meaningfulness and correlates: More than 50% of consumers rated their psychedelic experiences as highly or very highly meaningful, and many classified an experience among their top five most important life events. Meaningfulness correlated positively with frequency of meditation practice (Spearman r = 0.24, p < 0.0001), frequency of sports practice (r = 0.10, p = 0.004), trait openness (r = 0.23, p < 0.0001), agreeableness (r = 0.11, p = 0.003), relatedness (r = 0.12, p = 0.0007) and estimated lifetime use (r = 0.13, p = 0.0004). No significant correlations emerged between meaningfulness and trait mindfulness, affect, autonomy, competence, life satisfaction, extraversion, neuroticism, conscientiousness, or the SA‑45 psychopathology subscales. Attitudes toward psychedelic therapy: Overall, 60.7% of respondents said they would be open to trying psychedelic therapy if they developed psychological problems, 18.8% were not open and 20.5% were undecided. Consumers were substantially more likely than non‑consumers to endorse openness and intention to use psychedelics for treatment (for example, 75.5% of consumers were open versus 19.9% of non‑consumers; X2(2) = 310.6, p < 0.0001). Regression results (set and setting predicting outcomes): Stepwise regression models examined how location, companion type and motivation predicted personality, wellbeing and psychopathology measures. Key findings included: - Location: Natural settings consistently predicted better outcomes, including greater wellbeing and lower neuroticism and psychopathology. Home predicted meaningfulness but did not predict positive outcomes in regression models. Parties and retreats showed mixed or ambiguous effects. Clinic/research settings had too few responses to be informative. - Companion: Presence of a therapist was associated with a generally adverse pattern in personality, wellbeing and psychopathology measures, which the authors attribute to the clinical nature of therapy samples. A shaman or spiritual guide predicted increased mindful awareness (trend) and higher wellbeing but was also associated with worse hostility and a trend toward anxiety. Friends, partner and family predicted greater wellbeing and lower psychopathology; friends also predicted higher mindful awareness. Being alone predicted greater wellbeing, more mindful acceptance, and lower neuroticism and psychopathology. Membership of a religious community predicted greater wellbeing and mindfulness and a trend toward lower neuroticism. - Motivation: Escapism (using psychedelics to escape problems) consistently predicted the worst outcomes — higher psychopathology and lower wellbeing. Therapeutic motivation was associated with higher neuroticism, a tendency toward psychopathology, lower wellbeing and lower mindful acceptance but higher mindful awareness. Spiritual/religious motivation predicted lower neuroticism and psychopathology and greater wellbeing. Creativity enhancement surprisingly predicted more psychopathology and a tendency toward increased mindful awareness but lower mindful acceptance. ‘Not knowing’ as a motive predicted lower wellbeing. The authors grouped motives representing self‑knowledge, therapeutic, spiritual/religious and creativity as “growth motivations,” which predicted meaningful experiences and openness to therapy, whereas escapism, group acceptance and not knowing were labelled “problematic motivations” and predicted worse outcomes.

Borkel and colleagues interpret their findings as supportive of the long‑held clinical assumption that set and setting influence the subjective meaningfulness of psychedelic experiences and are associated with measures of wellbeing and psychopathology. The overall pattern aligned with prior observational work (for example, similarities with Lake and Lukas in common substances used, combinations with other drugs, microdosing prevalence and typical locations), although this sample differed in reporting self‑knowledge as the top motivation rather than fun seeking. The authors emphasise that growth motivations (self‑knowledge, therapeutic and spiritual/religious aims, creativity) and natural settings and the presence of significant others were associated with less psychopathology, greater wellbeing and higher reported meaningfulness; in contrast, problematic motivations such as escapism, group acceptance and not knowing predicted more psychopathology and lower wellbeing and did not predict meaningfulness. The investigators discuss several plausible mechanisms and implications. They highlight the positive associations between meaningfulness and practices such as meditation and sports, and with trait openness and social relatedness, suggesting these factors may predispose individuals to derive significance from psychedelic experiences. On the basis of the regression results, they propose experimental hypotheses for clinical trials and longitudinal research: for example, testing whether introducing natural elements to a clinical setting influences therapeutic outcomes, or whether the presence of significant others (friends, family, shamanic figures) modulates effectiveness. They also suggest that pre‑session motivations, particularly escapism, deserve scrutiny as potential predictors or risk factors in therapeutic contexts, and that meditative practice might be a useful covariate to control in trials. Limitations acknowledged by the authors include the correlational design, which precludes causal inference; sampling bias toward consumers (three quarters of respondents were users), although the authors consider this acceptable given the study focus on users; lack of dose measurement and the difficulty of retrospectively assessing dose across varied substances and formats; and the aggregation of different psychedelics in analyses, which prevents substance‑specific conclusions. The authors recommend development of validated dose instruments and substance‑specific analyses in future studies. They frame the present findings as hypothesis‑generating rather than definitive evidence for causal effects, and call for experimental and longitudinal work to test whether set and setting variables causally influence clinical outcomes.

The study provides detailed correlational evidence that set and setting variables are associated with the meaningfulness of psychedelic experiences and with measures of wellbeing and psychopathology in a large Spanish‑language sample. Growth motivations (self‑knowledge, therapeutic, spiritual/religious), natural environments and the presence of significant others were linked to less psychopathology, greater wellbeing and greater reported meaningfulness, whereas problematic motivations (escapism, group acceptance, not knowing) were associated with more psychopathology and lower wellbeing and did not predict meaningfulness. Given the study's correlational design, the authors stress the need for longitudinal and experimental research to establish causal relationships and to inform clinical recommendations.