Neuroticism is associated with challenging experiences with psilocybin mushrooms

Classic hallucinogens such as psilocybin produce a wide range of perceptual, cognitive and emotional effects that can be intensely positive or deeply challenging. Earlier research has pointed to set (the person’s internal state and intentions), setting (the environment) and personality traits as key sources of individual variability in psychedelic responses, but evidence linking specific personality dimensions to the frequency and intensity of challenging experiences is inconsistent. Small clinical and observational studies have suggested a positive association between neuroticism and ‘bad trips’, whereas a pooled analysis of controlled studies reported no relationship, possibly because those studies screened out participants with high neuroticism or provided highly supportive laboratory conditions that mitigate challenging effects. Barrett and colleagues set out to test whether neuroticism is associated with the strength of challenging experiences in large, naturalistic samples. To do so they analysed data from two separate online surveys of difficult experiences with psilocybin mushrooms, using established measures of challenging experience and Five Factor Model personality traits. The primary hypothesis was that higher neuroticism would predict stronger challenging experiences as measured by the Challenging Experience Questionnaire (CEQ).

The investigators analysed responses from two independent internet surveys. Study 1 comprised 1,993 participants and constituted a secondary analysis of previously reported data; Study 2 comprised 981 participants who completed a separate survey. In both studies participants were recruited mainly via websites frequented by people interested in psychedelics and were included only if they reported a difficult or challenging experience after ingesting an active dose of psilocybin mushrooms. Exclusion criteria included age under 18 at survey completion, having the challenging experience in a research-study context, reporting on another person’s experience, attributing the event to additional substances, or raising validity concerns in free responses. Participants were not compensated. Challenging experiences were measured with the 26-item Challenging Experience Questionnaire (CEQ), which yields seven latent factors: fear, grief, insanity (feeling of losing one’s sanity), death (feeling as though one is dying), isolation, physiological distress, and paranoia. In Study 1 CEQ items were extracted from larger hallucinogen-sensitive questionnaires (HRS, SOCQ, 5D-ASC); in Study 2 the CEQ was administered as a stand-alone instrument. Personality was assessed with the Ten Item Personality Inventory (TIPI) in Study 1, which provides brief factor estimates for the Five Factor Model including emotional stability (the inverse of neuroticism); Study 2 used the 44-item Big Five Inventory (BFI) to estimate neuroticism and other FFM factors. The main analytic approach was structural equation modelling (SEM). Analysis 1 in each study modelled the seven CEQ latent variables and estimated paths from each FFM factor to each CEQ factor. Analysis 2 modelled a second-level CEQ total latent variable (all seven CEQ factors loading onto a global CEQ) predicted by the five FFM factors. Bonferroni correction was applied for multiple comparisons (p < 0.0014 for Analysis 1 and p < 0.01 for Analysis 2). Model fit was assessed with standard indices (CFI, SRMR, RMSEA) with pre-specified thresholds indicating acceptable fit. Additional analyses included logistic regressions in Study 1 testing whether emotional stability predicted reported intentions for taking psilocybin (e.g. peer pressure, curiosity, recreational, self-exploration, spiritual exploration), and moderation analyses (Analyses 3 and 4) to test whether intention moderated the relationship between emotional stability/neuroticism and CEQ factors or CEQ total scores.

Study 1 (N = 1,993) found that lower emotional stability (i.e. higher neuroticism) measured by the TIPI was significantly and negatively associated with six of the seven CEQ latent variables in Analysis 1; the exception was the death latent variable, which was not associated with emotional stability but showed a positive association with openness. In Analysis 2 the CEQ total latent variable was significantly negatively associated with emotional stability (B = -0.250, SE = 0.030, Z = -8.380, p < 0.0001) and not with other TIPI scales. Model fit indices indicated acceptable fit for both analyses (Analysis 1: CFI = 0.915, SRMR = 0.041, RMSEA = 0.057 [95% CI: 0.054–0.059]; Analysis 2: CFI = 0.913, SRMR = 0.043, RMSEA = 0.055 [95% CI: 0.053–0.058]). Logistic regressions on Study 1 data showed that individuals with lower emotional stability were more likely to report taking psilocybin due to peer pressure (odds ratio for emotional stability = 0.887, z = -2.863, p < 0.005) and were less likely to report taking it for serious psychological self-exploration (odds ratio = 1.043, z = 2.496, p < 0.05) or spiritual exploration (odds ratio = 1.047, z = 2.625, p < 0.01). Free-response follow-up of the “Other” intention category did not provide clear evidence of widespread coercion. Moderation analyses (Analyses 3 and 4) did not find that intention significantly moderated the relationship between emotional stability and CEQ factor or total scores. Study 2 (N = 981) replicated the principal finding using the BFI: neuroticism was significantly and positively associated with each CEQ latent variable except the death factor, which showed no significant associations. Analysis 2 showed CEQ total scores were significantly associated with neuroticism (B = 0.259, SE = 0.042, Z = 6.091, p < 0.0001) and not with the other BFI scales. Model fit indices again indicated acceptable fit (Analysis 1: CFI = 0.911, SRMR = 0.045, RMSEA = 0.061 [95% CI: 0.058–0.064]; Analysis 2: CFI = 0.905, SRMR = 0.051, RMSEA = 0.059 [95% CI: 0.056–0.062]).

Barrett and colleagues interpret their results as evidence that higher neuroticism is associated with stronger challenging experiences with psilocybin mushrooms in large, naturalistic samples, and that this finding replicated across two independent surveys using different personality instruments (TIPI and BFI) and CEQ formats. The association with openness observed for the death latent variable in Study 1 was not replicated in Study 2, and so the authors regard that link as unreliable. They discuss plausible mechanisms consistent with existing personality research: neuroticism reflects a tendency toward negative emotionality and poorer stress-coping, which may extend to pharmacological stressors such as psychedelics. The common preparatory instruction in therapeutic work to “let go” may be more difficult for people high in neuroticism, potentially increasing the likelihood of challenging reactions. Although participants with higher neuroticism in Study 1 were somewhat more likely to report peer pressure as an intention for taking psilocybin, the authors note the effect size was moderate and moderation analyses did not support coercion as the central driver of the relationship between neuroticism and challenging experience. The investigators acknowledge important limitations. The cross-sectional, retrospective survey design precludes causal inference; challenging experiences might be more intense in neurotic individuals, or very challenging episodes might in some cases alter trait measures. Differences between these naturalistic samples and controlled laboratory studies that failed to find a relationship may reflect screening procedures that exclude high-neuroticism individuals, or the structured support provided in experimental settings that can mitigate challenging effects. The authors therefore recommend further research to test whether higher neuroticism predicts more challenging experiences in clinical settings and whether this influences therapeutic outcomes. For future work they suggest extending investigation beyond Five Factor Model traits to other personality constructs linked to psychopathology (for example alexithymia and behavioural inhibition/activation), and considering whether additional preparation or integration might improve therapeutic efficacy for people high in neuroticism. The authors emphasise that under supportive conditions with appropriate screening and integration, psychedelics may be therapeutic, but personality factors such as neuroticism warrant attention in predicting and managing challenging experiences.