An investigation of acute Physiological and Psychological Moderators of Psychedelic-induced Personality Change among Healthy Volunteers

Classical psychedelics such as psilocybin produce intense, transient alterations in consciousness, perception and emotion and have been associated with persistent psychological changes, notably in personality domains. Cross-sectional comparisons of regular psychedelic users and controls suggest higher openness and lower harm avoidance among users, but these designs cannot establish causality. Interventional and observational pre-post studies have produced mixed results, with the strongest and most consistent evidence supporting reductions in neuroticism (or harm avoidance) and, less consistently, increases in openness. There is limited work linking the acute psychological and neurophysiological states during psychedelic experiences to these longer-term personality shifts. Godfrey and colleagues set out to test whether a single high dose of psilocybin (25 mg) administered in a psychologically supportive laboratory context produces enduring personality change in psychedelic‑naïve healthy volunteers, and whether acute subjective or electrophysiological measures recorded during the experience moderate any such change. The investigators used a within‑subjects, fixed‑order design in which a sub‑perceptual 1 mg dose (quasi‑placebo) preceded the 25 mg session by one month; hypotheses focused on an increase in openness and a decrease in neuroticism after 25 mg only, with exploratory analyses testing acute psychological and EEG markers (including alpha power and Lempel‑Ziv complexity, LZc) as potential moderators.

The study recruited 28 psychedelic‑naïve healthy volunteers (12 female; mean age 40.6 ± 8.7). A fixed‑order, single‑blind design was implemented: participants received a sub‑perceptual 1 mg dose of psilocybin at the first session, and one month later a high 25 mg dose. To reduce expectancy effects and preserve blinding participants were told they would receive psilocybin in both sessions with dose varying up to 25 mg. Each dosing session lasted 6–8 hours and included psychological support by two guides, preparatory and one‑day post‑session integration meetings, music listening and encouragement of therapeutic intention setting. Personality was measured at three timepoints: baseline (one day before 1 mg), post‑1 mg (one month after 1 mg, i.e. one day before 25 mg) and post‑25 mg (one month after 25 mg). The 44‑item Big Five Inventory (BFI) assessed the five major domains and 20 items from the Big Five Aspect Scale (BFAS) provided finer resolution within Openness (Intellect and Aesthetic Openness). Internal consistency of scales ranged from 0.79 to 0.90. Acute psychological experience was measured at the end of each dosing day using the Altered States of Consciousness (ASC) questionnaire (five factors: oceanic boundlessness, dread of ego dissolution, visionary restructuralisation, auditory alteration, vigilance reduction), the Emotional Breakthrough Inventory (EBI) and single‑item visual analogue scales (0–100) for Intensity, Challenge and Meaning. The Psychological Insight Scale (PIS) was administered on the integration day (one day post dosing). EEG was recorded pre‑dose and ~2 hours post‑dose (peak effects) using a 24‑channel wireless dry electrode cap during 5 minutes of eyes‑closed resting state. Data were band‑pass filtered (1–45 Hz), re‑referenced to common average, artefact‑reduced (ICA for blinks) and epochs of 2 seconds were used. Average absolute alpha power (8–13 Hz) and Lempel‑Ziv complexity (LZc, an index of signal diversity computed on binarised sequences) were calculated at each timepoint and change scores (post minus pre) derived. Due to excessive noise 10 participants (35.7%) were excluded from EEG analyses; they remained in self‑report analyses. Statistical analysis used linear mixed‑effects models (LMEs; analogous to repeated measures ANOVA) to compare personality across the three timepoints. Where time had a main effect, pairwise comparisons were conducted. Moderation analyses tested whether acute psychological or EEG measures moderated significant personality changes; these exploratory moderation tests used both uncorrected and False Discovery Rate (FDR)‑adjusted p‑values (Benjamini‑Hochberg). A further set of analyses explored correlations between baseline personality and the acute moderators using Pearson correlation (uncorrected p < 0.05 reported alongside FDR adjustments).

Sample characteristics and data availability: 28 participants completed the protocol (12 female; mean age 40.6 ± 8.7). EEG recordings were excluded for 10 participants (35.7%) because of excessive noise, leaving 18 participants for EEG‑related analyses. Primary personality outcomes: Neuroticism showed a statistically significant reduction one month after the 25 mg psilocybin session but not after the 1 mg session, indicating dose specificity. Openness and agreeableness exhibited unexpected changes after the 1 mg session: both decreased following the sub‑perceptual dose. After the 25 mg session agreeableness increased relative to the post‑1 mg baseline, but the hypothesised increase in openness after 25 mg was not observed. The authors note that elevated baseline openness in this sample may have limited room for upward change. Moderation of neuroticism change: Two acute high‑dose psychological measures were associated with larger reductions in neuroticism measured pre‑25 mg to one month post‑25 mg. Being one standard deviation higher in the 25 mg Meaning rating was associated with an approximate 0.14 unit greater reduction in neuroticism (on the BFI 1–5 scale) and being one standard deviation higher in the 25 mg Dread of Ego Dissolution (DED) score was associated with an approximate 0.17 unit greater reduction. Neither moderation effect survived FDR correction for multiple comparisons. Other moderation and correlation findings: No significant moderators were detected for the reduction in openness after 1 mg, nor for changes in agreeableness after either dose (all uncorrected p > 0.05). Correlational analyses between baseline personality and high‑dose acute measures found several associations at uncorrected thresholds: higher pre‑25 mg Agreeableness correlated with greater high‑dose Oceanic Boundlessness (r = 0.40, p = 0.04; p(FDR) = 0.68), Intensity (r = 0.43, p = 0.02; p(FDR) = 0.68), and Meaning (r = 0.43, p = 0.02; p(FDR) = 0.68). Lower pre‑25 mg Intellect correlated with greater high‑dose DED (r = -0.52, p = 0.006; p(FDR) = 0.54). EEG and electrophysiological results: Baseline (pre‑25 mg) Conscientiousness correlated inversely with high‑dose absolute LZc (r = -0.52, p = 0.022). Placebo (1 mg) absolute LZc also correlated inversely with baseline (pre‑1 mg) Conscientiousness (r = -0.57, p = 0.011), suggesting this relationship may not be specific to high dose exposure. The study reported that 1 mg produced no notable changes in the EEG metrics recorded during the session, consistent with it being sub‑perceptual. The authors also noted a prior finding from the broader study that higher LZc under 25 mg predicted greater psychological insight, and that insight related to improved wellbeing, but detailed statistics for that chain were not reported in the extracted text. Other notes: The moderation effects for Meaning and DED on neuroticism reduction, and several baseline‑to‑acute correlations, were statistically meaningful at uncorrected levels but generally did not survive FDR correction, and so should be considered exploratory.

Godfrey and colleagues interpret the primary finding—a reduction in neuroticism one month after a single 25 mg psilocybin session—as consistent with a number of prior observational and interventional studies showing post‑psychedelic decreases in neuroticism or harm avoidance. They note, however, that previous laboratory‑based studies in healthy participants have often found no neuroticism change, and suggest contextual factors such as set and setting, and the inclusion of therapeutic preparation, music and compassionate support in the present protocol, may explain the discrepant results. The investigators acknowledge that preparatory intention‑setting and therapeutic framing could amplify expectancy effects, but also point out that expectancy was not adequately measured in this study. The unexpected reductions in openness and agreeableness after the 1 mg session are discussed as unlikely to reflect pharmacological action, given the sub‑perceptual nature of the dose and the lack of EEG change. The authors propose alternative explanations including regression to the mean (given atypically high baseline openness scores in the sample), demand characteristics or Hawthorne‑type inflation of baseline scores, and a possible disappointment/nocebo effect following the inert dose. They note that the moderators studied did not fully capture dimensions such as disappointment, and that these processes were not measured here. Regarding moderation findings, the study observed that higher subjective Meaning and greater Dread of Ego Dissolution during the 25 mg experience were associated with larger neuroticism reductions. The authors highlight that meaningful experiences have been linked to psychological benefits in previous work, and find it noteworthy that an aversive experiential component (dread of ego dissolution) was also associated with positive trait change. This contrasts with some clinical findings where greater dread has correlated with poorer outcomes; the investigators emphasise that the single‑item Challenge rating did not mirror the DED effect, suggesting the dread subscale may capture a distinct experiential quality. The discussion also notes that baseline personality traits appeared to predict aspects of the acute experience—for example, higher agreeableness predicted stronger subjective effects, and lower intellect predicted greater DED—implying that pre‑existing traits may shape acute psychedelic phenomenology. The authors acknowledge important limitations: modest sample size, exploratory nature of the moderation analyses, and the inherent confounds of a fixed‑order within‑subjects design (including order, placebo/nocebo and expectancy effects). They recommend replication in larger samples, measurement of expectancy and blinding integrity in future studies, and caution in interpreting findings that did not survive correction for multiple comparisons. Practical implications or clinical translation are not overstated; instead, the investigators suggest further work to clarify how acute experiential and neurophysiological states relate to sustained personality change and to assess safety and scalability considerations if baseline traits predict challenging experiences.

The extracted text contains a separate Conclusion heading, but the material under it in the provided extraction consists mainly of references to normative data sources for the personality instruments rather than a clear, summarising concluding paragraph. The paper’s principal concluding messages are therefore found in the Discussion: namely, that a single 25 mg psilocybin session in a supportive setting was associated with a reduction in neuroticism at one month, that some acute subjective features of the high‑dose experience were linked to greater reductions in neuroticism, and that findings require replication given sample size and design limitations.