Personality, as measured by the Big Five inventory, is conventionally treated as one of the most stable structures in adult psychology. Trait-level change across a decade in healthy adults is typically small, on the order of one to two T-score points per domain. Then in 2011 MacLean, Johnson, and Griffiths published a study in the Journal of Psychopharmacology showing that a single high-dose psilocybin session produced Openness changes larger than that decade-scale drift, sustained past 14 months, in the subgroup of participants who had genuine mystical-type experiences. Fifteen years later, the finding has been replicated, refined, and stress-tested across clinical and healthy populations.
This article walks through what the data actually shows, what it does not show, and what the gap between research conditions and real-world use means for anyone considering a psilocybin session in 2026. The pivotal sources are the MacLean 2011 healthy-volunteer study (PMID 21956378), the Erritzoe 2018 treatment-resistant depression study in Acta Psychiatrica Scandinavica (PMID 29923178), the Weiss 2023 RCT comparing psilocybin against escitalopram in Psychological Medicine (PMID 37264814), the Aday 2020 long-term effects meta-review in Neuroscience and Biobehavioral Reviews, and the MacLean 2012 follow-on analysis of the mystical-experience predictor.
For deeper coverage of related axes, see psychedelics and decision-making, the MEQ30 as a predictor of outcomes, the use of psychedelics around major role transitions, the structure of an integration session, and the specific case of high-functioning depression.
- MacLean, Johnson, and Griffiths (2011, n=51) found Openness increases that persisted past 12 months following one or two high-dose psilocybin sessions, larger than the personality drift typically observed across decades of normal adult life.
- Erritzoe and colleagues (2018, n=20 treatment-resistant depression) replicated the Openness finding and additionally showed Neuroticism reductions and Extraversion increases at three months post-session.
- Weiss and colleagues (2023) in a head-to-head RCT found that psilocybin produced larger and more consistent personality changes than escitalopram over the same window in depression treatment.
- Roughly 60 percent of participants across the available studies show a measurable Big Five shift at the one-year mark, with the effect clustering in those who reported mystical-type experiences and engaged in deliberate integration.
- Mystical-experience depth and session insightfulness are the two strongest predictors of trait change, per the Aday 2020 meta-review covering long-term follow-up data across multiple studies.
Why Does Personality Change Matter in This Conversation?
Personality at the trait level is the substrate that produces decisions, relationships, and risk-taking patterns over decades, which is why measurable change is the most consequential downstream effect a psychedelic session can produce. Aday and colleagues in 2020, reviewing long-term follow-up data across the available studies, identified Openness as the most reliably affected Big Five domain, with secondary effects on Neuroticism and Extraversion when sessions occurred in clinical populations.
For founders weighing the decision, this is the variable that matters more than acute mood lift. A two-week mood improvement that fades is not the same intervention as a measurable shift in how a person processes novelty, tolerates ambiguity, and engages with internal experience. The first reverts. The second changes the trajectory of decisions made in the following years. The honest framing of the psilocybin conversation has to start with the difference between these two outcomes.
The data is also unusually clean for a psychiatry-adjacent field. Big Five inventories like the NEO-PI-R have decades of normative data, well-characterized reliability, and known drift rates. When MacLean reported an Openness change larger than the decade-scale drift, that statement carries quantitative weight, not metaphorical weight. This is the rare case in psychedelic research where the measurement instrument is mature enough to make the finding falsifiable.
MacLean, Johnson, and Griffiths in 2011 administered the NEO-PI-R Big Five inventory to 51 healthy volunteers before and after one or two high-dose psilocybin sessions, with an average follow-up of 14 months. The Openness domain showed a statistically significant T-score increase, sustained past the one-year mark in the subgroup of participants who had genuine mystical-type experiences as measured by the MEQ30. The magnitude of this Openness change exceeded the typical decade-scale drift observed in adult normative samples. The clinical implication is that a single high-dose psilocybin session, conditioned on mystical-experience depth, can produce trait-level personality change of a magnitude that normal life experience produces over many years. The effect did not appear in participants whose sessions did not include a mystical-type experience, which means the dose alone is not the active ingredient.
What Did the MacLean 2011 Study Actually Find?
MacLean, Johnson, and Griffiths in 2011 enrolled 51 healthy volunteers, administered the NEO-PI-R before and after one or two supervised high-dose psilocybin sessions, and found an Openness increase that persisted past 12 months in the mystical-experience subgroup. The average follow-up was 14 months. The effect size was larger than decade-scale Openness drift in adult normative samples. This was the first rigorous demonstration that single-session psychedelic experience could produce durable trait-level change.
The Study Design and Population
Participants were healthy adults with prior interest in spiritual practice but no recent psychedelic use. Sessions took place in a clinically supervised setting with extensive preparation and trained monitors present. Doses were in the 20 to 30 mg/70kg range, which is well above threshold for mystical-type experiences. The Big Five was measured at baseline, one to two months post-session, and at long-term follow-up averaging 14 months.
What the Numbers Showed
Openness increased by approximately four T-score points in the mystical-experience subgroup, a change that is large by personality-psychology standards. The change was sustained past 12 months. The other four domains, Conscientiousness, Extraversion, Agreeableness, and Neuroticism, did not show statistically significant change in this healthy sample. The Openness signal was specific, not a global personality shift.
The Critical Conditioning Variable
The change was not produced by the dose itself. It was produced by the depth of the mystical experience during the session, as measured by the MEQ30. Participants who scored high on mystical experience showed the Openness change. Participants who received the same dose but did not have a mystical experience showed minimal change. This finding has shaped every subsequent psilocybin study and is the reason the MEQ30 has become a near-standard outcome predictor.
Erritzoe 2018 Extended the Finding to Clinical Populations
Erritzoe and colleagues in 2018 took the MacLean framework into a clinical population, measuring the Big Five in 20 treatment-resistant depression patients before and three months after two psilocybin sessions, and found reductions in Neuroticism alongside increases in Extraversion and Openness. The replication mattered because it answered the question of whether the MacLean finding generalized beyond healthy spiritual-practice volunteers.
Why the TRD Population Matters
Treatment-resistant depression is the population where the personality-change question has the most clinical weight. High Neuroticism is a documented vulnerability factor for recurrent depression. A reduction in trait Neuroticism, if durable, is not just a symptom change. It is a change in the substrate that generates the symptoms. The Erritzoe finding suggested that psilocybin was producing trait-level remodeling, not only state-level mood lift.
The Predictor of Neuroticism Reduction
The strongest predictor of trait Neuroticism reduction at three-month follow-up was insightfulness during the session, measured by self-report scales of personal insight and emotional breakthrough. This is the second major conditioning variable in the literature, alongside mystical-experience depth. The finding implies that the active session-level ingredient for Neuroticism change is something like a felt sense of psychological understanding, not the sensory or perceptual intensity of the experience.
Extraversion as a Secondary Signal
Extraversion also increased significantly in the Erritzoe sample, which is consistent with the broader clinical pattern of post-session social re-engagement after depression remission. This change is harder to interpret as pure trait change versus symptom remission, since depressed patients are typically socially withdrawn at baseline. The Aday 2020 meta-review treats the Extraversion signal as real but less specific than the Openness and Neuroticism findings.
The Weiss 2023 RCT Added a Head-to-Head Comparison
Weiss and colleagues in 2023, in a head-to-head randomized controlled trial comparing psilocybin against the SSRI escitalopram for major depression, found that psilocybin produced larger and more consistent personality changes over the same six-week window than the standard antidepressant comparison. The study, published in Psychological Medicine, was the first to directly contrast psilocybin against an active pharmacological comparator on personality outcomes.
Why a Head-to-Head Design Was Needed
The MacLean and Erritzoe findings were open to the interpretation that any meaningful clinical improvement would produce personality change, and that psilocybin was simply a more effective antidepressant than baseline. The Weiss RCT controlled for this. Both arms produced clinical improvement. Only the psilocybin arm produced the personality-level signal. The difference is not reducible to mood improvement, which is a meaningful constraint on the mechanism.
The Pattern of Change
Psilocybin participants showed larger reductions in Neuroticism and larger increases in Extraversion than escitalopram participants over the six-week measurement window. Openness changes were also larger in the psilocybin arm. The pattern is consistent with the Erritzoe findings in TRD and the MacLean findings in healthy volunteers, suggesting a stable cross-population signature rather than a population-specific artifact.
The Honest Limitation
Six weeks is short for personality measurement. The Weiss RCT does not yet have one-year follow-up data published, which means the durability question is open in this specific design. The MacLean 14-month and Aday meta-review data support durability under research conditions, but the Weiss arm cannot yet add direct evidence on that point. The conservative reading is that Weiss confirms the acute pattern and the cross-condition specificity, while durability remains anchored on MacLean and the longer-follow-up replications.
Weiss and colleagues in 2023 conducted a head-to-head randomized controlled trial comparing two 25 mg psilocybin sessions against six weeks of escitalopram in patients with major depressive disorder, with Big Five personality outcomes assessed at six weeks post-treatment. The psilocybin arm showed significantly larger reductions in Neuroticism and increases in Extraversion than the escitalopram arm over the matched window. Openness increases were also larger in psilocybin participants. The clinical implication is that the personality changes observed after psilocybin sessions are not simply downstream of antidepressant effect, since the active comparator produced clinical mood improvement without the same personality-level signal. The pattern is consistent across MacLean 2011 healthy volunteers, Erritzoe 2018 treatment-resistant depression, and Weiss 2023 major depression, supporting a stable cross-condition signature.
What Predicts Whether Personality Actually Changes?
Across the 15 years of available data, two session-level variables consistently predict trait change: mystical-experience depth as measured by the MEQ30, and session insightfulness measured by personal-insight and emotional-breakthrough scales. Aday 2020, aggregating across studies, estimated that roughly 60 percent of participants under research conditions show a measurable Big Five shift at the one-year mark. The non-responder rate is therefore meaningful and is largely explained by these two predictors.
Mystical-Experience Depth Drives Openness
The MEQ30 captures features like unity, transcendence of time and space, noetic quality, and ineffability. Participants who score high on these dimensions during the session show the Openness change. Participants who receive the same dose but do not access the mystical state show much smaller effects. This is the most robust finding in the literature and is the reason set, setting, and preparation receive so much weight in clinical protocols.
Session Insightfulness Drives Neuroticism Reduction
Insightfulness is a separable construct from mystical experience. It captures the felt sense of seeing one's own patterns clearly, of understanding the structure of a long-held emotional pattern, and of experiencing what some participants describe as emotional breakthrough. This is the predictor for Neuroticism reduction in the Erritzoe data. The clinical implication is that a session can be experientially profound on the mystical axis without producing the Neuroticism shift, and vice versa.
Integration Quality Determines Durability
Session-level predictors set the ceiling. Integration determines whether the ceiling is reached. The participants whose personality changes held at 12 months were almost always the ones who engaged with deliberate integration during the post-session plasticity window. The mechanism is straightforward. A new way of seeing has to be loaded into actual behavior to become a trait. Without behavioral consolidation, the new perception reverts to baseline within weeks.
"Across 900-plus integration sessions, the pattern that predicts durable change at the one-year mark is consistent. The participant had a session with genuine depth, and then they restructured at least one major behavior pattern in the following 90 days. The session set the ceiling. The behavior change made the ceiling stick."
How Should Founders Translate This Data into a 2026 Decision?
The data supports a specific, conditional claim: a properly screened participant in a properly structured session has a measurable probability of producing durable personality change, but the conditioning variables are non-trivial and most retreat contexts do not reliably reproduce them. The Aday 2020 estimate of roughly 60 percent measurable shift at one year is a research-condition number. Translating it to real-world contexts requires honest accounting of what those conditions actually were.
What the Research Conditions Looked Like
MacLean, Erritzoe, and Weiss all involved rigorous medical screening that excluded bipolar spectrum, psychotic-spectrum, and high-cardiovascular-risk participants. Sessions included extensive preparation, trained monitors throughout, and structured integration follow-up. Doses were standardized and pharmaceutical-grade. The 60 percent number applies to this combined package, not to dose alone.
The Behavioral Consolidation Window
The first 90 days after a session are the consolidation window where new perception either loads into behavior or reverts. The Aday 2020 review identified integration engagement as the strongest predictor of effect durability at one year. In practical terms, this means a deliberate restructuring of at least one major life pattern. A return to baseline schedule, social context, and decision routines is the most common reason that session-level changes do not become trait-level changes.
What the data identifies as the active ingredients
- Adequate dose for mystical-type experience (typically 20-30 mg/70kg psilocybin in research protocols)
- Set and setting structured to support mystical-experience depth, with trained monitors present
- MEQ30 score in the mystical-experience range, captured post-session
- Session insightfulness and emotional breakthrough during the dosing window
- Two to four integration sessions in the four to eight weeks following the dose
- Restructuring of at least one major life or behavior pattern within the 90-day consolidation window
- Absence of the absolute contraindications discussed in our companion screening article
The Realistic Expectation
The realistic expectation for a properly screened, properly structured session is a meaningful probability, not a certainty, of producing personality-level change at the one-year mark. The probability is higher than any other single intervention currently available for trait Openness or Neuroticism in healthy adults. The probability is also lower than the marketing language around retreat contexts typically implies. The honest framing of the data, fifteen years in, is that this is a high-effect, conditional intervention that requires the conditions to actually be in place.