Effects of psilocybin therapy on personality structure

This open-label study (n=20) found that dosages of psilocybin (10, 25mg) in a supportive setting, for those with treatment-resistant depression (TRD), changed their personality. At 3-month follow-up, Neuroticism was decreased, Extraversion and Openness were increased. The changes were similar (but more pronounced) to changes after conventional antidepressant treatment.


Objective: To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment‐resistant depression (TRD).

Method: Twenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3‐month follow‐up using the Revised NEO Personality Inventory (NEO‐PI‐R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS‐SR16.

Results: Neuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO‐PI‐R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend‐level increases, and Agreeableness did not change.

Conclusion: Our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.”

Authors: David Erritzoe, Leor Roseman, Matthew M. Nour, Katherine MacLean, Mendel Kaelen, David J. Nutt & Robin L. Carhart-Harris


Significant outcomes

After psilocybin-facilitated therapy for treatment-resistant depression, personality traits Neuroticism and Extraversion decreased, while traits Conscientiousness (trend-level) and Openness increased.


Major depression affects 10 – 15% of the general population and is associated with high morbidity, socio-economic burden, and rates of completed suicide. Treatment-resistant depression (TRD) affects 30% of patients with major depression and up to 60% if TRD is defined as absence of remission.

In the 1990s, neurobiological and psychiatric interest in classic serotonergic psychedelic compounds began to re-emerge after decades of being suppressed. Psychedelic-assisted therapy is a new treatment paradigm that involves only one or two sessions in which a moderate to high dose of a psychedelic compound is given in a supportive environment.

The mechanisms underlying the long-lasting therapeutic effects of psychedelic therapy remain unknown, but there is a relationship between the therapeutic outcome and the subjective experiences during the psychedelic sessions. Moreover, psilocybin and LSD may increase the NEO-PI-R (39) personality trait Openness to Experience in healthy volunteers after a single dose.

The aim of this study was to explore whether psychedelic experiences change personality parameters in patients suffering from treatment-resistant depression.


Twenty patients suffering from treatment-resistant depression were enrolled in this open-label feasibility study. Five patients had previously tried a psychedelic drug, and all but three had undergone psychological therapy/counseling.

Study procedure

Patients were screened using a scripted telephone interview, then attended a screening visit, followed by two dosing sessions, separated by one week. The second session was the focus of the therapeutic process, and patients came back one day and again one week after the 25 mg session for integration.

Baseline personality scores as predictors of Peak Experience

The NEO-PI-R domain of Openness showed a borderline significant association with blissful state experienced during the psychedelic experience. Two facets of this personality domain, Openness to Fantasy and Openness to Aesthetics, also showed positive associations with blissful state.


In a psilocybin therapy study for treat-resistant major depression, patients’ personality measures changed significantly. Neuroticism, Extraversion, Openness, Conscientiousness, and Agreeableness were among the traits that changed.

The detected pre- to post-treatment changes in both trait and facet scores in our trial corresponded well with observations from a study of patients who successfully underwent pharmacotherapy, mostly with selective serotonin reuptake inhibitors (SSRIs), for major depression (42).

SSRI/SNRI-induced reductions in depression severity are associated with decreases in Neuroticism and increases in Extraversion, albeit at only trend-level significance. Increased Openness did not correlate with treatment response, although there is some evidence to suggest there is a moderate relationship between Openness and psychological wellbeing.

A meta-analysis of personality changes after therapeutic interventions revealed that only trait Openness did not robustly change (50). We identified 5 patient samples from 3 different trials in major depression where NEO-PI-R domain changes were reported after treatment with antidepressant medication (47, 51, 52).

Although the facet scores were not reported in these studies, the facets Openness to actions and to values significantly increased in our study. This finding suggests that the changes in Openness facets observed in our study may be different from the changes seen with conventional pharmacotherapy.

Studies investigating the relationship between psychedelics and personality among non-depressed individuals have shown that psychedelics may have long-lasting effects on personality. For example, a single high dose of psilocybin with psychological support can lead to long-lasting increases in trait Openness.

It is well established that trait Openness correlates reliably with liberal political perspective, and psychedelics have been found to modulate Openness. Psychedelics may also modulate political perspective by increasing pro-environmental behavior and nature-relatedness, as well as liberal and antiauthoritarian perspectives.

The Openness score among patients entering our trial was already slightly higher at baseline than the normative scores reported in the NEO-PI-R manual (66), and increased another 4.9 T-score points following the intervention. This differs from the other three personality traits in that it changed from an already higher than average baseline to an even higher level.

A single profound psychedelic experience can lead to lasting changes in personality, which is intriguing when considering the relative stability of personality once adulthood is reached. However, the literature on personality changes is limited and does not provide evidence for how fast personality can change.

Of the acute experience factors most related to personality change, greater insightfulness and spiritual experience were correlated with decreased Neuroticism and increased Extraversion at 3 months. Borderline relationships were seen between increased Extraversion and higher blissful state and Experience of unity scores. The major personality changes observed in this study were not strongly predicted by factors relevant to ‘mystical experience’. However, the somewhat more concrete notion of insightfulness showed more compelling relationships with the personality changes.

This study’s findings are inconsistent with those of MacLean et al. (40), who found that individuals who had a ‘mystical-type’ experience were more likely to show sustained increases in Openness several months later.

PET imaging has revealed that brain serotonin 2A receptor levels are positively associated with Neuroticism scores, and that dysfunctional attitude is associated with elevated serotonin 2A receptor levels in both depressed patients and individuals recovered from depression.

Although serotonin 2A receptors have not been directly associated with Openness, it is possible that serotonin 2A receptor function is linked to Openness, as well as cognitive flexibility and creative thinking.

In summary, patients suffering major depression showed changes in personality measures from baseline to 3 months post psilocybin therapy. These changes were consistent with what has been found previously among patients responding to antidepressant treatment.

Study details

Compounds studied

Topics studied
Depression Personality Treatment-Resistant Depression

Study characteristics
Open-Label Follow-up Re-analysis

20 Humans


Authors associated with this publication with profiles on Blossom

David Erritzoe
David Erritzoe is the clinical director of the Centre for Psychedelic Research at Imperial College London. His work focuses on brain imaging (PET/(f)MRI).

Leor Roseman
Leor Roseman is a researcher at the Centre for Psychedelic Research, Imperial College London. His work focussed on psilocybin for depression, but is now related to peace-building through psychedelics.

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

David Nutt
David John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.


Institutes associated with this publication

Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 10 - 25
mg | 2x

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up
This open-label study (n=20) expands on earlier work by Carhart-Harris and colleagues on the use of psilocybin-assisted therapy for treatment-resistant depression (TRD).

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
This is the first modern study (n=12) on psilocybin and its effects on treatment-resistant depression (TRD). It shows that two sessions with psilocybin (10mg and 25mg) in combination with psychological support can reduce depressive symptoms over periods of one week to three months after treatment. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred.

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