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Healthy VolunteersCreativityPersonality & Trait FactorsPsilocybinPlacebo

Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness

This re-analysis from two psilocybin trials with hallucinogen-naïve subjects (n=52) looked at personality changes in participants. It found significant increases in openness (but not neuroticism, extroversion, agreeableness, and conscientiousness), which remained higher than baseline for those who had a mystical experience up to a year.

Authors

Roland Griffiths
Matthew Johnson
Katherine MacLean

Published

September 28, 2011

Journal of Psychopharmacology

individual Study

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Abstract

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than one year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

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Research Summary of 'Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness'

Introduction

Maclean and colleagues situate their study within evidence that classic hallucinogens such as psilocybin, acting primarily at 5-HT2A receptors, can produce profound subjective changes and, in uncontrolled reports, lasting alterations in attitudes, values and behaviour. The paper highlights mystical-type experiences—characterised by unity, sacredness, ineffability, noetic quality and transcendence of time and space—as candidate mechanisms for enduring change. At the same time, the authors note that core personality traits, as described by the five-factor model (Neuroticism, Extroversion, Openness, Agreeableness, Conscientiousness), are typically stable in adulthood and that prospective, experimentally controlled demonstrations of personality change in healthy adults are lacking. This study combines data from two double-blind controlled investigations to test whether a single high dose of psilocybin (30 mg/70 kg) administered under supportive conditions produces changes in the five broad personality domains measured by the NEO Personality Inventory. Consistent with prior observations linking hallucinogen-occasioned mystical experiences to enduring personal change, the investigators hypothesised that individuals who experienced mystical-type effects during the high-dose session would show enduring increases in Openness assessed 1–2 months after the session and again more than 1 year later.

References (9)

Papers cited by this study that are also in Blossom

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Psychopharmacology (2011)

Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later

Griffiths, R. R. · Journal of Psychopharmacology (2008)

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer

Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)

Human hallucinogen research: guidelines for safety

Methods

Participants were community volunteers recruited for laboratory studies of psilocybin. After telephone pre-screening and in-person medical and psychiatric evaluation, the analyses included 52 hallucinogen-naïve participants (one participant was excluded for incomplete personality data and one for prior psilocybin experience). The sample was generally highly educated and reported regular spiritual activity; participants were not paid and provided informed consent under institutional review board approval. Maclean and colleagues combined two double-blind designs. In Study 1 each participant completed 2–3 eight-hour sessions and received one high psilocybin dose (30 mg/70 kg) and an active control (methylphenidate 40 mg/70 kg) on other sessions. In Study 2 participants completed five sessions with ascending or descending psilocybin doses (5, 10, 20 and 30 mg/70 kg) and a placebo session; the present analyses focus on effects associated with the 30 mg/70 kg session. Sessions were separated by at least 3 weeks. Preparation and support were extensive, and during sessions participants were encouraged to lie down, wear an eye mask, listen to a standard music programme, and focus inward. Primary outcome measurement was the revised NEO Personality Inventory (NEO‑PI‑R), administered at screening, 1–2 months after the high-dose session (post-test), and at approximately 14 months follow-up. Mystical-type experiences during sessions were assessed about 7 hours after drug administration with the States of Consciousness Questionnaire (SOCQ), which yields six subscales; a 'complete mystical experience' was predefined as scoring 60% or higher on each subscale. Additional session measures included a modified Mysticism Scale (lifetime and experience-specific), and the APZ instrument with scales for oceanic boundlessness (OSE), visionary restructuralization (VUS), and dread of ego dissolution (AIA). Scores were standardised where appropriate (NEO T scores: M = 50, SD = 10). Statistical analyses were performed in SPSS v18.0. The core approach used multivariate repeated measures ANOVA to test change from screening to post-test across the five NEO factors, followed by Pearson and Spearman correlations between Openness change and session measures. Stepwise linear regressions tested whether SOCQ mystical scores explained additional variance in Openness change beyond other correlated questionnaires (Mysticism Scale, OSE, VUS, AIA). Finally, the investigators compared participants who met the pre-specified criteria for a complete mystical experience (n = 30) with those who did not (n = 22) to examine group-by-time interactions in Openness and its six facets.

Results

Across the combined sample, Openness increased significantly from screening to the 1–2 month post-test (mean change +2.8 T points; F(1,51) = 5.47, p = 0.023, partial eta squared = 0.10). A subgroup analysis of participants who did not receive a high dose on their first session (n = 30) showed no significant Openness change after that first session (F(1,29) = 0.52, p = 0.48). The other four NEO factors showed no significant mean changes from screening to post-test: Neuroticism (mean −0.5; F(1,51) = 0.24, p = 0.62), Extroversion (mean +0.8; F(1,51) = 0.79, p = 0.38), Agreeableness (mean +1.7; F(1,51) = 2.31, p = 0.16), and Conscientiousness (mean −0.9; F(1,51) = 1.22, p = 0.28). Test–retest correlations across assessments ranged from r = 0.61 to 0.84, indicating overall trait stability. Individual differences in mystical-type experience correlated with Openness change. SOCQ mystical scores (mean across six subscales) correlated with increases in Openness (r = 0.42, p = 0.002), and this relationship held with Spearman rank correlations (r_s = 0.47, p < 0.001). Other session measures also correlated with Openness change: Mysticism Scale (r = 0.33, p = 0.017), OSE (r = 0.44, p = 0.001), VUS (r = 0.41, p = 0.003), and AIA (r = 0.31, p = 0.024). Stepwise regression analyses indicated that SOCQ mystical score accounted for significant additional variance in Openness change beyond each of these alternate measures. Reported R-squared change values for adding SOCQ to models already including another questionnaire were: Mysticism Scale ΔR2 = 0.046 (p = 0.033), OSE ΔR2 = 0.047 (p = 0.031), VUS ΔR2 = 0.042 (p = 0.036), and AIA ΔR2 = 0.12 (p = 0.001). Comparing groups defined by the a priori 'complete mystical experience' criterion revealed a significant time × group interaction on Openness (F(1,50) = 9.32, p = 0.004, partial eta squared = 0.16). Participants who met the complete mystical experience criteria (n = 30) showed a robust increase in Openness from screening to post-test (mean +5.7; t(29) = 3.44, p = 0.002), whereas those who did not meet the criteria (n = 22) did not (mean −1.2; t(21) = 0.87, p = 0.39). Five of the six Openness facets—Fantasy, Aesthetics, Feelings, Ideas and Values—showed the same interaction pattern; the Actions facet did not reach significance. At long-term follow-up (mean 16 months), participants who had a complete mystical experience maintained higher Openness relative to screening (mean +4.2; F(1,29) = 4.17, p = 0.050, partial eta squared = 0.13), with no significant decline from the post-test level. Participants without a complete mystical experience had virtually unchanged Openness at follow-up compared with screening (mean −0.3; p = 0.86). The investigators note that results were similar across the two component studies, and including three participants who had a complete mystical experience at a 20 mg session (but not at 30 mg) did not alter findings.

Discussion

Maclean and colleagues interpret their findings as evidence that a single high-dose psilocybin session, administered under supportive conditions, produced statistically and clinically meaningful increases in the personality domain of Openness in healthy adults. They emphasise that the magnitude of change for participants who had a complete mystical experience (more than 4 T-score points from screening to follow-up) exceeds typical age-related shifts in Openness (about 1 T-score point per decade) and is larger than some changes reported following other interventions such as antidepressant treatment or intensive counselling. The authors link increases in Openness to the content of mystical-type experiences: Openness encompasses aesthetic appreciation, imagination, emotional awareness and intellectual engagement, and significant increases across nearly all Openness facets suggest potential gains in aesthetic and cognitive domains. They contrast their positive long-term findings with a prior controlled LSD study that failed to demonstrate personality change at 6 months, and suggest that differences in participant motivation, preparatory support and spiritual orientation may account for divergent outcomes. The SOCQ emerged as a stronger predictor of Openness change than other session measures; however, the investigators acknowledge that the SOCQ has limited published psychometric validation and that continued evaluation of its sensitivity and validity is needed. They also discuss alternative personality inventories such as the Temperament and Character Inventory and suggest that related constructs (for example, Self-Transcendence) might also change following mystical-type experiences. Key limitations noted by the authors include the need for replication in larger and more diverse samples, the self-selected nature of the sample (many participants were spiritually active and highly motivated), and the fact that the study examined change after a single high-dose session. They acknowledge that multiple sessions might affect additional personality domains and that clinical populations might show different patterns (for example, decreases in Neuroticism have been observed in other treatment contexts). Finally, the investigators outline implications for clinical psychiatry and future research: the findings motivate further investigation of biological and psychological mechanisms linking psilocybin and mystical experience to personality and suggest examining how pharmacological and non-pharmacological conditions might occasion mystical experiences and their long-term consequences.

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INTRODUCTION

Psilocybin and other classic hallucinogens with actions mediated at the 5-HT 2A receptor siteproduce a unique profile of subjective effects including robust changes in perception, cognition, affect, volition, and somaesthesia. In early trials of hallucinogens administered under supportive conditions, 50-80% of participants claimed lasting beneficial changes in personality, values, attitudes and behavior. Some of the most frequent subjective reports included greater appreciation of music, art and nature, greater tolerance of others, and increased creativity and imagination. Consistent with these findings,recently reported that nearly 40% of participants in several laboratory studies of psilocybin claimed positive long-term changes in aesthetic experience and in their relationship with the environment (i.e. nature) following their psilocybin sessions. The long-term positive impact of hallucinogens may depend on their ability to occasion profound insights and mystical-type experiences. The core features of mystical experience, as defined byand, are feelings of unity and interconnectedness with all people and things, a sense of sacredness, feelings of peace and joy, a sense of transcending normal time and space, ineffability, and an intuitive belief that the experience is a source of objective truth about the nature of reality. Because such experiences appear to enable individuals to transcend their usual patterns of thinking, feeling, and acting, it is plausible that they could occasion changes in core dimensions of personality. In support of this, a doubleblind controlled study bydemonstrated that a single psilocybin session occasioned mystical experiences associated with positive changes in behaviors, attitudes and values more than a year later. Moreover, independent ratings from participants' romantic partners, coworkers, and friends corroborated the first-person reports. These findings suggest fundamental changes in personal concerns, goals, and identity, which are considered to be important dimensions of personality (e.g. in the framework described in. However, the impact of psilocybin-occasioned mystical experience on core personality traits is unknown. There is general agreement that personality traits are relatively enduring styles of thinking, feeling, and acting. The most widely accepted model of personality structure is the five-factor model, which describes five broad domains of personality, each encompassing many related traits: Neuroticism, Extroversion, Openness, Agreeableness and Conscientiousness. Many studies have confirmed that these personality factors are heritableand reliable across cultures, suggesting a universal human personality structure that is rooted in biology. Longitudinal studies have shown that individual personality is predominantly stable across the lifespan. Although there are mean-level personality changes after age 30, these shifts are typically gradual and subtle (1-2 T-score points per decade;. Despite the relatively stable nature of personality, researchers have hypothesized that significant life events could change adult personality quite dramatically. Studies investigating individual differences in personality trait change have found that certain life experiences are associated with changes in adult personality (see review in. For example, personality changes have been associated with divorce (e.g. increases in Extroversion and Openness in women,, remarriage (e.g. decreases in Neuroticism in men,, and career success (e.g. decreases in Conscientiousness in individuals who were fired versus promoted,. However, such correlational studies cannot address the causal link between particular events and subsequent personality change. Relatively little research has investigated personality change in the laboratory, likely because events that might be expected to change personality are difficult to create under experimental (i.e. randomized or assigned) conditions. Some studies have shown changes in personality after experimental treatment interventions in patients, such as several weeks of antidepressant medication (e.g.and intensive outpatient counseling for substance abuse rehabilitation. Personality changes have also been shown in healthy adults after 3 months of intensive contemplative training in attention and emotion regulation. These personality changes, as well as socioemotional and behavioral improvements, were maintained several months after completion of training, suggesting possible long-term benefits. To our knowledge, no study has prospectively demonstrated personality change in healthy adults after an experimentally manipulated discrete event. Although it has been speculated that treatment with classic hallucinogens could be a method for occasioning dramatic and rapid personality change, a controlled study of LSD in healthy volunteers failed to find significant changes in a large battery of empirical measures of personality, aesthetic sensitivity, and creativity 6 months after LSD sessions. Nevertheless, these investigators confirmed the subjective claims of long-term change frequently reported in uncontrolled trials. The subjective claims of hallucinogen-occasioned long-term changesappear to align with the modern personality construct of Openness, which encompasses aesthetic appreciation and sensitivity, imagination and fantasy, and broad-minded tolerance of others' viewpoints and values. The present report combines data from two double-blind controlled studies of psilocybinto analyze changes in Openness and the other four broad personality domains using the NEO Personality Inventory. Personality change was assessed 1-2 months after a high-dose psilocybin session and again more than 1 year later to determine the persistence of personality change. Consistent with previous results indicating a correlation between mystical experiences during the session and longterm spiritual significance and personal meaning attribution, we hypothesized that mystical experiences during the psilocybin session would lead to enduring increases in Openness.

PARTICIPANTS

Recruitment methods and screening procedures were similar across the two studies. Participants were recruited from the local community by flyers announcing 'a study of states of consciousness brought about by psilocybin, a naturally occurring psychoactive substance used sacramentally in some cultures'. The first phase of screening involved a scripted telephone interview, which was used to pre-screen for the major inclusion/exclusion criteria. Common reasons for not passing the telephone screen included distance from study site, extensive prior hallucinogen use, and inability to make the time commitment required for participation. Individuals who passed the telephone screen (approximately 20% of those screened) were evaluated in person for inclusion/exclusion criteria and medical and psychiatric health, as described previously for human research with classic hallucinogens. The inclusion/exclusion criteria were similar across the two studies, although participants in Study 2 were permitted to have limited prior experience with hallucinogens. The single participant in Study 2 who had prior lifetime experience with psilocybin was excluded from the present analyses. In addition, one participant in Study 1had incomplete personality data and was excluded. Thus, the present analyses included 52 hallucinogen-naı¨ve participants (Table). Participants were generally well educated (54% had postgraduate degrees) and spiritually active (90% regularly participated in religious services, discussion groups, prayer, or meditation). Participants did not receive monetary compensation but generally reported being motivated by curiosity about the effects of psilocybin and the opportunity for extensive selfreflection. The Institutional Review Board of the Johns Hopkins University School of Medicine approved the studies, and all participants gave their informed consent before participation. Psilocybin sessions Dose conditions. Participants completed 2-5 8-h drug sessions, with consecutive sessions separated by at least 3 weeks. Participants were informed that they would receive a 'moderate or high dose' of psilocybin during one of their drug sessions, but neither the participant nor the session monitors knew when this session would occur. In Study 1, each participant received psilocybin (30 mg/70 kg body weight) on one session and an active control drug, methylphenidate (40 mg/70 kg), on the other one or two sessions. In Study 2, each participant received four doses of psilocybin (5, 10, 20 and 30 mg/70 kg) in ascending or descending order (50% random assignment) across four sessions, with a fifth placebo session quasi-randomly inserted in the sequence. In the present report, we analyzed mystical experiences and changes in personality associated with the high-dose (30 mg/70 kg) psilocybin session. Session protocol. Participants received extensive preparation and met with session monitors for at least 8 h on several different occasions prior to their first drug session, in line with recommendations for hallucinogen research. The drug was orally administered in capsule form with 100 mL water at the beginning of each session. During the session, participants were encouraged to lie down on a couch, use an eye mask to block external visual distraction, wear headphones through which a music program was played, and focus their attention on their inner experiences.

MEASURES

NEO Personality Inventory (NEO-PI). Personality was assessed at screening, 1-2 months after each drug session, and approximately 14 months after the last drug session using a computer-based version of the revised NEO-PI. This 240-item instrument measures the five factors of personality and the six facets that define each factor. The facets of Openness are Fantasy (e.g. 'I have a very active imagination'), Aesthetics (e.g. 'I am intrigued by patterns I find in art and nature'), Feelings (e.g. 'I experience a wide range of emotions and feelings'), Ideas (e.g. 'I often enjoy playing with theories or abstract ideas'), Values (e.g. 'I consider myself broad-minded and tolerant of other people's lifestyles'), and Actions (e.g. 'I think it's interesting to learn and develop new hobbies'). Items were answered on a 5-point scale ranging from strongly disagree to strongly agree, and raw scores were standardized as T scores (M ¼ 50, SD ¼ 10) using the combined-sex norms reported in the NEO-PI-R manual. States of Consciousness Questionnaire (SOCQ). Mystical-type phenomena during the drug sessions were assessed using 43 mystical experience items embedded within a 100-item instrument, the States of Consciousness Questionnaire (SOCQ), which assesses phenomenological content during altered states of consciousness. The mystical experience items have been shown to be sensitive to the effects of psilocybin) and other hallucinogens. The SOCQ was administered after each session (approximately 7 h after capsule administration). Items were answered on a 6-point scale ranging from 0 (none, not at all) to 5 (extreme, more than ever before in my life and stronger than 4). Data on each of the following six subscales were expressed as percentage of maximum possible score: unity; transcendence of time and space; ineffability and paradoxicality; sacredness; noetic quality; and positive mood. Consistent with previous research, a 'complete mystical experience' was defined as having a score of 60% or higher on each subscale. A total score was also calculated as the mean across all items in the six subscales. Mysticism Scale. The Mysticism Scale was originally developed to assess mystical experiences across the lifetime and has been validated in several studies, including crossculturally. Items were answered on a 9-point scale ranging from -4 (this description is extremely not true of my own experience) to þ4 (this description is extremely true of my own experience). Total score (sum across 32 items) was used to quantify lifetime mystical experiences at screening (see Table). In addition, a modified version of the Mysticism Scale was used to assess mystical effects during the drug sessions. Participants completed the experience-specific version approximately 7 h after capsule administration and answered the items in reference to their experiences since receiving the capsule that morning. APZ. The APZ is a 72-item yes/no questionnaire designed to assess altered states of consciousness, including those produced by hallucinogens. The three scales Educational achievement was scored on the following scale: 1 ¼ high school diploma; 2 ¼ some college; 3 ¼ college degree; 4 ¼ some graduate study; 5 ¼ graduate degree. Mystical experiences across the lifetime were quantified as total score on the Hood Mysticism Scale at screening. Personality was assessed using a computer-based version of the revised NEO Personality Inventory. No significant study-group differences in demographic or personality variables were evident at screening (p-values > 0.10). on the APZ are OSE ('oceanic boundlessness'; this scale assesses phenomena such as unity, bliss, and transcendence of time and space); VUS ('visionary restructuralization'; this scale assesses visual pseudo-hallucinations, illusions, and synaesthesias); and AIA ('dread of ego dissolution'; this scale assesses dysphoric feelings such as anxiety, fear, and feeling trapped). Data on each scale were expressed as percentage of maximum possible score.

ANALYSIS

We combined data from two double-blind psilocybin studies to achieve greater statistical power to detect personality change at the group level and to examine personality change in sub-groups of individuals who differed in mystical-type psilocybin effects. Because Study 2 involved multiple doses of psilocybin in addition to the single high dose used in Study 1, it was not possible to completely isolate the highdose session in Study 2. However, the session protocol implemented in Study 2 was identical to that used in Study 1. Furthermore, changes in personality following the highdose session were always assessed within 1-2 months of the high-dose session and before any subsequent session. We hypothesized that mystical experiences during the psilocybin session, as measured by the SOCQ, would lead to increases in Openness. We investigated this prediction using three analysis approaches (all analyses conducted in SPSS version 18.0). First, we used multivariate repeated measures analysis of variance (ANOVA) to analyze changes in Openness and the other four NEO-PI factors (Neuroticism, Extroversion, Agreeableness, and Conscientiousness) from screening to post-test (1-2 months after the high-dose psilocybin session). After confirming that Openness changed significantly following the high-dose session, we calculated Pearson's linear correlations between changes in Openness and session-day measures (the SOCQ, the Mysticism Scale, the OSE, the VUS, and the AIA). We then confirmed via regression analysis that mystical experience, as measured by the SOCQ, was a significant predictor of changes in Openness. Specifically, we conducted a series of linear regression analyses that tested the predictive power of the SOCQ above and beyond the predictive power of the four questionnaire measures that also correlated with Openness change (the Mysticism Scale, the OSE, the VUS, and the AIA). In each of four models (one model for each questionnaire), we tested the following predictors of Openness at post-test in a stepwise manner: 1) Openness at screening, 2) an alternate questionnaire measure (e.g. total score on the Mysticism Scale), and 3) mystical score on the SOCQ. We hypothesized that mystical score on the SOCQ (Step 3) would explain significantly more variability in Openness than each of the alternate questionnaire measures (Step 2), as indicated by significant estimates of R-squared change from Step 2 to Step 3. Finally, we compared Openness change in participants who met the criteria for having had a complete mystical experience during their high-dose session (n ¼ 30) with participants who did not meet the criteria (n ¼ 22). We used the 'complete mystical experience' classification (60% on each subscale of the SOCQ) rather than data-driven classification (e.g. median split) for several reasons. First, median split analyses have been associated with reductions of power and effect size. Second, classification based on subscale scores takes into account the breadth of mystical-type effects, which total score does not. For example, a participant could have a high total score while not endorsing many sacredness items. Finally, designating participants who met the criteria for a complete mystical experience allowed a comparison with previous studies.

CHANGES IN PERSONALITY FOLLOWING THE PSILOCYBIN SESSION

Consistent with our hypothesis, the repeated measures ANOVA showed that Openness increased significantly from screening to post-test (M ¼ þ2.8, F(1, 51) ¼ 5.47, p ¼ 0.023, 2 p ¼ 0:10). Moreover, because participants received the high dose on different sessions, it was possible to conduct a comparison analysis of changes in Openness following the first session in the subgroup of participants who did not receive a high dose of psilocybin on that session (n ¼ 30 participants received inactive placebo, methylphenidate, or 5 mg/70 kg of psilocybin on their first session). There were no significant changes in Openness after the first session in this subgroup (F(1, 29) ¼ 0.52, p ¼ 0.48). Finally, with regard to changes in the other four personality factors after the high-dose session, there were no significant changes from screening to post-test in Neuroticism (M ¼ À0.5; F(1, 51) ¼ 0.24, p ¼ 0.62), Extroversion (M ¼ þ0.8; F(1, 51) ¼ 0.79, p ¼ 0.38), Agreeableness (M ¼ þ1.7; F(1, 51) ¼ 2.31, p ¼ 0.16), or Conscientiousness (M ¼ À0.9; F(1, 51) ¼ 1.22, p ¼ 0.28), and test-retest correlations were high across assessments (rs ¼ 0.61-0.84). Taken together, these results indicate predominantly stable personality traits with specific increases in Openness following the high-dose session.

RELATIONSHIP BETWEEN SESSION-DAY EFFECTS AND CHANGES IN OPENNESS

We hypothesized that individual differences in mystical experience during the psilocybin session, as measured by the SOCQ, would be related to individual differences in Openness change. There was considerable variability in mystical-type effects during the high-dose session, with nearly the full range of possible scores (range: 0.03-1.00) represented across the six subscales of mystical experience. Consistent with our hypothesis, mystical experience (mean score across all of the items in the six subscales) correlated significantly with increases in Openness (r ¼ 0.42, p ¼ 0.002; Figure). Importantly, mystical experience did not correlate significantly with screening levels of Openness (r ¼ 0.12, p ¼ 0.41) or its facets; the highest correlation was with Feelings (r ¼ 0.24, p ¼ 0.09). Changes in Openness were also correlated with scores on the Mysticism Scale (r ¼ 0.33, p ¼ 0.017), the OSE (r ¼ 0.44, p ¼ 0.001), the VUS (r ¼ 0.41, p ¼ 0.003), and the AIA (r ¼ 0.31, p ¼ 0.024). The significant relationships shown by Pearson's linear correlations were also shown by Spearman's rank order correlations between change in Openness and the SOCQ (r s ¼ 0.47, p < 0.001), the Mysticism Scale (r s ¼ 0.40, p ¼ 0.003), the OSE (r s ¼ 0.45, p ¼ 0.001), the VUS (r s ¼ 0.47, p < 0.001), and the AIA (r s ¼ 0.33, p ¼ 0.018). However, a series of stepwise regression analyses showed that the SOCQ explained significantly more variability in Openness change than the Mysticism Scale (R-squared change ¼ 0.046, p ¼ 0.033), the OSE (R-squared change ¼ 0.047, p ¼ 0.031), the VUS (R-squared change ¼ 0.042, p ¼ 0.036), and the AIA (R-squared change ¼ 0.12, p ¼ 0.001).

EFFECT OF MYSTICAL EXPERIENCE ON CHANGES IN OPENNESS

We further examined the relationship between mystical experience and increases in Openness by comparing participants who met the criteria for having had a complete mystical experience during their high-dose session (n ¼ 30) with participants who did not meet the criteria (n ¼ 22). ANOVA revealed a significant interaction between time (screening vs. post-test) and group (complete mystical experience vs. no complete mystical experience) (F(1, 50) ¼ 9.32, p ¼ 0.004, p 2 ¼ 0.16). Follow-up t-tests confirmed that the complete mystical experience group showed significant increases in Openness from screening to post-test (M ¼ þ5.7; t(29) ¼ 3.44, p ¼ 0.002) while the other group did not (M ¼ À1.2; t(21) ¼ 0.87, p ¼ 0.39) (Figure). Five of the six facets of Openness showed this same pattern when examined individually: the interaction between time and group was significant for Fantasy (p ¼ 0.029, p 2 ¼ 0.09), Aesthetics (p ¼ 0.010, p 2 ¼ 0.13), Feelings (p ¼ 0.038, p 2 ¼ 0.08), Ideas (p ¼ 0.014, p 2 ¼ 0.11), and Values (p ¼ 0.036, p 2 ¼ 0.09), but not Actions (p ¼ 0.19). Follow-up t-tests for the five facets showing significance confirmed that the complete mystical experience group increased in these facets while the other group did not (Figure).

FOLLOW-UP

The persistence of increases in Openness was assessed at a follow-up assessment conducted more than 1 year after the high-dose session (M ¼ 16 months). In participants who had a complete mystical experience (n ¼ 30), Openness levels at follow-up decreased slightly from post-test but did not differ significantly from Openness levels at post-test (p ¼ 0.12) and remained significantly higher than at screening (M ¼ þ4.2; F(1, 29) ¼ 4.17, p ¼ 0.050, p 2 ¼ 0.13). In contrast, participants who did not have a complete mystical experience (n ¼ 21) had nearly identical Openness levels at follow-up and screening (M ¼ À0.3; p ¼ 0.86). 1,2

DISCUSSION

We observed significant increases in Openness after a highdose psilocybin session that were larger in magnitude than changes in personality typically observed in healthy adults over decades of life experience. Moreover, in participants who met criteria for having had a complete mystical experience during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. This is the first study to demonstrate changes in personality in healthy adults after an experimentally manipulated discrete event. To our knowledge, the only other experimental (i.e. randomized) intervention reported to change healthy adults' personality involved hundreds of hours of solitary meditation over the course of 3 months. The present findings are suggestive of lasting change in core personality traits. However, it will be important to replicate these results in larger groups of individuals with diverse baseline personality profiles. It is informative to compare the magnitude of Openness change observed in the present study with previous findings of longitudinal personality change. During normal aging, Openness typically decreases linearly at a rate of approximately 1 T-score point per decade (see Figurein. In comparison, participants in the present study who had a complete mystical experience during their psilocybin session increased more than 4 T-score points from screening to follow-up. Notably, this increase is larger than increases in Openness seen in individuals treated successfully with antidepressant medication (see Figureinand intensive outpatient counseling for substance abuse (see Tablein. Openness includes a relatively broad range of intercorrelated traits covering aesthetic appreciation and sensitivity, fantasy and imagination, awareness of feelings in self and others, and intellectual engagement. People with high levels of Openness are 'permeable to new ideas and experiences' and 'motivated to enlarge their experience into novel territory'. Openness is strongly associated with creativity, and some of its facets (Ideas, Values) are correlated with general fluid intelligence and cognitive ability. Although the present study did not directly investigate the corollary benefits of increased Openness, significant increases in nearly all of the facet scores indicate the potential for improvements in aesthetic and cognitive domains. Very few controlled studies have attempted to characterize the effects of classic hallucinogens on aesthetic and creative outcomes. One previous well-controlled study of LSDfound evidence for short-term improvements on measures of artistic ability (e.g. figure drawings), aesthetic sensitivity (e.g. compatibility between participant and expert ratings of paintings), and creativity (e.g. generating alternate uses for a common object). However, they failed to find significant improvements in creativity or aesthetic measures at a 6-month follow-up. Notably, the McGlothlin study included graduate students who were paid for participation, generally showed little interest in LSD, and received minimal preparation and support for the LSD sessions. In contrast, the present study included unpaid community volunteers who were motivated by curiosity about the effects of psilocybin and received extensive interpersonal preparation and support for the psilocybin sessions. It is likely that differences in participant motivation and preparation contributed to different longterm outcomes following hallucinogen sessions. In addition, nearly all of the participants in the present study regularly engaged in spiritual activities such as religious services, prayer, and meditation. It is possible that such individuals are particularly sensitive to the mystical-type effects of psilocybin, which were predictive of increases in Openness. Cross-sectional methods have been used to examine differences in personality, attitudes and values between regular hallucinogen users and controls. A study in Brazil byfound that individuals who used the hallucinogenic plant ayahuasca as a spiritual sacrament had lower trait levels of excitability, disorderliness and impulsivity, and higher trait levels of confidence, gregariousness and optimism compared with community members who did not use ayahuasca.found that individuals who used hallucinogens valued spirituality, concern for others, concern for the environment (i.e. nature), and creativity more highly than individuals who used other illicit drugs (e.g. marijuana, amphetamine, heroin). Although the findings are suggestive of personality changes that might be associated with hallucinogen exposure, it is not possible to isolate the effects of hallucinogens per se because of the self-selection bias that may confound results of cross-sectional studies. Longitudinal studies will be required to replicate hallucinogen-related changes in personality, attitudes, and values. The NEO-PI is one of the most widely used measures of personality in modern psychology. Nevertheless, it is useful to consider alternate methods of classifying personality. For example, the Temperament and Character Inventory (TCI) measures personality as a combination of temperament or automatic responses to emotional stimuli and character or self-aware concepts that are associated with voluntary intentions and attitudes (see review in. The TCI scales are considered distinct from the factors in the NEO-PI. However, a factor analysis showed that TCI scales loaded on the five NEO-PI factors. In particular, the Self-Transcendence scale of the TCI loaded on Openness, effectively representing 'openness to spiritual experience'. Given the connection between mystical experience and increases in Openness observed in the present study, it is likely that Self-Transcendence might also increase following a high-dose psilocybin session. In contrast to the numerous questionnaires available for assessing personality, very few questionnaire measures have been developed to assess mystical experiences. Despite the generally infrequent use of the SOCQ, it has been used effectively along with the more widely used and validated Mysticism Scaleto characterize hallucinogen effects. Although a psychometric validation of the SOCQ has not been published, data from a study in our laboratory involving several hundred respondents indicate that the mystical items in the SOCQ have a reliable factor structure and that the factor scores differentiate self-reported mystical experiences from otherwise profound positive experiences. In the present study, the SOCQ was a better predictor of changes in Openness than other questionnaire measures of mystical effects (e.g. the Mysticism Scale) and positively experienced hallucinogen effects (e.g. the OSE). Overall, these results suggest a specific role for the SOCQ in quantifying mystical experiences and predicting personality change, although it will be necessary to continue to examine the sensitivity and validity of the SOCQ in characterizing the mystical-type effects of psilocybin and other classic hallucinogens. The findings have important implications for the application of psilocybin and classic hallucinogens in clinical psychiatry. Recent reviews have suggested that hallucinogens could have positive effects on the outcomes of clinical disorders, particularly anxiety and mood disorders. Clinical work along these lines was initiated in the 1950s and suggested possible improvements after hallucinogen treatment in individuals with terminal cancerand substance dependence. Although there is still much to learn about the mechanisms by which hallucinogens might produce positive changes, the increases in Openness observed in the present study indicate novel avenues of future research into the biological and psychological mechanisms of psilocybin treatment. It will also be important in future treatment studies to examine the effects of psilocybin and mystical experience on changes in maladaptive personality traits. For example, although we did not observe decreases in mean Neuroticism (feeling tense, anxious, moody, or insecure), which was nearly 1 SD below normal at baseline, reductions in Neuroticism have been observed in patients undergoing treatment for depressionand substance abuse. Similarly, reductions in Neuroticism might accompany reductions in anxiety and depressed mood following psilocybin treatment in patient populations (e.g. individuals with advanced-stage cancer;. In addition, although the present study focused on personality change following a single high-dose session, it is possible that multiple sessions would be associated with changes in additional domains besides Openness. In conclusion, the present results indicate that a high dose of psilocybin administered under supportive conditions produced increases in Openness, consistent with participants' subjective claims of the long-term effects of hallucinogens. Importantly, participants who had a complete mystical experience during their high-dose session, but not others, showed enduring increases in Openness, suggesting that other mystical experiences could occasion similar change. Qualitative research has documented sudden and dramatic positive changes in attitudes, values and behaviors following spontaneous mystical or spiritual experiences. Further, correlational research has highlighted a role for spirituality in addiction recoveryand in coping with life-threatening illnesses such as cancer, which may account for the potential efficacy of psilocybin in the aforementioned treatment of addictions and cancer distress. Future research should continue to investigate the conditions -both pharmacological and non-pharmacological -that might occasion mystical experiences, as well as describe their potential longterm consequences. 1. The overall pattern of results was similar between Study 1 and Study 2. In participants who had a complete mystical experience, there were no differences between the studies in Openness change ( p ¼ 0.11) or in Openness at screening ( p ¼ 0.28), post-test ( p ¼ 0.69) or follow-up ( p ¼ 0.36). 2. Three participants in Study 2 met the criteria for a complete mystical experience during their 20 mg/70 kg (i.e. moderately high dose) psilocybin session but not during their 30 mg/70 kg (i.e. high dose) session. Including these participants in the 'complete mystical experience' group (n ¼ 33) did not change the reported results.

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