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Psilocybin

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

In a double‑blind study of 36 hallucinogen‑naïve adults, a high dose of psilocybin given under supportive conditions occasioned mystical‑type experiences that 14 months later were rated by many participants among the five most personally meaningful and spiritually significant of their lives and increased well‑being for 64%. Regression analyses showed that the intensity of the mystical experience on the session day mediated these long‑term attributions, and it was the only measured construct to change from screening.

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Authors

Roland Griffiths
Matthew Johnson
William Richards

Published

May 30, 2008

Journal of Psychopharmacology

individual Study

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Abstract

Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose. This report presents the 14-month follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naïve adults reporting regular participation in religious/ spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a 'complete' mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.

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

References (12)

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The psychopharmacology of hallucinogens

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Carter, O. L., Hasler, F. ;., Pettigrew, J. D. et al. · Psychopharmacology (2007)

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Doblin, R. · Journal of Transpersonal Psychology (1991)

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Gouzoulis-Mayfrank, E., Thelen, B., Habermeyer, E. et al. · Psychopharmacology (1999)

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Introduction

Psilocybin has a long history of sacramental use and anecdotal claims that it can occasion experiences with lasting positive personal and spiritual significance. Earlier clinical research on classical hallucinogens was limited by insufficient preparation and support, leading to adverse reactions, and human research largely ceased after the 1960s. More recent controlled studies have reintroduced rigorous methods; however, questions remain about whether psilocybin can produce lasting changes in well-being or spiritual attribution when administered under optimised, supportive conditions. This study by Griffiths and colleagues set out to evaluate the long-term psychological and spiritual effects of a high oral dose of psilocybin (30 mg/70 kg) relative to an active comparator, methylphenidate (40 mg/70 kg), in 36 hallucinogen-naïve, spiritually active adults. Specifically, the investigators examined outcomes assessed immediately after dosing, at 2 months, and at a 14-month follow-up, and tested whether mystical-type experiences during the session predicted later attributions of personal meaning, spiritual significance and changes in well-being and behaviour.

Methods

This was a double-blind, within-subjects study in which 36 medically and psychiatrically screened, hallucinogen-naïve adults (mean age 46, range 24–64; 97% college graduates) underwent two or three supervised 8-hour drug sessions at roughly 2-month intervals. Thirty participants received two sessions (one psilocybin and one methylphenidate in counterbalanced order) and six participants received two methylphenidate sessions followed by an unblinded psilocybin session; because outcomes were similar across these groups, all 36 subjects were analysed together. Participants and monitors remained blinded until after the 14-month follow-up. Sessions were conducted in a living-room-like setting with two monitors per participant. Before dosing, the primary monitor met each volunteer on four occasions to build rapport. During sessions participants were encouraged to lie down, wear an eye mask and headphones, and direct attention inward to a programme of classical music. Drugs were administered orally: psilocybin 30 mg/70 kg and methylphenidate 40 mg/70 kg. Outcome assessments were collected at multiple time points. During sessions, monitors rated peak behavioural and mood dimensions (0–4 scale). About 7 hours post-dosing participants completed subjective-state measures: the Hallucinogen Rating Scale (HRS), the APZ (altered states) questionnaire, the Mysticism Scale (state and lifetime versions), and the Pahnke-Richards Mystical Experience Questionnaire (assessing domains such as unity, transcendence of time/space, ineffability, sacredness, noetic quality and positive mood). Two months after sessions and again at a 14-month follow-up participants completed standardised measures of personality (NEO PI-R), affect (PANAS-X), quality of life, spirituality (Spiritual Transcendence Scale, Faith Maturity Scale, FACIT-Sp-NI), the Persisting Effects Questionnaire (attitudes, mood, social/behavioural changes and three global items on personal meaning, spiritual significance, and change in well-being), and open-ended clinical interviews. For the retrospective 14-month Retrospective Questionnaire, volunteers identified the session with the most pronounced changes (all but one chose the psilocybin session) and completed the Pahnke-Richards items and 89 Persisting Effects items referring back to that session. Statistical analysis pooled the full sample (N = 36). Screening scores were converted to T-scores against population norms. Repeated-measures ANOVA with Bonferroni-corrected t-tests examined changes across screening, 2 months and 14 months on personality, affect, quality of life and spirituality measures. ANOVA and z-tests of proportions compared persisting effect endorsements across conditions/time-points. Pearson correlations were used to relate 14-month ratings of personal meaning and spiritual significance to screening measures and to session-day data (monitor peak ratings, HRS and APZ subscales, Mysticism and Pahnke-Richards scores). Multiple regression examined whether immediate post-session Mysticism Scale scores predicted follow-up attributions independently of three measures of drug-effect intensity (peak monitor overall effect, HRS Intensity subscale, and single-item HRS Intensity). A significance threshold of p < 0.05 was used generally, with p < 0.01 for correlations.

Results

Baseline screening indicated the sample was generally well adjusted, low in neuroticism and negative affect and high in extraversion, openness, agreeableness and spirituality (group mean T-scores: Neuroticism 41.8; Extraversion 55.3; Openness 65.7; Agreeableness 55.7; Spiritual Transcendence 63.1). Of the eight screening questionnaires reassessed over time, only the Mysticism Scale–Lifetime showed a significant increase at both 2 months and 14 months compared with screening. On the Pahnke-Richards Mystical Experience Questionnaire, psilocybin produced significantly greater elevations than methylphenidate across all seven mystical domains and on the mean total score when rated immediately post-session and retrospectively at 14 months; retrospective 14-month ratings did not differ significantly from immediate post-session ratings. By a priori criteria (domain scores ≥0.6), 22 of 36 volunteers met criteria for a ‘complete’ mystical experience immediately after psilocybin, and 21 met the criteria at the 14-month follow-up. Persisting effects measured by the Persisting Effects Questionnaire showed that psilocybin produced significant increases in positive attitudes, mood, social effects and behaviour relative to methylphenidate when rated at 2 months and again at 14 months; ratings of negative changes were very low and not significantly different across conditions. At the 14-month follow-up, 58% of volunteers rated the psilocybin session as among the five most personally meaningful experiences of their lives and 67% rated it among the five most spiritually significant experiences; 11% and 17% respectively rated it as the single most meaningful or spiritually significant experience. In addition, 64% reported moderate or large increases in well-being or life satisfaction attributed to the session, and 61% reported moderate to extreme positive behavioural change. Correlational analyses examined predictors of the 14-month attributions. Ratings of personal meaning were significantly correlated with baseline negative affect on the PANAS-X (r = -0.51), Quality of Life Inventory raw score (r = +0.47), Faith Maturity Scale (r = +0.41) and Measure of Actualization Potential (r = +0.44). No significant correlations were found between follow-up attributions and NEO subscales, Mysticism Scale–Lifetime, Spiritual Transcendence Scale or FACIT-Sp-NI. Session-day measures showed strong associations with later attributions. Personal meaning correlated with HRS subscales somaesthesia (r = 0.35), affect (r = 0.49), perception (r = 0.42) and cognition (r = 0.46); APZ subscales oceanic boundlessness (OSE) (r = 0.55) and visual restructuralization (VUS) (r = 0.54); and with post-session total scores on the Mysticism Scale and the Pahnke-Richards questionnaire (both r = 0.65). Spiritual significance correlated strongly with OSE (r = 0.56), VUS (r = 0.48), post-session Mysticism Scale total (r = 0.77) and Pahnke-Richards total (r = 0.66). Peak monitor ratings of overall drug effect, anxiety/fearfulness, tearing/crying, joy, peace/harmony or distance from ordinary reality were not significantly correlated with personal meaning or spiritual significance. Regression analyses that controlled for measures of drug-effect intensity showed that Mysticism Scale scores measured immediately post-session remained highly significant predictors of 14-month personal meaning and spiritual significance. Controlling for three separate intensity indices reduced the r-values slightly but they remained robust: for personally meaningful, r = 0.65 controlling for monitor-rated overall effect and r = 0.61 controlling for two subject-rated intensity measures; for spiritually significant, r-values ranged 0.74–0.78 when controlling for intensity. Qualitative data from the Retrospective Questionnaire (verbatim comments from 24 volunteers who rated the experience among their top five spiritual experiences) revealed themes such as unity of all things, dissolution of the separate self, encounters with an ultimate reality or God, and intense affective responses. Open-ended clinical interviews at 14 months produced no reports of persisting perceptual disturbances or subsequent recreational hallucinogen abuse; overall participants remained well adjusted. The original study had documented transient fear reactions during sessions in 11 volunteers and brief paranoia in six; these effects did not persist beyond the session.

Discussion

Griffiths and colleagues interpret the principal finding as that, when administered in a carefully prepared and supportive setting, a high dose of psilocybin occasioned mystical-type experiences that many participants subsequently attributed lasting personal meaning and spiritual significance to, with effects persisting to 14 months. The investigators highlight that 58% and 67% of volunteers rated the session among the five most personally meaningful and spiritually significant experiences of their lives respectively, and that the majority reported increases in well-being, life satisfaction or positive behavioural change. The authors position these results relative to earlier work by emphasising that optimised preparation and interpersonal support appear to increase the likelihood of positively valued outcomes and reduce adverse reactions compared with earlier, less controlled contexts. They note that the psilocybin-occasioned experiences resembled classical mystical experiences as assessed by validated instruments (Mysticism Scale, Pahnke-Richards), and that immediate post-session measures of mystical experience were the strongest predictors of later attributions even after statistically controlling for intensity of drug effects. Qualitative comments further corroborated core mystical themes such as unity, ego dissolution and encounters with a transcendent reality. Several limitations and uncertainties are acknowledged. The sample was relatively homogeneous—hallucinogen-naïve, well educated, middle-aged and already engaged in religious or spiritual activities—which limits generalisability and may have increased the likelihood that participants would interpret their experiences as spiritually meaningful. The Mysticism Scale–Lifetime showed increases over time, but because that version assesses lifetime experience it cannot be unambiguously attributed to the psilocybin session alone. The authors also caution against underestimating risks of hallucinogen exposure: during sessions some volunteers experienced significant fear or transient paranoid ideation, and other documented risks include precipitation or exacerbation of psychiatric disorders, persistent perceptual disturbances and potential for abuse. In terms of implications, the investigators suggest that the ability to prospectively occasion mystical-type experiences could have therapeutic relevance, given older, descriptive studies linking such experiences to positive outcomes in addiction and in psychological distress associated with serious illness. They recommend systematic replication, including studies that compare participants with differing spiritual or religious backgrounds, and further controlled therapeutic trials using contemporary methodological standards. Finally, the authors propose that controlled induction of mystical-type experiences may enable rigorous scientific study of their causes, consequences and neurobiological underpinnings.

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RESULTS

Inspection of the data indicated that the results from the 30 subjects, who received each drug once, were similar to results from the six subjects, who received methylphenidate twice followed by psilocybin once. Therefore, data from all 36 subjects are analysed below. Data from the first methylphenidate session were used for the six, who received it twice. To characterize the study sample on measures of personality, affect, quality of life and spirituality relative to the general population, individual subject data at screening were converted to T-scores using norms for: the five factors of the NEO PI-R; the Positive and Negative Affect factors of the PANAS-X; raw score on the Quality of Life Inventory; the overall mean on the Measure of Actualization Potential; total score on the Mysticism Scale-Lifetimeand total score of the Spiritual Transcendence Scale (Ralph L.. T-scores below 45 or above 55 were considered low or high, respectively, on that dimension. Repeated measures analysis of variance (ANOVA) was conducted to examine changes in the measures of personality, affect, quality of life and spirituality that were assessed at screening, 2 months after the psilocybin session, and 14 months after the last session (N = 36). Bonferroni-corrected t-tests were used to assess differences among the three time-points. ANOVA with Bonferroni-corrected t-tests were also conducted with the Persisting Effects Questionnaire data (n = 29) assessed at 2 months post-methylphenidate and post-psilocybin, and again retrospectively for psilocybin at the 14-month followup, and with the Pahnke-Richards Mystical Experience Questionnaire data (N = 36) assessed 7 h post-methylphenidate and post-psilocybin, and again retrospectively for psilocybin at the 14-month follow-up. To examine differences in the proportion of subjects endorsing specific answers on the Persisting Effects Questionnaire, ztests of proportions compared data at 2 months postmethylphenidate, 2 months post-psilocybin and again retrospectively for psilocybin at the 14-month follow-up. For ratings of personally meaningful and spiritually significant, endorsement was defined as rating either 'among the top 5' or 'the single most'. For ratings of increased well-being or life satisfaction, endorsement was defined as rating 'increased moderately' or 'increased very much'. For ratings of positive behavioural change, endorsement was defined as rating 'moderate', 'strong' or 'extreme'. Pearson's correlations were calculated to examine the relationships between: (1) volunteer's ratings of personal meaning and spiritual significance at the 14-month follow-up and (2) the following screening measures: scores on the five factor subscales of the NEO PI-R, total scores on the Mysticism Scale, Spiritual Transcendence Scale, Faith Maturity Scale, and FACIT-Sp-NI, and mean overall score on the Measure of Actualization Potential Questionnaire. Pearson's correlations were calculated between: (1) volunteer's ratings of personal meaning and spiritual significance at the 14-month follow-up and (2) data obtained on the psilocybin session day. The psilocybin session data used for these calculations were: peak monitor ratings of six dimensions of participant's behaviour during sessions (overall drug effect, anxiety or fearfulness, distance from ordinary reality, tearing/ crying, joy/intense happiness, and peace/harmony); the six subscales of the HRS; the three subscales of the APZ questionnaire; total scores on the post-session Mysticism Scale and mean score on the post-session Pahnke-Richards Mystical Experience Questionnaire. The follow-up data used for these calculations were the volunteer ratings of personal meaning and spiritual significance attributed to the psilocybin session experience. Significant correlations between the total scores on the Mysticism Scale and follow-up measures of personal meaning or spiritual significance were further examined using a multiple regression model to control for any confounding by intensity of drug effect. Three separate measures of drug effect intensity were examined: peak monitor ratings of overall drug effect; subject-rated intensity as measured by the Intensity subscale of the HRS and subject-rated intensity from the single item rating 'Intensity' in the HRS. In separate analyses for each intensity measure, the intensity measure was entered into the regression first and the post-session Mysticism Scale score was entered second to assess its effect on the follow-up measures independently of intensity. For statistical tests, p < 0.05 was considered significant except for correlations (for which a more conservative p < 0.01 was used) and for the Bonferroni-corrected t-tests.

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