Mystical-Type Experiences Occasioned by Psilocybin Mediate the Attribution of Personal Meaning and Spiritual Significance 14 Months Later

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*** PREPUBLICATION PAGE PROOFS (PUB DATE 01 JULY 08) *** Original Papers Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later RR Griffiths Journal of Psychopharmacology xxx(xx) (2008) 1–12 © 2008 British Association for Psychopharmacology ISSN 0269-8811 SAGE Publications Ltd, Los Angeles, London, New Delhi and Singapore 10.1177/0269881108094300 Department of Psychiatry and Behavioral Sciences and Department
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  Mystical-type experiences occasionedby psilocybin mediate the attributionof personal meaning and spiritualsignificance 14 months later  RR Griffiths Department of Psychiatry and Behavioral Sciences and Department of Neuroscience, Johns Hopkins University School of Medicine,Baltimore, Maryland, USA. WA Richards Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA. MW Johnson Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. UD McCann Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. R Jesse Council on Spiritual Practices, San Francisco, California, USA. Abstract Psilocybin has been used for centuries for religious purposes; however,little is known scientifically about its long-term effects. We previouslyreported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose. This report presents the 14-monthfollow-up and examines the relationship of the follow-up results to dataobtained at screening and on drug session days. Participants were 36hallucinogen-naïve adults reporting regular participation in religious/ spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on oneof two or three sessions, with methylphenidate (40 mg/70 kg)administered on the other session(s). During sessions, volunteers wereencouraged to close their eyes and direct their attention inward. At the14-month follow-up, 58% and 67%, respectively, of volunteers rated thepsilocybin-occasioned experience as being among the five most personallymeaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or lifesatisfaction; 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 measuresof personality, affect, quality of life and spirituality assessed across thestudy, only a scale measuring mystical experience showed a differencefrom screening. When administered under supportive conditions,psilocybin occasioned experiences similar to spontaneously occurringmystical experiences that, at 14-month follow-up, were considered byvolunteers to be among the most personally meaningful and spirituallysignificant of their lives. Key words entheogen; hallucinogen; humans; mystical experience; psilocybin;psychedelic; religion; spiritual  Introduction Although many have anecdotally claimed that psilocybin, theprincipal psychoactive component of various hallucinogenicmushroom species, can facilitate experiences providing sus-tained, positively valued impact, little is known scientificallyabout such effects. Psilocybin has been used as a sacramentfor centuries, possibly millennia, in structured religious cere-monies (Wasson, 1980; Stamets, 1996; Metzner, 2004). Likeother classical hallucinogens [ d- lysergic acid diethylamide(LSD), mescaline, N,N- dimethyltyrptamine (DMT)], the effectsof psilocybin are primarily mediated at 5-HT 2A receptor sites(Nichols, 2004), and the acute subjective effects include robustchanges in perception, cognition, affect, volition andsomaesthesia (Isbell, 1959; Wolbach, et al  ., 1962; Rosenberg, et al  ., 1964).The degree to which responses to psilocybin are influencedby nonpharmacological variables was not understood by early Original Papers  Journal of Psychopharmacology  xxx(xx) (2008) 1 – 12 © 2008 British Associationfor PsychopharmacologyISSN 0269-8811SAGE Publications Ltd,Los Angeles, London,New Delhi and Singapore10.1177/0269881108094300 Corresponding author: Roland Griffiths, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore,Maryland, USA. Email: rgriff@jhmi.edu *** PREPUBLICATION PAGE PROOFS (PUB DATE 01 JULY 08) ***  researchers (e.g. Isbell, 1959; Malitz, et al  ., 1960; Rinkel, et al  .,1960; Hollister, 1961). By providing more preparation andinterpersonal support during drug action, subsequent researchdescribed more positively valued experiences and fewer adverseeffects (e.g. panic and paranoia) (Chwelos, et al  ., 1959; Leary, et al  ., 1963; Metzner, et al  ., 1965; Pahnke, 1969). In response tothe hallucinogen abuse of the 1960s, human hallucinogenresearch largely ceased and has only recently resumed.Notably, Vollenweider and colleagues in Switzerland andGouzoulis-Mayfrank and colleagues in Germany have studiedthe neurocognitive, perceptual and psychosis-mimicking effect-s of psilocybin (e.g. Vollenweider, et al  ., 1998; Gouzoulis-Mayfrank, et al  ., 1999; Hasler, et al  ., 2004; Carter, et al  ., 2005,2007).Recently, we used rigorous double-blind methods toevaluate the acute (7 h) and longer term (2 months) psycho-logical effects of a high dose of psilocybin (30 mg/70 kg)relative to an active comparison compound (40 mg/70 kgmethylphenidate) in 36 hallucinogen-naïve volunteers(Griffiths, et al  ., 2006). In contrast to the aforementionedrecent psilocybin studies, the study optimized the potential forpositively valued experiences by providing 8 h of preparationand by instructing volunteers to focus explicitly on thephenomenology of the drug experience rather than performtasks. The results showed psilocybin to occasion experienceswith substantial personal meaning and spiritual significancewhen evaluated 2 months after psilocybin. We have subse-quently conducted a follow-up study evaluating effects at14 months after their last drug session. Volunteers completedquestionnaires that assessed personality, affect, quality of life,spiritual experience, and persisting changes in attitude andbehaviour attributed to the blinded psilocybin session. Thisreport analyses these 14-month follow-up results and thecontribution of baseline characteristics and immediate drugeffects to long-term persisting effects. Methods Participants Participants were recruited through flyers announcing a studyof states of consciousness brought about by a naturally occur-ring psychoactive substance used sacramentally in some cul-tures. The 36 study participants were medically and psychiatri-cally healthy and without histories of hallucinogen use. Sixteenparticipants were males [incorrectly reported as 14 in the previ-ous publication (Griffiths, et al  ., 2006)]. Participants had anaverage age of 46 years (range 24  –  64); 97% were college grad-uates and 56% had post-graduate degrees. All were employedfull- or part-time. Fifty-three per cent indicated affiliation witha religious or spiritual community, such as a church, synagogueor meditation group. All volunteers indicated at least intermit-tent participation in religious or spiritual activities, such as reli-gious services, prayer, meditation or study groups. Volunteersdid not receive monetary compensation for participation.Additional information about participant recruitment anddemographics has been described previously (Griffiths, et al  .,2006). Study design The study compared the effects of orally administeredpsilocybin (30 mg/70 kg) and methylphenidate hydrochloride(40 mg/70 kg) using a double-blind design that involved twoor three 8-h drug sessions conducted at 2-month intervals.Thirty-six volunteers were randomly assigned to receive eithertwo sessions ( n = 30) or three sessions ( n = 6). The volunteerswho received two sessions were then randomly assigned toreceive psilocybin or methylphenidate on the first session(15 per group), with the alternative drug administered on thesecond session. The third group ( n = 6) received methylpheni-date on the first two sessions and unblinded psilocybin on thethird session. The purpose of having the possibility of a thirdsession was to help control for expectancy effects (Griffiths, et al  ., 2006). Preparation and drug session procedures Participants and monitors were informed that participantswould have either two or three sessions, that in at least onesession they would receive a moderate or high dose of psilocybin, and that an inactive placebo, a low dose of psilocybin, or various other drugs could be administered inthe other session(s). Participants and monitors were unblindedto drug conditions after all participants had completed the 14-month follow-up. The primary monitor met with eachvolunteer on four occasions before the first session to developrapport and trust.The 8-h drug sessions were conducted in a living room-likeenvironment. During the session, two monitors were presentwith a single participant. Participants were encouraged tofocus their attention inward by lying down on the couch andwearing an eye mask and headphones through which aprogramme of classical music was played. Additional detailsof instructions to volunteers, volunteer  –  monitor meetingsbefore and after sessions, and outcome measures have beendescribed previously (Griffiths, et al  ., 2006). Measures of personality, affect, quality of life and  spirituality assessed at screening, 2 months after each session, and at the 14-month follow-up The following instruments were assessed: NEO PersonalityInventory (NEO PI-R) (Costa and McCrae, 1992); Positiveand Negative Affect Scale –  Expanded Form (PANAS-X) forhow one feels generally (Watson and Clark, 1994); Quality of Life Inventory raw score (Frisch, 1994); Measure of Actuali-zation Potential (Leclerc, et al  ., 1999); Mysticism Scale 2 Psilocybin and mystical-type experiences *** PREPUBLICATION PAGE PROOFS (PUB DATE 01 JULY 08) ***  (described below); Spiritual Transcendence Scale (Piedmont,1999, 2007); Faith Maturity Scale –  12 item version (Benson, et al  ., 1993); Functional Assessment of Chronic IllnessTherapy –  Non-Illness –  Spiritual Well-Being Scale (FACIT-Sp-NI-12) (Peterman, et al  ., 2002). Measures assessed throughout the session At 0.5  –  6 h after capsule administration, monitors rated severaldimensions of participant behaviour and mood, including arating of the overall drug effect on a 5-point scale from0 = none to 4 = extreme. Data were the mean of the two moni-tors peak scores (i.e. the maximum value from 0.5 to 6 h aftercapsule administration for each monitor). Measures assessed 7 h after drug administration When the major drug effects had subsided, the participantcompleted two questionnaires assessing subjective drug effects:Hallucinogen Rating Scale (HRS) (Strassman, et al  ., 1994) andAPZ (assessing altered states of consciousness) (Dittrich, 1998).Participants also completed two questionnaires assessingmystical experience. The Mysticism Scale (9-point version)has been extensively studied, demonstrates cross-cultural gener-alizability, and is well-regarded in the psychology of religion(Hood, et al  ., 2001; Spilka, et al  ., 2003). When administered7 h after drug administration, participants were instructed tocomplete the questionnaire with reference to their experiencessince they received the capsules that morning. For the lifetimeversion of the questionnaire, participants were instructed toanswer with reference to their total life experiences.As part of the States of Consciousness Questionnaire,volunteers completed the Pahnke-Richards Mystical Experi-ence Questionnaire (Griffiths, et al  ., 2006), which assessesseven domains of mystical experiences: internal unity (pureawareness; a merging with ultimate reality); external unity(unity of all things; all things are alive; all is one); transcen-dence of time and space, ineffability and paradoxicality (claimof difficulty in describing the experience in words); sense of sacredness (awe); noetic quality (claim of intuitive knowledgeof ultimate reality) and deeply felt positive mood (joy, peace,love). Ratings were made on a 6-point scale relative to theparticipant ’ s overall life experience. Data on each scale wereexpressed as a proportion of the maximum possible score.A mean total score was calculated as the mean of the followingsix domains: unity (either internal or external, whichever wasgreater), transcendence of time and space, ineffability, sense of sacredness, noetic quality and positive mood. Based on priorresearch (Pahnke, 1969; Griffiths, et al  ., 2006), criteria fordesignating a volunteer as having had a ‘ complete ’ mysticalexperience were that scores on each of the six domainswere ≥ 0.6. Measures assessed two months post-session For this assessment, participants completed the previouslydescribed standardized measures and the Persisting EffectsQuestionnaire, a measure of changes in attitudes, mood, andsocial and other behaviours (Griffiths, et al  ., 2006). The ques-tionnaire also included three questions: (I) How personallymeaningful was the experience? (1, no more than routine,everyday experiences; 2, similar to meaningful experiencesthat occur on average once or more a week; 3, similar tomeaningful experiences that occur on average once a month;4, similar to meaningful experiences that occur on averageonce a year; 5, similar to meaningful experiences that occuron average once every 5 years; 6, among the 10 most meaning-ful experiences of my life; 7, among the five most meaningfulexperiences of my life; 8, the single most meaningful experienceof my life); (II) Indicate the degree to which the experience wasspiritually significant to you? (1, not at all; 2, slightly; 3, mod-erately; 4, very much; 5, among the five most spirituallysignificant experiences of my life; 6, the single most spirituallysignificant experience of my life) and (III) Do you believe thatthe experience and your contemplation of that experience haveled to change in your current sense of personal well-being orlife satisfaction? (rated from +3 = increased very much to − 3 = decreased very much). This questionnaire was developedafter the initiation of the study and was completed by 29 of the36 participants (approximately the same per cent within allthree groups). 14-month follow-up This assessment was conducted 14 months after the last session,which was 16 months after the psilocybin session in volunteerswho received psilocybin in session 1, and 14 months afterpsilocybin in volunteers who received psilocybin in sessions2 or 3. For this assessment, all 36 participants completed theRetrospective Questionnaire as well as the previously describedstandardized measures. At this same time, volunteers partici-pated in an open-ended clinical interview reflecting on studyexperiences and current life situation.For purposes of completing the Retrospective Question-naire, volunteers were first asked to identify on which sessionthey experienced the ‘ most pronounced changes in yourordinary mental processes ’ . All but one volunteer identifiedthe psilocybin session. That volunteer, who reported havingunusual experiences during both sessions, was asked tocomplete the questionnaire with regard to the psilocybinsession. The remaining volunteers completed the questionnairein reference to the identified session.Forty-three items in this questionnaire comprised thepreviously described Pahnke-Richards Mystical ExperienceQuestionnaire, which was completed looking back on thesession and rating the degree to which various phenomenawere experienced during the session. The rationale for reasses-sing these ratings at the 14-month follow-up was that the Psilocybin and mystical-type experiences 3 *** PREPUBLICATION PAGE PROOFS (PUB DATE 01 JULY 08) ***  ratings were made relative to the participant ’ s overall lifeexperience, which could have changed over the interveningfollow-up period. Eighty-nine items comprised the previouslydescribed Persisting Effects Questionnaire. For these items,volunteers were asked to rate any current persisting effectsthat they attribute to the experience. Within the RetrospectiveQuestionnaire, volunteers were also asked to provide writtendescriptions of what was most memorable and what was mostspiritually significant about the experience. Statistical analysis Inspection of the data indicated that the results from the30 subjects, who received each drug once, were similar toresults from the six subjects, who received methylphenidatetwice followed by psilocybin once. Therefore, data from all36 subjects are analysed below. Data from the first methyl-phenidate session were used for the six, who received it twice.To characterize the study sample on measures of persona-lity, affect, quality of life and spirituality relative to the generalpopulation, individual subject data at screening were convertedto T  -scores using norms for: the five factors of the NEO PI-R(Costa and McCrae, 1992); the Positive and Negative Affectfactors of the PANAS-X (Watson and Clark, 1994); rawscore on the Quality of Life Inventory (Frisch, 1994); the over-all mean on the Measure of Actualization Potential (Leclerc, et al  ., 1999); total score on the Mysticism Scale-Lifetime(Hood and Williamson 2000; Ralph W. Hood Jr, 2007,personal communication) and total score of the SpiritualTranscendence Scale (Ralph L. Piedmont, 2007, personal com-munication). T  -scores below 45 or above 55 were consideredlow or high, respectively, on that dimension.Repeated measures analysis of variance (ANOVA) was con-ducted to examine changes in the measures of personality,affect, quality of life and spirituality that were assessed atscreening, 2 months after the psilocybin session, and 14 monthsafter the last session ( N  = 36). Bonferroni-corrected t -tests wereused to assess differences among the three time-points.ANOVA with Bonferroni-corrected t -tests were also conductedwith the Persisting Effects Questionnaire data ( n = 29) assessedat 2 months post-methylphenidate and post-psilocybin, andagain retrospectively for psilocybin at the 14-month follow-up, and with the Pahnke-Richards Mystical Experience Ques-tionnaire data ( N  = 36) assessed 7 h post-methylphenidate andpost-psilocybin, and again retrospectively for psilocybin at the14-month follow-up.To examine differences in the proportion of subjects endor-sing specific answers on the Persisting Effects Questionnaire, z -tests of proportions compared data at 2 months post-methylphenidate, 2 months post-psilocybin and again retro-spectively for psilocybin at the 14-month follow-up. For ratingsof personally meaningful and spiritually significant, endorse-ment was defined as rating either ‘ among the top 5 ’ or ‘ thesingle most ’ . For ratings of increased well-being or life satisfac-tion, endorsement was defined as rating ‘ increased moderately ’ or ‘ increased very much ’ . For ratings of positive behaviouralchange, endorsement was defined as rating ‘ moderate ’ , ‘ strong ’ or ‘ extreme ’ .Pearson ’ s correlations were calculated to examine the rela-tionships between: (1) volunteer ’ s ratings of personal meaningand spiritual significance at the 14-month follow-up and (2) thefollowing screening measures: scores on the five factor sub-scales of the NEO PI-R, total scores on the Mysticism Scale,Spiritual Transcendence Scale, Faith Maturity Scale, andFACIT-Sp-NI, and mean overall score on the Measure of Actualization Potential Questionnaire.Pearson ’ s correlations were calculated between: (1) volun-teer ’ s ratings of personal meaning and spiritual significanceat the 14-month follow-up and (2) data obtained on the psilo-cybin session day. The psilocybin session data used for thesecalculations 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 sub-scales of the HRS; the three subscales of the APZ question-naire; total scores on the post-session Mysticism Scale andmean score on the post-session Pahnke-Richards MysticalExperience Questionnaire. The follow-up data used for thesecalculations were the volunteer ratings of personal meaningand spiritual significance attributed to the psilocybin sessionexperience.Significant correlations between the total scores on theMysticism Scale and follow-up measures of personal meaningor spiritual significance were further examined using a multipleregression model to control for any confounding by intensity of drug effect. Three separate measures of drug effect intensitywere examined: peak monitor ratings of overall drug effect;subject-rated intensity as measured by the Intensity subscaleof the HRS and subject-rated intensity from the single itemrating ‘ Intensity ’ in the HRS. In separate analyses for eachintensity measure, the intensity measure was entered into theregression first and the post-session Mysticism Scale score wasentered second to assess its effect on the follow-up measuresindependently of intensity.For statistical tests, p < 0.05 was considered significantexcept for correlations (for which a more conservative  p < 0.01 was used) and for the Bonferroni-corrected t -tests. Results Measures of personality, affect, quality of life and  spirituality assessed at screening, 2 months after the psilocybin session, and at the 14-month follow-up The measures of personality, affect, quality of life, and spiritu-ality assessed at screening indicated that the volunteers weregenerally well-adjusted, outgoing, open and high in spirituality.More specifically, relative to adult norms, the mean T  -score for 4 Psilocybin and mystical-type experiences *** PREPUBLICATION PAGE PROOFS (PUB DATE 01 JULY 08) ***
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