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Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

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Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level (“standard”) support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282
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https://doi.org/10.1177/0269881117731279
Journal of Psychopharmacology
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Introduction
Quantum change experiences refer to sudden, distinctive,
benevolent, and often profoundly meaningful experiences that
are said to result in personal transformations that affect a
broad range of personal emotions, cognitions and behaviors
(Miller, 2004; Miller and C’de Baca, 2001). The phenomenon
of quantum change is differentiated from the usual process of
behavioral change, which occurs in small incremental steps
(James, 1902). Such experiences, which have been described
in anecdotal reports dating back centuries, have been vari-
ously labeled as mystical experiences, conversion experi-
ences, religious experiences, peak experiences, transcendental
experiences, transforming moments, or epiphanies (e.g.
James, 1902; Maslow, 1968; Miller and C’de Baca, 2001;
Stace, 1960). Although numerous cases of such quantum
change experiences have been described, they have generally
not been examined in prospective experimental studies
because such experiences occur at low rates and usually
unpredictably (Paloutzian and Park, 2013).
Administration of psilocybin, a classic psychedelic, provides
a model for experimental investigation of quantum change expe-
riences. Controlled, double-blind clinical trials in healthy volun-
teers show that under supportive conditions psilocybin can
Psilocybin-occasioned mystical-type
experience in combination with
meditation and other spiritual practices
produces enduring positive changes in
psychological functioning and in trait measures
of prosocial attitudes and behaviors
Roland R Griffiths1,2, Matthew W Johnson1, William A Richards3, Brian
D Richards3, Robert Jesse4, Katherine A MacLean5, Frederick S Barrett1,
Mary P Cosimano1 and Maggie A Klinedinst1
Abstract
Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring
changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were
randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level (“standard”) support for spiritual-practice
(LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on
sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/
staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included
rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects.
At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness,
gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings.
Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion
enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning.
Trial Registration
ClinicalTrials.gov Identifier NCT00802282
Keywords
Psilocybin, psychedelic, entheogen, meditation, mystical experience, traits
1 Department of Psychiatry and Behavioral Sciences, Johns Hopkins
University School of Medicine, Baltimore, MD, USA
2
Department of Neuroscience, Johns Hopkins University School of
Medicine, Baltimore, MD, USA
3
Department of Psychiatry, Johns Hopkins Bayview Medical Center,
Baltimore, MD, USA
4Council on Spiritual Practices, Occidental, CA, USA
5Center for Optimal Living, New York, NY, USA
Corresponding author:
Roland Griffiths, Johns Hopkins Bayview Medical Center, 5510 Nathan
Shock Drive, Baltimore, MD 21224-6823, USA.
Email: rgriff@jhmi.edu
731279JOP0010.1177/0269881117731279Journal of PsychopharmacologyGriffiths et al.
research-article2017
Original Paper
2 Journal of Psychopharmacology 00(0)
reliably occasion deeply personally meaningful and often spiritu-
ally significant experiences (e.g. mystical-type experiences)
(Griffiths et al., 2006, 2011; Pahnke, 1963) having many charac-
teristics similar to those described for quantum change experi-
ences (Miller and C’de Baca, 2001). Such psilocybin effects are
dose dependent (Griffiths et al., 2011) and have been demon-
strated under conditions that provide substantial controls for
expectancy bias (Griffiths et al., 2006, 2016). Although partici-
pants often attribute enduring positive changes in well-being and
worldview to such experiences, there is little evidence from stud-
ies in healthy volunteers that psilocybin produces enduring
changes on well-validated trait measures of disposition or per-
sonality (Darling et al., 2004; Doblin, 1991; Griffiths et al., 2008;
2011; Leary et al., 1963; Pahnke, 1963; Studerus et al., 2011).
For example, a previous study in 36 participants who received a
high dose of psilocybin showed enduring positive changes in
moods, attitudes, and behavior attributed to the psilocybin expe-
rience, but no significant changes from screening to 14-month
follow-up on various measures of personality, quality of life,
faith maturity, and spiritual well-being (Griffiths et al., 2008). A
later post-hoc analysis which combined data from that study with
data from a similar subsequent study with 18 participants
(Griffiths et al., 2011) showed that psilocybin-occasioned mysti-
cal-type experiences were associated with increases in the per-
sonality trait of openness (MacLean et al., 2011).
Although an older literature on psilocybin-assisted psycho-
therapy in psychiatric patient populations suggests that adminis-
tration of psilocybin in a psychotherapeutic context may produce
enduring decreases in psychopathology and increases in positive
worldview and dispositional characteristics, methodological lim-
itations render those reports inconclusive (Passie, 2004, 2007).
However, recent placebo-controlled trials in psychologically dis-
tressed cancer patients showed that psilocybin produced
decreases in anxiety and depression and increases in quality of
life that persisted for at least a month and possibly 6 months or
more (Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016).
The present study in healthy participants sought to extend
understanding of possible enduring effects of quantum change
experiences generally and psilocybin-occasioned experiences
specifically by manipulating psilocybin dose and the intensity
with which participants were encouraged to engage in meditation
and other spiritual practices. Acute psilocybin effects, retrospec-
tive attributions to the experience, and enduring changes in
prosocial attitudes and behaviors, and psychological functioning
were assessed. More specifically, the present study used an
across-group design to compare these outcomes in three groups
of 25 healthy participants: (1) low-dose (active placebo) psilocy-
bin with moderate-level (“standard”) support for spiritual prac-
tice; (2) high-dose psilocybin with standard support; and (3)
high-dose psilocybin with high support.
Materials and methods
Participants
Participants were recruited from the local community through fly-
ers seeking volunteers interested in developing their spiritual lives
by participating in a study of the combined effects of meditation
and psilocybin, a psychoactive substance found in mushrooms
used as sacraments in some cultures. In total, 1305 individuals
were screened by telephone and 184 were further screened in per-
son. Primary reasons for exclusion between phone screen and in-
person screening were prior use of psychedelics (312); medical/
psychiatric exclusion (288); pre-existing regular meditation or
other spiritual practice (261); logistics or lack of interest (220).
Eighty-five volunteers were enrolled in the study and 10 did not
complete the study. Reasons for non-completion included illness
or a disqualifying medical or psychological issue (five volunteers),
noncompliance with study procedures for personal or job-related
reasons (three volunteers), and missing data on key measures (two
volunteers). The 75 study completers (40% male) were medically
healthy (as determined by medical history, physical examination,
an electrocardiogram, routine medical blood laboratory tests, and
urine testing for common drugs of abuse), and psychiatrically
healthy. They were without personal or family histories of psy-
chotic disorders or bipolar I or II disorder as determined by struc-
tured clinical interviews. Individuals with current alcohol or other
drug dependence (including nicotine) were excluded, as were indi-
viduals with a past history within the past 5 years of alcohol or
drug dependence (excluding nicotine). Twenty-five percent of par-
ticipants reported past use of a psychedelic, with a mean of 25.1
years since last use. Participants were excluded if they reported
any history of either spontaneous or psychedelic-occasioned sali-
ent mystical-type experiences. Participants had a mean age of 42
years (range 22 to 69) and a mean weight of 71.5 kg (range 49.2 to
97.5); 89% had college or post-graduate degrees and 87% were
full-time employees or students. Although 31% reported practicing
seated meditation, the mean frequency of practice was very low
(1.1 times per month for the group). Volunteers did not receive
monetary compensation for participation. Based on interviews,
their motivation for participation was their interest in learning
meditation, exploring their spiritual lives, and their curiosity about
the effects of psilocybin. The Johns Hopkins IRB approved the
study. Written informed consent was obtained from participants.
Study design and overview
The study procedures followed recommendations provided for
safe conduct of research administering high doses of a classic
psychedelic (Johnson et al., 2008). This study investigated the
effects of psilocybin dose and the frequency and intensity of sup-
port provided for spiritual practice (i.e. meditation, spiritual
awareness practice, journaling) on a battery of attitudinal and
behavioral outcome measures in 75 healthy participants. The
psilocybin dose manipulation was double-blind.
The duration of each volunteer’s participation was approxi-
mately 6 to 8 months. After enrollment and before the first of two
psilocybin sessions (described below), each participant had sev-
eral preparation meetings with two study staff trained to serve as
session “guides.” The two psilocybin sessions were separated by
about 1 month. Some measures were assessed during and imme-
diately after sessions, and various longitudinal measures were
evaluated immediately after study enrollment (i.e. baseline
assessment) and 4 months after the second psilocybin session
(i.e. 6-month assessment).
Assignment to the three experimental groups. After screen-
ing and study enrollment, each participant was randomized to
one of three groups of 25 each: (1) very low-dose psilocybin (1
Griffiths et al. 3
mg/70 kg on sessions 1 and 2—functionally a placebo) with stan-
dard support for spiritual practice (LD-SS); (2) high-dose psilo-
cybin (20 and 30 mg/70 kg on sessions 1 and 2, respectively)
with standard support for spiritual practice (HD-SS); and (3)
high-dose psilocybin (20 and 30 mg/70 kg on sessions 1 and 2,
respectively) with high support for spiritual practice (HD-HS).
An urn randomization procedure (Stout et al., 1994) was used to
balance the three groups as closely as possible on six dichoto-
mous variables (gender, age at study intake, lifetime psychedelic
use, baseline lifetime Hood Mysticism Scale score, baseline fre-
quency of meditation, and staff judgment about whether the par-
ticipant was especially likely to engage in spiritual practices).
Table 1 shows that these and other demographic characteristics
did not differ across the three experimental groups.
Instructions to participants and guides, and the purpose of
a third session. Study instructions and procedures were
designed to minimize some of the effects of expectancy. Partici-
pants and guides were told that participants would receive psilo-
cybin during each session, that dose levels could range between
very low to high, that each participant would receive two or more
different dose levels across two or three sessions, and that all
participants would have at least one session with a moderately
high or high dose of psilocybin. Although the most important
comparative data on attitudinal and behavioral change were
obtained in the first two sessions and subsequent follow-up, 39
participants were assigned to receive a third session after the
6-month data assessment in which they received 30 mg/70 kg
psilocybin. This design feature was used in part to control expec-
tancies through the 6-month follow-up evaluation. Although par-
ticipants and guides were informed that over two or three sessions
all participants would receive one or more high doses of psilocy-
bin, they were not informed which participants or how many par-
ticipants would be scheduled for a third session, nor were they
told that the third session would be a high dose. In fact, all 25
participants in the low-dose psilocybin group (LD-SS) were
assigned to receive a third session. An additional 14 participants
(eight and six from HD-SS and HD-HS, respectively) were also
assigned to receive a third session. Nine of these 14 participants
were distributed within the first one-third (25) participants
enrolled in the study. The purpose of scheduling a third session in
these 14 participants was to obscure the study design from the
guides early in the trial and reduce the possibility that guides
would have strong expectancies whether or not a participant
would have a third session. Data from the third session and data
from several exploratory measures are beyond the scope of this
report and are not presented.
Guide–participant meetings and support for
spiritual practice
The guide–participant meetings served the functions of establishing
rapport, providing specific preparation for the psilocybin sessions
(see Johnson et al., 2008), and providing instructions and support
Table 1. Participant demographics.
Measure Low-Dose High-Dose High-Dose Group
Standard-Support
(N=25)
Standard-Support
(N=25)
High-Support
(N=25)
Comparisons
Gender (Male/Female) 9/16 13/12 8/17 N.S.
Age in years (mean, SEM) 40.2 (2.5) 41.0 (2.7) 45.6 (2.3) N.S.
Weight in kilograms (mean, SEM) 69.0 (2.2) 72.6 (2.4) 72.9 (2.6) N.S.
Race/Ethnicity
White 76% 88% 92% N.S.
Black/African American 8% 4% 4%
Asian 16% 8% 4%
Hispanic 4% 8% 4%
Education (college or post-graduate degree) 96% 84% 88% N.S.
Employment
Full-time job or student 84% 84% 92% N.S.
Part-time, retired or unemployed 16% 16% 8%
Life-time Use of Psychedelics
Percent reporting any past use132% 28% 20% N.S.
Current Meditation
Percent reporting some meditation 24% 36% 32% N.S.
Times per month for the group (mean, SEM) 1.08 (0.44) 1.36 (0.46) 1.00 (0.37) N.S.
Mysticism Scale Score (mean, SEM) 175.0 (8.1) 166.3 (13.8) 190.3 (10.0) N.S.
Judged very likely to do spiritual practices28% 8% 8% N.S.
N.S. = No significant differences between groups; ANOVA was used for continuous variables; Chi-square was used for categorical variables, with White compared to other
racial categories combined and Full-time job or student compared to other employment categories combined.
1Mean number of years since last use among those who reported using was 25.1 years.
2Judgment made by based on an interview by one of the investigators.
4 Journal of Psychopharmacology 00(0)
for spiritual practices. The primary guides had established personal
meditation practices as well as extensive experience supporting
psilocybin sessions. An assistant guide was usually present at these
meetings. Except for the dialogue-group meetings described below,
the same primary and assistant guides were paired with a given par-
ticipant throughout the study. Guide–participant meetings began
and ended with a brief period of meditation.
Standard-Support groups. The frequency of guide–participant
meetings differed across the standard vs. high-support condi-
tions. Before the first psilocybin session (in the 1-month period
following enrollment) guides and participants in the two stan-
dard-support groups (Low-Dose Standard-Support group; High-
Dose Standard-Support group) had three 1-hour meetings and
one 2-hour meeting (5 total contact hours). After each of the first
two psilocybin sessions, participants in the standard-support
group met for 1 hour within one or two days (usually one day)
and had a 10 minute teleconference with guides about 2 weeks
later. Thus, the total guide–participant contact hours for those in
the Standard-Support groups from study acceptance to the
6-month follow-up was about 7 hours and 20 minutes.
High-Support group. Before the first session (in the 1 month
period following enrollment) participants and guides in the High-
Dose High-Support group had five 2-hour meetings (10 total con-
tact hours). Between the first and second psilocybin sessions (1
month apart) there were three 1-hour participant–guide meetings
(3 total contact hours). As with the Standard-Support groups, the
first of these meetings was scheduled within a day or two follow-
ing the session. During the 4-month period after the second psilo-
cybin session, 1-hour participant–guide meetings occurred within
a day or two of the session, at weekly intervals for the first 2 weeks,
and at twice-monthly intervals for the remainder of the 4 months
(10 contact hours). Also during the 4-month period after the second
psilocybin session, participants in the High-Support group partici-
pated in twice-monthly 90-minute dialogue-group sessions.
Approximately eight study participants plus one or two facilitators
(study staff) participated in each session. The group membership
changed over sessions as individual participants entered and left
the group as they progressed through the study. The facilitators
provided an opportunity to discuss psilocybin experiences but
mainly encouraged dialogue about successes and challenges in
implementing and sustaining the regular spiritual practices of med-
itation, spiritual awareness, and journaling. The total guide–partic-
ipant contact hours for the High-Support group from study
acceptance to the 6-month follow-up was 35 hours.
Spiritual practice support. At the first guide–participant meet-
ing, each participant was given: (1) a copy of the book, Meditation:
A Simple 8-Point Program for Translating Spiritual Ideals into
Daily Life (Easwaran, 1991/1978); (2) a blank journal; and (3) a
one-page outline of spiritual practice suggestions. All participants
were required to read the book on meditation and integration of
spiritual values into daily life. This book was used as a primary
teaching resource because its approach provides an easily under-
stood, nonsectarian program for spiritual living that has shown
increases in measures of spirituality, well-being, self-efficacy, and
health outcomes (Flinders et al., 2007; Oman et al., 2006, 2008a,b).
The spiritual practice suggestions had three primary elements:
meditation (10 to 30 minutes of sitting meditation daily); daily
awareness practice (use of mantra and one-pointed attention in
daily activities); and daily self-reflective journaling of insights,
benefits, and challenges of spiritual practice in daily life. Partici-
pants were also encouraged to engage in activities they personally
judged to facilitate spiritual growth (e.g. being in nature, contem-
plative movement, artwork, or service activities). At each of the
guide–participant meetings, the guide asked about, encouraged,
and offered instructions in the participant’s implementation of the
spiritual practice suggestions.
Psilocybin sessions
Psilocybin doses were prepared in opaque, size 0 gelatin capsules
of identical appearance, with lactose as the inactive capsule filler.
On each session, a single capsule was administered with 180 mL
water. As described in more detail previously (Griffiths et al.,
2006), psilocybin sessions were conducted in an aesthetic living-
room-like environment with two guides present. Participants
were instructed to consume a low-fat breakfast before arriving at
the research unit at about 08:15 in the morning. A urine sample
was taken to verify abstinence from common drugs of abuse and
that female participants were not pregnant. For most of the time
during the session, participants were encouraged to lie down on
the couch, use an eye mask to block external visual distractions,
and use headphones through which a program of classical and
world music was played. The same music program was played
for all participants in all sessions. Throughout the session, guides
were nondirective and supportive and they encouraged partici-
pants to focus their attention on their inner experiences.
Measures assessed throughout the session
Ten minutes before and 30, 60, 90, 120, 180, 240, 300, and 360
minutes after capsule administration, blood pressure, heart rate,
and monitor ratings were obtained by session guides as described
previously (Griffiths et al., 2006). Blood pressure (systolic and
diastolic pressure using oscillometric method with the blood-pres-
sure cuff placed on the arm) and heart rate were monitored using a
Non-Invasive Patient Monitor Model 507E (Criticare Systems,
Inc., Waukesha, WI). At the same time-points the two session
guides completed the Monitor Rating Questionnaire, which
involved rating or scoring several dimensions of the participant’s
behavior or mood (Table 2). The dimensions that are expressed as
peak scores in Table 2 were rated on a 5-point scale from 0 to 4.
Data were the mean of the two monitor ratings at each time-point.
Measures assessed 7 hours after drug
administration
When psilocybin effects had subsided, participants completed four
questionnaires: Hallucinogen Rating Scale (HRS) (Strassman
et al., 1994); 5-Dimension Altered States of Consciousness (5D-
ASC) (Dittrich, 1998); Mysticism Scale (Experience-specific ver-
sion rated on a 9-point scale) (Hood et al., 2001, 2009); and the
States of Consciousness Questionnaire (SOCQ) (Griffiths et al.,
2006). Thirty items on the SOCQ comprise the Mystical Experience
Questionnaire (MEQ30), which has been shown to be sensitive to
mystical-type subjective effects of psilocybin in laboratory studies
as well as in survey studies of psilocybin mushroom use (Barrett
Griffiths et al. 5
et al., 2015; MacLean et al., 2012). A total score (mean of all 30
items) and four factor scores were assessed: (1) Mystical, compris-
ing items assessing internal and external unity, sacredness, and
noetic feelings; (2) Positive mood (e.g. joy, peace awe); (3)
Transcendence of time and space; (4) Ineffability. A participant
was designated as having had a “complete” mystical experience if
scores on each of the four factors was 60% of the maximum pos-
sible factor score (Barrett et al., 2015). The MEQ30 is a psycho-
metrically more rigorous derivation of the Pahnke–Richards scale,
which has been described previously (Griffiths et al., 2006).
Spiritual practices assessed at the 6-month
follow-up
Spiritual practices questionnaire. This questionnaire assessed
engagement with the three primary spiritual practices that were
the focus of the spiritual practice teachings, the guide–participant
meetings, and the dialogue-group meetings. Participants were
instructed to complete the questionnaire based on their spiritual
practices over the past 4 months (since the second psilocybin ses-
sion). Participants rated the frequency and duration of their usual
meditation practice, the frequency of their daily awareness prac-
tice (e.g. mantra repetition during daily activities), and the fre-
quency of their self-reflective journaling.
Persisting effects assessed at the 6-month
follow-up
Persisting effects questionnaire. This questionnaire assessed
changes in attitudes, moods, behavior, and spiritual experience and
has been shown sensitive to the effects of psilocybin 14 months
after a psilocybin session (Griffiths et al., 2011). Participants were
asked to rate any current persisting effects that they attributed to
the experiences during either or both of the two psilocybin ses-
sions. One hundred forty items were rated on a 6-point scale
(0=none, not at all; 1=so slight cannot decide; 2=slight; 3=moder-
ate; 4=strong; 5=extreme, more than ever before in your life and
stronger than 4). Within the questionnaire, the items were labeled
in six categories: Attitudes about life (13 positive and 13 negative
items); Attitudes about self (11 positive and 11 negative items);
Mood changes (9 positive and 9 negative items); Relationships (9
positive and 9 negative items); Behavioral changes (1 positive and
1 negative item); Spirituality (22 positive and 21 negative items).
The positive and negative items were intermixed within each cat-
egory. For purposes of scoring the resulting 12 scales (positive and
negative scales for each of six categories) scores were expressed as
the percentage of the maximum possible score.
The questionnaire included three additional questions (see
Griffiths et al., 2006 for more specific wording): (1) How personally
meaningful was the experience? (rated from 1 to 8, with 1=no more
than routine, everyday experiences; 7=among the five most mean-
ingful experiences of my life; and 8=the single most meaningful
experience of my life); (2) Indicate the degree to which the experi-
ence was spiritually significant to you? (rated from 1 to 6, with
1=not at all; 5=among the five most spiritually significant experi-
ences of my life; 6=the single most spiritually significant experience
of my life); (3) Do you believe that the experience and your contem-
plation of that experience have led to change in your current sense of
personal well-being or life satisfaction? (rated from +3=Increased
very much; 0=No change; –3=Decreased very much).
Longitudinal measures assessed at baseline
and at the 6-month follow-up
At baseline (immediately after study enrollment) and at the
6-month follow-up, a battery of measures focused on attitudes,
dispositions, and behaviors thought to be relevant to changes that
Table 2. Cardiovascular measures and guide ratings of volunteer behavior and mood assessed throughout the session.
Measure Low-Dose High-Dose High-Dose
Standard-Support Standard-Support High-Support
Cardiovascular Measures (peak effects)
Systolic blood pressure (mm Hg) 129.38 (2.37) 145.50 (2.62)*** 148.54 (3.33)***
Diastolic blood pressure (mm Hg) 77.44 (1.71) 83.46 (1.68)** 85.22 (1.50)***
Heart rate (beats per minute) 75.74 (1.81) 91.04 (2.70)*** 89.96 (2.77)***
Guide Ratings (peak effects, max score=4)
Overall drug effect 1.17 (0.09) 2.68 (0.14)*** 2.82 (0.10)***
Anxiety or Fearfulness 0.31 (0.09) 1.01 (0.17)* 1.43 (0.33)***
Distance from ordinary reality 0.75 (0.11) 2.46 (0.18)*** 2.43 (0.11)***
Systematized ideas of reference 0.04 (0.02) 0.14 (0.05) 0.17 (0.06)*
Yawning 0.46 (0.15) 0.76 (0.23) 1.16 (0.24)*
Tearing/Crying 0.19 (0.11) 1.02 (0.17) 2.56 (0.72)***+
Nausea/vomiting 0.06 (0.04) 0.44 (0.15)* 0.5 (0.11)**
Joy/intense happiness 0.46 (0.09) 1.98 (0.20)*** 1.8 (0.16)***
Peace/harmony 0.87 (0.13) 2.00 (0.20)*** 1.72 (0.13)***
Psychological Discomfort 0.14 (0.06) 0.75 (0.17)** 0.87 (0.17)***
Physical Distress 0.07 (0.03) 0.56 (0.18)** 0.57 (0.13)**
Data are means of the peak response in each of the two psilocybin sessions in each participant. Group means with 1 SEM in parentheses (n=25) are shown.
Within a row, asterisks indicate a significant difference from the Low-Dose Standard-Support group (*p<.05, **p<.01, ***p<.001, Planned comparisons), and + indicates
a significant difference between the High-Dose High-Support and High-Dose Standard-Support groups (p<.05, Planned comparisons).
6 Journal of Psychopharmacology 00(0)
could occur with engagement in psilocybin-facilitated spiritual
practice was assessed. These measures included the previously
described Hood Mysticism Scale (Lifetime) completed with refer-
ence to lifetime experience (Hood et al., 2001); Faith Maturity
Scale, a questionnaire assessing the degree to which a person
embodies the priorities, commitments, and perspectives of faith as
these have been understood in mainline Protestant traditions
(Benson et al., 1993); Brief RCOPE, a measure of religious/spir-
itual coping with stressful life events (Pargament, 1999; Pargament
et al., 1998); Daily Spiritual Experience Scale, a measure of an
individual’s perception of and interaction with the transcendent in
daily life (Underwood, 2006; Underwood and Teresi, 2002),
scored from 5 (Many times a day) to 0 (Never/almost never);
Death Transcendence Scale, a 26 item questionnaire rated on a
7-point scale that assesses five subscales reflecting attitudes about
death (Hood and Morris, 1983; VandeCreek, 1999); Gratitude
Questionnaire (GQ-6), a measure of gratefulness and appreciation
in daily life (McCullough et al., 2002); Coherence and Death
Acceptance subscales of the Life Attitude Profile - Revised (LAP-
R), these 15 questions assess a dimension (Coherence subscale) of
life meaning reflecting a logically integrated analytical and intui-
tive understanding of self, others, and life in general and a dimen-
sion (Death Acceptance subscale) reflecting death acceptance
(Reker, 2007); Trait Forgiveness Scale, a measure of trait forgive-
ness (Berry et al., 2005); TRIM-18, a scale assessing forgiveness
of interpersonal transgression (McCullough et al., 2006); the
3-item Forgiveness subscale of the BMMRS (The Fetzer Institute,
1999); Santification of Strivings rated life strivings on the dimen-
sions of sacred, spiritual, holy, heavenly, and blessed (Mahoney
et al., 2005); Schwartz Value Scale, a measure of relative impor-
tance of various life values (Schwartz, 1992, 1994); Inclusion of
Others in the Self scale (IOS), a measure of interpersonal close-
ness (Aron et al., 1992), mean score of ratings of closest person,
closest family member, least close family member, a stranger, and
a difficult personal relationship; ASPIRES (Assessment of
Spirituality and Religious Sentiments), a community observer-
rated and self-rated questionnaire assessing a construct that
reflects an individual’s effort to create a broad sense of personal
meaning in his or her life, reflected in three factors: Prayer
Fulfillment, Universality, and Connectedness (Piedmont, 2010);
the Dispositional Positive Emotions Scale, a measure assessing
seven scales of positive emotion (joy, contentment, pride, love,
compassion, amusement, and awe) (Shiota et al., 2006); Life-
Orientation Test-Revised (LOT-R), a measure of optimism associ-
ated with health outcomes (Scheier et al., 1994); Satisfaction with
Life Scale (Pavot and Diener, 1993); Purpose in Life Test (PIL), a
assessment of meaningfulness in life (Crumbaugh and Maholick,
1964); the Nonattachment Scale (NAS), a questionnaire designed
to assess the Buddhist concept of nonattachment (Sahdra et al.,
2010); and the revised NEO Personality Inventory (NEO) (Costa
and McCrae, 1992).
Community observer ratings of changes in participants’
behavior and attitudes. This previously described measure
was shown to be sensitive to enduring effects of psilocybin
(Griffiths et al., 2006, 2011, 2016). After acceptance into the
study, each participant designated as raters three adults who were
expected to have continuing contact with the participant (e.g.
family members, friends, or colleagues at work). Ratings were
conducted via a structured telephone interview approximately 1
week after the participant had been accepted into the study, 3 to 4
weeks after the last session, and as part of the 6-month follow-up.
The interviewer provided no information to the rater about the
participant. The structured interview consisted of asking the rater
to rate the participant’s behavior and attitudes using a 10 point
scale (from 1=not at all, to 10=extremely) on 13 items: inner
peace; patience; good-natured humor/playfulness; mental flexi-
bility; optimism; anxiety; interpersonal perceptiveness and car-
ing; negative expression of anger; compassion/social concern;
expression of positive emotions (e.g. joy, love, appreciation);
self-confidence; forgiveness of others; and forgiveness of self.
For the first rating assessment, which occurred soon after accep-
tance into the study, raters were instructed to base their ratings on
observations of and conversations with the participant over the
past 3 months. On subsequent assessments, raters were told their
previous ratings and were instructed to rate the participant based
on interactions over the last several weeks. Data from each inter-
view with each rater were calculated as a total score, with anxiety
and anger scored negatively. Changes in each participant’s
behavior and attitudes after drug sessions were expressed as a
mean change score (i.e. difference score) from the baseline rating
across the raters. At the same assessment times, the community
observer who knew the participant best (as judged by the partici-
pant at baseline) also completed via telephone interview the 35
item Observer Rated ASPIRES questionnaire, which assesses
spirituality and religious sentiments (Piedmont, 2010). Seven of
225 (<6%) scheduled ratings by community observers at 6
months were missed due to failure to return calls or to the rater
not having contact with the participant over the rating period.
Data analyses
Pearson Chi-square (SPSS version 22.0.0.0) was used to compare
experimental groups on dichotomous variables (demographics
and proportion of group endorsing specific responses). Planned
comparisons among groups were conducted with z-tests of
proportions.
For time-course data during psilocybin sessions, for each par-
ticipant, peak score during the time-course was defined as the
maximum value from pre-capsule to 6 hours post-capsule and
time to peak effect was defined as the time to peak score. ANOVA
(SAS version 9.2, PROC GLM) with planned comparisons
between groups were used to analyze data at each time-point,
peak effects, and time to peak effects for Sessions 1 and 2 sepa-
rately. A similar analysis was conducted using mean peak data
from Sessions 1 and 2 combined. Similar analyses were con-
ducted comparing peak effects and time to peak effect between
sessions 1 (20 mg/70 kg) and 2 (30 mg/70 kg) collapsing across
the two high-dose groups (n=50).
A similar approach (ANOVA with planned comparisons
between groups) was used to examine demographic data for con-
tinuous variables, data obtained 7 hours after psilocybin adminis-
tration (end of session), and single time-point data from the
6-month follow-up (e.g. spiritual practices and persisting effects
attributed to psilocybin).
Longitudinal measures (i.e. those measures assessed imme-
diately after study enrollment and at the 6-month follow-up),
were analyzed with a repeated measures regression model with
AR(1) covariance structure (SAS version 9.2, PROC MIXED)
with planned comparisons between groups. Measures that
Griffiths et al. 7
showed significant differences between groups at baseline were
reanalyzed as difference from baseline scores using ANOVA
(SAS version 9.2, PROC GLM) with planned comparisons
between groups. If difference scores at 6 months were not sig-
nificantly different between groups, those measures were
dropped from further analysis. For the remaining longitudinal
measures, planned comparisons between groups at 6 months
were conducted. Finally, to determine if there were changes
over time within each group, planned comparisons between
baseline and 6-month data were examined.
Hierarchical regression analysis was used to explore the rela-
tionship of spiritual practices and psilocybin-occasioned mysti-
cal experience to various outcome measures. For this analysis,
the three spiritual practice measures (minutes per day of media-
tion; times per day of spiritual awareness practice; times per
week of spiritual journaling) were entered together in the first
step of the regression model. In the second step, the mean of the
Mystical Experience Questionnaire (MEQ30) total scores (com-
pleted after both psilocybin sessions) was entered into the regres-
sion model. In another analysis, MEQ30 mean total score was
entered into the regression model first.
Results
Integrity of blinding procedures
After the psilocybin sessions had been completed, the five
study staff members who had served as primary guides for the
study completed a questionnaire that asked about their under-
standing of the study drug and dose conditions. Although all
correctly believed that psilocybin had been administered, most
made incorrect inferences about the drug or dose conditions,
with three of five believing that doses higher than 30 mg/70 kg
had been administered, two believing that four or more psilo-
cybin dose levels had been administered; two believing that a
drug other than psilocybin was administered (guesses included
MDMA, ketamine, and dextromethorphan), and two believing
that a true placebo had been administered. Surprisingly, some
of these incorrect inferences were contrary to study design
parameters that had been described verbally and in the consent
form to participants and these primary study guides (e.g.
administration of something other than psilocybin). None cor-
rectly understood the study design, although two correctly
inferred that two lower dose sessions were followed by a high-
dose third session.
Cardiovascular measures and guide ratings
assessed throughout the session
Time-course. As expected, inspection of mean group data over
time in the low-dose group (LD-LS) for sessions 1 and 2 showed
evidence of only modest effects of 1 mg/70 kg psilocybin. In this
group, cardiovascular effects generally reached peak at 30 min-
utes after capsule administration, while guide ratings reached
peak at 120 minutes (Figure 1). Also as expected and as illus-
trated for guide ratings in Figure 1, the two high-dose groups
showed similar time-courses and, compared with the low-dose
group, effects in the two high-dose groups were larger, with peak
cardiovascular effects occurring at 30 to 180 minutes and peak
guide ratings occurring at 180 minutes. Analysis of differences
in time to peak effects between the first and second sessions (20
vs. 30 mg/70 kg) for the two high-dose groups separately and
combined did not show significant differences in time to peak
effects for guide ratings. For the cardiovascular measures, only
time to peak heart rate showed a significant difference, with
peak effects occurring significantly earlier at the high dose (112
± 13 vs. 163 ± 14 minutes for sessions 1 (20 mg/70 kg) and 2 (30
mg/70 kg) respectively, mean ± SEM for the two high-dose
groups combined).
Peak effects. Analysis of differences in peak effects for guide rat-
ings between the first and second sessions (20 vs. 30 mg/70 kg) for
the two high-dose groups separately and combined did not show
significant differences. For the cardiovascular measures, peak sys-
tolic and diastolic pressures were modestly but significantly higher
after the high dose (mean ± SEM for the two high-dose groups
combined: 144 ± 2 vs. 150 ± 2 mm Hg systolic pressure for low
and high doses, respectively, and 83 ± 1 vs. 86 ± 1 mm Hg diastolic
pressure for low and high doses, respectively).
Given that differences between sessions 1 and 2 were mini-
mal, and to simplify comparison across the three experimental
Figure 1. Within-session time-course of guide ratings of overall psilocybin effect during the sessions.
Data points are means; brackets show ± 1 SEM (n=25); time 0=before capsule administration). The High-Dose High-Support and the High-Dose Standard-Support groups
were significantly different from the Low-Dose Standard-Support group at all post-capsule time-points. The two high-dose groups were not significantly different at any
time-points except for 60 and 90 minutes in Session 2.
8 Journal of Psychopharmacology 00(0)
groups, mean peak cardiovascular effects and guide ratings
across the two sessions were used in subsequent analyses. For all
three cardiovascular measures and for almost all of the guide rat-
ings, the HD-SS and HD-HS groups were significantly higher
than the LD-SS group (Table 2 and Figure 2). The HD-HS group
differed from the HD-SS group only on guide ratings of tearing/
crying, which were higher in the HD-HS group.
Drug effect and mystical-type effect
measures assessed 7 hours after psilocybin
administration
In an analysis similar to that described above for the peak scores
during the session, participant-rated drug effect and mystical-
type effect measures after psilocybin sessions did not show sig-
nificant differences between sessions 1 and 2. Therefore, mean
data across the two sessions were used in the analyses below.
Subjective effects questionnaires. Two participant-rated sub-
jective effect questionnaires (HRS and 5D-ASC) completed at
the end of the sessions showed a pattern of results across the
experimental groups similar to peak effects from the cardiovas-
cular and guide rated measures assessed throughout the session
(Table 3). Specifically, the HD-HS and HD-SS groups were con-
sistently higher than the LD-SS group, with no differences
between the two high-dose groups. Results from these subjective
measures, which were developed for sensitivity to hallucinogens,
showed that psilocybin produced the expected range of subjec-
tive changes including changes in somatic effects, positive and
negative affect, perception, cognition, and volition.
Measures of mystical experience. Also at 7 hours after capsule
administration, participants completed two questionnaires
(MEQ30 and Mysticism Scale) designed to assess mystical experi-
ence (Table 3 and Figure 3). As with the other end-of-day ratings,
the HD-HS and HD-SS groups were consistently higher than the
LD-SS group. Furthermore, all the subscales from these question-
naires (which are believed to assess various aspects of mystical
experience) are numerically higher in the HD-HS group than the
HD-SS group and, for three of the four measures on the Mysticism
Scale, these differences were significant (Table 3). The proportion
of participants who met a priori criteria for having had a “com-
plete” mystical experience on the MEQ30 on session 1 and 2,
respectively, were 0% and 4% (LD-SS), 48% and 50% (HD-SS),
and 44% and 52% (HD-HS). Overall, 4%, 61%, and 64% of par-
ticipants in the LD-SS, HD-SS, and HD-HS groups had “com-
plete” mystical experiences at either or both sessions 1 and 2.
Spiritual practices assessed at the 6-month
follow-up
Spiritual practices questionnaire. Consistent with the more
frequent and intensive support provided in the high spiritual
support condition, rates of meditation, spiritual awareness
practice, and journal writing in the HD-HS group were about
twice the rates in the two standard-support groups, which were
quite similar. Likewise, the percentage of participants meditat-
ing daily, engaging in spiritual practices daily, or journaling
weekly was higher in the HD-HS group. As shown in Table 4
and Figure 4, the HD-HS group was significantly higher than
the LD-SS and HD-SS groups on five and four, respectively, of
Figure 2. Guide ratings of volunteer behavior and mood assessed throughout the psilocybin sessions (Illustrative results from Table 2).
Data are means of the peak response in each of the two psilocybin sessions in each participant. Bars show group means; brackets show 1 SEM; * indicates a significant
difference from Low-Dose Standard-Support (Planned comparisons, p<.05); there were no significant differences between the High-Dose High-Support and High-Dose
Standard-Support groups.
Griffiths et al. 9
these measures of engagement with spiritual practice. More-
over, the HD-HS group showed numerically larger effects for
all six measures.
Persisting effects assessed at the 6-month
follow-up
Table 5 and Figure 5 show participant ratings at the 6-month
follow-up of effects that the participants attributed to either or
both of the two psilocybin sessions. With regard to positive
changes in attitudes, mood, altruism, and behavior as well as
increased spirituality, the two high-dose groups were signifi-
cantly higher than the LD-SS group on all these measures. Table
S1 shows that the effect sizes for these comparisons were very
large (mean Cohen’s d=1.65). In addition, the HD-HS group was
significantly higher than the HD-SS group on altruistic/positive
social effects, positive behavior changes, and increased spiritual-
ity. Negative ratings of these same dimensions were very low and
did not differ between groups except for negative attitudes about
self that showed very small but significant increases in the
HD-HS group. Of the eight participants in the HD-HS group that
endorsed any increase in negative attitudes about self, all also
rated the experience as having increased their sense of personal
well-being or life satisfaction at the 6-month follow-up.
Both the high-dose groups also rated the personal meaning,
spiritual significance, and change in well-being or life satisfac-
tion attributed to the sessions significantly higher than the LD-SS
group (Table 5 and Figure 5). Similar findings were shown for
the percentage of each group providing strong endorsements of
these same three dimensions. For example, 12%, 76%, and 96%
of the LD-SS, HD-SS, and HD-HS groups, respectively, rated the
experience(s) among the top five most spiritual experiences of
their lives, with 0%, 40%, and 56%, respectively, indicating it to
be the single most spiritually significant experience of their life.
Longitudinal measures and community
observer ratings assessed at 6 months
Analysis of longitudinal measures. Per the plan in the Data
Analysis section, three longitudinal measures were dropped
from analysis (Forgiveness subscale of the BMMRS; self-rated
ASPIRES; and the Satisfaction with Life Scale) because of sig-
nificant between-group differences at baseline and no signifi-
cant difference in change from baseline. The Purpose in Life
Test, Nonattachment Scale, and the LOT-R [a measure of opti-
mism] both showed significant increases from baseline to 6
months in the two High-Dose groups. The Openness scale of
the NEO showed a significant increase from baseline to 6
Table 3. Participant ratings on subjective effects and mystical experience questionnaires completed 7 hours after psilocybin administration.
Measure Low-Dose High-Dose High-Dose
Standard-Support Standard-Support High-Support
Hallucinogen Rating Scale (HRS)
Intensity (max score=4.25) 1.33 (0.16) 2.92 (0.16)*** 2.89 (0.11)***
Somesthesia (max score=4) 0.47 (0.07) 1.48 (0.14)*** 1.53 (0.11)***
Affect (max score=4) 0.70 (0.08) 1.82 (0.14)*** 1.98 (0.09)***
Perception (max score=4) 0.41 (0.08) 1.78 (0.17)*** 1.74 (0.12)***
Cognition (max score=4) 0.52 (0.09) 1.90 (0.19)*** 2.02 (0.13)***
Volition (max score=4) 1.16 (0.08) 1.65 (0.09)** 1.59 (0.10)***
5 Dimension Altered States of Consciousness (5D-ASC)
Oceanic Boundlessness (OBN)(max score=100) 16.54 (3.54) 61.47 (5.56)*** 69.50 (3.80)***
Dread of Ego Dissolution (DED)(max score=100) 4.73 (0.91) 20.92 (3.03)** 22.25 (4.42)**
Visionary Restructuralization (VRS)(max score=100) 16.90 (3.46) 57.68 (5.24)*** 61.69 (3.44)***
Auditory Alterations (AUA)(max score=100) 4.45 (1.25) 17.04 (2.73)** 19.17 (4.02)**
Vigilance Reduction (VIR)(max score=100) 20.86 (2.53) 32.76 (2.94)** 32.05 (3.52)**
Mystical Experience Questionnaire (MEQ30) a
Mystical (max score=100) 13.9 (3.5) 60.5 (7.3)*** 71.8 (3.6)***
Positive mood (max score=100) 30.0 (3.6) 74.5 (4.3)*** 79.8 (3.8)***
Transcendence of time and space (max score=100) 22.3 (4.1) 66.6 (5.6)*** 70.6 (3.7)***
Ineffability (max score=100) 20.1 (4.1) 74.4 (6.3)*** 76.3 (3.9)***
Total (max score=100) 19.4 (3.3) 65.9 (6.0)*** 73.6 (3.1)***
Mysticism Scale
Interpretation (max score=108) 48.82 (4.40) 82.42 (5.63)*** 96.08 (2.39)***+
Introvertive (max score=108) 48.00 (3.74) 84.00 (5.13)*** 93.20 (2.28)***
Extrovertive (max score=72) 27.44 (3.01) 48.62 (4.28)*** 58.86 (2.37)***+
Total (max score=288) 124.26 (10.55) 215.04 (14.52)*** 248.14 (6.14)***+
For each participant, ratings were collapsed across the two psilocybin sessions. Data are means with 1 SEM shown in parentheses (n=25); data for the 5D-ASC and MEQ30
are expressed as a percentage of the maximum possible score.
Within a row, asterisks indicate a significant difference from the Low-Dose Standard-Support group (*p<.05, **p<.01, ***p<.001, Planned comparisons), and + indicates
a significant difference between the High-Dose High-Support and High-Dose Standard-Support groups (p<.05, Planned comparisons).
10 Journal of Psychopharmacology 00(0)
months in the HD-HS group, but did not show a significant
between-group difference at 6 months on Openness or the
other four NEO scales. The DPES showed neither a significant
increase from baseline to 6 months nor significant between-
group differences at 6 months.
Table 6 shows the 23 longitudinal measures that demon-
strated significant between-group differences at 6 months
(Table S2 shows corresponding effect sizes). In the LD-SS
group, only one measure (a measure of forgiveness) was sig-
nificantly different between baseline and 6 months (Table 6,
boldface font). In contrast, in the two high dose groups, most
of the 23 measures were significantly different between the
baseline and 6-month assessment (boldface font). For all 23
measures, the HD-HS group showed numerically larger effects
(in the expected direction) than the HD-SS group (Table 6 and
Figure 6), with significant differences on seven measures.
Furthermore, the HD-HS group differed significantly on all 23
measures from the LD-SS group and, in contrast, on 14 of 23
measures from the HD-SS group.
Community observer ratings. In addition to the various par-
ticipant-rated longitudinal measures, it is noteworthy that sev-
eral observer-rated measures (total score, prayer fulfillment,
and universality on the ASPIRES and total change score on the
community observer ratings of positive change in behavior and
attitudes) generally showed the same pattern of differences
across groups with the HD-HS group showing the largest effects
(Table 6 and Figure 7).
Figure 3. Participant ratings on mystical experience questionnaires completed 7 hours after psilocybin administration (Illustrative results from
Table 3).
Data for the Mystical Experience Questionnaire (MEQ30) are percentages of the maximum possible score; data for the Mysticism Scale are total scores. Bars show group
means; brackets show 1 SEM; * indicates a significant difference from the Low-Dose Standard-Support group; + indicates a significant difference between the High-Dose
High-Support and the High-Dose Standard-Support groups (Planned comparisons, p<0.05).
Griffiths et al. 11
Relationship of spiritual practice and
psilocybin-occasioned mystical experience to
various outcome measures
Hierarchical regression analysis was used to determine the rela-
tionship of spiritual practice and psilocybin-occasioned mysti-
cal experience to various outcome measures from Tables 5 and
6 that showed between-group differences at 6 months. For this
analysis, the three spiritual practice measures (minutes per day
of mediation; times per day of spiritual awareness practice;
times per week of spiritual journaling) were entered together in
the first step of the regression model. Mean total score from the
Mystical Experience Questionnaire (MEQ30) was entered into
the regression model in the second step. As shown in Table 7,
spiritual practices accounted for a significant proportion of var-
iance (R2) in 13 of 19 outcome measures, with R2 ranging from
.050 to .293 (mean=.139). As also shown in the table, mystical
experience score (MEQ30) accounted for a significant propor-
tion of variance in 18 of 19 measures after accounting for the
impact of spiritual practices, with the change in R2 ranging from
.031 to .619, (mean=.266). In contrast to MEQ30 score which
was significant for 18 measures even after accounting for the
contribution of spiritual practices, the rightmost columns of the
table show that, for the overall regression model, meditation,
awareness practice, and journaling were significant for six, two
and one of the outcome measures, respectively. Not shown in
the table, when MEQ30 score was entered as the first step of a
regression model, it accounted for a significant proportion of
variance in all 19 outcome measures, with R2 ranging from .123
to .747 (mean=.351).
Open-ended clinical interview at the 6-month
follow-up
An open-ended clinical interview at the final follow-up visit was
used to obtain spontaneous reports of possible persisting adverse
events. There were no reports of bothersome or clinically sig-
nificant persisting perception phenomena sometimes attributed
to psychedelic use. Likewise, there were no reports of any
non-study use of psychedelics since study enrollment. All 75
volunteers appeared to continue to be psychiatrically healthy,
high-functioning, productive members of society.
Adverse effects
No serious adverse events attributed to psilocybin administration
or the study procedures occurred. A number of adverse events
occurred during psilocybin sessions, none of which was deemed
to be serious. Consistent with previous research (Griffiths et al.,
2006, 2011, 2016), there were transient moderate increases in sys-
tolic and/or diastolic blood pressure after psilocybin. In one par-
ticipant, diastolic blood pressure was elevated (126 mmHg) about
an hour after psilocybin administration in the first session. The
increase met protocol criteria for administration of sublingual
nitroglycerin. The session was completed uneventfully. Although
this participant reported that the session experience was positively
meaningful and expressed a desire to continue with the study, the
participant was discontinued from further participation.
Discussion
The present study with psilocybin extends a large descriptive lit-
erature on non-drug and psilocybin-occasioned transformative
mystical- and insightful-type experiences (i.e. quantum change
experiences, Miller, 2004) by using a prospective experimental
design to test for enduring positive changes on well-validated trait
measures of prosocial attitudes and behaviors, psychological func-
tioning, and ratings of the participant by community observers.
The rigorous double-blind design, which minimized expectancy
effects, showed that psilocybin-occasioned mystical experience
contributed significantly to the enduring positive changes. The pre-
sent study results contrast those from previous studies of psilocy-
bin (Darling et al., 2004; Doblin, 1991; Griffiths et al., 2008; 2011;
Leary et al., 1963; Pahnke, 1963; Studerus et al., 2011) and the
classic psychedelic LSD (McGlothlin et al., 1967; Weil et al.,
1965) in healthy volunteers, which have provided little evidence of
enduring positive changes on well-validated trait measures of
Table 4. Spiritual practices at 6 months.
Measure Low-Dose High-Dose High-Dose
Standard-Support Standard-Support High-Support
Meditation
Minutes per day for all days 10.23 (2.24) 9.93 (1.69) 19.33 (0.20)**+++
Percentage of group meditating daily 32% 20% 64%*++
Spiritual awareness practice
Times per day for all days 2.16 (0.74) 3.05 (0.87) 5.19 (0.97)*
Percentage of group practicing daily 56% 68% 96%**+
Journal writing
Times per week 1.76 (0.49) 1.78 (0.50) 4.44 (0.52)***+++
Percentage of group journaling daily 12% 16% 40%
Data, which were obtained at the 6-month follow-up, show retrospective ratings for the past 4 months; rate data are means with 1 SEM shown in parentheses (n=25);
proportion data are the percentage of group (n=25) reporting the spiritual practice.
Within a row, asterisks indicate a significant difference from the Low-Dose Standard-Support group (*p<.05, **p<.01, ***p<.001), and plus symbols indicate a significant
difference between the High-Dose High-Support group and the High-Dose Standard-Support group (+p<.05, ++p<.01, +++p<.001). Significance levels were determined
with z-tests for proportions for percentile data and with Planned comparisons for other numerical ratings.
12 Journal of Psychopharmacology 00(0)
disposition. This difference seems likely due to the experimental
context of the present study, which provided encouragement for
engagement in a nonsectarian program of meditation and other
practices that emphasized the integration of spiritual values in
daily life (e.g. prosocial values, self-knowledge through examining
the nature of mind, and cultivating a sense of wonder).
Effects of psilocybin dose
Effects of psilocybin dose on session days. The time-course
and profile of acute psilocybin effects were consistent with previ-
ous studies that have administered these doses of psilocybin to
healthy volunteers under similar conditions (Griffiths et al., 2006,
2011). Comparing the low-dose group with each of the two high-
dose groups, psilocybin modestly increased blood pressure and
heart rate and significantly affected a range of measures assessed
by guides during sessions and by participants immediately after
sessions (Tables 2 and 3). The profile of these acute psilocybin
effects included perceptual changes (e.g. visual pseudo-hallucina-
tions, illusions, and/or synesthesia), labile moods (e.g. feelings of
transcendence, grief, joy, and/or anxiety), and cognitive changes
(e.g. sense of meaning, insight, and/or ideas of reference).
In the high-dose conditions, 20 mg/70 kg was administered in
session 1 followed by 30 mg/70 kg in session 2. The rationale for
administering the doses in the ascending sequence was based on
previous research suggesting that ascending doses are more
likely to than descending doses to produce long-lasting positive
changes in attitudes, behavior, and remembered mystical-type
experiences (Griffiths et al., 2011). Peak blood pressure was very
modestly higher after the 30 vs. 20 mg/70 kg psilocybin dose but
there were no significant differences between these doses on rat-
ing by guides during sessions or in participant ratings at the end
of the session. It is possible that the fixed sequence of doses con-
tributed to a failure to detect significant differences in acute sub-
jective effects between the two doses.
Figure 4. Spiritual practices at 6 months (from Table 4).
Data, which were obtained at the 6-month follow-up, show retrospective ratings for the past 4 months. Bars displaying rate data show means; brackets show 1 SEM
(n=25). Meditation rate data are minutes per day for all days. Bars displaying proportion data show the percentage of the group (n=25) reporting the practice during the
indicated time interval. * indicates a significant difference from the Low-Dose Standard-Support group; + indicates a significant difference between the High-Dose High-
Support group and the High-Dose Standard-Support group (Planned comparisons, p<0.05).
Griffiths et al. 13
Spiritual practices at 6 months. The study did not provide
evidence that psilocybin dose affected engagement with spiri-
tual practices. As expected, compared with the two standard
spiritual support conditions, participants in the high spiritual
support condition showed greater engagement with the three pri-
mary spiritual practices that were taught and encouraged during
the guide–participant and dialogue-group meetings (Table 4 and
Figure 4). For the last 4 months of the study, participants in the
high-support condition reported average rates of meditation
(19.3 minutes per day), spiritual awareness practice (5.2 times
per day), and journaling (4.4 times per week) that were about
double those reported in the standard-support groups. Likewise,
the proportion of volunteers meditating daily, doing spiritual
practices daily, or journaling daily was generally significantly
higher than that in the two standard-support groups. However,
the LD-SS and HD-SS groups were not significantly different on
any of these six measures, indicating that, under the conditions
of the study, psilocybin did not facilitate engagement with these
spiritual practices.
Persisting effects attributed to psilocybin assessed at 6
months. Consistent with a previous study (Griffiths et al., 2011),
compared with the low-dose group, the high psilocybin dose
groups showed greater increases in persisting positive effects that
participants attributed to their psilocybin session experiences
(Table 5 and Figure 5). The domains of positive changes were:
attitudes about life, attitudes about self, mood, altruism/positive
social effects, behavior, and increased spirituality. Also relative to
the low-dose group, the two high-dose groups attributed signifi-
cantly greater personal meaning, spiritual significance, and
change in well-being or life satisfaction to the psilocybin experi-
ence. Similar significant differences between the low-dose group
and two high-dose groups were also shown on the percentage of
each group providing strong endorsements of personal meaning,
spiritual significance, and change in well-being or life satisfaction
(Table 5 and Figure 5).
Longitudinal measures assessed at 6 months. The most
intriguing assessments in this study were a series of longitudinal
measures, some of which are well-validated trait measures of
psychological well-being, prosocial disposition, and spiritual
worldview (Table 6). In contrast to prior psilocybin research with
healthy volunteers which has generally not demonstrated endur-
ing changes such measures (Griffiths et al., 2008), the present
study showed generally large significant effects of psilocybin
dose across a range of longitudinal measures (Table 6; Table S2
Table 5. Participant ratings of effects attributed to psilocybin session experiences at 6 month assessment.
Measure Low-Dose High-Dose High-Dose
Standard-Support Standard-Support High-Support
Attitudes, Moods, Behavior, & Spirituality
Positive attitudes about life 22.71 (5.11) 61.66 (6.18)*** 73.11 (4.14)***
Negative attitudes about life 0.98 (0.37) 1.66 (0.63) 3.02 (1.17)
Positive attitudes about self 23.85 (4.92) 55.35 (6.01)*** 68.73 (4.22)***
Negative attitudes about self 0.44 (0.27) 2.04 (0.65) 4.00 (1.54)*
Positive mood changes 21.42 (4.42) 51.47 (5.96)*** 65.42 (4.73)***
Negative mood changes 1.07 (0.60) 0.71 (0.28) 1.69 (1.30)
Altruistic/positive social effects 21.24 (4.44) 53.24 (5.85)*** 67.02 (4.22)***+
Antisocial/negative social effects 0.8 (0.49) 0.36 (0.36) 1.16 (0.60)
Positive behavior changes 27.20 (4.98) 61.60 (6.76)*** 78.40 (5.26)***+
Negative behavior changes 0.8 (0.82) 0.00 (0) 0.00 (0)
Increased spirituality 20.76 (4.95) 58.69 (6.36)*** 73.62 (4.00)***+
Decreased spirituality 1.14 (0.44) 0.84 (0.36) 1.26 (0.94)
How personally meaningful was experience?
Mean (max score=8) 3.80 (0.35) 6.76 (0.31)*** 7.20 (0.14)***
% rating top 5 most personally meaningful 12% 84% *** 84% ***
% rating the single most personally meaningful 0% 28%* 36%**
How spiritually significant was the experience?
Mean (max score=8) 2.60 (0.26) 4.68 (0.34)*** 5.52 (0.12)***+
% rating top 5 most spiritually significant 12% 76% *** 96%***+
% rating the single most spiritually significant 0% 40% ** 56% ***
Did the experience change your sense of of well-being or life satisfaction?
Mean (max/min score= -3 to +3) 1.08 (0.23) 2.20 (0.23)*** 2.60 (0.13)***
% rating moderately or very much (+2 or +3) 20% 72% *** 92%***
Data on attitudes, mood, altruistic/social effects, behavior, and spirituality are means expressed as percentage of maximum possible score, with 1 SEM shown in paren-
theses (n=25); data for the final three questions are either mean raw scores with 1 SEM shown in parentheses or percentages of group (n=25).
Within a row, asterisks indicate a significant difference from the Low-Dose Standard-Support group (*p<.05, **p<.01, ***p<.001), and + indicates a significant difference
between the High-Dose High-Support group and the High-Dose Standard-Support group (+p<.05). Significance levels were determined with z-tests for proportions for
percentile data and with Planned comparisons for other numerical ratings.
14 Journal of Psychopharmacology 00(0)
shows corresponding effect sizes). Specifically, the effect of psi-
locybin dose is shown by comparing the LD-SS group with the
HD-SS group. Of the 23 longitudinal measures in Table 6, the
HD-SS group was significantly different from the LD-SS group
on 14 measures, all in the expected direction. Furthermore,
within-group analysis showed that change from baseline
(6-month minus baseline score) were significant on only one of
23 measures in the LD-SS group in contrast to 17 of 23 measures
in the HD-SS group.
Contrary to popular beliefs that psychedelic experiences
lead to rejection of traditional worldviews (Stevens, 1987), in
the current study, the life value of Tradition on the Schwartz
Value Scale increased significantly from baseline to 6 months
in the HD-HS group and was significantly higher in this group
than the LD-SS group at 6 months. This subscale comprises
items assessing respect for tradition, moderation of feelings
and action, humility, accepting life’s circumstances, and hold-
ing religious belief and faith. It is plausible that administering
psilocybin in the context of encouraging spiritual practices
accounts for this effect, which is consistent with the observa-
tion that indigenous sacramental use of psilocybin-containing
mushrooms, peyote, ayahuasca and other classic psychedelic-
containing substances is often strongly grounded in cultural
traditions (Schultes et al., 1998).
In the present study, the personality domain of Openness
increased from screening to 6 months in the HD-HS group but
not in the HD-SS or LD-SS groups. Further, there were no
between-group differences in Openness at 6 months. Further
analyses of these data (not presented) did not show significant
relationships between several measures of mystical-type
Figure 5. Participant ratings of effects attributed to psilocybin session experiences at the 6-month follow-up (Illustrative results from Table 5).
Data on altruistic/social effects, behavior changes, and spirituality are expressed as percentage of maximum possible score (bars show means, brackets show 1 SEM,
n=25). Data for the questions about spiritual significance and change in well-being or life satisfaction are either raw scores (bars show means, brackets show 1 SEM,
n=25) or percentages of the group (n=25). * indicates a significant difference from the Low-Dose Standard-Support group; + indicates a significant difference between
the High-Dose High-Support group and the High-Dose Standard-Support group (Planned comparisons, p<0.05).
Griffiths et al. 15
experience and changes in Openness. These findings contrast
with the results from a previous analysis that showed that psil-
ocybin-occasioned mystical experience was associated with
increases in Openness from screening to 1–2 months and to 14
months after psilocybin (MacLean et al., 2011). Increases in
Openness have been shown 2 weeks after administration of
LSD in healthy individuals (Lebedev et al., 2016). Another
study showed that increases in Openness predicted greater
reduction in post-traumatic stress disorder symptoms among
individuals receiving MDMA-assisted psychotherapy (Wagner
et al., 2017). The failure to observe significant increases in
Openness in the current study may be attributable to engage-
ment in the program of spiritual practices or to some other
aspect of the study design.
Table 6. Longitudinal measures assessed at 6 months that showed significant between group differences.
Measure Low-Dose High-Dose High-Dose
Standard-Support Standard-Support High-Support
Mysticism Scale: (Lifetime)
Interpretation (max score=108) 75.64 (3.25) 87.58 (5.10)* 99.96 (2.05)***+
Introvertive (max score=108) 60.72 (3.83) 86.96 (5.75)*** 95.08 (2.31)***
Extrovertive (max score=172) 40.12 (3.26) 49.22 (4.53) 59.80 (2.90)***+
Total Score (max score=288) 176.48 (9.65) 223.76 (14.78)** 254.84 (5.82)***+
Faith Maturity Scale (FMS)
Total Score (max score=84) 43.96 (2.36) 52.60 (3.24)* 58.52 (2.15)***
Religious Coping (Brief RCope)
Positive Religious Coping (max score=21) 2.89 (0.89) 7.28 (1.19)** 7.88 (1.44)**
Daily Spiritual Experience Scale (DSES)
Total (questions 1-14; max score=70) 28.04 (3.32) 37.88 (3.66)* 41.56 (2.80)**
How close do you feel to God (max score=4) 1.63 (0.16) 2.12 (0.15)* 2.36 (0.15)**
Death Transcendence Scale (26 items)
Mysticism scale (max score=35) 20.76 (1.83) 26.16 (2.12)* 30.96 (1.25)*
Religious scale (max score=35) 20.72 (1.67) 26.36 (1.86)* 27.67 (1.17)*
Total Score (max score=182) 113.92 (3.33) 125.68 (4.61)* 131.25 (3.53)*
Gratitude Questionnaire (GQ-6)
Total Score (max score=43) 37.4 (0.82) 39.16 (0.66) 39.52 (0.58)*
Life Attitude Profile (LAP-R)
Coherence (Life meaning)(max=56) 36.08 (1.74) 38.60 (1.85) 43.40 (1.60)*+
Trait Forgiveness Scale
Total Score (max score=50) 37.88 (1.32) 37.36 (1.43) 41.08 (0.83)+
Forgiveness of Transgression (TRIM-18)
Benevolence Motivation (max score=30) 18.63 (1.11) 22.88 (1.36)* 23.80 (0.89)*
Avoidance Motivation (max score=35)122.38 (1.41) 16.50 (1.67)* 17.20 (1.50)*
Sanctification of Strivings
Life strivings as sacred/spiritual (max score=5) 2.43 (0.25) 2.76 (0.26) 3.47 (0.20)*+
Schwartz Value Scale
Tradition (mean centered score) −1.58 (0.22) −1.17 (0.24) −0.79 (0.19)*
Interpersonal Closeness (IOS)
Mean rating (max score=7) 2.82 (0.20) 3.37 (0.29) 3.70 (0.29)*
Observer-rated spiritual/religious sentiments (ASPIRES)
Prayer Fulfillment (max score=50) 32.35 (1.51) 39.58 (1.24)*** 40.72 (0.94)**
Universality (max score=35) 24.17 (0.96) 27.04 (1.19) 28.08 (0.68)**
Total (max score=115) 76.30 (2.65) 88.42 (2.51)** 89.60 (1.69)**
Observer-rated positive changes in behavior & attitudes
Total change score 3.24 (0.75) 5.39 (0.93) 9.20 (1.40)***+
Outcome measures are shown in the table if there was one or more significant difference between groups at 6 months; measures showing a between-group difference at
baseline were excluded unless the between-group difference was also shown in the planned comparison of change from baseline score (6-month minus baseline score).
Data are means with 1 SEM shown in parentheses (n=25).
Within a row, asterisks indicate a significant difference from the Low-Dose Standard-Support group (*p<.05, **p<.01, ***p<.001, Planned comparison), and + indicates a
significant difference between the High-Dose High-Support group and the High-Dose Standard-Support group (Planned comparisons, p<.05).
Within a row, boldface font indicates a significant difference within the group between baseline and 6 months (Planned comparisons, p>.05); for all such significant dif-
ferences, 6-month scores were higher than baseline scores except for Avoidance Motivation in the TRIM-18 which were lower.
1Lower scores on this scale indicate more forgiveness.
16 Journal of Psychopharmacology 00(0)
Evidence that high support for spiritual
practices increased both the acute and
enduring effects of psilocybin
Session day effects. On several measures that were assessed on
session days, the effects of the high dose of psilocybin were
greater in the high spiritual practices support group than in the
standard-support groups. Guide ratings of tearing/crying during
the session and participants scores on the Mysticism Scale (total
score and two subscales) were significantly higher in the HD-HS
vs. HD-SS groups (Tables 2 and 3). Furthermore, on other partic-
ipant-rated measures thought to reflect aspects of mystical-type
Figure 6. Longitudinal measures assessed at the 6-month follow-up (Illustrative results from Table 6).
Bars show means; brackets show 1 SEM (n=25); indicates a significant difference between baseline and 6 months; * indicates a significant difference from the
Low-Dose Standard-Support group; + indicates a significant difference between the High-Dose High-Support group and the High-Dose Standard-Support group (Planned
comparisons, p<0.05). For comparison, dotted lines show mean scores from previous studies for each measure: Mysticism Scale (college students, Hood et al., 2001;
Ralph W. Hood Jr, personal communication); Faith Maturity Scale (university students, Loma Linda University, 2007), Daily Spiritual Experience Scale (general population
survey data, Underwood, 2006); Gratitude Questionnaire-6 (adults, McCullough et al., 2002); Life Meaning (college and community sample, Reker, 2007); Trait Forgive-
ness Scale (college students, Berry et al., 2005); Forgiveness Benevolence Motivation (college students, Tsang et al., 2006); Sanctification of Strivings (adults, Mahoney
et al., 2005).
Griffiths et al. 17
experience (total scores and subscale scores of the MEQ30, and
the Oceanic Boundlessness subscale of the 5D-ASC) the HD-HS
group was numerically higher than the HD-SS group. These
results contrast with the subjective ratings unrelated to mystical
experience (Table 3), for which there were no significant differ-
ences or consistent trends between the two high-dose groups. The
higher ratings on measures of mystical-type experiences in the
HD-HS vs. the HD-SS group likely reflects that, before the first
session, the high-support group received about twice as much
meeting time with guides, with the majority of this extra time
focused on discussion of and support for spiritual practices.
Persisting effects attributed to psilocybin assessed at 6
months. As with measures of mystical experience assessed on
psilocybin session days, there was evidence for the HD-HS group
showing greater effects than the HD-SS group. Significant differ-
ences were shown on altruism/positive social effects, positive
behavior change, and increased spirituality, as well as ratings and
percentage of strong endorsements of spiritual significance
(Table 5, Figure 5). Strikingly, more than half (56%) of partici-
pants in the high spiritual support condition rated their experi-
ence in one or both psilocybin sessions as the single most
spiritually significant experience of their life, with 96% rating it
as among the top five most spiritually significant experiences.
These results indicate that administering psilocybin in a context
of high support for spiritual practices increases both the reported
spiritual significance of the experience per se and the attribution
to it of increased spirituality.
Longitudinal measures assessed at 6 months. As with mea-
sures of mystical experience assessed on session days and persist-
ing positive effects attributed to psilocybin at 6 months, the
longitudinal measures provide evidence for greater effects in the
HD-HS group than the HD-SS group (Table 6 and Figure 6). Across
groups, the HD-HS group showed numerically greater effects than
the HD-SS group on 22 of the 23 measures, and showed statistically
significant differences on seven of 23 measures. Furthermore, the
HD-HS group differed significantly from the LD-SS group on all
23 measures, in contrast to the HD-SS group, which differed from
the LD-SS group on 14 of 23 measures. These measures included
positive changes in interpersonal closeness, gratitude, life meaning/
purpose, forgiveness, death transcendence, daily spiritual experi-
ences, religious faith and coping, sanctification of life strivings, as
well as ratings of participants by community observers. The effect
sizes for these comparisons were quite large (mean Cohen’s d=1.0
across all 23 measures, Table S2). Finally, within the HD-HS group,
6-month scores were significantly different from baseline on 20 of
23 measures (compared with 17 significant differences from base-
line in the HD-SS group).
Relationship of spiritual practices and
psilocybin-occasioned mystical experience to
outcome measures
Prior research suggests an important role of psilocybin-occasioned
mystical experience in the observed enduring positive changes in
psychological well-being, prosocial disposition, and spiritual
worldview (Garcia-Romeu et al., 2014; Griffiths et al., 2008, 2016;
Ross et al., 2016). In the present study, hierarchical regression anal-
ysis was used to examine the relationship of mystical experience
and specific spiritual practices to the various outcome measures that
showed between-group differences at 6 months (Table 7). The
measure of mystical experience used for this analysis was the mean
total score on the Mystical Experience Questionnaires (MEQ30)
that were completed immediately following the two psilocybin ses-
sions (4 and 5 months before the 6-month follow-up). Spiritual
practices were assessed at the 6-month assessment with a question-
naire in which participants retrospectively rated over the past 4
months the three spiritual practices that were taught and encouraged
during the study (minutes per day of mediation; times per day of
spiritual awareness practice; times per week of spiritual journaling).
When mystical experience alone was entered into a regression
model, it accounted for a significant proportion of variance in all 19
outcome measures studied. In a separate hierarchical regression
analysis, when the three spiritual practices were entered first into
the regression model, they accounted for a significant proportion of
the variance in 13 of 19 outcome measures studied. However, when
mystical experience was subsequently entered into the model, it
accounted for a significant proportion of variance in 18 of 19 meas-
ures after accounting for the impact of spiritual practices. For the
overall regression model, meditation was significant on six meas-
ures (Faith Maturity Scale, Daily Spiritual Experience Scale,
Figure 7. Two observer-rated measures of participant attitudes and behavior assessed at the 6-month follow-up (from Table 6).
Bars show means; brackets show 1 SEM (n=25); for both measures, * indicates a significant difference from the Low-Dose Standard-Support group; + indicates a sig-
nificant difference between the High-Dose High-Support group and the High-Dose Standard-Support group (Planned comparisons, p<0.05). For the ASPIRES, which was
assessed both at baseline and the 6-month follow-up, indicates a significant difference between baseline and 6 months (Planned comparisons, p<0.05). Also for the
ASPIRES, dotted line shows mean norm score (Piedmont, 2010).
18 Journal of Psychopharmacology 00(0)
Table 7. Hierarchical regression analysis of the relationship of spiritual practices and mystical experience to the outcome measures.
Outcome Measure Spiritual Practices*
entered first
Change in model adding post-
session mystical experience
score (MEQ30)
Beta (standardized coefficient)
t
p
R2F d f p R2
change
F d f pMeditation Awareness Journaling MEQ** Meditation Awareness Journaling MEQ Meditation Awareness Journaling
Mysticism Scale: (Lifetime) – total score 0.113 2.97 3 70 0.038 0.560 118.34 1 69 0.000 0.268 1.052 1.790 14.342 −1.09 0.06 0.34 10.88 0.282 0.949 0.736
Faith Maturity Scale 0.231 7.01 3 70 0.000 0.264 36.00 1 69 0.000 0.077 0.301 0.512 4.100 2.54 1.10 0.53 6.00 0.013 0.276 0.600
Positive Religious Coping 0.201 5.87 3 70 0.001 0.066 6.19 1 69 0.015 0.041 0.160 0.272 2.183 1.22 0.95 1.84 2.49 0.227 0.344 0.070
Daily Spiritual Experience Scale – total score 0.293 9.52 3 69 0.000 0.254 38.12 1 68 0.000 0.087 0.340 0.578 4.679 3.43 2.08 −0.04 6.17 0.001 0.042 0.966
Death Transcendence Scale – total score 0.058 1.44 3 70 0.239 0.285 29.93 1 69 0.000 0.124 0.486 0.826 6.616 −0.37 −0.52 0.70 5.47 0.712 0.606 0.489
Gratitude Questionnaire 0.050 1.24 3 70 0.302 0.166 14.62 1 69 0.000 0.023 0.089 0.151 1.208 1.98 −0.31 −1.75 3.82 0.052 0.761 0.085
Coherence (Life meaning and purpose) 0.084 2.11 3 69 0.107 0.329 38.06 1 68 0.000 0.052 0.204 0.347 2.811 1.64 −1.08 0.38 6.17 0.105 0.282 0.708
Trait Forgiveness Scale 0.083 2.10 3 70 0.108 0.100 8.43 1 69 0.005 0.043 0.167 0.284 2.277 1.79 0.12 −0.09 2.90 0.078 0.901 0.927
Forgiveness – benevolence motivations 0.116 2.96 3 68 0.038 0.196 19.04 1 67 0.000 0.038 0.148 0.250 2.041 2.24 0.43 −0.63 4.36 0.029 0.673 0.533
Forgiveness – avoidance motivations 0.120 3.10 3 68 0.032 0.081 6.77 1 67 0.011 0.054 0.211 0.357 2.914 −2.77 −0.31 0.91 −2.60 0.007 0.761 0.367
Sanctification of Strivings 0.173 4.86 3 70 0.004 0.131 12.99 1 69 0.001 0.008 0.031 0.053 0.422 1.32 0.94 1.10 3.60 0.191 0.351 0.275
Schwartz Value Scale – Tradition 0.060 1.49 3 70 0.224 0.091 7.37 1 69 0.008 0.008 0.030 0.051 0.411 0.06 0.66 0.46 2.72 0.954 0.515 0.644
Interpersonal closeness 0.079 2.01 3 70 0.121 0.065 5.26 1 69 0.025 0.010 0.037 0.064 0.509 0.98 0.95 0.10 2.29 0.332 0.348 0.923
Observer-rated spiritual/religious sentiments 0.141 3.73 3 68 0.015 0.291 34.36 1 67 0.000 0.076 0.281 0.485 3.868 2.68 0.50 −1.38 5.86 0.009 0.617 0.173
Observer-rated positive behavior and attitude
change score 0.248 7.71 3 70 0.000 0.031 2.97 1 69 0.089 0.037 0.146 0.249 1.995 0.85 2.00 2.11 1.72 0.400 0.049 0.039
Positive attitudes about life, self, mood,
altruism, behavior, and spirituality*** 0.170 4.44 3 65 0.007 0.542 120.35 1 64 0.000 0.001 0.005 0.008 0.069 0.85 0.77 0.75 10.97 0.397 0.445 0.458
Personal meaning of session experiences 0.132 3.50 3 69 0.020 0.551 118.26 1 68 0.000 0.009 0.036 0.059 0.472 −2.17 0.56 0.71 10.88 0.033 0.578 0.482
Spiritual significance of session experiences 0.132 3.49 3 69 0.020 0.619 169.17 1 68 0.000 0.007 0.027 0.045 0.359 −0.90 0.69 0.36 13.01 0.372 0.490 0.719
Change in well-being/life satisfaction 0.166 4.57 3 69 0.006 0.436 74.53 1 68 0.000 0.006 0.023 0.038 0.303 −0.73 1.26 1.08 8.63 0.471 0.214 0.284
The first 15 measures are total scores from measures shown in Table 6 and the last four measures are from Table 5; bold font indicates probability <.05.
*Spiritual Practices were: Meditation (minutes per day), Spiritual Awareness Practice (times per day), and Journaling (times per week).
**MEQ: Mean total score of the Mystical Experience Questionnaire (MEQ30).
***This participant-rated measure is a composite total score of the 6 subscales in Table 5 that assessed positive effects attributed to psilocybin session experiences.
Griffiths et al. 19
Forgiveness-benevolence motivations, Forgiveness-avoidance
motivations, Observer-rated spiritual and religious sentiments, and
Participant retrospective rating of the personal meaning of the ses-
sion experiences); spiritual awareness practices were significant on
two measures (Daily Spiritual Experience Scale, and Observer-
rated changes in behavior and attitudes); and journaling was signifi-
cant on one measure (Observer-rated changes in behavior and
attitudes).
Overall, these results suggest that both mystical experience
and spiritual practices contribute to positive outcomes, with mys-
tical experience making a substantially greater contribution. The
fact that the measure of mystical experience preceded the assess-
ment of outcome measures by 4–5 months strengthens the inter-
pretation that mystical experience and/or its neurophysiological
or other correlates are likely determinants of the enduring posi-
tive attitudinal, dispositional, and behavioral effects of psilocy-
bin when administered under spiritually supported conditions.
It is interesting that a previous study with a relatively high
dose (200 μg) of LSD, a different classic psychedelic, produced
only moderate increases in total mystical experience scores
(MEQ30), with only 12.5% of participants meeting criteria for a
complete mystical experience (Liechti et al., 2017). Whether this
lower rate of mystical experience reflects pharmacodynamic dif-
ferences between psilocybin and LSD, the use of a relatively
lower dose of LSD than psilocybin, and/or differences between
the studies in set, setting, or participant characteristics is unknown
(Barrett and Griffiths, 2017). Future research should directly
compare LSD and psilocybin within subjects, ideally using pro-
cedures to minimize expectancy effects.
There was little evidence that the standard-support interven-
tion alone affected longitudinal measures at 6 months. Of the 23
longitudinal measures (Table 6), only one measure in the LD-SS
group showed a significant difference from baseline (immedi-
ately after study enrollment) to 6 months. Furthermore, across
the longitudinal measures shown in Figures 6 and 7, the LD-SS
group tended to be similar or lower than comparison data (e.g.
norms) from previous studies. The absence of robust effects of
the standard-support intervention contrasts with previous studies
that showed a more intensive 8- or 9-session program using a
similar intervention resulted in a variety of positive changes in
spirituality, well-being, self-efficacy, and mental health outcomes
(Flinders et al., 2007; Hedberg et al., 2006; Oman et al., 2006,
2008a,b). The lack of greater efficacy for the standard-support
intervention in the present study was likely due to the minimal
level of teaching and support provided to the LD-SS group.
Experimental design strengths and
limitations
Strengths of the present study include the double-blind design,
the use of a very low (possibly inactive) psilocybin dose as a
control, and instructions to participants and guides, all serving to
obscure the actual dose conditions and thereby minimizing par-
ticipant and guide expectancy effects. This strategy has been used
in previous psilocybin research (Griffiths et al., 2016). In the pre-
sent study, the effects of very low dose of psilocybin (1 mg/70
kg) were compared with the high-dose conditions. The low dose
was below a dose (3.15 mg/70 kg) that did not produce statisti-
cally significant effects in a previous study (Hasler et al., 2004).
Participants and guides did report some psilocybin-like effects
after the very low dose (e.g. Tables 2, 3, and 5), as might be
expected under conditions in which participants (most of whom
were psychedelic-naive) had been told they would receive psilo-
cybin. For instance, three of 25 (12%) of participants in the low-
dose condition rated their psilocybin session experiences to be
among the five most spiritually significant of their lives. Although
the low-dose condition served as an important comparison to the
high-dose conditions, in absence of a true placebo-dose condi-
tion, it is not possible to determine if the very low dose was phar-
macologically active.
The integrity of blinding the guides to the study conditions
was assessed with a post-study questionnaire that asked guides
about their understanding of study drug and dose conditions.
The finding that most guides made incorrect inferences about
drug or dose conditions suggests substantial success of the
blinding conditions. Guides were not required to make guesses
about drug conditions after each session because we did not
want to make this a focus of interest for guides. However, the
absence of such guide ratings on each session precludes draw-
ing a stronger conclusion about the success of blinding guides
to study conditions.
The experimental design of the present study can be viewed
as representing 3 of 4 cells of a balanced 2×2 design with dose
(low dose vs. high dose) and spiritual support (standard support
vs. high support) as factors. The fourth cell of a completely bal-
anced design would be the low-dose high-support condition.
Addition of that group would have permitted evaluation of the
effects of high support independent of psilocybin. Although we
considered the benefits of the balanced 2×2 design, we decided
against it because of substantially increased study costs and
because of concern that participants in this group, who receive
only a low dose of psilocybin, might be less likely to comply with
the more intensive schedule of participant–guide and dialogue-
group meetings required in the high-support condition.
Additional limitations of the present study were the homoge-
neity of the participant population (predominately White, college
educated, and employed) and the absence of brain-based or phys-
iological measures of change or task-based measures such as
assessment of implicit bias, emotion regulation, or social behav-
ior. Finally, because the high-support condition involved group
discussion of both spiritual practices and psilocybin experiences,
the effect of group discussion of spiritual practice alone cannot
be determined.
Conclusion
Although previous research shows that psilocybin, under appro-
priate conditions, can reliably occasion mystical-type experi-
ences to which participants frequently attribute enduring positive
changes in well-being and worldview, there has been little evi-
dence from studies in healthy volunteers that psilocybin produces
enduring changes on well-validated trait measures of disposition
or personality. In the present study, psilocybin was administered
in the context of undertaking a nonsectarian program of medita-
tion and other spiritual practices that emphasized integration of
spiritual values in daily life. The study showed robust interactive
positive effects of psilocybin dose and added support for
spiritual practices on a wide range of longitudinal measures
at 6 months including interpersonal closeness, gratitude,
life meaning/purpose, forgiveness, death transcendence, daily
20 Journal of Psychopharmacology 00(0)
spiritual experiences, religious faith and coping, and rating of
participants by community observers. Analyses suggest that the
determinants of these effects were the intensity of the psilocybin-
occasioned mystical experience and the rates of engagement with
meditation and other spiritual practices. Most broadly, as a model
system for studying so-called quantum change experiences,
which have been described for centuries but which have eluded
rigorous prospective experimental analysis, further investigation
of psilocybin-occasioned experiences may have broad implica-
tions for the development of drug and non-drug interventions in
both therapeutic and nontherapeutic applications in order to
engender enduring positive trait-level changes in attitudes and
behavior and in healthy psychological functioning.
Acknowledgements
The authors thank Frederick Reinholdt, M.S., Albert Garcia-Romeu,
Ph.D., Daniel Evatt, Ph.D., Haley Sweet, Rosemary Flickinger and 13
other staff members for their roles as session guides. We also thank David
Nichols, Ph.D. for synthesizing the psilocybin, Linda Felch M.A. for sta-
tistical analyses, Dr. Annie Umbricht for medical management, and Dr.
David Addiss and Wayne Ramsey of the Fetzer Institute for help in scien-
tific development and administrative support of this study. We are also
grateful to Drs. Kenneth Pargament, Doug Oman, and Ralph Hood for
helpful comments on the design of the study.
Declaration of conflicting interests
The author(s) declared the following potential conflicts of interest with
respect to the research, authorship, and/or publication of this article:
Roland Griffiths is on the Board of Directors of the Heffter Research
Institute. Robert Jesse, convener of the Council on Spiritual Practices,
participated in designing the study and writing the manuscript, but was
not involved in data collection, analysis, or interpretation.
Funding
The author(s) disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Conduct of this
research was primarily supported by grants from the Fetzer Institute and
the Council on Spiritual Practices. Some support was also provided by
the Heffter Research Institute. Effort for Roland Griffiths, Ph.D. in writ-
ing this paper was partially provided by NIH grant RO1DA03889.
Supplemental Material
Supplementary material is available for this article online.
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... For psychedelics, persisting effects on personality or wellbeing can be found up to 12 months after a single dose administration (25), whereas increased mindfulness capacities have been found to persist up to 3 months (43). It has been suggested by some studies that the intensity or quality of the psychedelic experience determines the treatment outcome (52)(53)(54). Specifically, it has been repeatedly found that psychedelic-induced mystical-type experiences and ego dissolution, the latter a phenomenon characterized by the reduction in self-referential awareness, disruption selfworld boundaries, and increased feelings of unity with one's surroundings (55), correlates with long-term (positive) outcomes (23,(52)(53)(54)(56)(57)(58). Thus, in the present study we also assessed whether we could predict sub-acutechanges in anxiety based on acute ratings of ego dissolution. ...
... It has been suggested by some studies that the intensity or quality of the psychedelic experience determines the treatment outcome (52)(53)(54). Specifically, it has been repeatedly found that psychedelic-induced mystical-type experiences and ego dissolution, the latter a phenomenon characterized by the reduction in self-referential awareness, disruption selfworld boundaries, and increased feelings of unity with one's surroundings (55), correlates with long-term (positive) outcomes (23,(52)(53)(54)(56)(57)(58). Thus, in the present study we also assessed whether we could predict sub-acutechanges in anxiety based on acute ratings of ego dissolution. ...
... Additionally, we sought to examine previously reported associations between anxiety and personality (77,78) as well as between anxiety and mindfulness capacities (49,50). Given that ratings of ego dissolution have been shown to correlate with persisting effects after a psychedelic experience in both clinical and naturalistic studies (23,(52)(53)(54)56, 57), we tested for the possible associations between EDI scores and changes in anxiety. Canonical correlations (79) were conducted to evaluate the association between psilocybin-induced changes in (i) selfrated mindfulness capacities and neuroticism, (ii) ratings of ego dissolution, and (iii) state and trait anxiety. ...
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... An important principle of a context-dependent or relational approach to psychedelics is that the psychedelic experience itself is an important mediator of subsequent therapeutic outcomesand there is much evidence to support this (Carbonaro et al., 2016;Carhart-Harris et al., 2016b;Davis et al., 2019Davis et al., , 2020Davis et al., , 2021bGarcia-Romeu et al., 2015;Gasser et al., 2015;Griffiths et al., 2016Griffiths et al., , 2018MacLean et al., 2011;Passie, 1997;Roseman et al., 2018;Ross et al., 2016;Schmid and Liechti, 2017). Specifically, a number of studies have found that 'peak' or 'mystical' -type experiences, which feature feelings of unity, transcendence of time, space and self, and positive mood, are predictive of subsequent positive therapeutic outcomes (Bogenschutz et al., 2015;Davis et al., 2019;Garcia-Romeu et al., 2015;Griffiths et al., 2016;Murphy et al., 2022;Pahnke, 1963;Roseman et al., 2018;Ross et al., 2016). ...
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... Prospective studies demonstrate that psilocybin induces acute mystical-type experiences as well as enduring increases on a spirituality scale that assessed a broad sense of meaning and connectedness to humanity, life, and the God of their understanding/ultimate reality (Davis et al., 2021;Griffiths et al., 2011Griffiths et al., , 2016. A prospective randomized study of psilocybin in beginning meditators showed similar effects at four months after administration including significant increases in a participant-rated death transcendence scale and observer-rated spiritual/religious sentiments for months after sessions, again defined broadly to reflect beliefs and feelings of connectedness, universality, and closeness to the god of their understanding (Griffiths et al., 2018). Likewise, cross-sectional studies have reported increases in broadly defined spiritualtype beliefs after psychedelic use (Davis et al., 2020;Griffiths et al., 2019;Yaden, Le Nguyen, et al., 2017). ...
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This paper presents a theory of potentially universal aspects in the content of human values. Ten types of values are distinguished by their motivational goals. The theory also postulates a structure of relations among the value types, based on the conflicts and compatibilities experienced when pursuing them. This structure permits one to relate systems of value priorities, as an integrated whole, to other variables. A new values instrument, based on the theory and suitable for cross-cultural research, is described. Evidence relevant for assessing the theory, from 97 samples in 44 countries, is summarized. Relations of this approach to Rokeach's work on values and to other theories and research on value dimensions are discussed. Application of the approach to social issues is exemplified in the domains of politics and intergroup relations.
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In four studies, the authors examined the correlates of the disposition toward gratitude. Study 1 revealed that self-ratings and observer ratings of the grateful disposition are associated with positive affect and well-being prosocial behaviors and traits, and religiousness/spirituality. Study 2 replicated these findings in a large nonstudent sample. Study 3 yielded similar results to Studies 1 and 2 and provided evidence that gratitude is negatively associated with envy and materialistic attitudes. Study 4 yielded evidence that these associations persist after controlling for Extraversion/positive affectivity, Neuroticism/negative affectivity, and Agreeableness. The development of the Gratitude Questionnaire, a unidimensional measure with good psychometric properties, is also described.
Chapter
This chapter begins with a brief review of descriptions and definitions of mystical-type experiences and the historical connection between classic hallucinogens and mystical experiences. The chapter then explores the empirical literature on experiences with classic hallucinogens in which claims about mystical or religious experiences have been made. A psychometrically validated questionnaire is described for the reliable measurement of mystical-type experiences occasioned by classic hallucinogens. Controlled laboratory studies show that under double-blind conditions that provide significant controls for expectancy bias, psilocybin can occasion complete mystical experiences in the majority of people studied. These effects are dose-dependent, specific to psilocybin compared to placebo or a psychoactive control substance, and have enduring impact on the moods, attitudes, and behaviors of participants as assessed by self-report of participants and ratings by community observers. Other studies suggest that enduring personal meaning in healthy volunteers and therapeutic outcomes in patients, including reduction and cessation of substance abuse behaviors and reduction of anxiety and depression in patients with a life-threatening cancer diagnosis, are related to the occurrence of mystical experiences during drug sessions. The final sections of the chapter draw parallels in human neuroscience research between the neural bases of experiences with classic hallucinogens and the neural bases of meditative practices for which claims of mystical-type experience are sometimes made. From these parallels, a functional neural model of mystical experience is proposed, based on changes in the default mode network of the brain that have been observed after the administration of classic hallucinogens and during meditation practices for which mystical-type claims have been made.
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Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.