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This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.
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ORIGINAL INVESTIGATION
Psilocybin occasioned mystical-type experiences:
immediate and persisting dose-related effects
Roland R. Griffiths &Matthew W. Johnson &
William A. Richards &Brian D. Richards &
Una McCann &Robert Jesse
Received: 5 February 2011 / Accepted: 13 May 2011 / Published online: 15 June 2011
#Springer-Verlag 2011
Abstract
Rationale This dose-effect study extends previous observa-
tions showing that psilocybin can occasion mystical-type
experiences having persisting positive effects on attitudes,
mood, and behavior.
Objectives This double-blind study evaluated psilocybin (0,
5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive
conditions.
Methods Participants were 18 adults (17 hallucinogen-
naïve). Five 8-h sessions were conducted individually for
each participant at 1-month intervals. Participants were
randomized to receive the four active doses in either
ascending or descending order (nine participants each).
Placebo was scheduled quasi-randomly. During sessions,
volunteers used eyeshades and were instructed to direct
their attention inward. Volunteers completed questionnaires
assessing effects immediately after and 1 month after each
session, and at 14 months follow-up.
Results Psilocybin produced acute perceptual and subjec-
tive effects including, at 20 and/or 30 mg/70 kg, extreme
anxiety/fear (39% of volunteers) and/or mystical-type
experience (72% of volunteers). One month after sessions
at the two highest doses, volunteers rated the psilocybin
experience as having substantial personal and spiritual
significance, and attributed to the experience sustained
positive changes in attitudes, mood, and behavior, with the
ascending dose sequence showing greater positive effects.
At 14 months, ratings were undiminished and were
consistent with changes rated by community observers.
Both the acute and persisting effects of psilocybin were
generally a monotonically increasing function of dose, with
the lowest dose showing significant effects.
Conclusions Under supportive conditions, 20 and 30 mg/
70 kg psilocybin occasioned mystical-type experiences
having persisting positive effects on attitudes, mood, and
behavior. Implications for therapeutic trials are discussed.
Keywords Psilocybin .Dose effects .Hallucinogen .
Entheogen .Psychedelic .Mystical experience .Fear .
Spiritual .Religion .Positive psychology .Humans
Introduction
Psilocybin, which is the principal psychoactive component
of Psilocybe and other genera of mushrooms, has likely
been used for millennia within some cultures in structured
manners for divinatory or religious purposes (Wasson 1980;
Stamets 1996; Metzner 2004; Guzmán 2008). Like other
classic hallucinogens [d-lysergic acid diethylamide (LSD),
mescaline, and N,N-dimethyltryptamine (DMT)], the effects
R. R. Griffiths (*):M. W. Johnson :U. McCann
Department of Psychiatry and Behavioral Sciences, Johns
Hopkins University School of Medicine,
5510 Nathan Shock Drive,
Baltimore, MD 21224-6823, USA
e-mail: rgriff@jhmi.edu
R. R. Griffiths
Department of Neuroscience,
Johns Hopkins University School of Medicine,
5510 Nathan Shock Drive,
Baltimore, MD 21224-6823, USA
W. A. Richards :B. D. Richards
Department of Psychiatry,
Johns Hopkins Bayview Medical Center,
2516 Talbot Road,
Baltimore, MD 21216-2032, USA
R. Jesse
Council on Spiritual Practices,
Box 460220, San Francisco, CA 94146-0220, USA
Psychopharmacology (2011) 218:649665
DOI 10.1007/s00213-011-2358-5
of psilocybin are primarily mediated at 5-HT
2A
receptor
sites (Glennon et al. 1984; Nichols 2004), and the acute
subjective effects include robust changes in perception,
cognition, affect, volition, and somesthesia (Isbell 1959;
Wolbach et al. 1962; Rosenberg et al. 1964). In early
clinical research with psilocybin, the affective character of
subjective experiences often varied from positive to
negative, and highly valued personal or mystical-type
experiences were rare (e.g., Isbell 1959; Malitz et al.
1960; Rinkel et al. 1960; Hollister 1961). Subsequent
research that generally used higher psilocybin doses and
provided more preparation and interpersonal support
reported a higher rate of affectively positive experiences,
sometimes of a mystical nature, that were rated as being of
personal significance (Leary et al. 1963; Metzner et al.
1965; Pahnke 1969).
Recently, we used rigorous double-blind methods to
evaluate the acute (7 h) and longer-term (2 months and
14 months) psychological effects of a high dose of
psilocybin (30 mg/70 kg) relative to an active comparison
compound (40 mg/70 kg methylphenidate) in 36
hallucinogen-naïve volunteers (Griffiths et al. 2006,
2008). The study was designed to optimize the potential
for positively valued experiences by providing 8 h of
preparation, administering psilocybin in a pleasant, sup-
portive setting, and instructing volunteers to focus explic-
itly on their subjective or inner experience rather than, for
example, perform tasks. The results showed that psilocybin
occasioned mystical-type experiences and, sometimes,
significant fear. The mystical-type experiences were rated
as having substantial and persisting personal meaning and
spiritual significance to which volunteers attributed sus-
tained positive changes in attitudes, moods, and behavior.
The present study was undertaken using similar procedures
to characterize the acute and persisting effects of a range of
lower doses of psilocybin (0, 5, 10, 20, 30 mg/70 kg). The
study was also designed to compare the ascending and
descending sequences of drug dose exposure.
Materials and methods
Participants
Participants were recruited from the local community
through flyers announcing a study of states of conscious-
ness brought about by psilocybin, a naturally occurring
psychoactive substance used sacramentally in some cul-
tures. Two hundred seventy-nine individuals were screened
over the telephone and 31 were further screened in person.
The 18 study participants (eight males) 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), psychiatrically healthy, and without family histories
of psychotic disorders or bipolar I or II disorder (as
determined by structured clinical interviews). Individuals
with current alcohol or drug dependence (including
nicotine) were excluded, as were individuals with a past
history within the past 20 years of alcohol or drug
dependence (excluding nicotine). Participants were halluci-
nogen naïve, except for one who reported using psilocybin
mushrooms on two occasions more than 20 years previ-
ously. Participants had an average age of 46 years (range 29
to 62) and were well educated; all had at least some college,
94% were college graduates, and 56% had post-graduate
degrees. Fifty-six percent were employed full time, 33%
part time, and 11% were retired. Fifty percent indicated
affiliation with a religious or spiritual community, such as a
church, synagogue, or meditation group. While not an
inclusion criterion, all 18 volunteers indicated at least
intermittent participation in religious or spiritual activities
such as religious services, prayer, or meditation, with 39%
reporting daily activities and an additional 39% reporting at
least weekly activities. Volunteers did not receive monetary
compensation for participation. Based on interviews, their
motivation for participation was curiosity about the effects of
psilocybin and the opportunity for extensive self-reflection in
the context of the day-long drug sessions and the meetings
with the monitors that occurred before and after sessions. The
Institutional Review Board of the Johns Hopkins University
School of Medicine approved the study, and all volunteers
gave their informed consent before participation.
Study design and overview
The study procedures followed recommendations provided for
safe conduct of research administering high doses of a classic
hallucinogen (Johnson et al. 2008). The study examined
psilocybin (0, 5, 10, 20, and 30 mg/70 kg) using a double-
blind, between-group, crossover design that involved five 8-
h drug sessions conducted at approximately 1-month inter-
vals, and a 14-month follow-up. Eighteen volunteers were
randomly assigned to receive the active psilocybin doses in
either an ascending dose sequence or a descending sequence.
Although each volunteer received the 0 mg/70 kg condition
once, across the nine volunteers in each of the ascending and
descending sequences, the 0 mg/70 kg condition occurred
twice on sessions 1, 2, 4, and 5, and once on session 3. The
purpose of this quasi-random scheduling of placebo was to
obscure the dose sequence to the participants and monitors
(see Instructions to participants and monitorssection
below). Outcome measures obtained throughout the drug
sessions included blood pressure and monitor ratings of
participant mood and behavior. At about 7 h after drug
ingestion (when the primary drug effects had subsided),
650 Psychopharmacology (2011) 218:649665
participants completed several questionnaires designed to
assess various aspects of hallucinogen experience (described
below). Various longitudinal and persisting effects measures
were assessed at screening, 1 month after each drug session,
and at 14 months after the last session.
Instructions to participants and monitors
Participants and monitors were informed that participants
would receive placebo and four different doses (ranging from
low to high) of psilocybin in mixed order across sessions.
Neither participants nor monitors were informed that the
active psilocybin doses would be tested in an ascending or
descending sequence. The only exception to this was that two
of the seven assistant monitors were not blind to the
ascending/descending nature of the experimental design;
however, they were blind to the outcome of randomization.
Drug conditions
Psilocybin doses and placebo (0 mg/70 kg) were prepared
in identically appearing opaque, size 0 gelatin capsules,
with lactose as the inactive capsule filler. On each session, a
single capsule was administered with 180 ml water.
Meetings with monitor before and after sessions
The primary monitor (usually along with the assistant
monitor) met with each participant on four occasions before
his or her first session (for 8 h total), once for about an hour
on the day following each of the five sessions, and one
more time about 3 weeks after each session. The purpose
and content of these meetings are described elsewhere
(Griffiths et al. 2006; Johnson et al. 2008). Monitors and
assistant monitors were trained by personnel with extensive
prior experience monitoring hallucinogen sessions.
Drug sessions
As described in more detail previously (Griffiths et al.
2006), drug sessions were conducted in an aesthetic living-
room-like environment with two monitors present. Partic-
ipants were instructed to consume a low-fat breakfast
before coming to the research unit. A urine sample was
taken to verify abstinence from common drugs of abuse
(cocaine, benzodiazepines, and opioids including metha-
done). Although the presence of THC was not tested, none
of the volunteers reported recent use of cannabis. 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 distraction, and use headphones through which a
music program was played. The same music program was
played for all participants in all sessions. Participants were
encouraged to focus their attention on their inner experi-
ences throughout the session.
Measures assessed throughout the session
Ten minutes before and 30, 60, 90, 120, 180, 240, 300, and
360 min after capsule administration, blood pressure, heart
rate, and monitor ratings were obtained.
Blood pressure and heart rate: Blood pressure (systolic
and diastolic pressure using oscillometric method with the
blood-pressure cuff placed on the arm) and heart rate were
monitored using a Non-Invasive Patient Monitor Model
507E (Criticare Systems, Inc., Waukesha, WI, USA).
Monitor Rating Questionnaire: At the same time points at
which the physiological measures were taken, the two session
monitors completed the Monitor Rating Questionnaire, which
involved rating or scoring several dimensions of the partic-
ipantsbehaviorormood(Table1). The dimensions that are
expressed as peak scores in Table 1were rated on a five-
point scale from 0 to 4. Dimensions expressed as total
duration in Table 1were rated as the estimated number of
minutes since the last rating. Data were the mean of the two
monitor ratings at each time point.
Measures assessed 7 h after drug administration
At about 7 h after capsule administration when the major
drug effects had subsided, the participant completed three
questionnaires developed for assessing the subjective
effects of hallucinogen drugs and two questionnaires
developed for assessing mystical experience. Participants
typically completed these questionnaires in about 40 min.
Hallucinogen Rating Scale: This 99-item questionnaire,
which was designed to show sensitivity to the hallucinogen
N,N-dimethyltryptamine (DMT) (Strassman et al. 1994),
consists of six subscales assessing various aspects of
hallucinogen effects (Intensity, Somesthesia, Affect, Per-
ception, Cognition, and Volition).
APZ: The APZ is a 72-item yes/no questionnaire designed to
assess altered states of consciousness, including those produced
by hallucinogens (Dittrich 1998). The three major scales on
the APZ are the OSE (oceanic boundlessness; a state common
to classic mystical experiences including feelings of unity and
transcendence of time and space), the AIA (dread of ego
dissolution; dysphoric feelings), and the VUS (visionary
restructuralization; includes items on visual pseudo-hallucina-
tions, illusions, and synesthesias). Data on each scale were
expressed as a proportion of the maximum possible score.
Psychopharmacology (2011) 218:649665 651
Addiction Research Center Inventory (ARCI): The ARCI
was developed to differentiate subjective effects among
several classes of psychoactive drugs including the halluci-
nogens (Haertzen 1966). The short form of the ARCI consists
of 49 true/false questions and contains five major scales:
lysergic acid diethylamide (LSD), a hallucinogen-sensitive
scale that is often interpreted as providing a measure of
dysphoric changes; pentobarbital, chlorpromazine, alcohol
group (PCAG), a sedative sensitive scale; benzedrine group
(BG) and amphetamine (A) scales, amphetamine-sensitive
scales; and morphine-benzedrine group (MBG), often inter-
preted as a measure of euphoria (Martin et al. 1971;Jasinski
1977). Participants were instructed to answer the questions on
the ARCI with reference to the effects they experienced since
they received the capsule that morning.
States of Consciousness Questionnaire: This 100-item
questionnaire is rated on a six-point scale [0=none, not at
all; 1=so slight cannot decide; 2=slight; 3 = moderate; 4 =
strong (equivalent in degree to any previous strong
experience or expectation of this description); 5=extreme
(more than ever before in my life and stronger than 4)].
Forty-three items on this questionnaire comprised the
current version of the PahnkeRichards mystical experience
items, which was shown sensitive to psilocybin (Electronic
Supplementary Table 1in Griffiths et al. 2006). An earlier
version of this scale was also previously shown sensitive to
psilocybin and other hallucinogens (Pahnke 1963; Turek et
al. 1974; Richards et al. 1977). The 43 items provide scale
scores for each of seven domains of mystical experiences:
internal unity (pure awareness; a merging with ultimate
reality); external unity (unity of all things; all things are
alive; all is one); sense of sacredness (reverence; sacred);
noetic quality (claim of an encounter with ultimate reality;
more real than everyday reality); transcendence of time and
space, deeply felt positive mood (joy, peace, love);
Table 1 Cardiovascular measures and monitor ratings of volunteer behavior and mood assessed throughout the session
Measure Psilocybin dose (mg/70 kg)
0 5 10 20 30
Cardiovascular measures (peak effects)
Systolic blood pressure (mmHg) 132.6 (3.6) 143.3 (4.3)
a
145.7 (4.6)
a
145.7 (4.2)
a
153.1 (4.2)
b
Diastolic blood pressure (mmHg) 77.5 (1.9) 83.4 (2.1)
a
83.9 (2.0)
a
84.3 (2.5)
a
88.8 (2.4)
b
Heart rate (beats per minute) 74.8 (2.5) 78.7 (2.7)
a
77.9 (2.0)
a
81.2 (3.0)
a,b
83.0 (2.4)
b
Monitor ratings (peak effects, max score= 4)
Overall drug effect 0.69 (0.15) 2.03 (0.13)
a
2.44 (0.19)
b
3.06 (0.15)
c
3.42 (0.15)
c
Sleepiness/sedation 1.11 (0.22) 0.69 (0.18) 0.78 (0.20) 0.58 (0.16) 0.58 (0.14)
Unresponsive to questions 0.17 (0.09) 0.19 (0.12)
a
0.44 (0.14)
b
0.97 (0.30)
c
1.14 (0.24)
d
Anxiety or fearfulness 0.28 (0.10) 0.61 (0.19)
a
0.75 (0.15)
b
1.06 (0.22)
c
1.19 (0.22)
d
Stimulation/arousal 0.53 (0.19) 1.19 (0.13)
a
1.64 (0.19)
b
1.97 (0.20)
b,d
2.17 (0.22)
c,d
Distance from ordinary reality 0.75 (0.17) 1.92 (0.19)
a
2.36 (0.21)
b
2.97 (0.17)
c
3.22 (0.15)
c
Ideas of reference/paranoid thinking 0.03 (0.03) 0.00 (0.00)
a
0.08 (0.05)
a
0.14 (0.06)
a
0.44 (0.14)
b
Yawning 0.22 (0.10) 0.53 (0.15)
a
0.97 (0.27)
a,b
1.36 (0.37)
b,c
1.81 (0.39)
c
Tearing/crying 0.61 (0.24) 1.00 (0.29)
a
1.25 (0.26)
b
1.50 (0.33)
c
1.81 (0.24)
d
Nausea 0.00 (0.00) 0.33 (0.10)
a
0.42 (0.15)
b
0.31 (0.13)
c
0.47 (0.13)
d
Spontaneous motor activity 0.22 (0.09) 0.64 (0.15)
a
0.78 (0.20)
a
1.14 (0.32)
a,c
1.47 (0.35)
b,c
Restless/fidgety 0.17 (0.07) 0.44 (0.18)
a
0.58 (0.12)
b
0.89 (0.19)
c
0.81 (0.17)
d
Joy/intense happiness 0.64 (0.19) 1.19 (0.22)
a
1.42 (0.27)
a,b
1.81 (0.33)
b,c
2.14 (0.31)
c
Peace/harmony 0.78 (0.19) 1.39 (0.22)
a
1.64 (0.22)
a,b
2.11 (0.30)
b
2.03 (0.27)
b
Monitor ratings (total duration in
minutes, max score= 360)
Talking with monitor 85.94 (7.32) 85.42 (6.90) 83.06 (8.08) 83.75 (10.29) 85.03 (11.32)
Physical contact with monitor
(e.g., reassuring touch)
21.64 (7.26) 35.61 (9.33)
a
45.00 (12.05)
b
69.94 (21.31)
c
86.00 (21.15)
d
Sleep 13.72 (6.80) 3.83 (3.31) 2.67 (1.99) 3.42 (2.13) 0.61 (0.44)
Strong anxiety 0.33 (0.34) 0.61 (0.63) 1.14 (0.69) 1.81 (0.80) 11.11 (6.75)
Data are means with 1 SEM shown in parentheses (N=18); within a row, bold font indicates significant difference from 0 mg/70 kg; for active
doses, values not sharing a common letter are significantly different (Fishers LSD p<0.05)
652 Psychopharmacology (2011) 218:649665
paradoxicality and ineffability (claim of difficulty in
describing the experience in words). Data on each domain
scale were expressed as a percentage of the maximum
possible score. As in previous studies (Pahnke 1969;
Griffiths et al. 2006), criteria for designating a volunteer
as having had a completemystical experience were that
scores on each of the following six scales had to be at least
60%: unity (either internal or external, whichever was
greater), sense of sacredness, noetic quality, transcendence
of time and space, positive mood, and ineffability. A mean
total score was calculated as a mean of all items from the
preceding six scales. The remaining 57 items in the States
of Consciousness Questionnaire served as distracter items.
Mysticism Scale (Experience-specific): This 32-item ques-
tionnaire, which assesses primary mystical experiences, has
been extensively studied and shows cross-cultural reliabil-
ity (Hood et al. 2001,2009) and has previously been shown
sensitive to psilocybin (Griffiths et al. 2006). A total score
and three empirically derived factors are measured: Inter-
pretation (corresponding to three mystical dimensions
noetic quality, sacredness, and deeply felt positive mood);
Introvertive Mysticism (corresponding to the mystical
dimensions of internal unity, transcendence of time and space,
and ineffability); and Extrovertive Mysticism (corresponding
to the dimension of the unity of all things/all things are alive).
Items were rated on a nine-point scale (Griffiths et al. 2006).
For this experience-specific version of the questionnaire used
7 h after drug administration, participants were instructed to
complete the questionnaire with reference to their experi-
ences since they received the capsule that morning.
Persisting effects assessed 1 month after sessions
At 3 to 4 weeks after each session, and before any
additional session, participants returned to the research
facility and completed a series of questionnaires to assess
possible changes in various standardized measures of
personality, mood, and spirituality (not included in this
report) as well as possible persisting changes in attitudes,
mood, behavior, and spirituality. Participants typically
completed these questionnaires in about 75 min.
Persisting Effects Questionnaire: This 143-item question-
naire sought information about changes in attitudes, moods,
behavior, and spiritual experience that, on the basis of prior
research (Pahnke 1969; Doblin 1991; Griffiths et al. 2006),
would be sensitive to the effects of psilocybin a month after
the session. One hundred forty of the items were rated on a
six-point scale (0=none, not at all; 1=so slight cannot decide;
2= slight; 3=moderate; 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 (nine positive and nine negative items); Relationships
(nine positive and nine negative items); Behavioral changes
(one positive and one negative item); Spirituality (22 positive
and 21 negative items). The positive and negative items were
intermixed within each category. For purposes of scoring the
resulting 12 scales (positive and negative scales for each of the
six categories), scores were expressed as the percentage of the
maximum possible score. The version of the questionnaire
used (available from the authors upon request) was an
expanded version of that described by Griffiths et al. (2006).
Scale scores on the original and the expanded version were
highly correlated (0.9580.997) on scales showing reasonable
variability. Scales measuring negative effects did not have
enough responses and therefore did not have enough
variability for these calculations to be meaningful.
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 meaningful experiences
of my life; and 8= the single most meaningful experience of
my life). (2) Indicate the degree to which the experience was
spiritually significant to you? (rated from 1 to 6, with 1= not at
all; 5= among the five most spiritually significant experiences
of my life; 6=the single most spiritually significant experi-
ence of my life). (3) Do you believe that the experience and
your contemplation 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).
Retrospective persisting effects assessed at 14-month
follow-up
At 14 months after the last session, participants completed a
Retrospective Questionnaire and an open-ended clinical
interview reflecting on study experiences and current life
situation. For purposes of completing the Retrospective
Questionnaire, volunteers were reminded that over the five
sessions they had received four different doses of psilocy-
bin. They were then informed on which two sessions they
had received the two highest doses of psilocybin, although
they were not informed which of the two was the highest
dose. One hundred forty-three items comprised the previ-
ously described Persisting Effects Questionnaire. For these
items, volunteers were asked to rate any current persisting
effects that they attribute to the experiences during either or
both the two highest dose sessions. Volunteers were also
asked to provide written descriptions about the session
experiences, including how their behavior changed in
Psychopharmacology (2011) 218:649665 653
response to the experiences. Forty-three items on this
questionnaire were the previously described mystical experi-
ence items from the States of Consciousness Questionnaire,
which were completed twicelooking back separately on
each of the two sessions associated with the two highest
doses. In four final questions, participants were asked, of all
five sessions, which session was associated with the strongest
effect, which was most personally meaningful, which was
most spiritually significant, and which would they chose to
repeat if they had the opportunity to do so.
Longitudinal measures assessed at baseline, after session 5,
and at 14-month follow-up
More than a dozen longitudinal measures were assessed at
screening or shortly after enrollment, after sessions, and at
the 14-month follow-up. The results from most of these
measures will be combined with results from a previous
study (Griffiths et al. 2006) and reported separately. Three
measures are reported here.
Mysticism Scale (Lifetime): Participants were instructed to
complete this previously described questionnaire with
reference to their lifetime experience.
Death Transcendence Scale: The 26-item Death Transcen-
dence Scale (Hood and Morris 1983; VandeCreek 1999)
was administered because a potentially important clinical
application of psilocybin is in treatment of individuals who
are anxious or depressed in response to terminal illness
(Grob et al. 2011). Items were rated on a nine-point scale
and five subscales were scored: Mysticism, Religious,
Nature, Creative, and Biosocial.
Community Observer Ratings of Changes in Participants
Behavior and Attitudes: This previously described measure
was shown sensitive to psilocybin 2 months after a high dose
session (Griffiths et al. 2006). 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 approx-
imately 1 week after the participant had been accepted into
the study, 3 to 4 weeks after the last session, and as part of
the 14-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 volunteers
behavior and attitudes using a 10-point scale (from 1=not at
all to 10= extremely) on 11 items: inner peace, patience,
good-natured humor/playfulness, mental flexibility, opti-
mism, anxiety, interpersonal perceptiveness and caring,
negative expression of anger, compassion/social concern,
expression of positive emotions (e.g., joy, love, apprecia-
tion), and self-confidence. On the first rating occasion, which
occurred soon after acceptance 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
interview with each rater were calculated as a total score,
with anxiety and anger scored negatively. Changes in each
participants behavior and attitudes after drug sessions were
expressed as a mean change score (i.e., difference score)
from the baseline rating across the raters. Rating completion
rate was 96%; seven ratings were missed due to a failure to
return calls or to the rater not having contact with the
volunteer over the rating period.
Post-study monitor ratings of enduring effects
in participants
At the conclusion of the study, the primary and assistant
monitor for each volunteer were asked to assess any
enduring changes in the volunteers attitudes and behav-
iors that the monitor believed resulted directly or
indirectly from the psilocybin session experiences in the
study. Three ratings were done on a seven-point scale
(3=decreased very much; 0= no change; +3 = increased
very much): (1) change in volunteers sense of personal
well-being or life satisfaction; (2) change in quality of
volunteers social relationships (e.g., spouse, family,
friends, and acquaintances); and (3) change in the
volunteers sense of spirituality, broadly construed. Score
for each volunteer was the mean of the primary and
assistant guide ratings for each question.
Data analyses
Cardiovascular and Monitor Ratings assessed throughout
the session: Two sets of analyses were conducted. For the
time-course data, planned comparisons were conducted
comparing the effect of each of the active psilocybin doses
with 0 mg/70 kg at each time point. For the second set of
analyses, for each participant, peak scores during the time
course were defined as the maximum value from pre-
capsule to 6 h post-capsule, and temporal measures (e.g.,
minutes talking or sleeping) were summed across the eight
post-capsule time points. A repeated measures regression
model with AR(1) covariance structure was used with Dose
(0, 5, 10, 20, 30 mg/70 kg), Time (10 min before and 0.5, 1,
1.5, 2, 3, 4, 5, and 6 h after capsule administration), Dose
Sequence (ascending vs. descending), and interactions
among these as the effects in the model. Fishers LSD post
hoc tests were used to compare the drug conditions. Two of
654 Psychopharmacology (2011) 218:649665
the seven assistant guides were not blind to the ascending/
descending nature of the experimental design, so the
analysis described above was repeated excluding ratings
from these two monitors. Because there were no differences
in the statistical significance of Sequence or Sequence
interactions and only minor other differences occurred, the
data presented are from all monitor ratings.
Measures assessed 7 h after drug administration and measures
assessed 1 month after sessions: For the hallucinogen-
sensitive questionnaires and the mystical experience ques-
tionnaires assessed 7 h after sessions and for the Persisting
Effects Questionnaire assessed 1 month after sessions, a
repeated measures regression was used with Dose (0, 5, 10,
20, 30 mg/70 kg) and Dose Sequence (ascending vs.
descending) and their interaction as effects in the model.
Fishers LSD post hoc tests were used to compare the drug
conditions. For analysis of dichotomous responses across
the five drug conditions for measures shown in Table 5
(Persisting Effects Questionnaire), CochransQ, a non-
parametric, binary repeated measures test, was conducted
with a factor of Dose (0, 5, 10, 20, 30 mg/70 kg). Planned
comparisons for these data were conducted using Wald chi-
square tests to compare active doses to 0 mg/70 kg.
Retrospective persisting effects assessed at 14-month
follow-up: For analysis of the eight scales from the mystical
experience items of the States of Consciousness Question-
naire, a repeated measures regression was used with Condition
(7 h after 0 mg/70 kg, 7 h after 30 mg/70 kg, and 14-month
retrospective for 30 mg/70 kg), Dose Sequence, and their
interaction as effects in the model. Fishers LSD post hoc tests
were used to compare the conditions. For analysis of
dichotomous responses across three sets ofconditions (1 month
after 0 mg/70 kg; combined data for 1-month follow-ups after
both the 20 and 30 mg/70 kg dose sessions; 14-month follow-
up data for retrospective rating for either or both the 20 and/or
30 mg/70 kg dose sessions), CochransQwas conducted with
a factor of Condition (the three conditions described above).
Planned comparisons were conducted using Wald chi-square
tests to compare the three conditions.
Longitudinal measures assessed at screening, after ses-
sion 5, and at 14-month follow-up: For analysis of the
measures of mystical experience, of death transcendence,
and of community observer ratings of changes in partic-
ipantsbehavior and attitudes assessed at screening, 1 month
after session 5, and at 14-month follow-up, a repeated
measures regression was used with Time (screening, after
session 5, and 14-month follow-up) and Dose Sequence
and their interaction as effects in the model. Planned
comparisons were used to compare screening values with
the two post-drug time points.
For all statistical analysis, results were considered signifi-
cant at p<0.05.
Results
Integrity of blinding procedures
At the conclusion of the study, the primary and assistant guides
completed a questionnaire that asked about their understanding
of the experimental design. None of the three primary guides
or the five assistant guides who were blind the ascending or
descending nature of the doses sequences guessed or reported
awareness of this aspect of the study procedures.
Cardiovascular measures and monitor ratings assessed
throughout the session
Psilocybin produced significant and orderly dose- and time-
related effects on cardiovascular measures and monitor ratings
assessed throughout the session. At the two highest doses (20
and 30 mg/70 kg), onset of significant effects generally
occurred at the 30- or 60-min assessment, with effects usually
peaking from 90 to 180 min and decreasing toward pre-drug
levels over the remainder of the session (see Fig. 1for
illustrative measures). Table 1shows the mean effects at each
dose for these measures. For measures sensitive to psilocybin,
effects were generally a monotonically increasing function of
dose. For most measures, the 5 mg/70 kg dose was
significantly greater than placebo and the 20 and/or 30 mg/
70 kg dose(s) were significantly greater than the lower active
doses. There were no significant Sequence or Dose ×
Sequence interactions. The blood pressures of the four
volunteers who had the highest pressures 60 min or longer
after the 30 mg/70 kg psilocybin were 187/84, 166/64, 182/
88, and 178/95 mmHg. These pressures were considered high
enough to warrant further repeated blood pressure assess-
ment; however, they were not judged to be of sufficient
magnitude to necessitate pharmacological treatment.
Drug effect and mysticism measures assessed 7 h after drug
administration
Subjective effects questionnaires: The three questionnaires
developed for sensitivity to the subjective effects of halluci-
nogens showed orderly dose-related increases (Table 2). All
six scales of the Hallucinogen Rating Scale, all three scales
on the APZ Questionnaire, and the A and LSD scales of the
ARCI showed significant and monotonically increasing
effects as a function of dose, with significant effects on
most measures at even the lowest dose of 5 mg/70 kg. These
effects, which are typical of hallucinogens, include percep-
tual changes (e.g., visual pseudo-hallucinations, illusions,
Psychopharmacology (2011) 218:649665 655
and/or synesthesias), labile moods (e.g., feelings of transcen-
dence, grief, joy, and/or anxiety), and cognitive changes
(e.g., sense of meaning, insight, and/or ideas of reference).
There were no significant Sequence or Sequence×Dose
interactions.
Measures of mystical experience: Also at 7 h after capsule
administration, volunteers completed two questionnaires
designed to assess mystical experience (Table 3). The total
score and all three empirically derived factors of the
Mysticism Scale and all seven scales on States of
Consciousness Questionnaire showed significant and
monotonically increasing effects as a function of dose,
with significant effects at the 5 mg/70 kg dose. The
proportion of volunteers who met a priori criteria for
having had a completemystical-type experience on the
States of Consciousness Questionnaire was also an increas-
ing function of dose: 0, 5.6%, 11.1%, 44.4%, and 55.6% at
0, 5, 10, 20, and 30 mg/70 kg, respectively. Overall, 72.2%
of volunteers had completemystical experiences at either
or both the 20 and 30 mg/70 kg session. Only the
Mysticism Scale showed an effect of Sequence or a
Dose×Sequence interaction. This effect was largely due to
differences in response to placebo. Examination of the
position of the placebo condition within the sequence
suggested this result was spurious.
Psilocybin-induced fear/anxiety or delusions
Although volunteers were carefully screened and psy-
chologically prepared, and close interpersonal support
was provided during sessions, on questionnaires com-
pleted at the end of the session, 39% of participants
(seven of 18) had extreme ratings of fear, fear of
insanity, or feeling trapped at some time during the
session. Such episodes occurred in six of seven of these
participants after the 30 mg/70 kg dose and in one of
seven after the 20 mg/70 kg dose. Monitor ratings of
peak anxiety/fear during the session showed dose-rated
increases, with each dose producing a significantly
higher rating than the lower doses (Table 1). After
30 mg/70 kg, monitor ratings of anxiety/fear across the
session showed varying time courses of onset and
duration, with peak effects of anxiety/fear being rated as
early as 60 min in some participants, but as late as 180 or
240 min in others (see Fig. 2for illustrative data). Forty-
four percent of participants (eight of 18) reported
delusions or paranoid thinking sometime during the
session; such episodes occurred in seven of eight of these
Overall Drug Effect
0
1
2
3
4
0 60 120 180 240 300 360
Observer Rating (mean score)
Joy/Intense Happiness
0
1
2
3
4
0 60 120 180 240 300 360
Minutes
Observer Rating (mean score)
mm Hg
0 mg
5 mg
10 mg
20 mg
30 mg
115
120
125
130
135
140
145
0 60 120 180 240 300 360
60
65
70
75
80
85
90
0 60 120 180 240 300 360
mm Hg
Systolic Blood Pressure
Diastolic Blood Pressure
0 mg
5 mg
10 mg
20 mg
30 mg
0 mg
5 mg
10 mg
20 mg
30 mg
0 mg
5 mg
10 mg
20 mg
30 mg
Fig. 1 Within-session time course of psilocybin. Systolic and
diastolic blood pressure and monitor ratings of overall drug effect,
and joy/intense happiness as a function of time since capsule ingestion
(time 0=before drug administration). Data points are means; filled
data points indicate a significant difference from 0 mg/70 kg at the
indicated time point (planned comparisons)
656 Psychopharmacology (2011) 218:649665
participants after the 30 mg/70 kg dose and in one of seven
after 20 mg/70 kg dose. Examples of delusions included the
belief that a child or loved one had died during the time of the
session, or that the session monitors were malevolently
manipulating the participant. Three of eight volunteers who
had such episodes were those who also rated extreme fear or
fear of insanity. Inspection of the data indicated that delusions
and extreme ratings of fear/anxiety were not differentially
affected by dose sequence.
These psychological struggles did not affect the overall
rate of having completemystical experiences as rated by
volunteers at the end of the session day. Five of seven
(71%) of participants reporting extreme fear, insanity, or
feeling trapped provided data consistent with complete
mystical experiences, and four of eight (50%) of partic-
ipants who had delusions or paranoid thinking provided
data consistent with completemystical experiences.
These rates of completemystical experience are generally
similar to the rate for the group as a whole (56%). Although
psychological struggles did not affect the overall rate of
completemystical experience, it should be noted that
neither of the two volunteers who had the most sustained
anxiety during the 30 mg/70 kg session (Fig. 2, square and
circle symbols) had a completemystical experience. In
addition to not affecting rate of mystical experience,
inspection of the data indicated no consistent relationship
between psychological struggle and subsequent ratings of the
session as having personal meaning and spiritual significance.
No volunteer rated the overall experience as having decreased
her or his sense of well-being or life satisfaction.
The volunteer who had the most sustained anxiety
during the 30 mg/70 kg dose session (Fig. 2, square
symbols) provides an interesting case example. Likely as a
consequence of the sustained psychological struggle during
the session, this volunteer also had the lowest mystical
experience rating immediately after the session of all 18
volunteers studied. Immediately after the session, this
volunteer, who for decades had held reincarnation as part
of her worldview, reported that it was the worst experience
of her life and that she would rather spend three lifetimes
on a mountaintop meditating than repeat what she had just
experienced during the session. Although she considered
dropping out of the study after this first session and she
remained hesitant to receive psilocybin again, over the next
several weeks she increasingly felt that she had learned
something useful from the experience. At 1 month, she
rated the experience as having slight spiritual significance
and as having slightly increased her sense of well-being or
life satisfaction. Because she remained curious about the
effects of psilocybin, she decided to continue to participate
in the study. She received 20 mg/70 kg psilocybin on the
second session. In contrast to her first session, her post-
session ratings fulfilled criteria for a completemystical
experience and, at 1 month, she retrospectively rated this
Table 2 Volunteer ratings on three subjective effects questionnaires completed 7 h after drug administration
Questionnaire and subscale description Psilocybin dose (mg/70 kg)
0 5 10 20 30
Hallucinogen Rating Scale
Intensity 0.94 (0.17) 1.85 (0.15)
a
2.50 (0.14)
b
2.64 (0.15)
b
2.69 (0.13)
b
Somesthesia 0.35 (0.07) 1.32 (0.14)
a
1.56 (0.16)
a
1.91 (0.17)
b
2.12 (0.15)
b
Affect 0.93 (0.11) 1.48 (0.16)
a
1.76 (0.16)
a,b
1.95 (0.14)
b,c
2.16 (0.16)
c
Perception 0.23 (0.07) 1.14 (0.16)
a
1.38 (0.18)
a
1.72 (0.17)
b
2.09 (0.20)
c
Cognition 0.70 (0.14) 1.33 (0.20)
a
1.63 (0.18)
a
2.08 (0.19)
b
2.26 (0.22)
b
Volition 1.04 (0.08) 1.52 (0.12)
a
1.69 (0.11)
a,b
1.79 (0.12)
b
1.81 (0.16)
b
APZ Questionnaire
OSE (oceanic boundlessness) 2.67 (0.56) 5.72 (0.76)
a
5.89 (0.76)
a,c
7.22 (0.70)
b,c
8.33 (0.73)
b
AIA (dread of ego dissolution) 0.50 (0.24) 2.50 (0.79)
a
3.11 (0.65)
a,c
4.17 (0.61)
b,c
4.89 (0.84)
b
VUS (visionary restructuralization) 1.78 (0.48) 6.06 (0.82)
a
7.28 (0.64)
a,b
7.67 (0.68)
b
8.44 (0.82)
b
Addiction Research Center Inventory (ARCI)
PCAG (sedative) 5.28 (0.50) 6.28 (0.87) 7.22 (0.81) 6.78 (0.80) 7.22 (0.96)
BG (amphetamine/self-control) 4.94 (0.36) 4.83 (0.38) 5.56 (0.60) 5.06 (0.55) 4.72 (0.53)
A (amphetamine) 2.78 (0.35) 4.94 (0.39) 5.17 (0.52) 4.83 (0.48) 5.06 (0.62)
MBG (euphoria) 5.61 (0.86) 8.11 (1.05) 8.06 (0.84) 7.89 (0.90) 8.28 (1.13)
LSD (hallucinogen/dysphoria) 2.56 (0.29) 6.06 (0.64)
a
6.39 (0.64)
a,c
7.39 (0.65)
b,c
7.83 (0.57)
b
Data are mean scores with 1 SEM shown in parentheses (N= 18); within a row, bold font indicates significant difference from 0 mg/70 kg; for
active doses, values not sharing a common letter are significantly different (Fishers LSD p<0.05)
Psychopharmacology (2011) 218:649665 657
experience as the single most personally meaningful and
spiritually significant of her life.
Persisting effects assessed 1 month after sessions
Persisting Effects Questionnaire: As shown in Table 4,
psilocybin produced significant and generally monotonical-
ly increasing effects as a function of dose in positive ratings
of attitudes about life, attitudes about self, mood, social
effects, and behavior. Negative ratings of these same
dimensions were very low and did not differ across the
doses except for negative attitudes about self that showed
small but significant increases at the two lowest doses.
Table 4also shows that ratings of the personal meaning-
fulness and spiritual significance of the experience, and
ratings of well-being or life satisfaction were significant
and a monotonic increasing function of dose. Of the
persisting effects measures shown in Table 4, all six of
the positive subscales (attitudes about life, attitudes about
self, mood, altruism, behavior, and spirituality) and one of
the three questions (sense of well-being/life satisfaction)
showed significant Dose× Dose Sequence interactions.
Inspection of these data showed that this effect was
primarily due to the ascending dose sequence producing
relatively larger effects at the 20 and 30 mg/70 kg doses
Monitor Rating of Anxiety or Fearfulness
Minutes
0
0.5
1
1.5
2
2.5
3
3.5
30 60 90 120 180 240 300 360
Fig. 2 Time course of monitor ratings of anxiety or fearfulness after
30 mg/70 kg in the five volunteers whose mean ratings were 2.0 or
higher at one or more time point. Data points are mean ratings of the
two session monitors. Different symbols represent different volunteers.
The figure illustrates the unpredictable time course of anxiety or fear
across the session
Table 3 Volunteer ratings on two mystical experience questionnaires completed 7 h after drug administration and at 14-month follow-up
Questionnaire and subscale
description
7 h after drug administration 14-month follow-up
(30 mg/70 kg)
**
Psilocybin dose (mg/70 kg)
0
*
5
*
10
*
20
*
30
*
States of Consciousness
Questionnaire
Internal unity 15.2 (4.6) 38.0 (6.7)
a
44.6 (5.1)
a
64.4 (6.0)
b
70.2 (6.2)
b
76.5 (6.4)
External unity 12.4 (3.7) 32.6 (6.0)
a
35.0 (6.0)
a
53.3 (5.6)
b
60.7 (6.7)
b
63.5 (7.4)
Sacredness 23.7 (5.5) 48.7 (6.9)
a
54.0 (6.4)
a
71.1 (5.8)
b
77.1 (6.4)
b
83.3 (4.7)
Noetic quality 19.4 (5.3) 47.5 (6.7)
a
54.4 (5.8)
a,b
65.3 (6.0)
b,c
70.6 (6.5)
c
76.9 (6.4)
Transcendence of time
and space
18.3 (4.8) 40.4 (6.8)
a
44.4 (5.6)
a
65.4 (6.2)
b
78.2 (5.2)
c
82.6 (5.2)
Deeply felt positive mood 26.8 (4.7) 47.6 (5.4)
a
57.5 (6.3)
a,b
68.3 (5.5)
b,c
73.2 (6.5)
c
77.3 (5.7)
Ineffability 19.3 (6.0) 48.4 (6.3)
a
59.1 (5.8)
a
73.1 (6.6)
b
81.3 (6.0)
b
81.1 (4.6)
Total 21.0 (4.7) 45.1 (5.9)
a
52.0 (5.2)
a
68.3 (5.0)
b
75.6 (5.4)
b
80.1 (4.9)
Mysticism Scale
Interpretation 57.1 (6.5) 83.5 (5.3)
a
84.1 (5.2)
a
95.7 (3.7)
b
99.1 (2.6)
b
N/A
Introvertive 54.4 (7.1) 77.6 (6.2)
a
79.7 (5.1)
a
93.0 (3.7)
b
97.4 (3.4)
b
N/A
Extrovertive 30.7 (4.7) 48.2 (4.7)
a
49.4 (5.0)
a
57.1 (3.9)
b
61.3 (3.8)
b
N/A
Total (max score=288) 142.2 (17.7) 209.2 (15.4)
a
213.2 (14.4)
a
245.8 (9.0)
b
257.9 (8.9)
b
N/A
Data are mean scores with 1 SEM shown in parentheses (N=18); data for the States of Consciousness Questionnaire are expressed as a percentage
of the maximum possible score
*
Data in these columns show rating data 7 h after the indicated dose of psilocybin; within the same row for these columns, bold font indicates
significant difference from 0 mg/70 kg; for active doses, values not sharing a common letter are significantly different (Fishers LSD p<0.05)
**
For the States of Consciousness Questionnaire, data in this column show ratings of the 30 mg/70 kg session experience at the 14-month follow-
up; each value in this column was significantly greater than the value at 0 mg/70 kg after 7 h (as indicated by bold font) but was not different from
the value at 30 mg/kg 1 month (Fishers LSD p<0.05); 14-month follow-up data were not obtained for the experience-specific version of the
Mysticism Scale (indicated by N/A), although data were obtained for the Lifetime version (see text)
658 Psychopharmacology (2011) 218:649665
and relatively smaller effects at lower doses compared to
the descending dose sequence. Figure 3shows this effect
for two representative measures: persisting effects on well-
being/life satisfaction and on positive mood.
Table 5shows the percentages of volunteers who endorsed
specific outcomes on four items on the Persisting Effects
Questionnaire. Endorsement increased as a function of
dose. Notably, 61% of volunteers considered the psilocybin
experience during either or both the 20 and 30 mg/70 kg
sessions to have been the single most spiritually significant
of their lives, with 83% rating it in their top five. Consistent
with this, 94% and 89% of volunteers, respectively,
indicated that the experiences on those same sessions
increased their well-being or life satisfaction and positively
changed their behavior at least moderately. Of the 90 total
sessions, none were rated as having decreased well-being or
life satisfaction.
Retrospective persisting effects assessed at 14-month
follow-up
The right-most columns of Tables 3,4, and 5show that the
retrospective ratings at the 14-month follow-up on the
States of Consciousness Questionnaire mystical experience
items and on the Persisting Effects Questionnaire were
undiminished from ratings obtained 1 month after sessions.
No participant rated that their behavior was affected
negatively or that their well-being/life satisfaction was
decreased as a result of the psilocybin experiences on the
two highest dose sessions. The analysis of the States of
Consciousness Questionnaire mystical experience items
showed significant Condition × Dose Sequence Interactions
on Internal Unity, Mood, and Total score. Inspection of
these data showed that the ascending dose sequence was
associated with relatively larger effects at 30 mg/70 kg both
post-session and at 14-month follow-up.
Table 4 Volunteer ratings of persisting effects 1 and 14 months after sessions
Questionnaire and subscale
description
1 month after sessions 14-month
follow-up (20 or
30 mg/70 kg)
**
Psilocybin dose (mg/70 kg)
0
*
5
*
10
*
20
*
30
*
Persisting Effects Questionnaire
Positive attitudes about life 33.3 (6.6) 45.9 (5.6)
a
50.3 (6.6)
a
62.2 (5.6)
b
65.9 (5.9)
b
68.8 (4.8)
Negative attitudes about life 0.6 (0.4) 0.8 (0.5) 1.4 (0.6) 0.8 (0.4) 0.6 (0.4) 3.2 (1.3)
Positive attitudes about self 31.9 (6.1) 44.4 (5.4)
a
46.5 (6.2)
a, c
54.2 (5.5)
b, c
58.9 (6.0)
b
61.1 (5.4)
Negative attitudes about self 0.1 (0.1) 2.1 (0.6)
a
1.5 (0.6)
a, b
0.7 (0.5)
b, c
1.1 (0.4)
a, c
2.3 (0.9)
Positive mood changes 26.8 (5.4) 36.4 (5.1)
a
42.9 (6.2)
a, b
51.3 (5.8)
b
52.7 (6.0)
b
55.3 (5.9)
Negative mood changes 0.3 (0.2) 0.4 (0.3) 1.1 (0.7) 0.8 (0.4) 0.2 (0.2) 1.7 (0.8)
Altruistic/positive social effects 28.3 (6.0) 37.1 (5.3)
a
42.4 (6.5)
a
52.0 (5.9)
b
54.6 (5.7)
b
54.1 (6.5)
Antisocial/negative social effects 0.2 (0.2) 1.3 (0.9) 0.9 (0.7) 1.2 (0.9) 0.8 (0.9) 2.5 (0.9)
Positive behavior changes 35.6 (8.1) 45.6 (6.4)
a
58.9 (8.7)
a, b
57.8 (7.6)
a, b
71.1 (6.7)
b
68.9 (5.9)
Negative behavior changes 0.0 (0.0) 2.2 (2.3) 2.2 (2.3) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Increased spirituality 31.1 (6.2) 42.3 (6.7)
a
48.2 (7.0)
a, b
57.9 (6.2)
b
58.3 (5.8)
b
71.6 (6.3)
Decreased spirituality 0.4 (0.3) 0.2 (0.2) 0.6 (0.3) 0.6 (0.4) 0.8 (0.4) 1.1 (0.6)
How personally meaningful was
the experience? (max score= 8)
3.33 (0.40) 5.06 (0.36)
a
5.56 (0.43)
a
6.67 (0.31)
b
6.67 (0.34)
b
7.22 (0.22)
How spiritually significant was the
experience? (max score= 6)
2.72 (0.35) 3.28 (0.27)
a
3.94 (0.32)
a, c
4.67 (0.31)
b, c
4.94 (0.33)
b
5.28 (0.23)
Did the experience change your
sense of well-being or life
satisfaction? (max score=3)
1.11 (0.23) 1.72 (0.25)
a
2.0 (0.25)
a, c
2.5 (0.22)
b
2.39 (0.21)
b, c
2.39 (0.22)
Data are mean scores with 1 SEM shown in parentheses (N= 18); data on attitudes, mood, altruistic/social effects, and behavior changes are
expressed as percentage of maximum possible score; data for the final three questions are raw scores
*
Data in these columns show rating data 1 month after the indicated dose of psilocybin; within the same row for these columns, bold font
indicates significant difference from 0 mg/70 kg; for active doses, values not sharing a common letter are significantly different (Fisher s LSD
p<0.05)
**
Data in this column show ratings at the 14-month follow-up; ratings were completed with respect to experiences during either or both the 20
and 30 mg/70 kg dose sessions (see Materials and methods); no statistical comparison was conducted
Psychopharmacology (2011) 218:649665 659
When asked at 14 months which of the five sessions
seemed strongest, 83% and 17% of volunteers indicated the
session associated with 30 and 20 mg/70 kg, respectively;
most personally meaningful (44%, 44%, and 11% at 30, 20,
and 10 mg/70 kg, respectively); most spiritually significant
(56%, 33%, and 11% at 30, 20, and 10 mg/70 kg,
respectively); and which session they would want to repeat
if they had an opportunity to do so (67%, 28%, and 6% at
30, 20, and 10 mg/70 kg, respectively). Consistent with the
flattened doseeffect curve for persisting effects shown in
Fig. 3, most volunteers in the ascending dose sequence
rated the highest dose session (30 mg/70 kg) as the most
personally meaningful (67%) and spiritually significant
(78%) of the five sessions; in contrast, a smaller proportion
of volunteers in the descending sequence rated the highest
dose session as most personally meaningful (22%) and
spiritually significant (22%). The mean ± 1 SEM dose of the
sessions that were rated as being the most personally
meaningful were 25.6±2.6 and 21.1 ± 1.8 in the ascending
and descending dose sequence, respectively (NS); similar
ratings of spiritual significance were 27.8 ± 2.6 and 21.1 ±
1.5, respectively (p<0.05, ttest).
Also at the 14-month follow-up, participants provided
written descriptions, based on their memories of their two
highest dose sessions, of how they thought their behavior
changed in response to those experiences. As summarized
in Table 6, only two volunteers indicated no positive
change in their behavior. The domains of change most
frequently cited were better social relationships with family
and others, increased physical and psychological self-care,
and increased spiritual practice.
Longitudinal measures assessed at baseline, after session 5,
and at 14-month follow-up
Longitudinal measures of mystical experience, of death
transcendence, and of community observer ratings of changes
in participantsbehavior and attitudes showed effects gener-
ally consistent with the previously described persisting effects.
After session 5 and at 14-month follow-up, the total score (as
well as each of the three subscales) of the Mysticism Scale
(Lifetime) was significantly higher than at screening (217.9±
10.8, 264.1±6.8, and 260.4±7.6, means and SEMs for total
scores at screening, post-session 5, and 14-month follow-up,
respectively) (planned comparisons, p<0.0001). The Reli-
gious subscale of the Death Transcendence Scale, which
assesses a sense of continuity after death, showed similar
increases (28.72± 1.57, 31.00± 0.99, and 31.28± 1.07, means
and SEMs for screening, post-session 5, and 14-month
follow-up, respectively) (planned comparisons, p<0.05). The
other subscales were not significant. For the community
observer ratings of participantsbehavior and attitudes,
change scores from those taken about 1 week after study
enrollment (mean±SEM) were significant both after session 5
(8.85±1.64) and at the 14-month follow-up (5.36±1.68)
(planned comparisons, p<0.001).
Post-study monitor ratings of enduring effects
in participants
The post-study monitor ratings of enduring effects in
participants were consistent with the participant self-
ratings and the community observer ratings of changes in
participantsbehavior and attitudes. Mean ± SEM of mon-
itor ratings of the volunteerspersonal well-being/life
satisfaction, quality of social relationships, and sense of
spirituality were all in the positive direction (2.33 ±0.14,
1.64±0.14, and 2.41±0.15, respectively).
Open-ended clinical interview at the 14-month follow-up
An open-ended clinical interview at the 14-month follow-
up was conducive to the spontaneous reporting of possible
Increased Well-Being and/or Life Satisfaction
0
0.5
1
1.5
2
2.5
3
0 5 10 20 30
Ascending Doses
Descending Doses
*
Persisting Positive Mood
0
20
40
60
80
0 5 10 20 30
Dose (m
g
/70 k
g
)
Ascending Doses
Descending Doses
*
Participant RatingParticipant Rating (% of Maximum)
Fig. 3 Effects of dose sequence on ratings of persisting effects of
well-being/life satisfaction and positive mood completed 1 month after
sessions. Data points are means and brackets show 1 SEM for
participants in the ascending dose sequence (triangles) and the
descending dose sequence (circles). Dose× Dose Sequence interac-
tions were significant. Asterisks indicate a significant difference
between the ascending and descending dose sequence at the indicated
dose (Fishers LSD post hoc)
660 Psychopharmacology (2011) 218:649665
persisting adverse events. There were no reports of
bothersome or clinically significant persisting perception
phenomena sometimes attributed to hallucinogen use.
Likewise, there were no reports of any non-study use of
hallucinogens since study enrollment. All 18 volunteers
appeared to continue to be psychiatrically healthy, high-
functioning, productive members of society.
Discussion
The present study demonstrated orderly dose-related
increases in the effects of psilocybin on volunteer and
observer ratings of drug effect and on the cardiovascular
measures of blood pressure and heart rate. Notably, even
the 5 mg/70 kg (71 μg/kg) dose of psilocybin produced
significant subjective, physiological, and observer-rated
effects. This is the lowest dose of psilocybin demonstrated
to produce significant effects. A previous study showed
dose-related effects of psilocybin at doses of 45, 115, 215,
and 315 μg/kg, however, did not show statistically
significant effects at the lowest dose (Hasler et al. 2004).
Consistent with previous findings, the present study
showed orderly time-related observer-rated and cardiovas-
cular effects during the session, with significant effects at
the highest doses generally occurring at 3060 min,
peaking at 90180 min, and decreasing toward pre-drug
levels over the remainder of the session (Griffiths et al.
2006).
The present study extends previous observations show-
ing that psilocybin can occasion mystical-type experiences
having sustained personal and spiritual significance
(Pahnke 1963; Doblin 1991; Griffiths et al. 2006,2008).
Two volunteer-rated measures of mystical-type experience
completed at the end of the session days showed dose-
related increases, with 72% of volunteers fulfilling criteria
for having had a completemystical experience at either
or both of the two highest dose sessions. Retrospective
ratings of mystical experience and spiritual significance did
not diminish in time. One month after either or both the two
Table 5 Percentage of volunteers endorsing specific outcomes on four persisting effects items 1 and 14 months after sessions
Questionnaire items 1 month after sessions 14-month follow-up
(20 or 30 mg/70 kg)
***
Psilocybin dose (mg/70 kg)
0
*
5
*
10
*
20
*
30
*
20 or 30
**
How personally meaningful was the experience?
Single most meaningful experience of life 0.0 0.0 5.6 16.7 33.3 44.4 38.9
Top 5 most meaningful, including single most 0.0 11.1 33.3 77.8 61.1 77.8 94.4
How spiritually significant was the experience?
Single most spiritually significant experience of life 0.0 0.0 5.6 27.8 44.4 61.1 44.4
Top 5 most spiritually significant, including single most 11.1 11.1 44.4 66.7 77.8 83.3 94.4
Did the experience change your sense of well-being
or life satisfaction?
Increased well-being/life satisfaction (very much) 5.6 27.8 38.9 72.2 55.6 77.8 61.1
Increased well-being/life satisfaction (moderately or
very much)
38.9 55.6 72.2 83.3 88.9 94.4 83.3
Your behavior changed in ways you would consider positive
since the experience
Positive behavioral change (strong or extreme) 22.2 16.7 50.0 38.9 55.6 55.6 44.4
Positive behavioral change (moderate, strong, or extreme) 33.3 50.0 61.1 61.1 88.9 88.9 88.9
Data in table show the percentage of volunteers endorsing the specific outcome
*
Data in these columns are the percentage of volunteers endorsing the specific outcome 1 month after the indicated dose of psilocybin; within the
same row for these columns, bold font indicates significant difference in pair-wise comparisons to 0 mg/70 kg (Cochran's Qshowed p<0.001 for
all variables; planned comparisons performed with Wald test; see Materials and methodsfor details)
**
Data in this column are the percentage of volunteers endorsing the specific outcome 1 month after either or both the 20 and 30 mg/70 kg dose
sessions; bold font indicates significant difference in pair-wise comparisons to 0 mg/70 kg (Cochran's Qshowed p<0.05 for all variables; planned
comparisons performed with Wald test; see Materials and methodsfor details)
***
Data in this column are the percentage of volunteers at 14-month follow-up endorsing the specific outcome with respect to experiences during
either or both the 20 and 30 mg/70 kg dose sessions (see Materials and methods); each value in this column was significantly greater than the
value at 0 mg/70 kg (as indicated by bold font) but was not significantly different from the value at 20 or 30 mg/kg at 1 month (Cochran's Q
showed p<0.05 for all variables; planned comparisons performed with Wald test; see Materials and methodsfor details)
Psychopharmacology (2011) 218:649665 661
highest dose sessions, 83% of participants rated the
experience as the single most or among the five most
spiritually significant experiences of their life. At the 14-
month follow-up, this number was even higher (94%).
Likewise, at 14 months, retrospective ratings of mystical
experience at the highest dose were generally slightly
higher than at the 1-month rating time. Finally, longitudinal
measures of lifetime mystical experience and of death
transcendence (Religious subscale) were significantly in-
creased over screening levels at both 1 month and
14 months after the final session. The significant increase
in the Religious subscale of the Death Transcendence Scale
is notable in this group of healthy volunteers because
questions in this subscale assess a sense of continuity after
death (e.g., death is a transition to something even greater
than this life; death is never just an ending, but a part of a
process). This effect may be relevant to the proposed
palliative effects of psilocybin and similar hallucinogens in
treating existential anxiety in terminal illness (Kast 1967;
Richards et al. 1972; Grob et al. 2011).
The present study also extends previous observations
indicating that psilocybin can occasion persisting positive
changes in attitudes, mood, life satisfaction, behavior, and
altruism/social effects (Griffiths et al. 2006,2008). All of
these domains showed dose-related increases 1 month after
sessions, with effects at the highest doses sustained at the
14-month follow-up. One month after sessions at either or
both the two highest dose sessions, 94% of volunteers
endorsed that the experience increased their sense of well-
being or life satisfaction moderately or very much, and 89%
rated moderate or higher changes in positive behavior. At
the 14-month follow-up, these ratings remained high. The
Table 6 Self-reported behavior changeverbatim written comments about the nature of behavioral changes volunteers attributed to either or both
the two highest dose psilocybin session experiences in the Retrospective Questionnaire completed at the 14-month follow-up
Volunteer Verbatim comments
201 Virtually eliminated all religious practices; much more spiritual now. Accepting of my parents and have a more open and honest
dialogue with them. Less judgmental and more open hearted. Taken a more active role in pursuing what I want for myself.
202 I have an increased commitment to spiritual practices; I think my heart is more open to all interactions with other people; more
aware of choices, take time to pause and choose, more breaks; better boundaries at work and personal relationships.
205 I have a stronger desire for devotion, have increased yoga practice and prayer. I have better interaction with close friends and family
and with acquaintances and strangersI feel more certain of my career as an author. I need less food to make me full. My alcohol
use has diminished dramaticallyI consider myself to be better [at self-care] now than before the study
206 Feel closer to family and friends. Incorporating Ayurvedic theory into diet and self care. [Also changed her meditation and
yoga practice]
207 More regular meditation; more mindful with family; more generous with strangers; started new yoga practice; more relaxation
of pace of change.
210 I feel that I relate better in my marriage. There is more empathya greater understanding of people and understanding their
difficulties and less judgment. Less judging of myself too.
211 I take more time in nature, with art. I feel closer to children and parents. I am more comfortable with friends and acquaintances.
I am more committed to my career. I eat better and have taken up dance
213 Increased time for meditation. I think I'm even warmer towards people and more accepting. I now believe I have something
important to tell people about how the universe works. I am slowing learning to give myself a break.
214 [This participant endorsed no specific behavior change, although did report an increased sense of spirituality.]
215 I try to judge less and forgive more. I no longer worry about money.
217 More frequent and enjoyable meditation; more desire to connect with loving energy and have loving energy flow through me
to others; less willingness to allow manipulative or abusive treatment to happen without my confronting it.
218 A greater integration of the pieces of my life; more spirit less religion; less fear of being wrong.
219 More fulfilling meditation; more appreciation of and openness to others [and] my own emotional reactions.
222 Less concerned with the appearance of spirituality, while realizing more that everything is sacred. I feel more accommodating
and forgiving toward both friends and strangers, and less anxious to label them or convert them to my viewpoint. I am learning
to recognize and release old definitions of myself.
223 During my sessions, much was shown to me about letting go of attachment around my son. More and more, sensuality and
passion and gratitude continue to unfold and deepen within me.
226 The energy experience stoked my curiosity about the spiritual awakening stimulus of kundalini [spiritual energy] and has opened
a new path for me!
228 [This participant endorsed no specific behavior change, although did report a deeper appreciation of positive emotional
experience and empathy.]
230 I am more aware and accepting [of everyone]. I have a thousand ideas to write about and am making time and space in my life
to accommodate them.
662 Psychopharmacology (2011) 218:649665
types of behavior change most frequently cited by
volunteers were better social relationships with family and
others, increased physical and psychological self-care, and
increased spiritual practice (Table 6). Ratings by commu-
nity observers before and after the study as well as ratings
by study monitors after the study were consistent with the
persisting positive changes in behavior and attitudes
claimed by the volunteers. The persisting positive changes,
particularly in attitudes, mood, and life satisfaction,
occasioned by psilocybin appear similar in kind and breadth
to the enduring changes reported in case studies of
individuals who have had spontaneously occurring mystical
or insightful types of experiences (Miller and Cde Baca
2001).
A novel aspect of the present study was that it
compared effects in volunteers who received the four
active psilocybin doses in either an ascending or a
descending dose sequence. Although the acute measures
of psilocybin effects were not affected by the dose
sequence, volunteer-rated positive changes in attitudes
and behavior assessed 1 month after each session showed
Dose×Dose Sequence interactions reflecting relatively
larger effects at the highest psilocybin doses than the
lower doses in the ascending dose sequence compared to
the descending sequence (Fig. 2). Analogous differences
occurred at the 14-month follow-up assessment on the
mystical experience items of the States of Consciousness
Questionnaire and on retrospective ratings of the personal
meaning and spiritual significance associated with various
session doses. Overall, these findings suggest that the
ascending dose sequence is somewhat more likely than the
descending sequence to produce long-lasting positive
changes in attitudes, behavior, and remembered mystical-
type experiences. Thus, it appears that having experience
with lower doses facilitates the likelihood of having
sustained positive effects after a high dose of psilocybin.
The biological or psychological mechanisms underlying
this effect are unknown. This finding suggesting an
advantage of an ascending dose sequence may have
clinical application in the design of therapeutic studies of
psilocybin (Griffiths and Grob 2010;Grobetal.2011). It
is noteworthy, however, that this finding is contrary to
some older recommendations of psychotherapists who
administered classic hallucinogens. Specifically, in one
report (Blewett and Chwelos 1959), psychotherapists
inferred from their clinical experience that a single high-
dose overwhelming experience was more therapeutic than
an approach that began with small doses and gradually
increased the dose over successive experiences.
Also of relevance to the design of future research
trials with psilocybin, the present study provides infor-
mation about the relative likelihood of different doses of
psilocybin to occasion acute adverse subjective effects as
well as mystical-type effects having persisting positive
effects. The acute anxiety/fear-producing effects of
psilocybin, as assessed by monitor and volunteer ratings,
increased with increasing doses. Thirty-nine percent of
volunteers reported extreme fear, fear of insanity, or
feeling trapped sometime during the session (0 at placebo
or the two lower doses, 1 at 20 mg/70 kg, and 6 at
30 mg/70 kg). Furthermore, 44% of volunteers reported
delusions or paranoid thinking sometime during the
session (0 at placebo and the two lower doses, 1 at
20mg/70kg,and7at30mg/70kg).Inthepresent
study, such negative effects were well managed with
reassurance in the highly supportive setting. Interestingly,
these psychological struggles did not generally affect
rates of having completemystical experiences, possibly
because the negative feelings were most often of short
duration. However, under conditions in which volunteers
are less well screened and psychologically prepared, or
sessions are not as well supervised, there could be a
possibility that extreme anxiety and/or delusion could be
prolonged and result in dangerous behavior. Under such
conditions, administration of doses higher than about
20 mg/70 kg would be inadvisable. The unpredictable
time course across the session of anxiety or fear (Fig. 2)
underscores the importance that session monitors remain
vigilant throughout the session. Furthermore, the unpre-
dictable time course of anxiety, in combination with the
finding that even experienced session monitors cannot rate
with high reliability whether or not psilocybin has been
administered (Griffiths et al. 2006), suggests the potential
risk of the recommendation by some psychotherapists that
aboosterdose of a classic hallucinogen should be
administered relatively shortly after the initial dose if the
effects are less than expected (Blewett and Chwelos 1959;
Stolaroff 1997).
In a therapeutic or other research trial, the possibility of
such potentially adverse effects should be considered in
relationship to the potential persisting positive effects. The
proportion of volunteers having completemystical-type
experiences, which likely mediate persisting positive effects
(Richards et al. 1977; Griffiths et al. 2008), as well as the
persisting positive effects (Tables 4and 5) were generally
an increasing function of dose, with the percentage change
from 20 to 30 mg/70 kg varying widely (23% to a +99%),
with a mean of +17%. However, endorsement of having
had a completemystical experience or of having had the
single most spiritually significant experience of his/her life
increased 25% and 60%, respectively, from 20 to 30 mg/
70 kg. Likewise, endorsement of moderate to extreme
positive behavioral change, which may be the most relevant
outcome measure in some therapeutic trials, increased 45%
from 20 to 30 mg/70 kg. Thus, in addition to considering
the extent of screening and support provided to volunteers,
Psychopharmacology (2011) 218:649665 663
the decision to administer psilocybin doses higher than
about 20 mg/70 kg should be made on the basis of the type
of outcome desired.
The present study provided no evidence of adverse
effects of high dose psilocybin exposure other than the
episodes of psychological struggle during some portion of
the time of psilocybin action. This should not be interpreted
to suggest that casual use of high dose psilocybin is safe. It
is important to recognize that the present study was
conducted in carefully screened volunteers who received
ample preparation before sessions, were closely monitored
during sessions, and had some continuing contact with
study staff after sessions (see Johnson et al. 2008 for
detailed safety guidelines for minimizing risks of high dose
hallucinogen exposure in human research). The reported
potential risks of hallucinogen exposure include (1) panic
or fear reactions resulting in dangerous behavior during the
time of drug action, (2) precipitation or exacerbation of
enduring psychiatric conditions, (3) long-lasting perceptual
disturbances, and (4) development of an abusive pattern of
hallucinogen use (Abraham et al. 1996; Halpern and Pope
1999; Johnson et al. 2008).
The generalizability of the results of the present study is
limited by the study population, a group of hallucinogen-
naïve, well-educated, psychologically stable, mostly
middle-aged adults, most of whom reported at least weekly
participation in religious or spiritual activity. It would be
particularly interesting to determine whether volunteers
who identified as atheist or agnostic would be as likely to
have mystical-type experiences and whether they would
ascribe spiritual significance to such experiences. It would
also be interesting to compare hallucinogen-naïve volun-
teers with past users to provide information about whether
the novelty of effects in naïve volunteers contributes to the
high persisting ratings of personal meaning and spiritual
significances.
Overall, the present study shows that psilocybin can
dose-dependently occasion mystical-type experiences
having persisting positive effects on attitudes, mood,
and behavior. The observations that episodes of extreme
fear, feeling trapped, or delusions occur at the highest
dose in almost 40% of volunteers, that anxiety and fear
have an unpredictable time course across the session, and
that an ascending sequence of dose exposure may be
associated with long-lasting positive changes have impli-
cations for the design of therapeutic trials with psilocy-
bin. Considering the rarity of spontaneous mystical
experiences in the general population, the finding that
more than 70% of volunteers in the current study had
completemystical experiences suggests that most
people have the capacity for such experiences under
appropriate conditions and, therefore, such experiences
are biologically normal.
Acknowledgments Conduct of this research was supported by
grants from the Council on Spiritual Practices, the Heffter Research
Institute, and the Betsy Gordon Foundation. Effort for Roland
Griffiths, Ph.D. in writing this paper was partially provided by NIH
grant RO1DA03889. We thank David Nichols, Ph.D. for synthesizing
the psilocybin, Mary Cosimano, M.S.W. for her role as a primary
session monitor, Maggie Klinedinst for data management, and Linda
Felch, M.A. and Paul Nuzzo, M.A. for statistical analyses. We also
thank Larry Carter, Ph.D., Ryan Lanier, Ph.D., Benjamin McKay,
Chad Ressig, Ph.D., and Ryan Vandrey, Ph.D. for serving as assistant
session monitors. The study was conducted in compliance with United
States laws.
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Psychopharmacology (2011) 218:649665 665
... 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. ...
... (4) "How personally psychologically insightful to you were the experiences?" (57,75). ...
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... Mystical experiences through psychedelics or meditation disrupt the mechanisms in brain activity underling a sense of a self-contained "self" separate from the rest of the natural realm and make one feel connected to others and the rest of the world, and secularists see this in terms of the natural world alone. The effect on beliefs may last for years and can lead to lasting increases in altruistic and pro-social behavior (Griffiths et al. 2006(Griffiths et al. , 2008(Griffiths et al. , 2011. This natural spirituality appears more tied to mystical experiences than other types of psychedelic experiences (Letheby 2021, p. 200). ...
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... The purpose of this essay is to draw attention to emerging research on psychedelic-assisted therapy as a potential mechanism to foster long-term behavioral change and aid in the desistance process (Aday et al., 2020;Griffiths et al., 2008Griffiths et al., , 2011MacLean et al., 2011). In doing so, the following sections (1) define psychedelic-assisted therapy, (2) introduce criminologists to historical and contemporary research on psychedelic therapy as means to induce positive behavioral change, (3) highlight the relevance of psychedelic-assisted therapy to existing criminological theories of desistance, namely those pointing to cognitive shifts and identity transformation as essential to the desistance process, and (4) document the potential challenges and ethical issues with the implementation of psychedelic-assisted therapy among criminal justice populations. ...
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... The 'mystical-type experience' reliably occasioned by high doses of classic serotonergic psychedelics like psilocybin and LSD is characterised by (amongst other things) 'ineffability' and 'oneness' (Griffiths et al. 2008;Griffiths et al. 2011;Barrett, Johnson, and Griffiths 2015). That such experiences are 'ineffable'literally unspeakable or indescribable indicates that they involve a suspension in the narrativizing activity of the (personal) self. ...
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