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Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms. NCT02061293. © The Author(s) 2015.
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DOI: 10.1177/0269881114565144
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Introduction
In the 1950s through early 1970s there was extensive research
on the use of LSD and other classic (5HT2A agonist or partial
agonist) hallucinogens in the treatment of addiction (Abuzzahab
and Anderson, 1971; Dyck, 2006; Grinspoon and Balakar, 1997;
Halpern, 1996; Mangini, 1998), existential distress in dying
patients (Grof et al., 1973; Pahnke et al., 1969; Richards, 1975;
Richards et al., 1977), pain (Kast, 1966; Kast and Collins, 1964),
and other conditions (Grinspoon and Balakar, 1997; Grof, 2008).
A recent meta-analysis (Krebs and Johansen, 2012) examined
the six published randomized trials (Bowen et al., 1970; Hollister
et al., 1969; Ludwig et al., 1969; Pahnke et al., 1970; Smart
et al., 1966; Tomsovic and Edwards, 1970) of LSD treatment of
alcoholism. A total of 325 participants received active treatment
with LSD, and 211 received control treatment. At the first post-
treatment follow-up (ranging from 1 month to 12 months) the
odds ratio for improvement was 1.96, favoring LSD (95% confi-
dence interval 1.36–2.84, Z = 3.59, p = 0.0003).
The past decade has seen a rapid growth of interest in poten-
tial clinical applications of the classic hallucinogen psilocybin
(Bogenschutz, 2012; Burdick and Adinoff, 2013; Carhart-Harris
et al., 2012, 2013; Garcia-Romeu et al., 2013; Grob et al., 2011;
Kometer et al., 2012; Nichols, 2014). Using a double-blind,
cross-over design, Grob et al. administered psilocybin 0.2 mg/kg
vs. placebo to 12 patients with anxiety related to advanced cancer
(Grob et al., 2011). Participants showed significant improvement
with time, and there were statistical trends suggesting a positive
effect of psilocybin on mood. Additional clinical trials in cancer
patients are currently nearing completion at Johns Hopkins
University and New York University (Nichols, 2014). A recent
pilot study of psilocybin as an adjunct in smoking cessation treat-
ment resulted in remarkable rates of abstinence (80% point absti-
nence at 6-month follow-up) (Johnson et al., 2014). Extensive
clinical research with the classic hallucinogens (LSD, psilocybin,
DMT, mescaline) has established their relative safety within a
clinical research setting when subjects are carefully screened,
supervised, and followed up (Strassman, 1984). A number of arti-
cles and chapters have reviewed the literature on the use of hal-
lucinogens in the treatment of addictions (Abuzzahab and
Anderson, 1971; Dyck, 2006; Grinspoon and Balakar, 1997;
Halpern, 1996; Mangini, 1998), with the recent addition of two
reviews that incorporate current research on the effects of classic
hallucinogens more generally and discuss possible mechanisms of
action (Bogenschutz and Pommy, 2012; Ross, 2012).
Psilocybin-assisted treatment for alcohol
dependence: A proof-of-concept study
Michael P Bogenschutz1, Alyssa A Forcehimes1, Jessica A Pommy1,
Claire E Wilcox1, PCR Barbosa2 and Rick J Strassman1
Abstract
Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although
recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol
dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to
provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or
two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the
psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase
significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin
administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4)
strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-
efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled
trials with larger samples to investigate efficacy and mechanisms.
TRIAL REGISTRATION: NCT02061293
Keywords
Addiction treatment, alcoholism, hallucinogens, psilocybin, clinical trial, motivational interviewing
1
Department of Psychiatry, University of New Mexico Health Sciences
Center, Albuquerque, NM, USA
2
Departamento de Filosofia e Ciencias Humanas Ilheus, Universidade
Estadual de Santa Cruz, Bahia, Brazil
Corresponding author:
Michael P Bogenschutz, Department of Psychiatry, Center for
Psychiatric Research, University of New Mexico Health Sciences
Center, MSC11 6035, 1 University of New Mexico, Albuquerque, NM
87131-0001, USA.
Email: mbogenschutz@salud.unm.edu
565144JOP0010.1177/0269881114565144Journal of PsychopharmacologyBogenschutz et al.
research-article2014
Original Paper
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2 Journal of Psychopharmacology
Biological mechanisms
Although classic hallucinogens bind to many serotonin receptor
subtypes and other receptors (Ray, 2010), the psychoactive
effects of all classic hallucinogens appear to depend primarily on
their actions at 5HT2A receptors (Nichols, 2004; Vollenweider
and Kometer 2010; Vollenweider et al., 1998). Administration of
classic hallucinogens in rat models has been shown to induce
down-regulation of 5HT2A receptors, particularly those in the
anterior cingulate and frontomedial cortex, likely accounting for
the rapid development and reversal of behavioral tolerance to
most classic hallucinogens (Buckholtz et al., 1990; Gresch et al.,
2005).
The behavioral correlates and effects of 5HT2A receptor
activity are complex. Increased 5HT2A receptor binding has
been found in relation to pathological conditions in humans
including depression (Shelton et al., 2009), impulsive aggres-
sion (Rosell et al., 2010), neuroticism (Frokjaer et al., 2008),
borderline personality disorder (Soloff et al., 2007), and suicide
(Anisman et al., 2008). The relationship of 5HT2A receptor
binding/activity and alcoholism or alcohol exposure is less clear.
Family history of alcoholism may be associated with lower
5HT2A binding (Underwood et al., 2008), and alcoholism is not
consistently associated with change in 5HT2A receptor levels
(Thompson et al., 2012; Underwood et al., 2008). Among alcohol-
ics, one small post-mortem study reported that higher impulsivity
was associated with increased 5HT2A receptor binding
(Thompson et al., 2012). In animal models, alcohol exposure has
been associated with region-specific increases (Akash et al.,
2008) and decreases (George et al., 2010) in 5HT2A receptors
binding. Studies indicate that increased activity in 5HT2A-
mediated pathways relative to 5HT2C activity increases cue
response and impulsivity in rat models of cocaine addiction
(Cunningham and Anastasio, 2014). 5HT2A antagonists suppress
alcohol consumption in animal models (Johnson, 2008).
However, two large trials of the 5HT2A antagonist ritanserin
failed to demonstrate beneficial effects in people with alcohol
dependence (Johnson et al., 1996; Wiesbeck et al., 1999).
Animal studies suggest mechanisms by which acute activa-
tion of 5HT2A receptors could activate intracellular signaling
pathways resulting in persisting changes in cellular structure
and synapses. The classic hallucinogen DOI increases expres-
sion of glial cell line-derived neurotrophic factor (GDNF)
mRNA in glioiblastoma cells by a 5HT2A-dependent mechanism
(Tsuchioka et al., 2008). Through its action on 5HT2A receptors,
DOI has also been shown to increase levels of mRNA for brain-
derived neurotrophic factor (BDNF) in rat parietal cortex and
other neocortical regions, with decreases in the hippocampus
and no change in piriform cortex (Vaidya et al., 1997). These
findings are relevant because levels of BDNF and GDNF
are inversely related to alcohol consumption and conditioned
place preference in animal models (Ghitza et al., 2010). DOI
activates intracellular signaling cascades associated with den-
dritic spine remodeling on rat pyramidal cells, and transiently
increases the size of dendritic spines on cortical neurons (Jones
et al., 2009).
Psychological models of psychedelic treatment
Clinical work with classic hallucinogens has emphasized the cen-
tral role of the altered state of consciousness experienced during
the drug’s acute effects (Grof, 2008; Hoffer, 1967; Masters and
Houston, 2000; Pahnke et al., 1970; Sherwood et al., 1962). The
“psycholytic” model of treatment emphasized the use of classic
hallucinogens to enhance the process of psychodynamic psycho-
therapy by making unconscious material more accessible
(Leuner, 1967). The “psychedelic” treatment model on the other
hand emphasized the use of relatively high doses of classic
hallucinogens (usually LSD) to occasion a “peak-psychedelic” or
mystical experience of ego loss, often likened to psychological
death and rebirth (Kurland et al., 1967). The latter model was
used in most of the clinical studies conducted in North America
using LSD in the treatment of addiction or existential anxiety in
the dying. The concept of a singular transformative experience
leading to lasting behavior change is consistent with classic
descriptions of religious conversion (James, 1902), “spiritual
awakening” in the context of Alcoholics Anonymous (Forcehimes,
2004), and spontaneous Quantum Change experiences (Miller
and C’de Baca, 2001). Recent studies have demonstrated that the
self-reported “mystical” dimension of the psilocybin experience
(feelings of unity, sacredness, ultimate reality, transcendence of
time and space, deeply felt positive mood, and ineffability
(Pahnke, 1963)) significantly predicts the lasting personal sig-
nificance of the experience (Griffiths et al., 2008) and personality
change (Maclean et al., 2011) in normal volunteers receiving
psilocybin.
The evidence summarized above provides a convincing
rationale for investigating whether a classic hallucinogen can
improve treatment response among patients with alcohol depend-
ence. In spite of the accumulating evidence that psilocybin has
clinically relevant effects and is safe under controlled conditions,
there are no prior studies of psilocybin in the treatment of alcohol
dependence. We therefore undertook a proof-of-concept study
which aimed to quantify the psychoactive effects and tolerability of
oral psilocybin in alcohol-dependent participants, and to evaluate
outcomes during and after completion of treatment.
Methods
Study design
The study employed a single-group, within-subjects design.
Participants received a 12-week, 14-session manualized inter-
vention including two open-label psilocybin sessions in which
psilocybin was administered: the first after 4 weeks of psychoso-
cial treatment, the second after 8 weeks. Outcome data were
collected for a total of 36 weeks.
Participants
Participants were recruited from the community using advertise-
ments in local media and flyers. They were males and females
age 25–65 with a diagnosis of active alcohol dependence, ascer-
tained using the Structured Clinical Interview for DSM-IV
(SCID) (First et al., 1996), and at least two heavy drinking days
in the past 30 days, who were concerned about their drinking and
not currently in treatment. Participants were excluded if screen-
ing showed them to have exclusionary medical or psychiatric
conditions; family history of schizophrenia, bipolar disorder, or
suicide; cocaine, psychostimulant, or opioid dependence; or his-
tory of using hallucinogens more than 10 times (or any use in the
past 30 days). Participants were required to be abstinent and not
in alcohol withdrawal at the time of the psilocybin sessions.
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Bogenschutz et al. 3
Participants provided written informed consent, and all study
procedures were reviewed and approved by the IRB of the
University of New Mexico Health Sciences Center.
Interventions
Psychosocial intervention. The psychosocial intervention
comprised a total of 12 sessions: seven sessions of Motivational
Enhancement Therapy (MET: a structured approach using the
principles of motivational interviewing (Miller and Rolnick,
2013)), three preparation sessions, and two debriefing sessions.
Four sessions occurred before the first psilocybin session, four
sessions between the first and second psilocybin sessions, and
four sessions after the second psilocybin session. The psychoso-
cial intervention was conducted by a team of two therapists. One
performed the seven MET sessions focused on changing drinking
behavior, while the other was responsible for preparation before,
support during, and debriefing after the psilocybin sessions. Both
therapists were present for the preparation and debriefing sessions,
as well as the psilocybin sessions. Three of the authors (MB, AF,
CW) served as study therapists. Therapy sessions were audiore-
corded. The first and third MET sessions were coded using the
Motivational Interviewing Treatment Integrity (MITI 3.1) coding
system (Moyers et al., 2005) by a rater trained to reliability.
Dosing and administration of study medications. On the
morning of the psilocybin sessions, participants were required
to be afebrile, non-hypertensive, non-tachycardic, abstinent
from alcohol for at least 24 hours, and without evidence of alco-
hol withdrawal. Urine drug screens were negative for cocaine,
psychostimulants, and opioids, and breath was negative for
alcohol. The psilocybin sessions took place in a room that was
specially prepared to provide a living-room-like environment
for the sessions. Individualized doses of psilocybin (based on
participant weight) were prepared by the study pharmacist on the
morning of the session, and placed in a single gelatin capsule.
Participants ingested the psilocybin capsule followed by 4
ounces of water. They were instructed to lie on a couch wearing
eyeshades and headphones (providing a standardized program
of music), and to direct their attention toward their internal
experience. Participants remained under observation for at least
8 hours following psilocybin administration. Both therapists
were present throughout the session. Interactions with the par-
ticipants were supportive and non-directive. Medications were
available for administration if needed to treat hypertension
(sublingual nitroglycerin 0.4 mg), anxiety (lorazepam 1–2 mg
PO/IM), or acute psychosis (ziprasidone 10–20 mg PO/IM).
Beginning 7 hours after drug administration, participants com-
pleted questionnaires and assessments, and a brief clinical inter-
view was performed, including mental status exam. Participants
were escorted home at the end of the session by a family member
or friend, who stayed with the participant overnight.
For the first psilocybin session, participants received a dose of
0.3 mg/kg. For the second session, the dose was increased to 0.4 mg/
kg unless the participant (i) was unwilling to increase the dose; (ii)
experienced adverse effects during the first session which suggested
that a higher dose would pose significant risk; or (iii) reported a
“complete” mystical experience during the first session (Griffiths
et al., 2006), indicating very strong effects from 0.3 mg/kg.
Assessments
Medical evaluation. Medical screening consisted of medical
history and physical examination, ECG, liver function tests,
complete blood count, blood chemistries, urinalysis, serum
pregnancy test, and body mass index. Women of childbearing
potential completed a menstrual calendar at each assessment
visit, and urine pregnancy tests were completed prior to each
drug administration session. The Clinical Institute Withdrawal
Scale—Alcohol, revised (CIWA-Ar) (Sullivan et al., 1989) was
used to assess alcohol withdrawal at screening and before the
psilocybin sessions.
Psychiatric and substance use disorder diagnoses. The
SCID (First et al., 1997) was used to diagnose DSM-IV Axis I
disorders including substance abuse and dependence diagnoses.
Acute hallucinogen effects. Self-report scales (administered 7
hours after drug administration) and monitor ratings (0–6 hours
after drug administration) were used to quantify acute subjective
effects. The Intensity subscale of the Hallucinogen Rating Scale
(HRS) (Strassman et al., 1994) was used as a global measure of
the intensity of the drug experience. The 5-Dimensional Altered
States of Consciousness Scale (5D-ASC) (Dittrich, 1998) has 94
items using the visual analog scale format, yielding five primary
dimensions: “Oceanic Boundlessness,” “Dread of Ego Dissolu-
tion,” “Visionary Restructuralization,” “Auditory Alterations,”
and “Altered Vigilance.” The States of Consciousness Scale is a
100-item questionnaire which has been used extensively to measure
states of consciousness in hallucinogen administration experi-
ments (Griffiths et al., 2006; Pahnke, 1963, 1969; Richards et al.,
1977; Turek et al., 1974). This scale contains the 43 items of the
Pahnke–Richards Mystical Experience Questionnaire (MEQ)
(Griffiths et al., 2006). The Addiction Research Center Inventory
(ARCI), 49-item version (Martin et al., 1971) was also adminis-
tered following each drug administration session. In addition, a
Monitor Session Rating Form (Griffiths et al., 2006) was com-
pleted by both monitors at intervals during the psilocybin sessions
to provide ratings of participants’ behavior and affect during the
session.
Substance use and consequences. The Time-Line Follow-
Back (TLFB) (Sobell and Sobell, 1992, 1995) procedure was
used to assess drinking behavior at baseline (covering the 12 weeks
preceding enrollment) and follow-up visits. Heavy drinking days
were defined as days during which participants consumed five or
more standard drinks if the participant was male, or four or more
standard drinks if the participant was female, a standard drink
being defined as 14 g of alcohol. Drinking days were defined as
days during which participants consumed any amount (even a
sip) of an alcoholic beverage. The Short Inventory of Problems
(SIP) (Miller et al., 1995), past 3 month version, was used to
measure consequences of alcohol use. Breath Alcohol Concen-
tration (BAC) was measured at each visit, but was used to ensure
safety of treatment and validity of assessments rather than as an
outcome measure.
Psychological assessments. The Stages of Change Readiness
and Treatment Eagerness Scale (SOCRATES 8A) (Miller and
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4 Journal of Psychopharmacology
Tonigan, 1996) was used as a measure of motivation. The Alcohol
Abstinence Self-Efficacy Scale (AASE) (Diclemente et al.,
1994) was used as a measure of self-efficacy to abstain from
drinking. The Penn Alcohol Craving Scale (PACS) (Flannery
et al., 1999) was used to assess craving. The Profile of Mood
States (POMS) (Mcnair et al., 1981) was used as a measure of
mood. Additional measures of persisting psychological effects
obtained but not discussed in this publication were the Hood
Mysticism Scale (Hood et al., 2001), the Persisting Effects
Questionnaire (Griffiths et al., 2006), the ASPIRES Spiritual
Transcendence Scale (Piedmont, 1999), the Brief Multidimen-
sional Measure of Religiousness/Spirituality (Fetzer Institute,
1999), the NEO Personality Inventory 3 (NEO-PI-3) (Mccrae
et al., 2005), and the Schwartz Value Survey (Schwartz, 1992,
2006).
Safety assessment. Vital signs were obtained at each visit and
measured frequently during psilocybin sessions: every half
hour for the first 2 hours, then hourly for the next 4 hours, with
more frequent readings as needed. Adverse events (AEs), when
present, were collected on an AE case report form at the end of
the psilocybin sessions and at all subsequent visits, including
assessment of clinical significance and relatedness to treatment.
Statistical analysis and power
Statistical analyses for this open-label pilot study were primarily
descriptive, but two a priori hypotheses were tested. To test for
changes in drinking behavior (percent heavy drinking days and
percent drinking days), consequences of drinking, and psycho-
logical outcomes, scores at follow-up time points were contrasted
with baseline and week 4 values using paired t-tests, and effect
sizes (Cohen’s d) (Cohen, 1988) were computed with correction
for correlation between time points (Morris and Deshon, 2002).
The primary drinking outcome was percent heavy drinking days,
and the primary contrast was baseline vs. weeks 5–12. With a
sample size of n = 10, the study had power of 0.803 to detect pre-
post changes of effect size d = 1.0, with α = 0.05 (2-tailed) prior to
correction for multiple comparisons. For drinking outcomes, the
Benjamini–Hochberg procedure (Benjamani and Hochberg,
1995) was used to control the false discovery rate at the 0.05 level.
Results
Participants
In total 70 individuals were screened for the study, of whom 10
were included in the study (Figure 1). Participants were four
women and six men with DSM-IV alcohol dependence. Two
participants were Native American/Alaska Native, one was
African American, four were Hispanic, and three were white
non-Hispanic. Four were single, three were married, and three
were divorced. Four were working full-time, five part-time, and
one was unemployed. Mean household income was $47,023 (SD
$35,262). Participants averaged 15.1 (SD 3.7) years of education
(12 years representing graduation from high school), and three
were college graduates.
Mean age was 40.1 years (SD 10.3, range 25–56), and mean
duration of alcohol dependence was 15.1 years (SD 11.5, range
4–32). Participants had a mean of 5.0 dependence criteria (SD
1.2, range 3–7). Eight out of 10 had evidence of physical depend-
ence (tolerance or withdrawal), but none had alcohol withdrawal
symptoms requiring treatment during the trial.
Treatment exposure and follow-up
Figure 1 summarizes participation in treatment and follow-up.
Ten participants completed the first psilocybin session. Of the
seven participants completing the second psilocybin session, six
received psilocybin 0.4 mg/kg and are included in analysis of
second session effects. One received psilocybin 0.3 mg/kg due to
meeting criteria for “complete mystical experience” in the first
session. Nine participants completed all follow-up assessments
and are included in outcome analyses. One participant discontin-
ued participation shortly after the first psilocybin session and did
not provide usable outcome data. A total of 14 MET sessions
were coded for fidelity using the MITI 3.1. Mean (SD) global
scores ranged from 4.43 (0.76) to 5.00 (0.00), well above the
proficiency benchmark of 4.0.
Acute effects
Figure 2 illustrates physiologic effects and monitor ratings dur-
ing the first psilocybin session, in which all participants
received psilocybin 0.3 mg/kg, and during the second psilocy-
bin session for the six participants who received psilocybin 0.4
mg/kg. Systolic or diastolic blood pressure was modestly but
significantly increased from 30 minutes to 180 minutes in one
or both conditions. Heart rate (not shown) did not change sig-
nificantly. Monitor ratings of global drug effect and “distance
from ordinary reality” peaked between 120 and 180 minutes,
and were significantly elevated at most time points. Differences
in these measures between the two doses were not statistically
significant (paired t-tests, df = 5).
Table 1 shows mean scores on self-report measures of sub-
jective experience obtained 7 hours following administration
of psilocybin 0.3 mg/kg in the first session and for the six par-
ticipants who received psilocybin 0.4 mg/kg in the second session.
Intensity of effects varied markedly from patient to patient. On
average, acute effects on the MEQ and HRS are numerically
lower in magnitude than those seen at comparable doses in normal
volunteers (Griffiths et al., 2011). For the six participants who
received psilocybin 0.4 mg/kg in the second session, subjective
ratings were not significantly different between the two sessions
(paired t-tests, df = 5), but were strongly correlated between
the sessions for most of the scales intended to measure halluci-
nogen effects.
Clinical outcomes
Percent heavy drinking days decreased during weeks 5–12 rela-
tive to baseline (mean difference (SD) = 26.0 (22.4), 95% CI
8.7–43.2, t(8) = 3.477, p = 0.008), and also decreased relative to
weeks 1–4 (during psychosocial treatment but prior to psilocy-
bin) (mean difference (SD) = 18.2 (20.0), 95% CI 2.8–33.5, t(8)
= 2.723, p = 0.026). Percent drinking days also decreased during
weeks 5–12 relative to baseline (mean difference (SD) = 27.2
(23.7), 95% CI 9.0–45.4, t(8) = 3.449, p = 0.009) and relative to
weeks 1–4 (mean difference (SD) = 21.9 (21.8), 95% CI 5.1–
38.6, t(8) = 3.010, p = 0.017). Figure 3 illustrates change in
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Bogenschutz et al. 5
percent heavy drinking days and percent drinking days over the
course of the study. Improvement is not statistically significant
during the first 4 weeks of participation, when participants
received weekly counseling but had not yet received psilocybin.
Following the first psilocybin session, percent heavy drinking
days and percent drinking days are significantly lower than
baseline at all follow-up points. Further, these measures are
significantly decreased relative to weeks 1–4 with the exception
of heavy drinking days during weeks 9–12 (p = 0.059). Fifteen
out of 16 contrasts were significant at the nominal 0.05 level,
and all of these remained significant at a false discovery rate of
0.05. Effect sizes are large (greater than 0.8) with one exception,
Cohen’s d ranging from 0.75 to 1.38. Table 2 summarizes addi-
tional outcomes for study participants. Significant improvement
70 began screening
51 excluded prior to consent
16 declined participation/lost to follow-up
11 exclusionary psychiatric or drug use disorder
9 lifetime hallucinogen use more than 10 occasions
5 exclusionary medications
4 exclusionary medical conditions
3 age greater than 65
2 did not meet current drinking inclusion criteria
1 active legal issues
19 consented
9 excluded
3 lost to follow-up/declined participation
2 reported family history of suicide
1 did not meet current drinking inclusion criteria
1 excluded for medical condition
1 reported past suicide attempt
10 received
psilocybin
10 completed first psilocybin session (week 4, psilocybin 0.3 mg/kg)
7 completed second psilocybin session (week 8)
6 received psilocybin 0.4 mg/kg
1 received psilocybin 0.3 mg/kg
3 did not complete second psilocybin session
1 missed second session due to unrelated medical condition but completed all other aspects of the study
1 dropped out of treatment after week 7 but completed follow-up assessments
1 withdrew participation after week 4
10 included in analyses of first session acute effects
9 included in analyses of drinking outcomes
9 completed all follow-up assessments
1 withdrew participation after week 4
Figure 1. Participant flow.
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6 Journal of Psychopharmacology
relative to baseline and/or week 4 is noted at multiple time
points for drinking consequences, craving, self-efficacy, and
motivation. Changes in POMS scores were not significant with
one exception (increased Vigor at week 24 relative to baseline).
Relationships between acute effects and
treatment response
Because the acute effects of psilocybin were quite variable, it was
possible to explore the relationships between the intensity of
acute effects and changes in drinking behavior. Table 3 shows
correlations between three summary measures of the intensity of
acute effects in the first psilocybin session and short-term clinical
outcomes. Large correlations were observed between measures
of acute effect intensity and change in drinking behavior, as well
as changes in craving and self-efficacy in some cases.
Supplemental Figure 1 displays scatterplots of the individual data
points underlying these correlations.
Treatment-related adverse events
Five participants reported mild headaches which resolved within
24 hours following psilocybin administration, consistent with
prior reports (Johnson et al., 2012). One participant had nausea
with one episode of emesis during one psilocybin session. One
participant with irritable bowel syndrome experienced diarrhea
during one psilocybin session. One participant reported insomnia
on the night following a psilocybin session. No participant
required medication or other intervention for blood pressure,
anxiety, or other psychiatric symptoms. There was no report
of illicit hallucinogen use by any participant during study
participation.
Discussion
Overall, the response of our alcohol-dependent participants to psil-
ocybin was qualitatively similar to that which has been reported in
other samples (Hasler et al., 2004; Griffiths et al., 2006, 2011;
Grob et al., 2011). Medication-related AEs were transient and
mild. However, subjective response was highly variable among
participants in this study, and numerically weaker on average for
some of the measures than that reported in normal volunteers at
comparable doses (Griffiths et al., 2011). This is consistent with
observations beginning in the 1950s that alcoholics tended to
require larger doses of LSD to have a strong effect (Chwelos et al.,
1959). Our findings suggest that some alcohol-dependent patients
are relatively insensitive to the effects of psilocybin, although
larger samples will be necessary to confirm this. The lack of sig-
nificant differences between the 0.3 mg/kg and 0.4 mg/kg doses is
most likely accounted for by the small sample size (n = 6) and/or
idiosyncratic responses in a small number of participants.
Participants exhibited significant improvement in drinking,
with large pre–post effect sizes, as well as significant changes in
psychological measures relevant to drinking. Importantly, much
of the improvement occurred following the administration of
psilocybin, at which time participants had already received 4
weeks of psychosocial treatment and 4–6 hours of assessment.
Also, strong correlations were observed between measures of
intensity of the acute drug effects and clinical outcomes. Although
change in drinking was correlated with the mystical quality of the
experience, it was similarly associated with ratings of other acute
effects. More work will necessary to determine whether there are
particular characteristics of the acute psilocybin experience that
are predictive of therapeutic benefit in alcohol use disorder.
While clearly demonstrating feasibility, this study has major,
self-evident limitations including small sample size, lack of a
control group or blinding, and lack of biological verification of
alcohol use. Due to these limitations, it is not possible to separate
unequivocally the effects of attention, psychosocial treatment,
and time; expectancy effects related to knowledge of receiving
psilocybin; and the specific effects of psilocybin. However, the
70.00
80.00
90.00
100.00
110.00
120.00
130.00
140.00
150.00
160.00
Systolic Session1
Diastolic Session1
Systolic Session2
Diastolic Session2
Blood Pressure
0
0.5
1
1.5
2
2.5
Overall EffectSession 1
Distance fromOrdinary Reality Session1
Overall EffectSession 2
Distance fromOrdinary Reality Session2
Monitor Rangs
Figure 2. Within-session objective effects. Blood pressure (mm Hg)
monitor ratings (0–4 Likert Scale).
Means are shown for 10 participants receiving psilocybin 0.3 mg/kg in the first
session (solid lines), and the six participants who received psilocybin 0.4 mg/
kg in the second session (n = 6, dashed line) during the 6 hours following drug
administration. Solid markers indicate significant difference from baseline value.
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Bogenschutz et al. 7
Table 1. Acute effects of psilocybin 0.3 mg/kg and 0.4 mg/ kg.
0.3 mg/kg
Session 1 (n = 10)
0.4 mg/kg
Session 2 (n = 6)
r Sig.
Mean (SD) Min. Max. Mean (SD) Min. Max. (n = 6)
ASC OBN 960.4 (518.8) 91 1798 785.0 (977.3) 79 2107 0.649 0.163
ASC DED 499.6 (515.8) 38 1515 340.1 (445.2) 26 1021 0.808 0.052
ASC VRS 923.5 (396.8) 61 1516 610.2 (543.5) 188 1462 0.670 0.145
ASC AUA 302.5 (380.9) 26 1166 182.0 (288.5) 18 766 0.960 0.002
ASC VIR 394.2 (268.1) 49 819 244.4 (333.0) 36.5 883 0.828 0.042
G-ASC 2383.5 (1347.7) 235 4628 1735.3 (1761.1) 337.5 4590 0.827 0.042
MEQ total 0.473 (0.217) 0.016 0.768 0.387 (0.347) 0.011 0.924 0.843 0.035
HRS intensity 2.43 (1.03) 0 3.5 2.00 (1.14) 0.25 3.25 0.902 0.014
ARCI PCAG 8.00 (3.06) 3 12 5.50 (4.04) 1 12 0.287 0.581
ARCI BG 5.40 (1.58) 3 8 5.83 (2.99) 2 11 0.167 0.752
ARCI A 4.78* (2.37) 0 8 4.50 (2.88) 2 9 0.198 0.707
ARCI MBG 5.33* (3.61) 4 12 6.33 (4.55) 2 13 0.388 0.448
ARCI LSD 8.10 (3.21) 1 13 8.17 (2.99) 4 12 0.405 0.425
Shown are scores for all 10 participants in session 1, scores for the six participants who received psilocybin 0.4 mg/kg in the second session, and correlations between
scores for the two sessions for these six participants.
*n = 9 due to incomplete questionnaire from one participant.
ASC: 5-Dimensional Altered States of Consciousness Scale; OBN: Oceanic Boundlessness subscale; DED: Dread of Ego Dissolution subscale; VRS: Visionary Restructuraliza-
tion subscale; AUA: Auditory Alterations subscale; VIR: Vigilance Reduction subscale; G-ASC: summary score (sum of OBN, DED, and VRS); MEQ: Mystical Experience Ques-
tionnaire; HRS Intensity: Intensity subscale of the Hallucinogen Rating Scale; ARCI: Addiction Research Center Inventory; PCAG: Phenobarbital, Chlorpromazine, Alcohol
Group subscale (sedation); BG: Benzedrine group subscale (stimulant); A: Amphetamine subscale (stimulant); MBG: Morphine-Benzadrine group subscale (euphoria); LSD:
LSD subscale (dysphoria). Instruments are described in Methods section.
0
5
10
15
20
25
30
35
40
45
BaselineWeeks 1-4Weeks 5-8Weeks 9-12 Weeks13-24 Weeks25-36
%DrinkingDays
%Heavy Drinking Days
Drinking Days
Baselinevs.
Weeks 1-4 p= .164 d= 0.490
Weeks 5-8 p= .009 d= 1.194
Weeks 9-12 p= .015 d= 1.033
Weeks13-24 p= .006 d= 1.332
Weeks25-36 p= .007 d= 1.187
Weeks1-4 vs.
Weeks 5-8 p= .016 d= 1.109
Weeks 9-12 p= .033 d= 0.869
Weeks13-24 p= .014 d= 1.163
Weeks25-36 p=. 013 d= 1.036
HeavyDrinkingDays
Baselinevs.
Weeks 1-4 p= .158 d= 0.492
Weeks 5-8 p= .007 d= 1.249
Weeks 9-12 p= .019 d= 0.985
Weeks13-24 p= .010 d= 1.161
Weeks25-36 p= .004 d= 1.383
Weeks1-4 vs.
Weeks5-8 p= .022 d= 1.046
Weeks9-12 p= .059 d= 0.750
Weeks13-24 p= .038 d= 0.876
Weeks25-36 p= .018 d= 1.040
First
psilocybin
treatment
following
Week 4
assessment
Percent Drinking Days/Percent HeavyDrinkingDays
Figure 3. Drinking outcomes and effect sizes.
Means shown are for all available data (n = 10 at baseline, n = 9 at all other time points). p-values are from paired t-tests (df = 8). Cohen’s d is shown for the contrast
between baseline or weeks 1–4 and each follow-up time point.
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8 Journal of Psychopharmacology
Table 2. Secondary outcomes.
Baseline Week 4 Week 5 Week 8 Week 9 Week 12 Week 24 Week 36
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)
SIP
Physical 4.60 (2.27) 4.89 (3.14) 2.78 (2.95) 2.78 (3.35)
Interpersonal 4.80 (2.57) 4.44 (3.17) 2.56 (3.05)** 2.56 (2.88)**
Intrapersonal 7.30 (1.70) 6.00 (3.12) 3.89 (3.76)* 3.67 (3.74)*
Impulse control 2.90 (1.29) 3.89 (2.47) 2.56 (2.24) 2.56 (3.05)
Responsibility 4.50 (2.37) 4.22 (3.46) 3.67 (3.81) 2.67 (2.87)
PACS 16.00 (5.59) 14.10 (7.17) 11.89 (8.64) 11.56 (5.85)* 10.00 (6.61)**,§12.11 (8.28)* 13.00 (9.59) 8.11 (9.16)***,§
AASE
Temptation 38.30 (12.80) 38.10 (18.17) 28.11 (18.86) 32.78 (21.09) 24.56 (16.80)*,§32.56 (21.67) 26.63 (18.70)* 27.22 (21.86)§
Confidence 40.10 (12.58) 40.30 (16.66) 55.56 (10.88)*,§§ 49.00 (11.90) 53.67 (12.76)§50.00 (13.21) 50.44 (13.09) 54.00 (19.87)§
SOCRATES
Recognition 31.80 (3.22) 31.10 (5.26) 31.11 (5.33) 31.78 (5.89) 31.89 (5.33) 30.38 (8.02) 28.67 (7.89) 26.78 (9.56)
Ambivalence 15.70 (3.65) 13.90 (5.93) 14.22 (5.31) 14.56 (5.81) 13.11 (6.13) 13.00 (6.48) 12.00* (5.20) 11.56* (4.90)
Taking Steps 32.30 (3.20) 34.00 (5.03) 36.33 (2.65)* 36.33 (2.65)** 37.33 (3.46)**,§35.78 (3.80)* 36.00 (4.12)* 33.78 (5.36)
POMS
Tension 7.20 (5.27) 6.22 (3.42) 4.67 (3.54) 5.78 (4.44) 5.89 (4.88) 8.00 6.06 5.78 (5.97) 5.33 (6.04)
Depression 6.50 (5.60) 3.40 (4.45) 4.89 (6.41) 4.44 (3.50) 3.22 (4.38) 6.78 7.45 6.11 (6.11) 5.00 (4.58)
Anger 4.40 (4.09) 2.40 (3.13) 4.67 (4.61) 3.89 (4.62) 2.22 (2.64) 4.50 (6.61) 3.56 (5.48) 4.56 (6.46)
Vigor 5.60 (4.01) 6.50 (3.34) 8.56 (4.61) 8.11 (5.46) 9.00 (5.85) 7.75 4.10 9.56 (4.90)* 7.50 (2.78)
Fatigue 8.70 (5.79) 6.60 (5.78) 6.22 (6.44) 5.44 (4.75) 5.56 (4.28) 7.67 6.28 6.67 (5.96) 6.89 (4.08)
Confusion 6.10 (2.69) 3.90 (1.79)* 4.67 (2.96) 5.33 (3.71) 5.56 (3.43) 5.13 3.36 5.56 (2.19) 4.44 (2.51)
SIP: Short Inventory of Problems; PACS: Penn. Alcohol Craving Scale; AASE: Alcohol Abstinence Self-Efficacy; SOCRATES: Stages of Change Readiness and Treatment Eagerness Scale; POMS: Profile of Mood States.
*Different from baseline, p < 0.05; **Different from baseline, p < 0.01; ***Different from baseline, p < 0.001; §Different from week 4, p < 0.05; §§Different from week 4, p < 0.01.
n = 10 at baseline and 4 weeks, and n = 9 at weeks 5–36 with the following exceptions due to missing questionnaire items: n = 9 for PACS baseline; n = 8 for SOCRATES Recognition week 12, AASE Confidence week 12, AASE
Temptation week 24, POMS Anger week 12, POMS Confusion week 12, POMS Vigor week 12, and POMS Vigor week 36.
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Bogenschutz et al. 9
Table 3. Correlations between acute effects and change in drinking, craving, and self-efficacy (n = 9).
PDD PHDD PACS AASE
(wk. 8 – wk. 4) (wk. 8 – wk. 4) (wk. 5 – wk. 4) (wk. 5 – wk. 4)
HRS Intensity r = –.844 r = –.763 r = –.823 r = .753
(wk. 4) p = .004 p = .017 p = .006 p = .019
MEQ total r =–.885 r = –.852 r = –.810 r = .762
(wk. 4) p = .002 p = .004 p = .008 p = .017
G-ASC r =–.838 r =–.893 r =–.654 r =-.555
(wk. 4) p = .005 p = .001 p = .056 p = .121
PDD: Percent Drinking Days; PHDD: Percent Heavy Drinking Days; PACS: Penn Alcohol Craving Scale; 4AASE = Alcohol Abstinence Self-Efficacy Confidence score; HRS:
Hallucinogen Rating Scale Intensity score; MEQ: Mystical Experience Questionnaire; G-ASC: Altered States of Consciousness Scale summary score.
time course of the observed changes and the striking relation-
ship between intensity of response and clinical improvement
provide support for the concept that psilocybin may produce
lasting benefits in alcohol use disorder when administered
under controlled conditions to carefully screened patients,
in the context of appropriate psychosocial interventions.
Adequately powered randomized trials will be necessary to test
this hypothesis rigorously. Neuroimaging studies in alcohol use
disorder trial participants would help characterize the persisting
effects of psilocybin on brain activity (e.g. resting state func-
tional connectivity, cue response, stress response, response to
emotional stimuli, and inhibitory control). Studying the genetics
of response to psilocybin may shed light on the variability of
response, ultimately aiding in dose selection or identifying
patients particularly likely to benefit.
Acknowledgements
We wish to thank the following persons for their contributions to the
study. From the University of New Mexico, Albuquerque, NM: for data
collection, Rose C. Bigelow, MS; for fidelity monitoring, Christina E.
Ripp, MA; for data entry and cleaning, Robert G. Voloshin, DO, Alex M.
Pogzeba, BA, Christina E. Ripp, MA, Lindsay M. Worth, MPA; for qual-
ity assurance and regulatory compliance, Linda A. Schenkel; CCRC,
CPhT; for service on the Data and Safety Monitoring Committee for the
study, Jan A. Fawcett, MD, Theresa B. Moyers, PhD. From the University
of North Carolina: for providing the psilocybin used for this study, David
E. Nichols, PhD. From Johns Hopkins University: for providing training
for study interventionists, William A. Richards, PhD; for guidance on
intervention and assessment procedures, Roland R. Griffiths, PhD. From
the Heffter Research Institute: for advice and support in the design and
conduct of the study, George R. Greer, MD.
Declaration of Conflicting Interests
The authors declared the following potential conflicts of interest with
respect to the research, authorship, and/or publication of this article: Dr.
Bogenschutz reports grants from National Institute on Drug Abuse, dur-
ing the conduct of the study; and grants from the Lundbeck Foundation
and the Heffter Research Institute, outside the submitted work.
Funding
The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: The study was
supported by a grant from the Heffter Research Institute and NIH grant
1UL1RR031977.
References
Abuzzahab FS, Sr. and Anderson BJ (1971) A review of LSD treatment
in alcoholism. Int Pharmacopsychiatry 6: 223–235.
Akash KG, Anju TR, Peeyush KT, et al. (2008) Enhanced dopamine D2
receptor function in hypothalamus and corpus striatum: Their role
in liver, plasma and in vitro hepatocyte ALDH regulation in ethanol
treated rats. J Biomed Sci 15: 623–631.
Akash KG, Balarama KS and Paulose CS (2008) Enhanced 5-Ht(2a)
receptor status in the hypothalamus and corpus striatum of ethanol-
treated rats. Cell Mol Neurobiol 28: 1017–1025.
Anisman H, Du L, Palkovits M, et al. (2008) Serotonin receptor subtype
and P11 mRNA expression in stress-relevant brain regions of suicide
and control subjects. J Psychiatry Neurosci 33: 131–141.
Benjamani Y and Hochberg Y (1995) Controlling the false discovery
rate: A practical and powerful approach to multiple testing. J Royal
Stat Soc Series B (Method) 57: 289–300.
Bogenschutz MP (2012) Effects of psilocybin in the treatment of addic-
tions: A review and preliminary results from two ongoing trials.
Neuropsychopharmacology 38: S15-S16.
Bogenschutz MP and Pommy JM (2012) Therapeutic mechanisms of
classic hallucinogens in the treatment of addictions: From indirect
evidence to testable hypotheses. Drug Test Anal 4: 543–555.
Bowen WT, Soskin RA and Chotlos JW (1970) Lysergic acid diethylam-
ide as a variable in the hospital treatment of alcoholism: A follow-up
study. J Nerv Ment Dis 150: 111–118.
Buckholtz NS, Zhou DF, Freedman DX, et al. (1990) Lysergic acid
diethylamide (LSD) administration selectively downregulates
serotonin2 receptors in rat brain. Neuropsychopharmacology 3:
137–148.
Burdick BV and Adinoff B (2013) A proposal to evaluate mechanistic
efficacy of hallucinogens in addiction treatment. Am J Drug Alcohol
Abuse 39: 291–297.
Carhart-Harris RL, Erritzoe D, Williams T, et al. (2012) Neural cor-
relates of the psychedelic state as determined by fMRI studies with
psilocybin. Proc Natl Acad Sci U S A 109: 2138–2143.
Carhart-Harris RL, Leech R, Erritzoe D, et al. (2013) Functional connec-
tivity measures after psilocybin inform a novel hypothesis of early
psychosis. Schizophr Bull 39: 1343–1351.
Chwelos N, Blewett DB, Smith CM, et al. (1959) Use of D-lysergic acid
diethylamide in the treatment of alcoholism. Q J Stud Alcohol 20:
577–590.
Cohen J (1988) Statistical Power Analysis for the Behavioral Sciences
(2nd Edn). Hillsdale, NJ: Lawrence Erlbaum Associates, Inc.
Cunningham KA and Anastasio NC (2014) Serotonin at the nexus of
impulsivity and cue reactivity in cocaine addiction. Neuropharma-
cology 76 Pt B: 460–478.
Diclemente CC, Carbonari JP, Montgomery RP, et al. (1994) The Alco-
hol Abstinence Self-Efficacy Scale. J Stud Alcohol 55: 141–148.
by guest on January 14, 2015jop.sagepub.comDownloaded from
10 Journal of Psychopharmacology
Dittrich A (1998) The standardized psychometric assessment of altered
states of consciousness (ASCS) in humans. Pharmacopsychiatry 31:
80–84.
Dyck E (2006) ‘Hitting highs at rock bottom’: LSD treatment for alcohol-
ism, 1950–1970. Soc Hist Med 19: 313–329.
Fetzer Institute (1999) Multidimensional Measurement of Religiousness/
Spirituality for Use in Health Research. Kalamazoo, MI: Fetzer
Institute.
First MB, Spitzer RL, Gibbon M, et al. (1996) Structured Clinical Inter-
view for DSM-IV Axis I Disorders-Patient Edition (Scid-I/P, Version
2.0). New York, NY: Biometrics Research Department, New York
State Psychiatric Institute.
First MB, Spitzer RL, Gibbon M, et al. (1997) Structured Clinical
Interview for DSM-IV Axis I Disorders-Patient Edition. New York,
NY: Biometrics Research Department, New York State Psychiatric
Institute.
Flannery BA, Volpicelli JR and Pettinati HM (1999) Psychometric prop-
erties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res 23:
1289–1295.
Forcehimes AA (2004) De profundis: Spiritual transformations in Alco-
holics Anonymous. J Clin Psychol 60: 503–517.
Frokjaer VG, Mortensen EL, Nielsen FA, et al. (2008) Frontolimbic
serotonin 2a receptor binding in healthy subjects is associated with
personality risk factors for affective disorder. Biol Psychiatry 63:
569–576.
Garcia-Romeu AP, Johnson MW and Griffiths RR (2013) Examining the
psychological mechanisms of psilocybin-assisted smoking cessation
treatment: A pilot study. Abstract book. San Diego, CA: CPDD con-
ference, June 16–20, 2013.
George AK, Paul J, Kaimal SB, et al. (2010) Decreased cerebral cor-
tex and liver 5-HT2a receptor gene expression and enhanced ALDH
activity in ethanol-treated rats and hepatocyte cultures. Neurol Res
32: 510–518.
Ghitza UE, Zhai H, Wu P, et al. (2010) Role of BDNF and GDNF in drug
reward and relapse: A review. Neurosci Biobehav Rev 35: 157–171.
Gresch PJ, Smith RL, Barrett RJ, et al. (2005) Behavioral tolerance to
lysergic acid diethylamide is associated with reduced serotonin-
2a receptor signaling in rat cortex. Neuropsychopharmacology 30:
1693–1702.
Griffiths R, Richards W, Johnson M, et al. (2008) Mystical-type experi-
ences occasioned by psilocybin mediate the attribution of personal
meaning and spiritual significance 14 months later. J Psychophar-
macol 22: 621–632.
Griffiths RR, Johnson MW, Richards WA, et al. (2011) Psilocybin occa-
sioned mystical-type experiences: Immediate and persisting dose-
related effects. Psychopharmacology (Berl) 218: 649–665.
Griffiths RR, Richards WA, Mccann U, et al. (2006) Psilocybin can
occasion mystical-type experiences having substantial and sustained
personal meaning and spiritual significance. Psychopharmacology
(Berl) 187: 268–283; discussion 284–292.
Grinspoon L and Balakar JB (1997) Psychedelic Drugs Reconsidered.
New York: The Lindesmith Center.
Grob CS, Danforth AL, Chopra GS, et al. (2011) Pilot study of psilocybin
treatment for anxiety in patients with advanced-stage cancer. Arch
Gen Psychiatry 68: 71–78.
Grof S (2008) LSD Psychotherapy. 4 edn. Ben Lomond, CA: Multidisci-
plinary Association for Psychedelic Studies.
Grof S, Goodman LE, Richards WA, et al. (1973) LSD-assisted psycho-
therapy in patients with terminal cancer. Int Pharmacopsychiatry 8:
129–144.
Halpern JH (1996) The use of hallucinogens in the treatment of addiction.
Addict Res 4: 177–189.
Hasler F, Grimberg U, Benz MA, et al. (2004) Acute psychological and
physiological effects of psilocybin in healthy humans: A double-
blind, placebo-controlled dose-effect study. Psychopharmacology
(Berl) 172: 145–156.
Hoffer A (1967) A program for treatment of alcoholism: LSD, mal-
varia, and nicotinic acid. In: Abramson HA (ed) The Use of LSD
in Psychotherapy and Alcoholism. Indianapolis: Bobbs-Merrill.
pp. 343–406.
Hollister LE, Shelton J and Krieger G (1969) A controlled comparison of
lysergic acid diethylamide (LSD) and dextroamphetmine in alcohol-
ics. Am J Psychiatry 125: 1352–1357.
Hood RWJ, Ghorbani N, Watson PJ, et al. (2001) Dimensions of the
mysticism scale: Confirming the three-factor structure in the United
States and Iran. J Sci Study Relig 40: 691–705.
James W (1902) The Varieties of Religious Experience. Cambridge, MA:
Harvard University Press.
Johnson BA (2008) Update on neuropharmacological treatments for
alcoholism: Scientific basis and clinical findings. Biochem Pharma-
col 75: 34–56.
Johnson BA, Jasinski DR, Galloway GP, et al. (1996) Ritanserin in the
treatment of alcohol dependence – a multi-center clinical trial. Ritan-
serin Study Group. Psychopharmacology (Berl) 128: 206–215.
Johnson MW, Andrew Sewell R and Griffiths RR (2012) Psilocybin
dose-dependently causes delayed, transient headaches in healthy
volunteers. Drug Alcohol Depend 123: 132–140.
Johnson MW, Garcia-Romeu A, Cosimano MP, et al. (2014) Pilot study
of the 5-HT2AR agonist psilocybin in the treatment of tobacco
addiction. J Psychopharmacol 28: 983–992.
Jones KA, Srivastava DP, Allen JA, et al. (2009) Rapid modulation of
spine morphology by the 5-HT2A serotonin receptor through kali-
rin-7 signaling. Proc Natl Acad Sci U S A 106: 19575–19580.
Kast EC (1966) Pain and LSD-25: A theory of attenuation of anticipation.
In: Solomon D (ed) LSD: The Consciousness-Expanding Drug. New
York, NY: GP Putnam, 239–254.
Kast EC and Collins VJ (1964) Study of lysergic acid diethylamide as an
analgesic agent. Anesth Analg 43: 285–291.
Kometer M, Schmidt A, Bachmann R, et al. (2012) Psilocybin biases
facial recognition, goal-directed behavior, and mood state toward
positive relative to negative emotions through different serotonergic
subreceptors. Biol Psychiatry 72: 898–906.
Krebs TS and Johansen PO (2012) Lysergic acid diethylamide (LSD) for
alcoholism: Meta-analysis of randomized controlled trials. J Psycho-
pharmacol 26: 994–1002.
Kurland AA, Unger S, Shaffer JW, et al. (1967) Psychedelic therapy uti-
lizing LSD in the treatment of the alcoholic patient: A preliminary
report. Am J Psychiatry 123: 1202–1209.
Leuner H (1967) Present state of psycholytic therapy and its possibilities.
In: Abramson HA (ed) The Use of LSD in Psychotherapy and Alco-
holism. Indianapolis: Bobbs-Merrill, pp. 101–116.
Ludwig A, Levine J, Stark L, et al. (1969) A clinical study of LSD treat-
ment in alcoholism. Am J Psychiatry 126: 59–69.
Maclean KA, Johnson MW and Griffiths RR (2011) Mystical experiences
occasioned by the hallucinogen psilocybin lead to increases in the
personality domain of openness. J Psychopharmacol 25: 1453–1461.
Mangini M (1998) Treatment of alcoholism using psychedelic drugs:
A review of the program of research. J Psychoactive Drugs 30:
381–418.
Martin WR, Sloan JW, Sapira JD, et al. (1971) Physiologic, subjective,
and behavioral effects of amphetamine, methamphetamine, ephed-
rine, phenmetrazine, and methylphenidate in man. Clin Pharmacol
Ther 12: 245–258.
Masters R and Houston J (2000) The Varieties of Psychedelic Experi-
ence: The Classic Guide to the Effects of LSD on the Human Psyche.
Rochester, Vermont: Park Street Press.
Mccrae RR, Costa Jr, PT and Martin TA (2005) The Neo-Pi-3: A
more readable revised neo personality inventory. J Pers Assess
84: 261–270.
Mcnair DM, Lorr M and Droppleman LF (1981) Profile of Mood States.
San Diego, CA: Educational and Industrial Testing Service.
by guest on January 14, 2015jop.sagepub.comDownloaded from
Bogenschutz et al. 11
Miller WR and C’de Baca J (2001) Quantum Change : When Epiphanies
and Sudden Insights Transform Ordinary Lives. New York: Guilford
Press.
Miller WR and Rolnick S (2013) Motivational Interviewing: Helping
People Change. 3rd. ed. New York, NY: Guilford Press.
Miller WR and Tonigan JS (1996) Assessing drinker’s motivation for
change: The Stages of Change Readiness and Treatment Eagerness
Scale (Socrates). Psychology of Addictive Behaviors 10: 81–89.
Miller WR, Tonigan JS and Longabaugh R (1995) The Drinker Inventory
of Consequences (Drinc): An Instrument for Assessing Adverse Con-
sequences of Alcohol Abuse. Test Manual (Vol. 4). Rockville, MD:
US Government Printing Office.
Morris SB and Deshon RP (2002) Combining effect size estimates in
meta-analysis with repeated measures and independent-groups
designs. Psychological Methods 7: 105–125.
Moyers TB, Martin T, Manuel JK, et al. (2005) Assessing competence in
the use of motivational interviewing. J Subst Abuse Treat 28: 19–26.
Nichols DE (2004) Hallucinogens. Pharmacol Ther 101: 131–181.
Nichols DE (2014) The Heffter Research Institute: Past and hopeful
future. J Psychoactive Drugs 46: 20–26.
Pahnke W (1963) Drugs and mysticism: An analysis of the relationship
between psychedelic drugs and the mystical consciousness. Ph.D.
Thesis, Harvard University.
Pahnke WN (1969) Psychedelic drugs and mystical experience. Int Psy-
chiatry Clin 5: 149–162.
Pahnke WN, Kurland AA, Goodman LE, et al. (1969) LSD-assisted
psychotherapy with terminal cancer patients. Curr Psychiatr Ther
9: 144–152.
Pahnke WN, Kurland AA, Unger S, et al. (1970) The experimental use of
psychedelic (LSD) psychotherapy. JAMA 212: 1856–1863.
Piedmont RL (1999) Does spirituality represent the sixth factor of per-
sonality? Spiritual transcendence and the Five-Factor Model. J
Person 67: 985–1013.
Ray TS (2010) Psychedelics and the human receptorome. PLoS ONE 5:
e9019.
Richards WA (1975) Counseling, peak experiences and the human
encounter with death: An empirical study of the efficacy of DPT-
assisted counseling in enhancing the quality of life of persons with
terminal cancer and their closest family members. Ph.D. Thesis,
Catholic University of America, Washington, DC.
Richards WA, Rhead JC, Dileo FB, et al. (1977) The peak experience
variable in DPT-assisted psychotherapy with cancer patients. J Psy-
chedelic Drugs 9: 1–10.
Rosell DR, Thompson JL, Slifstein M, et al. (2010) Increased serotonin 2a
receptor availability in the orbitofrontal cortex of physically aggres-
sive personality disordered patients. Biol Psychiatry 67: 1154–1162.
Ross S (2012) Serotonergic hallucinogens and emerging targets for
addiction pharmacotherapies. Psychiatric Clin N Am 35: 357–374.
Schwartz SH (1992) Universals in the content and structure of values:
Theory and empirical tests in 20 countries. In: Zanna M (ed)
Advances in Experimental Social Psychology, Vol. 25. New York:
Academic Press, pp. 1–65.
Schwartz SH (2006) Les valeurs de base de la personne: Théorie,
mesures et applications [Basic human values: Theory, measurement,
and applications]. Revue française de sociologie 42: 249–288.
Shelton RC, Sanders-Bush E, Manier DH, Schwartz SH (2009)
Elevated 5-HT2a receptors in postmortem prefrontal cortex in major
depression is associated with reduced activity of protein kinase A.
Neuroscience 158: 1406–1415.
Sherwood JN, Stolaroff MJ and Harman WW (1962) The psychedelic
experience – a new concept in psychotherapy. J Neuropsychiatr 4:
69–80.
Smart RG, Storm T, Baker EF, Schwartz SH (1966) A controlled study
of lysergide in the treatment of alcoholism. 1. The effects on drinking
behavior. Q J Stud Alcohol 27: 469–482.
Sobell LC and Sobell MB (1992) Timeline follow-back: A technique
for assessing self-reported alcohol consumption. In: Litten RA and
Allen JP (eds) Measuring Alcohol Consumption: Psychosocial and
Biological Methods. Totowa, NJ: Humana Press, pp. 41–72.
Sobell LC and Sobell MB (1995) Alcohol Timeline Followback Users’
Manual. Toronto, Canada: Addiction Research Foundation.
Soloff PH, Price JC, Meltzer CC, et al. (2007) 5HT2a receptor binding
is increased in borderline personality disorder. Biol Psychiatry 62:
580–587.
Strassman RJ (1984) Adverse reactions to psychedelic drugs. A review of
the literature. J Nerv Ment Dis 172: 577–595.
Strassman RJ, Qualls CR, Uhlenhuth EH, et al. (1994) Dose-response
study of N,N-dimethyltryptamine in humans. II. Subjective effects
and preliminary results of a new rating scale. Arch Gen Psychiatry
51: 98–108.
Sullivan JT, Sykora K, Schneiderman J, et al. (1989) Assessment of alco-
hol withdrawal: The Revised Clinical Institute Withdrawal Assess-
ment for Alcohol Scale (CIWA-AR). Br J Addict 84: 1353–1357.
Thompson PM, Cruz DA, Olukotun DY, et al. (2012) Serotonin receptor,
Sert mRNA and correlations with symptoms in males with alcohol
dependence and suicide. Acta Psychiatr Scand 126: 165–174.
Tomsovic M and Edwards RV (1970) Lysergide treatment of schizo-
phrenic and nonschizophrenic alcoholics: A controlled evaluation.
Q J Stud Alcohol 31: 932–949.
Tsuchioka M, Takebayashi M, Hisaoka K, et al. (2008) Serotonin
(5-HT) induces glial cell line-derived neurotrophic factor (GDNF)
mRNA expression via the transactivation of fibroblast growth fac-
tor receptor 2 (FGFR2) in rat C6 glioma cells. J Neurochem 106:
244–257.
Turek IS, Soskin RA and Kurland AA (1974) Methylenedioxyamphet-
amine (MDA) subjective effects. J Psychedelic Drugs 6: 7–14.
Underwood MD, Mann JJ, Huang YY, et al. (2008) Family history of
alcoholism is associated with lower 5-HT2A receptor binding in the
prefrontal cortex. Alcohol Clin Exp Res 32: 593–599.
Vaidya VA, Marek GJ, Aghajanian GK, et al. (1997) 5-HT2A receptor-
mediated regulation of brain-derived neurotrophic factor mRNA in
the hippocampus and the neocortex. J Neurosci 17: 2785–2795.
Vollenweider FX and Kometer M (2010) The neurobiology of psyche-
delic drugs: Implications for the treatment of mood disorders. Nat
Rev Neurosci 11: 642–651.
Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Babler A, et al.
(1998) Psilocybin induces schizophrenia-like psychosis in humans
via a serotonin-2 agonist action. Neuroreport 9: 3897–3902.
Wiesbeck GA, Weijers HG, Chick J, et al. (1999) Ritanserin in relapse
prevention in abstinent alcoholics: Results from a placebo-controlled
double-blind international multicenter trial. Ritanserin in Alcohol-
ism Work Group. Alcohol Clin Exp Res 23: 230–235.
by guest on January 14, 2015jop.sagepub.comDownloaded from
... Small-scale clinical studies in patients with depression, anxiety, or drug dependence indicate that psychedelic-assisted therapy may lead to remission for more than six months (Bogenschutz et al., 2015;Carhart-Harris et al., 2018;Griffiths et al., 2016;. ...
... In summary, tests of despair-like behavior and behaviors related to hedonic responses in rodents have shown inconsistent acute effects of 5-HT2AR agonists. showed promising results, even at low doses (Moreno et al., 2006), and psilocybin also appears to be effective in treating substance use disorders (Bogenschutz et al., 2015;Garcia-Romeu et al., 2014;Johnson et al., 2014;. Rodent tests of compulsivelike behaviors measure different types of repetitive behaviors in rodents. ...
... Clinical efficacy of psychedelic-assisted psychotherapy in humans lasts well into follow-ups performed several months after the administration of the 5-HT2AR agonist (Bogenschutz et al., 2015;Carhart-Harris et al., 2018;Gasser et al., 2015;Johnson et al., 2014). In healthy volunteers, changes in the openness personality domain are still present after one year (MacLean et al., 2011) and participants also report lasting changes in pro-social attitudes . ...
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Psychedelic-assisted psychotherapy holds great promise in the treatment of mental health disorders. Research into 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelic compounds has increased dramatically over the past two decades. In humans, these compounds produce drastic effects on consciousness, and their therapeutic potential relates to changes in the processing of emotional, social, and self-referential information. The use of animal behavior to study psychedelics is under debate, and this review provides a critical perspective on the translational value of animal behavior studies in psychedelic research. Acute activation of 5-HT2ARs produces head twitches and unique discriminative cues, disrupts sensorimotor gating, and stimulates motor activity while inhibiting exploration in rodents. The acute treatment with psychedelics shows discrepant results in conventional rodent tests of depression-like behaviors but generally induces anxiolytic-like effects and inhibits repetitive behavior in rodents. Psychedelics impair waiting impulsivity but show discrepant effects in other tests of cognitive function. Tests of social interaction also show conflicting results. Effects on measures of time perception depend on the experimental schedule. Lasting or delayed effects of psychedelics in rodent tests related to different behavioral domains appear to be rather sensitive to changes in experimental protocols. Studying the effects of psychedelics on animal behaviors of relevance to effects on psychiatric symptoms in humans, assessing lasting effects, publishing negative findings, and relating behaviors in rodents and humans to other more translatable readouts, such as neuroplastic changes, will improve the translational value of animal behavioral studies in psychedelic research. SIGNIFICANCE STATEMENT: Psychedelics like LSD and psilocybin have received immense interest as potential new treatments of psychiatric disorders. Psychedelics change high-order consciousness in humans, and there is debate about the use of animal behavior studies to investigate these compounds. This review provides an overview of the behavioral effects of 5-HT2AR agonist psychedelics in laboratory animals and discusses the translatability of the effects in animals to effects in humans. Possible ways to improve the utility of animal behavior in psychedelic research are discussed.
... Classic psychedelics have been shown to catalyze relatively long-lasting improvements in mental health after a small number of doses, especially when combined with psychotherapy [2]. In patients suffering from depression, anxiety disorders, and addiction, the benefits of psychedelic-assisted psychotherapy can last for many months or years [3][4][5][6][7][8][9][10]. Additionally, healthy subjects report increased well-being up to a year after administration of psychedelics in a safe and supportive setting [11][12][13]. ...
... Important mesolimbic areas for addiction, including the ventral tegmental area, nucleus accumbens, and striatum, express relatively few 5-HT 2A receptors and are therefore unlikely to be much affected by psychedelic-induced plasticity [102,109]. Additionally, inhibitory neurons projecting from the PFC to areas of the mesolimbic pathway are much richer in 5-HT 2A receptors [102,110], and enhanced dendritic growth in these PFC neurons could conceivably contribute to the antiaddictive effect observed with psychedelics [3,10,111]. ...
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Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about the effects of psychedelics on neuroplasticity. Firstly, we review the evidence that psychedelics promote neuroplasticity and examine the cellular and molecular mechanisms behind the effects of different psychedelics on different aspects of neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes (e.g., brain-derived neurotrophic factor and immediate early genes). We then examine where in the brain psychedelics promote neuroplasticity, particularly discussing the prefrontal cortex and hippocampus. We also examine what doses are required to produce this effect (e.g., hallucinogenic doses vs. “microdoses”), and how long purported changes in neuroplasticity last. Finally, we discuss the likely consequences of psychedelics’ effects on neuroplasticity for both patients and healthy people, and we identify important research questions that would further scientific understanding of psychedelics’ effects on neuroplasticity and its potential clinical applications.
... Initial clinical trials focused on the benefits of psilocybin to reduced anxiety and improve mood of patients with cancer ( Griffiths et al., 2016 ;Grob et al., 2011 ). Additional psychedelics have been tested in conjunction with psychotherapy for the treatment of suicidal thoughts ( Witt et al., 2020 ), anxiety and depression Palhano-Fontes et al., 2019 ), addiction ( Bogenschutz et al., 2015 ;Winkelman, 2014 ), and for Post-Traumatic Stress Disorder (PTSD) ( Mitchell et al., 2021 ;Moreno et al., 2006 ). More recently, work has reported on neuroimaging findings Daws et al., 2022 ), and current studies are underway for patients with chronic anorexia nervosa (NCT04052568) and obsessive-compulsive disorder (NCT03356483). ...
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A scientometric analysis was realized to outline clinical research on psychedelics over the last century. Web of Science Core Collection was searched up to March 18, 2022, for publications on psychedelics. Network analyses and bibliometrics were combined, to identify research themes and trends with Bibliometrix and CiteSpace. The primary aim was to measure research trends evolution over time, and the secondary aims were to identify bibliometric performance and influence networks of publications, authors, institutions, and countries. Sensitivity analyses were conducted for 2016-2022, and 2021 time periods. We included 31,687 documents (591,329 references), which aggregated into a well-structured network with credible clustering. Research productivity was split into an early less productive period mainly focusing on safety issues, and a "psychedelic renaissance" after the 1990s. Major trends were identified for hallucino-gens/entheogens, entactogens, novel psychoactive substances (NPS), and on dissociative substances. There was a translational evolution from the bench to the bedside, with phase 2 and 3 trials and/or evidence synthesis in particular. The most recent trends concerned NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada were the most productive settings for the research overall, and more recently this geographical distribution became more prominent, reflecting legislative context/policy making. A translational evolution of psychedelics has been occurring, that has brought approval of esketamine for depression and will likely lead to approval of additional psychedelics across mental and physical conditions. Toxicology screening tools for NPS are urgently needed, which in turn might follow the same translational evolution of psychedelics in the future.
... Moreover, the studies helped establish the safety of psilocybin, which was well-tolerated and did not cause any serious negative physiological or psychological consequences. Other research has supported psilocybin's capacity to treat tobacco use disorder [31], alcohol use disorder [32], and obsessive compulsive disorder [33]. ...
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Purpose of Review Few treatments are available for patients with mood disorders or post-traumatic stress disorder (PTSD) who have already failed multiple interventions. After several decades when research into psychedelics was effectively halted by federal legislation, the past several years have shown the re-emergence of thoughtful investigations studying the utility of compounds such as 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin. Recent Findings Several studies have coupled the safe administration of psychedelic compounds in a controlled environment after several hours of preparation of study participants and followed by multiple sessions to integrate the psychedelic experience. The improvement participants experience appear related to the often profound perspective changes experienced and seem unlike the improvements seen in the currently available care paradigms. Studies cited include treatment resistant depression, end of life despair, and PTSD. Summary Psychedelic psychotherapy, a unique remarriage of biological therapy and psychotherapy, has the potential to transform mental health care.
... The evidence for psychedelic therapy's efficacy has been growing rapidly over the last decade. It has been indicated as an effective tool for reducing depression, anxiety, and anhedonia , 2017 in addition to nicotine (Johnson et al., 2014(Johnson et al., , 2017, alcohol (Bogenschutz et al., 2015 and opioid dependence (Brown & Alper, 2018), as well as distress related to terminal illness diagnosis (Griffiths et al., 2016;Grob et al., 2011). It has also been recognized for its potential to improve psychological wellbeing in general (MacLean et al., 2011), a phenomenon referred to as "the betterment of well people" (phrase coined by Bob Jesse and quoted inter alia in Pollan, 2018). ...
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Background and aims Despite promising findings indicating the therapeutic potential of psychedelic experience across a variety of domains, the mechanisms and factors affecting its efficacy remain unclear. The present paper explores this by focusing on two psychedelic states which have been suggested as therapeutically significant in past literature: ego-dissolution and connectedness. The aim of the study is to investigate the impact of ego-dissolution and connectedness on the therapeutic effects of the psychedelic experience. Methods The investigation was carried out as a mixed methods systematic review, with the data from four databases analysed thematically and results presented through narrative synthesis. Results The analysis and synthesis of findings from 15 unique studies ( n = 2,182) indicated that both ego-dissolution and connectedness are associated with a higher chance of improvement following a psychedelic experience. However, there seem to be differences in the way the two experiences affect individuals psychologically. Ego-dissolution appears to trigger psychological change but does not typically exceed the psychedelic experience in its duration, while connectedness can be more sustained and is associated with several positive, potentially therapeutic feelings. Conclusions Moreover, the findings of this review have implications for further theory-building about the mechanisms which enable therapeutic effects in psychedelic experience. This in turn might lead to improved models for psychedelic therapy practice. Emphasis on ego-dissolution during the preparation phase and on connectedness during integration is one suggestion presented here, alongside overarching implications for the mental health debate and general practice.
... Both therapeutic research and studies in nonclinical participants have reported that alterations in self-experience during the acute effects of classic psychedelics reliably predict durable and holistic positive change. Higher mystical experience scores have been correlated with better treatment outcomes of psilocybin-assisted therapy for substance use (Bogenschutz et al., 2015;Johnson et al., 2014) and anxiety and depression in cancer patients . Greater experience of oceanic boundlessness also predicted long-term benefits in patients with TRD . ...
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The extremes of human experiences, such as those occasioned by classic psychedelics and psychosis, provide a rich contrast for understanding how components of these experiences impact well-being. In recent years, research has suggested that classic psychedelics display the potential to promote positive enduring psychologic and behavioral changes in clinical and nonclinical populations. Paradoxically, classic psychedelics have been described as psychotomimetics. This review offers a putative solution to this paradox by providing a theory of how classic psychedelics often facilitate persistent increases in well-being, whereas psychosis leads down a "darker" path. This will be done by providing an overview of the overlap between the states (i.e., entropic processing) and their core differences (i.e., self-focus). In brief, entropic processing can be defined as an enhanced overall attentional scope and decreased predictability in processing stimuli facilitating a hyperassociative style of thinking. However, the outcomes of entropic states vary depending on level of self-focus, or the degree to which the associations and information being processed are evaluated in a self-referential manner. We also describe potential points of overlap with less extreme experiences, such as creative thinking and positive emotion-induction. Self-entropic broadening theory offers a heuristically valuable perspective on classic psychedelics and their lasting effects and relation to other states by creating a novel synthesis of contemporary theories in psychology. SIGNIFICANCE STATEMENT: Self-entropic broadening theory provides a novel theory examining the psychedelic-psychotomimetic paradox, or how classic psychedelics can be therapeutic, yet mimic symptoms of psychosis. It also posits a framework for understanding the transdiagnostic applicability of classic psychedelics. We hope this model invigorates the field to provide more rigorous comparisons between classic psychedelic-induced states and psychosis and further examinations of how classic psychedelics facilitate long-term change. As a more psychedelic future of psychiatry appears imminent, a model that addresses these long-standing questions is crucial.
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According to Stocker (in press), seeing in visual experience (visual perception and visual imagery) is organized by Talmyan concept structuring. Here, it is proposed that during seeing in extrovertive visionary experience and extrovertive mystical experience, this visual concept structuring is largely or totally suspended—except for the perspective point ( pp ), which seems to remain in place in all human seeing. Complemented with cognitive-semantic analysis, characterizations of extrovertive visionary experience draw from the writer and philosopher Aldous Huxley, and characterizations of extrovertive mystical experience additionally from the theologian Rudolph Otto and the philosopher Walter Stace. It is also examined how well extrovertive visionary experience and extrovertive mystical experience are captured with altered-state-of-consciousness questionnaires. Potential benefits for the mind from temporary suspension of Talmyan concept structuring are discussed.
Article
Background Clinical studies report preliminary therapeutic effects of classic psychedelic drugs in several psychiatric conditions and international drug trends show increased use of these compounds. However, the epidemiology of classic psychedelic drug use in Scandinavian countries remains sparsely investigated. To this end, we investigated the patterns of use and the subjectively perceived acute and persisting effects of lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), and mescaline, among Danish adults. Methods An anonymous online survey with 152 items was conducted using the secure survey web application REDCap. Results were presented descriptively and as comparisons between psychedelic drugs. Results Five-hundred participants (30.0% female, mean age 34.5 years) were included. Classic psychedelics were mostly used with therapeutic (28.0%) or spiritual (27.2%) intentions. Sixty-seven per cent used classic psychedelics once a year or less. Most participants (56.4%) preferred using psilocybin. Classic psychedelic use was for some individuals, associated with hazardous use of alcohol (39.4%). Among participants with a psychiatric treatment history, 80.9% reported subjective improvements in symptoms following classic psychedelic use. Participants’ most memorable experiences were moderate-to-strong mystical-type experiences (MEQ30 mean ± SD 3.4 ± 1.0; range 1–5) and had positive persisting effects on well-being (mean ± SD 2.1 ± 1.0), social relationships (mean ± SD 1.7 ± 1.2), meaning of life (mean ± SD 1.9 ± 1.1), and mood (mean ± SD 1.8 ± 1.1); range −3 to 3. DMT users experienced significantly greater subjective positive effects. Conclusions Classic psychedelics were mostly used therapeutically or spiritually and had self-reported positive persisting effects, but were also associated with hazardous use of alcohol, among Danish adults. DMT was associated with significantly greater positive effects compared to LSD and psilocybin.
Article
Subjective responses to psychoactive drugs have served as intriguing windows into consciousness as well as useful predictors. Subjective reactions to psychedelic molecules are particularly interesting given how they covary with subsequent improvements associated with psychedelic-assisted treatments. Although links between subjective reactions and decreases in treatment-resistant clinical depression, end-of-life anxiety, and maladaptive consumption of alcohol and nicotine appear in the empirical literature, the measurement of these subjective responses has proven difficult. Several scales developed over many decades show reasonable internal consistency. Studies suggest that many have a replicable factor structure and other good psychometric properties, but samples are often small and self-selected. We review the psychometric properties of some of the most widely used scales and detail their links to improvement in response to psychedelic-assisted treatments. Generally, assessments of mystical experiences or oceanic boundlessness correlate with improvements. Challenging subjective experiences, psychological insight, and emotional breakthroughs also show considerable promise, though replication would strengthen conclusions. We suggest a collaborative approach where investigators can focus on key responses to ensure that the field will eventually have data from many participants who report their subjective reactions to psychedelic molecules in a therapeutic setting. This may aid in predicting improvement amongst targeted conditions and wellbeing.
Article
Psychedelics are psychoactive substances that alter ordinary states of consciousness. The U.S. criminalized ingestion of these drugs approximately 60 years ago and use remains punishable by law. Prior to this time, the substances were differentially declared spiritual sacraments, medicines, and/or party drugs. (Auto)Ethnographies and other research often indicate psychedelic-induced experiences as remarkably personal, necessitating subjective interpretation. Empirical studies exploring patterns across psychedelic encounters are rare, but among the few that exist, users tend to be identified as either pursuing psycho-spiritual enlightenment or self-indulgent amusement. The present paper utilizes narratives collected through 37 in-depth interviews with adults from diverse social backgrounds who report a history of psychedelic consumption in non-clinical settings. The data suggest a potential 4-part categorization based on five factors: named forms of psychedelic substances used, reported frequency of psychedelic ingestions, stated reasons for consumption and desistance, self-imposed rules surrounding use, and descriptions of drug effects and experiences.
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Rationale: Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT2A agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness. Objective: Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters. Methods: Eight subjects received placebo (PL), and 45 ("very low dose, VLD”), 115 ("low dose, LD”), 215 ("medium dose, MD”), and 315 ("high dose, HD”) μg/kg body weight PY. The "Altered States of Consciousness Rating Scale” (5D-ASC), the "Frankfurt Attention Inventory” (FAIR), and the "Adjective Mood Rating Scale” (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined. Results: PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. "General inactivation”, "emotional excitability”, and "dreaminess” were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY. Conclusion: PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health
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Background: Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. Methods: Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a doubleblind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. Results: Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completly replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects. Clustering of HRS items, using either a clinical, mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously. Conclusions: These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT's properties in humans. They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric populations.
Article
The history of research with psychedelic drugs has produced a variety of methods for their use and conflicting claims about results. First came the wave of excitement among experimentalists in the 1950s when it was claimed that lysergic acid diethylamide (LSD) could produce a model psychosis which might be useful in understanding schizophrenia. While this promise was fading, enthusiastic reports about the possibility of LSD as an aid to psychotherapy in the treatment of alcoholism and other psychiatric disorders appeared. All these approaches were represented in 1959 at the first international conference devoted entirely to LSD.1 Since then, there have been at least five more published proceedings of such conferences on various aspects of psychedelic drugs.2-6 The most recent conference on various means of producing states of consciousness was sponsored by the Menninger Foundation and the American Association of Humanistic Psychology on April 7 to 11, 1969, in