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Lysergic Acid Diethylamide (LSD) for Alcoholism: Meta-Analysis of Randomized Controlled Trials


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Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.
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Journal of Psychopharmacology
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DOI: 10.1177/0269881112439253
published online 8 March 2012J Psychopharmacol
Teri S Krebs and Pål Ørjan Johansen
Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials
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DOI: 10.1177/0269881112439253
Alcohol is said to cause more overall harm than any other drug
(Nutt et al., 2010). Alcohol contributes to about 4% of total mor-
tality and about 5% of disability adjusted life-years to the global
burden of disease (Rehm et al., 2009). Despite the often extreme
individual and social consequences of alcohol misuse, many users
find it challenging to stop drinking. Alcoholism, also called alco-
hol dependence, continues to be difficult to treat, and many
patients do not achieve recovery from existing treatments
(Schuckit, 2009).
Numerous clinical investigators have claimed that treating
alcoholics with individual doses of lysergic acid diethylamide
(LSD), in combination with psychosocial interventions, can help
to prevent a relapse of alcohol misuse, for example, by eliciting
insights into behavioural patterns and generating motivation to
build a meaningful sober lifestyle (Dyck, 2008). LSD is well-
known for inducing spectacular and profound effects on the mind
(Henderson and Glass, 1994; Passie et al., 2008). It has previously
been used in standard treatment programs for alcoholism at many
clinics, but, unfortunately, assessments of the clinical value of
LSD have not been based on formal systematic review and meta-
analysis (Mangini, 1998). Hence, we have performed a quantita-
tive evaluation of the effectiveness of LSD for alcoholism, based
on data from randomized controlled clinical trials.
Search strategy and selection criteria
We searched the PubMed and PsycINFO databases (1943–2010),
without language restrictions, using the following terms: LSD,
lysergic, lysergide, psychedelic*, or hallucinogen*; and alcohol*,
addict*, or dependence. We independently inspected the search
results by reading the titles and abstracts. We retrieved each
potentially relevant publication located in the search and assessed
it for inclusion, subsequently examining the reference lists of eli-
gible studies and relevant review articles. We supplemented our
search for trials by contacting experts. If publications lacked
important information, we attempted to contact study investiga-
tors and institutions.
We specified inclusion and exclusion criteria and defined pri-
mary and secondary outcomes in the meta-analysis study proto-
col. We included randomized controlled trials of LSD for
alcoholism, in which control condition involved any type of treat-
ment, including doses of up to 50 mcg LSD as an active control. If
a trial included multiple randomized treatment arms, all partici-
pants in the eligible LSD arms and all participants in the eligible
control arms were pooled for analysis. We excluded participants
with schizophrenia or psychosis from analysis, as psychosis is
recognized as a contraindication for treatment with LSD (Johnson
et al., 2008; Passie et al., 2008).
Data extraction
Both reviewers independently extracted data and rated the risk of
bias of each included trial. Differences between the reviewers
were resolved through discussion. The following were recorded
Lysergic acid diethylamide (LSD) for
alcoholism: meta-analysis of
randomized controlled trials
Teri S Krebs1,2 and Pål-Ørjan Johansen1,2
Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we
performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers
independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified
six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36–2.84;
p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are
discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.
Alcoholism, alcohol-related disorders, hallucinogens, meta-analysis, psychedelics, substance-related disorders
1 Department of Neuroscience, Faculty of Medicine, Norwegian University
of Science and Technology (NTNU), Trondheim, Norway
2 Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Corresponding author:
Pål-Ørjan Johansen, Department of Neuroscience, Faculty of Medicine,
NTNU, N-7489 Trondheim, Norway
439253JOP0010.1177/0269881112439253Krebs and JohansenJournal of Psychopharmacology
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2 Journal of Psychopharmacology 0(0)
from each trial where available: intervention characteristics (LSD
dose, control condition, additional treatments); participant charac-
teristics (number, gender, age, inclusion and exclusion criteria);
information given to the participants on the study and the effects
of LSD; trial characteristics (publication year, location, funding
source); outcomes (primary and secondary outcomes, time of
follow-up, method of outcome assessment); evaluation of each
domain of the Cochrane risk of bias assessment tool (sequence
generation, allocation concealment, blinding, incomplete out-
come data, selective outcome reporting) (Higgins and Altman,
2008). Primary outcomes were alcohol misuse, defined as alcohol
use or consequences of alcohol use, as systematically measured
by interview or self-report at the first reported follow-up.
Secondary outcomes were alcohol misuse at short-term (approxi-
mately 3 months), medium-term (approximately 6 months) and
long-term (approximately 12 months) follow-up. We also
extracted data on abstinence, reports of adverse events and any
other secondary outcomes.
Data analysis
Categorical data on alcohol misuse were dichotomized into
‘improved’ or ‘not improved’. We counted as ‘improved’ outcome
categories indicating clear, substantial improvement in alcohol
misuse. Dichotomous and continuous outcome data were pooled
using the generic inverse variance method with a random effects
model. We calculated the effects of intervention results with esti-
mates of pooled odd ratios (ORs) and 95% confidence intervals
(CI) using Review Manager 5.0 (Nordic Cochrane Centre,
Cochrane Collaboration). The percentage of outcome heterogene-
ity attributable to between-trial heterogeneity was assessed by the
I2 statistic. Participants lost to follow-up were counted as not
improved. In a post hoc analysis of trials with available dichoto-
mized data, we calculated the pooled benefit difference on
improvement in alcohol misuse at first follow-up and also calcu-
lated the number needed to treat. The benefit difference (also
known as the risk difference) for each trial is the percentage of
improved patients in the LSD group minus the percentage of
improved patients in the control group. The number needed to
treat is the inverse of the pooled benefit difference and provides an
estimate of the average number of patients needed to be treated
with LSD rather than without LSD to achieve one additional
patient with improved outcome on alcohol misuse.
Description of studies
We identified six eligible randomized controlled 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), including
additional reports on three of the trials (Kurland et al., 1971;
Ludwig et al., 1970; Smart et al., 1967). Details of the search are
shown in Figure 1, details of the included studies are shown in
Tables 1 and 2. Among the excluded studies were five non-
randomized controlled trials (Ables and Eng, 1967; Ables et al.,
1970; Jensen, 1962; Jensen, 1963; Van Dusen et al., 1967), one
quasi-randomized controlled trial (allocation by alternating
assignment) (Osmond et al., 1967), two randomized
controlled trials without any outcome data related to alcohol use
(both measured only general psychological variables) (Denson
and Sydiaha, 1970; Ditman et al., 1970), and one randomized con-
trolled trial without extractable outcome data on alcohol misuse
(this trial reported only ‘no statistically significant difference’
between LSD and control groups on alcohol misuse at 12 months
follow-up) (Johnson, 1969).
The six eligible trials included a total of 536 adults; of these
325 (61%) had been randomly assigned to receive full-dose LSD
and 211 (39%) to a control condition. Participants were male in-
patients, except for two females and a small number of day-care
patients in one of the trials (Smart et al., 1966). All participants
were seeking treatment for ‘alcoholism’ as their primary problem
and had been admitted to alcohol-focused treatment programs
before clinical trial recruitment, see Table 1. Note, the DSM-I
defined alcoholism as a ‘well established addiction to alcohol
without recognizable underlying disorder’ (American Psychiatric
Association, 1952).
Among the reported exclusion criteria, trials excluded poten-
tial volunteers with ‘psychiatric complications’ (Bowen et al.,
1970), with a ‘past history of schizophrenic reaction or severe
affective disorder’ (Hollister et al., 1969), or overt psychosis
(Ludwig et al., 1969; Smart et al., 1966; Tomsovic and Edwards,
1970). One trial included a subgroup of patients with schizophre-
nia (Tomsovic and Edwards, 1970), which we excluded from the
meta-analysis. Two trials included additional non-randomized
control groups or non-randomized sub-studies, which we also
excluded from the meta-analysis (Bowen et al., 1970; Tomsovic
and Edwards, 1970).
Single oral doses of LSD ranged from approximately 210 mcg
(3 mcg/kg) to 800 mcg, with a median dose of 500 mcg, see Table
1. No studies used multiple doses of LSD. The control conditions
included low-dose LSD (25 mcg or 50 mcg), d-amphetamine (60
4275 records identified through
database searching
6 additional records identified
through other sources
4090 records excluded
based on titles or
68 records flagged for detailed
9 records included in meta-analysis
(6 trials)
4158 records screened after
duplicates removed
18 open-label or case
6 non-randomized
(5 trials)
5 quasi-randomized
(1 trial)
7 randomized, but no
extractable outcome
data (3 trials)
23 reviews or other
59 records excluded:
Figure 1. Selection of trials for meta-analysis.
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Krebs and Johansen 3
mg), ephedrine sulphate (60 mg), or non-drug control conditions,
see Table 1.
Before the experimental drug session, all participants had
equivalent treatment within each trial; however, between the trials
the preparation for the experimental drug session varied from
minimal to extensive, with most studies providing brief orienta-
tion, often with little or no description of the possible effects of
LSD. During the experimental drug session, the most common
treatment was simple observation with brief reassurance by clinic
staff, only three studies included treatment groups who received
clinical interviews, psychotherapy, or active guidance. In four
studies, the experimental drug session took place in comfortable
surroundings with music available. After the experimental drug
session, only one study included multiple review sessions focused
on discussing the experiences during the drug session, while the
other studies provided only one brief review session or no review
session at all. See Table 2 and the original study publications for
details of the treatment protocols.
Each trial used clearly defined, standardized methods to assess
outcomes on alcohol misuse, although methods varied between
trials, see Table 1. Extracted dichotomous or categorical outcomes
included maintained abstinence from alcohol, alcohol use rating
scales, or composite alcohol use and social adjustment rating
scales; the one continuous outcome was percentage change in
time abstinent from alcohol. Based on examining each categorical
scale, outcome categories labelled ‘slight or questionable’
(Tomsovic and Edwards, 1970), ‘moderate’ (Ludwig et al., 1969),
or ‘fair’ (Bowen et al., 1970) were counted as ‘unimproved’; how-
ever, note that including these outcome categories indicating pos-
sibly trivial improvement as ‘improved’ does not substantially
change the results.
Effect of LSD on alcohol misuse
The pooled odds ratio on improvement in alcohol misuse between
the LSD and control groups was 1.96 (95% CI, 1.36–2.84; p =
0.0003) at the first reported follow-up, see Figure 2. Among the
five trials with dichotomized data, 185 of 315 (59%) LSD patients
and 73 of 191 (38%) control patients were improved at the first
reported follow-up, and the pooled benefit difference was 16%
(95% CI, 8%−25%; p = 0.0003), or, equivalently, the number
needed to treat is six. Including an estimated dichotomized
outcome for the one trial that reported only continuous outcome
Table 1. Included randomized controlled trials of LSD for alcoholism.
LSD (n) Control (n) Blinding of
patients, staff,
outcome assessors
Alcohol misuse outcome,
criteria for improvement
(months follow-up)
at first
et al., 1966
800 mcg
60 mg
sulfate (10) or
no drug (10)
Male and female
alcoholics, ’all
had a long history
of excessive and
uncontrolled drinking’
Drinking History
% change in time
continuous (6 mo)
100% ARF,
Canada (NR)
et al., 1969
600 mcg
60 mg
Male veterans, ’acute
alcoholic episode’
within 2 weeks of
admission, ’all were
problem drinkers’
45, range
Drinking Behaviour
Interview, score 10,
’Abstinent’ or ’Social’
drinking (2, 6 mo)b
81% LSD;
VA Hospital,
Palo Alto,
et al., 1969
3 mcg/kg,
~210 mcg
No drug, sit
alone and write
for 3 hr (44)
until LSD session,
Male alcoholics, up
to four previous
admissions for
treatment of alcoholism
Abstinence (1, 3 mo);
Behavior Rating Scale,
change score 5, ’Much
improved’ (6, 12 mo)b
100% MSH,
Madison, WI,
et al., 1970
500 mcg
25 mcg LSD
Double-blind, not
stated if assessors
Male veterans,
voluntarily applied for
treatment of alcoholism
Adjustment Scale, score
6, ’Good adjustment’
(12 mo)
100% VA Hospital,
Topeka, KS,
et al., 1970
450 mcg
50 mcg LSD
Male alcoholics,
voluntarily applied for
treatment of alcoholism
NR Drinking Behaviour
Scale, score 8,
’Minimal departure from
total abstinence’ (6, 12
88% LSD;
Tomsovic &
Edwards, 1970
500 mcg
Treatment as
usual (45)
Double-blind until
LSD session, self-
report assessmentc
Male alcoholics,
average 12 years of
problem drinking
Mean 43 Drinking Adjustment
Scale, no more than
1 drinking episode in
follow-up period, ’Much
improved’ (3, 6, 12 mo)b
92% LSD;
VA Hospital,
ARF: Alcoholism and Drug Addiction Research Foundation; MPRC: Maryland Psychiatric Research Center; MSH: Mendota State Hospital; NIMH: National Institute of Mental
Health; NR: not reported; VA: Veterans Administration.
aAll participants were recruited after admission to alcoholism treatment programs.
bProvided data on abstinence from alcohol.
cAssessment also included interview of close relative.
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Table 2. Details of treatment programs in included trials of LSD for alcoholism.
Treatment program
(approximate length
in days)
Preparation for
LSD session
Treatment during
experimental session
Setting of
session room
Aftercare related to
experimental session
et al., 1966
Individual and group
therapy within a
therapeutic community
Brief orientation; not
told name of LSD nor
that an active control
drug was used
3 h interview, followed by
occasional observation
No music or visual
stimuli; all patients
strapped to bed by
waist belt
One follow-up
review session with
et al., 1969
Brief counselling on alcohol
misuse; focus on alcohol
withdrawal (7)
Brief orientation; not
told name of LSD nor
that an active control
drug was used
Brief supportive reassurance;
emphasis on self-examination
Music, comfortable
None mentioned;
discharged within
48 hours; overall
’little or no specific
et al., 1969
Highly structured intensive
milieu therapy, including
group therapy (30)
Brief orientation;
minimal discussion of
LSD effects
3 h (a) psychotherapy, (b)
hypnosis + psychotherapy, or
(c) silent observation, followed
by occasional observation
Not described No follow-up with
session therapist
et al., 1970
Interpersonal skill training
in groups (60)
Several group
orientation lectures on
LSD effects
Supportive reassurance; emphasis
on non-verbal introspection
Music, flowers, pictures,
’tasteful furniture’, two
quiet rooms
None mentioned
et al., 1970
Intensive individual
psychotherapy (49)
Extensive individual
preparation for LSD
Guidance aimed at eliciting
a ’peak or transcendental
Music, flowers,
pictures, ’comfortable
living room’
Multiple follow-up
review sessions
& Edwards,
Group psychotherapy (90) Lecture and reading
material; review of
problems and treatment
Supportive reassurance; not
encouraged to talk extensively
Music, flowers,
pictures, scenic view,
quiet room
One follow-up
review session in
group therapy
Figure 2. Improvement on alcohol misuse at the first available follow-up after LSD versus control treatments.
aContinuous outcome data.
data does not change the calculated pooled benefit difference or
number needed to treat.
There was a significant beneficial effect of LSD on alcohol
misuse in the short-term and medium-term, which was not statisti-
cally significant in the long-term, see Figure 3. At short-term fol-
low-up (2–3 months post-treatment), three trials reported
treatment response, and the pooled odds ratio between the LSD
and control groups was 1.85 (95% CI, 1.14–3.00; p = 0.01). At
medium-term follow-up (6 months post-treatment), five trials
reported treatment response, and the pooled odds ratio between
the LSD and control groups was 1.66 (95% CI, 1.11–2.47; p =
0.01). At long-term follow-up (12 months post-treatment), four
trials reported treatment response, and the pooled odds ratio
between the LSD and control groups was 1.19 (95% CI, 0.74–
1.90; p = 0.47).
Heterogeneity of the between-trial treatment outcome was
negligible in the pooled comparisons for alcohol misuse at the first
reported follow-up, short-term follow-up and medium-term fol-
low-up (I2 = 0%, for all p ≥ 0.60 for the χ2 test), and heterogeneity
was low at long-term follow-up (I2 = 15%, p = 0.32 for the χ2 test).
Effect of LSD on abstinence from alcohol
Among the three trials that reported maintained abstinence from
alcohol use, there was a beneficial effect of LSD at the first reported
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Krebs and Johansen 5
follow-up (1–3 months post-treatment) (OR, 2.07; 95% CI, 1.26–
3.42; p = 0.004) and short-term follow-up (2–3 months post-treat-
ment) (OR, 1.80; 95% CI, 1.07–3.04; p = 0.03), which was not
statistically significant at medium-term follow-up (6 months post-
treatment) (OR, 1.42; 95% CI, 0.65–3.10; p = 0.38), see Figure 4.
Heterogeneity of the between-trial treatment outcome was
negligible in the pooled comparisons for abstinence at first
reported follow-up and short-term follow-up (I2 = 0%, for both
p ≥ 0.38 for the χ2 test), while heterogeneity was moderate at
medium-term follow-up (I2 = 44%, p = 0.41 for the χ2 test).
Adverse events
Five trials reported a total of eight acute adverse reactions to LSD,
without any lasting harmful effects. Trial investigators did not
specifically mention whether there were adverse events among
participants in the control conditions. During the LSD experience,
two people ‘acted bizarrely’ (Tomsovic and Edwards, 1970), one
person became agitated (Hollister et al., 1969), another person had
a grand mal seizure during a period of agitation (this patient had a
history of alcohol withdrawal seizures and had been abstinent
from alcohol for only a few days) (Hollister et al., 1969) and two
people had unspecified ‘adverse reactions’ (Ludwig et al., 1969).
In the days after LSD, one person experienced transient ‘moderate
confusion’ (Hollister et al., 1969) and one person had a transient
‘adverse reaction’ (Pahnke et al., 1970). Additionally, investiga-
tors in one trial reported mild adverse reactions to LSD in a small
number of participants, including nausea, vomiting and ‘moderate
agitation’ that was relieved by social support, relaxation, or chang-
ing the lights and music (Hollister et al., 1969). Furthermore, in
one trial, about a third of the participants who received LSD
reported briefly experiencing ‘any perceptual thought or feeling
experience which impressed the patient with its vividness and
which was clearly related to the [LSD] experience’ on one or a
few occasions within a year after LSD, typically after using alco-
hol (Tomsovic and Edwards, 1970), while participants in another
trial specifically did not mention such experiences at follow-up
(Hollister et al., 1969).
Other outcomes
Other reported trial outcomes were difficult to assess and sum-
marize in detail, owing to large variation in the approaches
between the trials and lack of data for statistical analysis. However,
Figure 3. Improvement in alcohol misuse at short-, medium- and long-term follow-up after LSD versus control treatments.
aContinuous outcome data.
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no trials reported any detrimental effects of LSD on psychosocial
functioning or other outcomes. Of note, two of the three trials that
reported data on employment found statistically significant
improvements in employment in participants who received LSD
compared to those assigned to control conditions (Hollister et al.,
1969; Smart et al., 1966) but not Ludwig et al., (1969).
Risk of bias
Based on the definitions from the Cochrane risk of bias assess-
ment tool (Higgins and Altman, 2008), no trials were judged to
have a high risk of bias related to sequence generation or alloca-
tion concealment. All trials used random assignment and
attempted to conceal allocation; however, most trials did not
describe methods in detail. Two trials were judged to have a high
risk of bias due to inadequate blinding of patients or staff because
treatment allocation was concealed only until the time of the
possible LSD session (Ludwig et al., 1969; Tomsovic and
Edwards, 1970); the other four trials used double-blind designs
with active placebos. All trials were judged to have low or an
unclear risk of bias due to blinding of outcome assessment; in
four trials outcome was assessed by treatment-independent, allo-
cation-blind interviewers (Hollister et al., 1969; Ludwig et al.,
1969; Pahnke et al., 1970; Smart et al., 1966), in one trial the
outcome assessor was not explicitly described as allocation-
blind (Bowen et al., 1970) and in the remaining trial outcome
assessment was collected by self-report questionnaire, con-
firmed by telephone interview with a close relation (Tomsovic
and Edwards, 1970). Two trials were judged to have a high risk
of bias due to incomplete outcome data because participants
were excluded if they did not complete the intended treatment
program (Bowen et al., 1970) or if they received additional
doses of LSD (Pahnke et al., 1970). Retention rates were gener-
ally high, see Table 1, but two studies had substantial rates of
missing participants at follow-up (Hollister et al., 1969;
Tomsovic and Edwards, 1970). However, authors of both of
these trials expressed that missing participants had probably
relapsed to problem alcohol use, consistent with the strategy of
considering missing participants as unimproved. Two trials were
judged to have a high risk of bias because of possible selective
outcome reporting (Hollister et al., 1969; Ludwig et al., 1969);
both of these trials de-emphasized evidence for a treatment
effect at short-term follow-up and gave more detailed outcome
data on alcohol misuse at medium-term or late-term follow-up;
note, we were not able to obtain the protocol for any of the trials.
One trial was judged to have a high risk of bias due to baseline
imbalance (Pahnke et al., 1970); in this trial, participants who
received full-dose LSD were less likely than control participants
to be divorced, and more likely to have four or less prior admis-
sions for alcohol treatment, or to have graduated from high-
school. Importantly, however, also in this trial the treatment
groups were matched on baseline ratings of alcohol misuse.
Figure 4. Maintained abstinence from alcohol after LSD versus control treatments.
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Krebs and Johansen 7
Sensitivity analysis
For the primary outcome, improvement on alcohol misuse at first
follow-up, the beneficial effect of LSD remained statistically sig-
nificant (p ≤ 0.02) when excluding any two of the four larger tri-
als, with or without excluding either or both of the two smaller
trials. In a series of post hoc sensitivity analyses, excluding all
trials with a high risk of bias on each domain of the Cochrane risk
of bias assessment tool did not substantially change the primary
outcome. In particular, the effect of LSD increased and remained
significant when we excluded the two trials that used non-blinded
control conditions without an active placebo. Furthermore, the
primary outcome did not change when we limited analysis to the
four trials reporting outcome specifically on alcohol use, rather
than composite scores of alcohol use and social functioning, or
when we excluded the two trials with lower retention rates.
The findings on secondary outcomes of alcohol misuse at
short-term and medium-term follow-up and abstinence at first and
short-term follow-up are more sensitive to removing trials. In par-
ticular, none of the secondary outcomes remain statistically sig-
nificant (p ≥ 0.06) after removing the trial with the most favourable
effect of LSD in each respective analysis. Note that the analyses
of secondary outcomes are based on only three to five trials each.
In a pooled analysis of six randomized controlled clinical trials, a
single dose of LSD had a significant beneficial effect on alcohol
misuse at the first reported follow-up assessment, which ranged
from 1 to 12 months after discharge from each treatment program.
This treatment effect from LSD on alcohol misuse was also seen
at 2 to 3 months and at 6 months, but was not statistically signifi-
cant at 12 months post-treatment. Among the three trials that
reported total abstinence from alcohol use, there was also a sig-
nificant beneficial effect of LSD at the first reported follow-up,
which ranged from 1 to 3 months after discharge from each treat-
ment program.
The findings from randomized controlled trials of a sustained
treatment effect of a single dose of LSD on alcohol misuse, which
may fade within 12 months, are consistent with many reports of
clinical experience and with data from most non-randomized con-
trolled and open-label studies of LSD for alcoholism (reviewed in
Mangini (1998)). In particular, a quasi-randomized trial reported
beneficial effects of LSD on alcohol misuse at 3 months post-
treatment (Osmond et al., 1967). Additionally, four non-
randomized controlled studies reported beneficial effects of LSD
on alcohol misuse at follow-up periods ranging from 6 to 18
months. However, these studies were poorly described (Ables and
Eng, 1967; Ables et al., 1970; Jensen, 1962; Jensen, 1963). Also
consistent with our findings, three controlled studies, excluded
from this meta-analysis because the control groups were non-ran-
domized (Bowen et al., 1970; Van Dusen et al., 1967) or because
of lack of extractable data (Johnson, 1969), reported no significant
treatment effect of a single dose of LSD on alcohol misuse at 12
to 18 months follow-up. Importantly, in the Bowen et al. (1970)
and Van Dusen et al. (1967) studies, the comparison group did not
volunteer to possibly receive LSD, probably creating selection
bias (see, for example, Ditman et al. (1970) on differences between
alcoholics who volunteer and those who decline to participate in
an LSD study), and in the Johnson (1969) study all patients were
administered the tranquilizer chlorpromazine during the acute
LSD effects, probably attenuating the LSD effects. Additionally,
in a randomized controlled trial of a single dose of LSD for heroin
addiction, daily urine test data covering the entire follow-up
period showed a significantly lower rate of relapse in the LSD
group compared to no drug group at 3, 6, 9 and 12 months post-
treatment (Savage and McCabe, 1973).
Given the evidence for a beneficial effect of LSD on alcohol-
ism, it is puzzling why this treatment approach has been largely
overlooked. Based on reviewing the literature, we have four sug-
gestions for why this happened. First, the randomized controlled
trials were underpowered and most did not reach statistical sig-
nificance when considered individually. Second, trial authors
expected unrealistic results and tended to discount moderate or
short-term effects. Third, early non-randomized clinical trials
were poorly described and had methodological problems, creating
the mistaken impression that well-designed studies did not exist.
Finally, the complicated social and political history of LSD led to
increasing difficulties in obtaining regulatory approval for clinical
trials (reviewed in Mangini (1998)).
The effectiveness of a single dose of LSD compares well with
the effectiveness of daily naltrexone, acamprosate, or disulfiram
(Krampe and Ehrenreich, 2010; Rösner et al., 2010a, 2010b), see
Table 3 for data from recent meta-analyses of these three com-
monly prescribed, approved medications for reducing relapse in
alcohol dependence.
Table 3. Data from recent meta-analyses of randomized controlled clinical trials on the effectiveness of LSD, naltrexone, acamprosate and disulfiram
for alcoholism or alcohol dependence.
Outcome LSD, single dose Naltrexone, daily Acamprosate, daily Disulfiram, daily
Benefit difference
(95% CI) NNT
Benefit difference
(95% CI) NNT
Benefit difference
(95% CI) NNT
Benefit difference
(95% CI) NNT
Improvement on alcohol misuse,
or return to heavy drinking
16% (8%, 25%) 6 11% (7%, 15%) 9 1% (-2%, 5%) 100 Not reported
Maintained abstinence, or
return to any drinking
15% (4%, 25%) 7 3% (1%, 6%) 33 11% (7%, 15%) 9 11% (-1%, 22%) 9
LSD outcomes are at first follow-up after single dose and are compared to no drug or active placebo. Naltrexone and acamprosate outcomes are during daily drug treat-
ment and are compared to placebo. Disulfiram outcomes are during daily unsupervised drug treatment and are compared to other or no treatment. Data on naltrexone,
acamprosate and disulfiram extracted from published meta-analyses (Rösner et al., 2010a, 2010b; Krampe and Ehrenreich, 2010). Pooled benefit differences calculated
using a random-effects, inverse variance method. Benefit difference = % patients with beneficial outcome in experimental – % patients with beneficial outcome in con-
trol. Number needed to treat (NNT) = 1/(benefit difference).
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8 Journal of Psychopharmacology 0(0)
Regarding the effects of the LSD experience, investigators of
one trial noted, ‘It was rather common for patients to claim sig-
nificant insights into their problems, to feel that they had been
given a new lease on life, and to make a strong resolution to dis-
continue their drinking’ (Ludwig et al., 1969). Investigators of
another trial noted, ‘It was not unusual for patients following their
LSD experience to become much more self-accepting, to show
greater openness and accessibility, and to adopt a more positive,
optimistic view of their capacities to face future problems’ (Bowen
et al., 1970). The subjective effects and neurobiological mecha-
nisms of LSD are similar to other psychedelic substances such as
mescaline (contained in peyote and other psychedelic cactus),
psilocybin (magic mushrooms) and dimethyltryptamine (aya-
huasca) that have been used by humans for thousands of years
(Bruhn et al., 2002; McGlothlin, 1964), and in clinical studies the
effects of psychedelics are often regarded as highly valued and
meaningful (Griffiths et al., 2006; Grob et al., 2011; Studerus
et al., 2011). Regular consumption of peyote and ayahuasca have
been claimed by indigenous groups to be helpful in maintaining
sobriety from alcohol and other addictive drugs (Albaugh and
Anderson, 1974; Fábregas et al., 2010).
Estimates of the rate of adverse events of LSD in alcoholics
and others should include data from non-randomized as well as
randomized trials. Based on extensive animal research and human
experience, there is now widespread recognition that LSD and
similar psychedelic substances are physically safe, but acute psy-
chiatric adverse events such as anxiety and confusion should be
anticipated, and LSD administration should occur in a comforta-
ble environment with informed participants (Johnson et al., 2008;
Passie et al., 2008).
Several matters in this meta-analysis deserve discussion. First,
trials typically lacked detailed descriptions of the populations
studied, including diagnosis methods. However, all participants
were recruited into the trials after admission to alcohol treatment
programs with a primary diagnosis of alcoholism, making it likely
that the patients are representative of typical clinical practice.
Second, there were not enough trials to examine the effect of LSD
dose or other treatment variables; all of the trials used a high or
very high dose of LSD and employed different treatment frame-
works. Third, it is possible that additional randomized controlled
trials were never published or were missed by our literature
search. Fourth, three trials either concealed that LSD might be
used (Hollister et al., 1969; Smart et al., 1966) or gave very little
information about its likely effects (Ludwig et al., 1969), and in
two of these trials participants were left alone in a room during
much of the LSD effects (Ludwig et al., 1969; Smart et al., 1966);
including people who might be reluctant to participate in a trial of
LSD or who were unprepared for the LSD effects may have atten-
uated the treatment effect and increased the risk of adverse events.
Fifth, blinding is a common problem to clinical trials of active
interventions, including most pharmacological and behavioural
treatments; most trials included in this meta-analysis attempted to
minimize risks of bias related to blinding by using active place-
bos and/or using explicitly treatment-independent, allocation-
blind interviewers for outcome assessment. However, the use of
low-dose LSD as an active placebo in two of the trials may have
attenuated the between-group treatment effect. Finally, primary
outcome measures on improvement in alcohol misuse varied
between trials; however, all of the clinical trials used standard-
ized questionnaires. Additionally, three trials also reported data
on the same clearly-defined outcome: maintained abstinence
from alcohol use.
It is uncommon for a psychiatric drug to have a positive treat-
ment effect for months after a single dose. Indeed, investigators of
one LSD trial noted, ‘most alcoholics report a waning of the initial
inspiration, euphoria, and good intentions gleaned from the LSD
experience when they are again confronted with the former
stresses and difficulties in their lives’ (Bowen et al., 1970). As
suggested by many investigators, repeated doses of LSD – for
example weekly or monthly – might elicit more sustained effects
on alcohol misuse than a single dose of LSD (Bowen et al., 1970;
Osmond et al., 1967; Savage and McCabe, 1973; Smart et al.,
1966). We need further data on whether subgroups of individuals
exist for whom LSD present an increased beneficial effect or risk
for adverse events. Future clinical trials could combine a range of
doses of LSD with current evidence-based alcohol relapse preven-
tion treatments. As an alternative to LSD, it may be worthwhile to
evaluate shorter-acting psychedelics, such as mescaline, psilocy-
bin, or dimethyltryptamine.
This work was supported by the Research Council of Norway (grant num-
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... Dozens of clinical trials demonstrate promise for psychedelic-assisted therapy as an intervention for psychological and behavioral challenges that require significant cognitive and motivational shifts to produce change. For instance, prior research finds potential benefits for psychedelic-assisted therapy for promoting smoking cessation (Johnson et al., 2017;Noorani et al., 2018), alcohol cessation (Bogenshutz et al., 2015Garcia-Romeu et al., 2019;Krebs & Johansen, 2012;Nielson et al., 2018), as well as alleviating depression and anxiety (Davis et al., 2020a(Davis et al., , 2020bGriffiths et al., 2016;Ross et al., 2016), obsessive compulsive disorder (Moreno et al., 2006), end of life distress (Griffiths et al., 2016), and post-traumatic stress disorder (Krediet et al., 2020). The mechanism behind these benefits for dramatic behavioral change lies in evidence suggesting that psychedelicassisted therapy can engender profound experiences which facilitate long-lasting positive changes in attitudes, mood, altruism, behavior, psychological functioning, life satisfaction, and key personality domains such as openness (Griffiths et al., 2008MacLean et al., 2011). ...
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... A meta-analyses of early studies of LSD for AUD found that following LSD administration, 59% of participants were significantly improved at 1 month post-LSD follow-up and alcohol use remained significantly decreased at 6-month follow-up, compared to decreased use in only 38% of control participants [52]. A survey of individuals with AUD found that following non-clinical psychedelic use, 83% reported no longer meeting AUD criteria [53]. ...
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... Interest in psychedelics, compounds with mixed serotonin receptor agonist actions, such as psilocybin or lysergic acid diethylamide (LSD) as potential therapeutics for psychiatric disorders, has re-emerged during the last decade (Carhart-Harris and Goodwin, 2017), but the idea of using them to treat problematic alcohol use has its roots in 1950s (Dyck, 2006). A recent meta-analysis investigated these earlier clinical studies and, based on the results of six randomized studies with more than 500 participants, reported that a single dose of LSD is associated with reductions in alcohol misuse lasting even up to 12 months (Krebs and Johansen, 2012). A more recent small proof-of-concept trial with psilocybin also had similar results, showing reductions in both amount of alcohol drinking and in the number of heavy drinking days (Bogenschutz et al., 2015). ...
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Abstract Background: Psychedelics, like lysergic acid diethylamide (LSD), are again being studied as potential therapies for many neuropsychiatric disorders, including addictions. At the same time, the acute effects of psychedelics on rewarding behaviours have been scarcely studied. Aims: The current study aimed to clarify if LSD decreases binge-like ethanol drinking in mice, and whether the observed acute effects on ethanol consumption are generalizable to a natural reinforcer, sucrose, and if the effects resulted from aversive or reward-attenuating effects caused by LSD. Methods: The effects of acute LSD were examined using 2-bottle choice intermittent ethanol (20%) and sucrose drinking (10%), discrete-trial current-intensity threshold method of intracranial self-stimulation and short-term feeding behaviour assay in C57BL/6 male mice. Results: The results showed that acute 0.1 mg/kg, but not 0.05 mg/kg, dose (i.p.) of LSD reduced 2-h intermittent ethanol drinking transiently without any prolonged effects. No effects were seen in intermittent 2-h sucrose drinking. The tested LSD doses had neither effect on the intracranial self-stimulation current-intensity thresholds, nor did LSD affect the threshold-lowering, or rewarding, effects of simultaneous amphetamine treatment. Furthermore, LSD had small, acute diminishing effects on 2-h food and water intake. Conclusions: Based on these results, LSD decreases binge-like ethanol drinking in mice, but only acutely. This effect is not likely to stem from reward-attenuating effects but could be in part due to reduced consummatory behaviour.
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Existing pharmacological treatments for psychiatric disorders have demonstrated limited efficacy, delayed onset of action, and significant burden of side effects. Recent findings from human studies with psychedelics have shown promise, demonstrating rapid and sustained clinical benefits of these compounds for a variety of psychiatric disorders. Classical psychedelics have a rich history and some of these compounds have been used in shamanic and spiritual ceremonies for millennia. The psychoactive effects of these drugs, particularly on human consciousness, have generated great scientific curiosity, and early research on psychedelics suggested their clinical benefits for psychiatric conditions, including alcohol use disorders and anxiety and depressive symptoms in terminal illness and life-threatening conditions. Since the 1990s, after a period of dormancy that followed the criminalization of psychedelic drugs since the Controlled Substance Act of 1970, the continued interest in their unique psychoactive effects along with the pursuit for novel and more effective treatments in psychiatry have led to a renewed interest in research on these compounds. While preliminary findings on psychedelics are encouraging, current evidence is still insufficient to support extensive use of these drugs routinely. Long-term safety and efficacy of these compounds remain unclear, and several clinical trials are underway and may add clarity to these questions. Therefore, this article intends to provide an overview of the evidence to date on psychedelic drugs – particularly psilocybin, MDMA, and LSD – for the treatment of psychiatric disorders.
Substance-related disorders are complex psychiatric disorders that are characterized by continued consumption in spite of harmful consequences. Addiction affects various brain networks critically involved in learning, reward, and motivation, as well as inhibitory control. Currently applied therapeutic approaches aim at modification of behavior that ultimately leads to decrease of consumption or abstinence in individuals with substance use disorders. However, traditional treatment methods might benefit from recent neurobiological and cognitive neuroscientific research findings. Novel cognitive-behavioral approaches in the treatment of addictive behavior aim at enhancement of strategies to cope with stressful conditions as well as craving-inducing cues and target erroneous learning mechanisms, including cognitive bias modification, reconsolidation-based interventions, mindfulness-based interventions, virtual-reality-based cue exposure therapy as well as pharmacological augmentation strategies. This review discusses therapeutic strategies that target dysregulated neurocognitive processes associated with the development and maintenance of disordered substance use and may hold promise as effective treatments for substance-related disorders.
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Tässä kirjoituksessa käsittelemme ihmisen biologisen evoluution historiaa ja teknologisen kehityksen luomia haasteita ihmiskunnalle. Kirjoituksemme keskiössä on transhumanistisessa filosofiassa pitkään keskusteltu ajatus ihmisaivojen ”muuttamisesta” digitaaliseen muotoon, ja mitä tämän uuden ”digitaalisen ihmisen” luominen merkitsisi ihmiskunnan tulevaisuuden, ihmisten tietoisten kokemusten ja spirituaalisuuden näkökulmasta. Avainsanat: evoluutio, tekoäly, aivoemulaatioteknologia, spirituaalisuus, tietoisuus
This manuscript reviews research suggesting that classic psychedelics (5-HT2A receptor agonists) are effective in treating addictions including tobacco use disorder. I review historical research from the 1950s to 1970s suggesting that classic psychedelics are associated with addiction recovery across pharmacologically distinct drugs of addiction. I then review anthropological reports about ceremonial use of classic psychedelics and epidemiological studies that are consistent with anti-addiction efficacy. I review modern research using psilocybin in the treatment of alcohol use disorder and tobacco use disorder. Both lines of research show high success rates in preliminary studies. General anti-addiction efficacy across a variety of classes of addictive drugs is consistent with the notion that the persisting positive behavior change prompted by psychedelic therapy is due to amplification of psychotherapeutic processes. Future research should examine classic psychedelic treatment of additional substance use disorders including for opioids, cocaine, methamphetamine, and cannabis, and other disorders broadly characterized as addictions (e.g., obesity, problem gambling, hypersexual disorder). Future research should also explore addiction treatments with other classic psychedelics including LSD, mescaline, DMT, 5-MeO-DMT, and yet-to-be-discovered compounds. Experimental research is also needed to test different protocols for the delivery of classic psychedelic therapy for addictions. Given the staggering society costs of substance use disorders, including the mortality caused by tobacco smoking, it is critical that public funding be made available for scientists to follow up on promising early findings of classic psychedelics in addiction treatment. The costs and risks of not conducting such research are too great.
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BACKGROUND: Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate. OBJECTIVE: To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents. CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW: We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, Embase and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials. SELECTION CRITERIA: All double-blind randomised controlled trials (RCTs) which compare the effects of acamprosate with placebo or active control on drinking-related outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data (IPD) meta-analyses were used to verify the primary effectiveness outcomes. MAIN RESULTS: 24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (P = 0.861). AUTHORS' CONCLUSIONS: Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment
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Proper assessment of the harms caused by the misuse of drugs can inform policy makers in health, policing, and social care. We aimed to apply multicriteria decision analysis (MCDA) modelling to a range of drug harms in the UK. Method Members of the Independent Scientific Committee on Drugs, including two invited specialists, met in a 1-day interactive workshop to score 20 drugs on 16 criteria: nine related to the harms that a drug produces in the individual and seven to the harms to others. Drugs were scored out of 100 points, and the criteria were weighted to indicate their relative importance. Findings MCDA modelling showed that heroin, crack cocaine, and metamfetamine were the most harmful drugs to individuals (part scores 34, 37, and 32, respectively), whereas alcohol, heroin, and crack cocaine were the most harmful to others (46, 21, and 17, respectively). Overall, alcohol was the most harmful drug (overall harm score 72), with heroin (55) and crack cocaine (54) in second and third places. Interpretation These findings lend support to previous work assessing drug harms, and show how the improved scoring and weighting approach of MCDA increases the differentiation between the most and least harmful drugs. However, the findings correlate poorly with present UK drug classification, which is not based simply on considerations of harm.
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Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
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Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate.
LSD's short but colorful history in North America carries with it the distinct cachet of counterculture and government experimentation. The truth about this mind-altering chemical cocktail is far more complex—and less controversial—than generally believed. Psychedelic Psychiatry is the tale of medical researchers working to understand LSD’s therapeutic properties just as escalating anxieties about drug abuse in modern society laid the groundwork for the end of experimentation at the edge of psychopharmacology. Historian Erika Dyck deftly recasts our understanding of LSD to show it as an experimental substance, a medical treatment, and a tool for exploring psychotic perspectives—as well as a recreational drug. She recounts the inside story of the early days of LSD research in small-town, prairie Canada, when Humphry Osmond and Abram Hoffer claimed incredible advances in treating alcoholism, understanding schizophrenia and other psychoses, and achieving empathy with their patients. In relating the drug’s short, strange trip, Dyck explains how concerns about countercultural trends led to the criminalization of LSD and other so-called psychedelic drugs—concordantly opening the way for an explosion in legal prescription pharmaceuticals—and points to the recent re-emergence of sanctioned psychotropic research among psychiatric practitioners. This challenge to the prevailing wisdom behind drug regulation and addiction therapy provides a historical corrective to our perception of LSD’s medical efficacy.
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
This volume offers insight for parents, counselors, and educators as to why young people in the 1990s are using LSD--its appeal, the experience, and where kids are getting it. Current studies and anecdotes are woven with recent statistics to create a clear picture of contemporary LSD use. The introduction offers some history and background on the issues surrounding LSD. Chapter Topics include: (1) "What Is a Trip--and Why Take One?" (J. MacDonald, M. Agar); (2) "About LSD" (L. A. Henderson); (3) "Adverse Reactions to LSD" (L. A. Henderson); (4) "LSD Use and LSD Users: Questions and Answers about LSD" (L. A. Henderson); (5) "An LSD Distribution Network" (C. Favret); (6) "Legal Issues" (L. A. Henderson); and (7) "Summary and Implications" (W. J. Glass, L. A. Henderson, C. Favret). Information about resources and data sources are appended. (EMK)
Background: Alcohol dependence belongs to the globally leading health risk factors. Therapeutic success of psychosocial programs for relapse prevention is moderate and could be increased by an adjuvant treatment with the opioid antagonists naltrexone and nalmefene. Objectives: To determine the effectiveness and tolerability of opioid antagonists in the treatment of alcohol dependence. Search strategy: We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2010 and inquired manufacturers and researchers for unpublished trials. Selection criteria: All double-blind randomised controlled trials (RCTs) which compare the effects of naltrexone or nalmefene with placebo or active control on drinking-related outcomes. Data collection and analysis: Two authors independently extracted outcome data. Trial quality was assessed by one author and cross-checked by a second author. Main results: Based on a total of 50 RCTs with 7793 patients, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group RR 0.83 (95% CI 0.76 to 0.90) and decreased drinking days by about 4%, MD -3.89 (95% CI -5.75 to -2.04). Significant effects were also demonstrated for the secondary outcomes of the review including heavy drinking days, MD - 3.25 (95% CI -5.51 to -0.99), consumed amount of alcohol, MD - 10.83 (95% CI -19.69 to -1.97) and gamma-glutamyltransferase, MD - 10.37 (95% CI -18.99 to -1.75), while effects on return to any drinking, RR 0.96 (95 CI 0.92 to 1.00) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems (e.g. nausea: RD 0.10; 95% CI 0.07 to 0.13) and sedative effects (e.g. daytime sleepiness: RD 0.09; 95% CI 0.05 to 0.14). Based on a limited study sample, effects of injectable naltrexone and nalmefene missed statistical significance. Effects of industry-sponsored studies, RR 0.90 (95% CI 0.78 to 1.05) did not significantly differ from those of non-profit funded trials, RR 0.84 (95% CI 0.77 to 0.91) and the linear regression test did not indicate publication bias (P = 0.765). Authors' conclusions: Naltrexone appears to be an effective and safe strategy in alcoholism treatment. Even though the sizes of treatment effects might appear moderate in their magnitudes, these should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.