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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