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Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse

Marcus W. Meinhardt, Cansu Güngör, Ivan Skorodumov, Lea J. Mertens, Rainer Spanagel

Neuropsychopharmacology May 5, 2020 DOI: 10.1038/s41386-020-0694-z (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Preclinical animal study Peer reviewed
Population Male and female rats
Interventions Psilocybin LSD
Topics Addiction Psilocybin LSD
Keywords Relapse prevention Hallucinogen Animal model Clinical trial Animal studies Psychotherapist Pharmacology
Citations 66
Key points Neither high-dose nor microdosing regimens of psilocybin or LSD produced long-lasting reductions in relapse-like drinking in the alcohol deprivation effect model; only sub-chronic psilocybin had a short-lived anti-relapse effect.

Abstract

For most psychiatric disorders, including alcohol use disorder (AUD), approved pharmacological treatments are limited in their effectiveness, and new drugs that can easily be translated into the clinic are needed. Currently, great hope lies in the potential of psychedelics to effectively treat AUD. The primary hypothesis is that a single session of psychedelic-guided psychotherapy can restore normal brain function in AUD individuals and thereby reduce the risk of relapse in the long run. Here we applied three different treatment schedules with psilocybin/LSD in order to investigate relapse-like drinking in the alcohol deprivation effect (ADE) model. In contrast to the primary hypothesis, psychedelics had no long-lasting effects on the ADE in male and female rats, neither when administered in a high dosage regime that is comparable to the one used in clinical studies, nor in a chronic microdosing scheme. Only sub-chronic treatment with psilocybin produced a short-lasting anti-relapse effect. However, it is not a translatable treatment option to give psychedelics sub-chronically for relapse prevention. In conclusion, our results in the ADE model do not support the hypothesis that microdosing or high doses of psychedelic reduce relapse behavior. This conclusion has to be confirmed by applying other animal models of AUD. It could also well be that animal models of AUD might be unable to fully capture the therapeutic potential of psychedelic drugs and that only future large-scale clinical trials will be able to demonstrate the efficacy of psychedelics as a new treatment option for AUD.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • Neither high-dose nor microdosing regimens of psilocybin or LSD produced long-lasting reductions in relapse-like drinking in an alcohol deprivation effect model.

    Synthesized

Comparable studies

Other preclinical and animal studies on LSD for addiction, most cited first.

Study Year Design Participants
LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats. Rats (implied by typical place conditioning and taste reactivity paradigms) 1996 Experimental study
BEHAVIORAL AND ELECTROPHYSIOLOGICAL EFFECTS OF LYSERGIC ACID DIETHYLAMIDE (LSD) IN A MOUSE MODEL OF ALCOHOL USE DISORDER (AUD) 8-week-old male C57BL6/J mice, including an alcohol-exposed group and a control group 2025 Preclinical translational study in mice

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