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

Psychedelic-assisted psychotherapy is hypothesized to restore normal brain function in people with alcohol use disorder (AUD) and reduce relapse risk after a single session. In this study, three treatment schedules with psilocybin or LSD were tested in male and female rats using the alcohol deprivation effect (ADE) model of relapse-like drinking. Neither high doses comparable to clinical studies nor chronic microdosing produced long-lasting reductions in relapse-like drinking. Only sub-chronic psilocybin had a short-lasting anti-relapse effect, but this regimen is not considered a translatable treatment. The findings do not support the hypothesis that microdosing or high-dose psychedelics reduce relapse behavior in this model, though the authors note that animal models may not fully capture psychedelics' therapeutic potential.

Study at a glance

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.