Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies

Abstract

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT_2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.

Keywords: LSD; alcohol; ayahuasca; classic psychedelics; mescaline; psilocybin.

FIGURE 1

Classic psychedelics and 5‐HT2A receptor. 5‐HT2A receptor and chemical structures of classic psychedelics and serotonin. Although classic psychedelics also bind other serotonin receptors (such as 5‐HT1A and 5‐HT2C), 5‐HT2A is the main site of action responsible for the behavioural effects of psychedelics. The 5‐HT2A receptor is a G‐protein‐coupled receptor (GPCR) that contributes to multiple complex processes in the neocortex by way of multiple cellular mechanisms. Psychedelics can induce long‐term neuronal changes, affect gene expression and increase neuronal plasticity through the agonism of the 5‐HT2A receptor. Such alterations in synaptic plasticity may well explain some of the observed long‐term substantive behavioural and cognitive changes following psychedelic administration. Interestingly, an emerging body of evidence implicates the 5‐HT2A receptor as a novel target for pharmacologic intervention for the treatment of substance use disorder (SUD), AUD, and for smoking cessation.

FIGURE 2

Flow diagram of records identified, screened, and included