Modulation of Social Cognition via Hallucinogens and “Entactogens”, Katrin H. Preller and Franz X. Vollenweider, 2019

Modulation of Social Cognition via Hallucinogens and “Entactogens”

Katrin H. Preller and Franz X. Vollenweider

Frontiers in Psychiatry, décembre 2019

doi: 10.3389/fpsyt.2019.00881

Social cognition is a fundamental ability in human everyday lives. Deficits in social functioning also represent a core aspect of many psychiatric disorders. Yet, despite its significance, deficits in social cognition skills are insufficiently targeted by current treatments. Hallucinogens and entactogens have been shown to have the potential to modulate social processing. This article reviews the literature on the influence of hallucinogens and entactogens on social processing in controlled experimental studies in humans and elucidates the underlying neurobiological and neuropharmacological mechanisms. Furthermore, it identifies current knowledge gaps and derives implications for hallucinogen-assisted treatment approaches as well as the development of novel medication for trans-diagnostic impairments in social cognition.

Keywords : social cognition, psychedelics, serotonin, pharmacology, functional magnetic resonance imaging, emotions



Humans are a social species (1). Social processes range from societal matters like politics, to more private every-day activities like being successful in a working environment, finding an apartment, romantic partnerships, and the use of virtual social networks. To be able to function in this social environment, we use capabilities which are subsumed under the term “social cognition” (2). Social cognition has been defined as mental processes through which we perceive, think about, and act toward other people (3). Critically, deficits in social functioning represent a core aspect and important diagnostic criterion of many—if not all—psychiatric disorders (4). Not only do difficulties in social interaction abilities increase the risk of developing a psychiatric disorder, but they also contribute to the maintenance or worsening of symptoms, as therapeutic processes as well as support seeking and re integration into everyday activities, e.g., work-life, are social activities (4, 5). The importance of social cognition has also been recognized by the Research Domain Criteria (RDoC) initiative, which defines social processes as one of five trans-diagnostic dimensional constructs critical to human behavior and mental disorders (6–8). Yet, deficits in social cognition skills are insufficiently—if at all—targeted by current treatment approaches (9).

Hallucinogens are psychoactive substance which induce transient perceptual anomalies and an altered state of consciousness. The effect of entactogens is characterized by experiences of oneness and emotional openness. Entactogens as well as hallucinogens have been shown to successfully modulate social processing in rigorous scientific studies (10–12). This is important for two reasons (13) :

1) In the search for novel medication for transdiagnostic social dysfunction in psychiatric disorders, these substances provide a powerful tool to increase our understanding of the neural mechanisms underlying social processing and behavior. Due to their well-investigated receptor pharmacology, in particular with regard to hallucinogens, they can identify novel targets for the development of new therapeutics.

2) Given that drug development in psychiatry has stagnated for decades, new therapeutic models are urgently needed (14). Entactogens and hallucinogens have shown promising results in preliminary clinical trials in disorders also characterized by social impairments such as depression, anxiety, post-traumatic stress disorder (PTSD), and autism spectrum disorders (ASD) (15–19). These substances
could, therefore, represent important adjuncts to psychotherapy in psychiatric disorders.

The first part of this review focuses on the effects of hallucinogens and entactogens on social cognition in clinical populations (Modulation of Social Cognition in Clinical Populations). Acute Effects of Entactogens and Hallucinogens on Social Cognition in Healthy Volunteers reviews the acute
effects of entactogens and hallucinogens on social cognition in healthy volunteers. Long-Lasting Effects in Healthy Participants provides a summary of long-lasting hallucinogenand entactogen-induced effects on social cognition, and Neuropharmacological Underpinnings of Alterations in Social Cognition Induced by Hallucinogens and Entactogens explores the neuropharmacological basis of these modulatory effects.

This chapter is particularly important for informing the development of novel therapeutics targeting socio-cognitive deficits in psychiatric disorders. Complimentary to the work reviewed here, there is a broad body of literature on the effects of these substances on social cognition in animals (20). However, these studies are beyond the scope of this review and so will not be discussed here. Furthermore, this review focuses on experimental and controlled studies in humans and will not include literature on survey data or studies completed with recreational drug users. This review mainly discusses effects induced by two entactogens, 3,4-methylenedioxymethamphetamine (MDMA) and gamma-hydroxybutyrate (GHB), and two hallucinogens, lysergic acid diethylamide (LSD) and psilocybin. GHB, sometimes also referred to as liquid ecstasy, has been associated with the group of entactogens (21). However, it is important to note that the neuropharmacological mechanisms underlying GHB’s psychotropic effects differ strongly from MDMA and serotonergic hallucinogens (22). Yet, given that GHB has been reported to be used recreationally for its prosocial effects, empirical studies on GHB are included in this review. Experimental research on the influence of other hallucinogens and entactogens on social functioning in humans is currently lacking and should be investigated in future studies.