MDMA-Assisted Therapy as a Means to Alter Affective, Cognitive, Behavioral, and Neurological Systems Underlying Social Dysfunction in Social Anxiety Disorder.

Jason Luoma,M Kati Lear

doi:10.3389/fpsyt.2021.733893

Abstract

Social anxiety disorder (SAD) is a prevalent and often debilitating psychiatric disorder that can assume a chronic course even when treated. Despite the identification of evidence-based pharmacological and behavioral treatments for SAD, much room for improved outcomes exists and 3,4-methylenedioxymethamphetamine (MDMA) has been proposed as a promising adjunctive treatment to psychological interventions for disorders characterized by social dysfunction. A small randomized, placebo-controlled trial of MDMA-assisted therapy (MDMA-AT) for social anxiety in autistic adults offered encouraging results, but more research is sorely needed to explore the potential for MDMA-AT in treating SAD. This review aims to stimulate future study by summarizing research on disruptions in neurological, perceptual, receptive, and expressive systems regulating social behavior in SAD and proposing how MDMA-AT may alter these systems across four domains. First, we review research highlighting the roles of social anhedonia and reduced social reward sensitivity in maintaining SAD, with specific attention to the reduction in positive affect in social situations, infrequent social approach behaviors, and related social skills deficits. We posit that MDMA-AT may enhance motivation to connect with others and alter perceptions of social reward for an extended period following administration, thereby potentiating extinction processes, and increasing the reinforcement value of social interactions. Second, we review evidence for the central role of heightened social evaluative threat perception in the development and maintenance of SAD and consider how MDMA-AT may enhance experiences of affiliation and safety when interacting with others. Third, we consider the influence of shame and the rigid application of shame regulation strategies as important intrapersonal processes maintaining SAD and propose the generation of self-transcendent emotions during MDMA sessions as a mechanism of shame reduction that may result in corrective emotional experiences and boost memory reconsolidation. Finally, we review research on the role of dysfunctional interpersonal behaviors in SAD that interfere with social functioning and, in particular, the development and maintenance of close and secure relationships. We discuss the hypothesized role of MDMA-AT in improving social skills to elicit positive interpersonal responses from others, creating a greater sense of belonging, acceptance, and social efficacy.

Highlights

Social anxiety disorder (SAD) is the fourth most commonly diagnosed psychiatric disorder in the United States [1]
A stronger theory will help identify potential processes of change that could guide research to improve integration between drugs and psychotherapy. To address this gap in the literature, this review summarizes data on alterations in the affective, cognitive, and neurological systems related to social functioning in SAD and how MDMAassisted therapy may alter these functions
They established that the MDMA needed to be administered with another mouse present in order to achieve this enduring shift in social reinforcement, suggesting that the social context of MDMA administration is important. Another series of mouse studies by Curry et al [51] showed increased social behavior toward unfamiliar mice after multiple treatments with MDMA, with this effect being greater when the mice received MDMA while in the presence of another mouse. These results suggest that MDMA may enhance motivation to connect with others, enhance the likelihood that people find social interactions with strangers rewarding, and that this effect may extend beyond MDMA administration in a therapeutic, social context

Summary

Introduction

Social anxiety disorder (SAD) is the fourth most commonly diagnosed psychiatric disorder in the United States [1]. Epidemiological research has found that people with SAD report overall reduced quality of life, with negative consequences on their social and occupational lives, even at levels below the diagnostic threshold [3, 4]. SAD is often associated with the concurrence and development of other psychological disorders, alcohol use disorder [7, 8] and major depressive disorder (MDD) [9]. The exact nature of these relations remains unclear, SAD often occurs first and confers approximately a four-fold risk and five-fold risk for developing alcohol dependence [7] and MDD [10], respectively, relative to the general population. SAD increases the risk for chronic social isolation and loneliness, robust longitudinal predictors for cardiovascular disease and increased mortality [11]

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Conclusion