Effects of MDMA on sociability and neural response to social threat and social reward

Abstract

±3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) reportedly produces unique subjective effects, including increased sociability, feelings of closeness with others, and reduced interpersonal defensiveness. Despite their apparent importance in recreational and potential psychotherapeutic use of MDMA, the defining characteristics and neurobiological mechanisms of these interpersonal effects are poorly understood. We investigated acute effects of MDMA on self-reported sociability and neuronal activation in response to socially threatening (angry and fearful faces) and socially rewarding (happy faces) stimuli. Assessment of social threat response focused on amygdala activation, whereas assessment of social reward focused on ventral striatum activation. Healthy volunteers (N = 9) reporting past ecstasy use completed three experimental sessions, receiving MDMA (0.75 and 1.5 mg/kg) and placebo (PBO) under double-blind conditions. During peak drug effects, participants underwent functional magnetic resonance imaging while viewing standardized images depicting emotional facial expressions including angry, fearful, happy, and neutral expressions. They also completed standardized self-report measures of sociability. MDMA (1.5 mg/kg) increased self-reported sociability compared to MDMA (0.75 mg/kg) and PBO. MDMA (1.5 mg/kg) attenuated left amygdala response to angry facial expressions compared to PBO, but MDMA did not affect amygdala reactivity to fearful expressions. MDMA (0.75 mg/kg) enhanced ventral striatum response to happy expressions relative to PBO. These data present the first evidence that MDMA may increase sociability in humans both by diminishing responses to threatening stimuli and enhancing responses to rewarding social signals.