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

Abstract

RATIONALE ±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. MATERIALS AND METHODS 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 (0.75mg/kg, and 1.5mg/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. RESULTS MDMA (1.5mg/kg) increased self-reported sociability compared to MDMA (0.75mg/kg) and PBO. MDMA (1.5mg/kg) attenuated left amygdala response to angry facial expressions compared to PBO, but MDMA did not affect amygdala reactivity to fearful expressions. MDMA (0.75mg/kg) enhanced ventral striatum response to happy expressions relative to PBO. CONCLUSIONS 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.

Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing

“…Intranasal oxytocin produced small increases in selfreported sociability but, in contrast to MDMA, oxytocin (40 IU) enhanced recognition of negative emotional faces, suggesting that MDMA-and oxytocin-related effects are not synonymous. Overall, these data are consistent with previous reports of the prosocial effects of MDMA (Bedi et al, 2009(Bedi et al, , 2010Kirkpatrick et al, 2012;Tancer and Johanson, 2003) and extend these earlier findings by demonstrating modest correlations between the effects of MDMA and oxytocin in the same individuals. MDMA dose-dependently increased subjective ratings of sociability and 'positive' mood.…”

“…Interestingly, the drug also increased several 'negative' subjective ratings such as drug disliking, and feelings of anxiety and loneliness. Overall, these subjective data are consistent with other studies indicating that MDMA produces both 'positive' and 'negative' mood states under controlled laboratory conditions (Bedi et al, 2009(Bedi et al, , 2010Kirkpatrick et al, 2012;Tancer and Johanson, 2003). This mixed profile of both positive and negative subjective effects is consistent with the purportedly low abuse potential of MDMA relative to other amphetamines (Kirkpatrick et al, 2012).…”

“…We hypothesized that both MDMA and oxytocin would dose-dependently (1) increase self-report measures of sociability and desire to socialize and (2) enhance objective indicators of social function. Previous data from our laboratory and others indicate that MDMA dose-dependently increases both cardiovascular measures and feelings of euphoria, whereas intranasal oxytocin does not (Bedi et al, 2009(Bedi et al, , 2010de Oliveira et al, 2012;Norman et al, 2011;MacDonald and MacDonald, 2010). Therefore, we further predicted that only MDMA would increase self-reported 'positive' mood as well as heart rate and blood pressure.…”

“…Placebo capsules contained only lactose. These MDMA doses were selected based on our previous studies indicating that the drug reliably increases positive mood and alters emotional processing at these doses (Bedi et al, 2009(Bedi et al, , 2010. Intranasal oxytocin (20 and 40 IU) doses were prepared within 24 h of use.…”

Individual Differences in Acute Responses to MDMA in Humans: Effects of Sex and Past Ecstasy Use

“…One study (N = 10) was an fMRI investigation of MDMA (0.75mg/kg; 1.5 mg/kg) effects on social processing [3]. The second (N = 25) examined the effects of MDMA (0.75mg/kg; 1.5 mg/kg) and methamphetamine (20mg) on social cognition.…”