A double-blind, placebo-controlled study combined resting-state fMRI with a molecular atlas of serotonin receptors to examine how MDMA alters functional connectivity. Using the REACT method, the researchers found that MDMA-induced connectivity changes were specifically linked to brain regions rich in the serotonin transporter (5-HTT) and the 5-HT1A receptor, the drug's primary targets. Changes in 5-HT1A-enriched maps correlated with MDMA blood levels, while changes in 5-HT2A-enriched maps correlated with spiritual experiences reported by participants. The approach shows that MDMA's effects on brain connectivity can be explained by the distribution of its serotonergic targets, offering a new way to characterize psychoactive compounds.
MDMA increases cooperative behavior, but only when interacting with trustworthy partners. In a double-blind, placebo-controlled crossover study, 20 male participants received 100 mg MDMA or placebo and played an iterated Prisoner's Dilemma with opponents who varied in cooperation. MDMA enhanced cooperation with trustworthy opponents (odds ratio = 2.01) but not untrustworthy ones. MDMA specifically improved recovery from, not the impact of, breaches in cooperation. Brain activity increased in regions linked to social cognition, including precentral and supramarginal gyri, superior temporal cortex, central operculum/posterior insula, and supplementary motor area. Trust ratings did not change. The effect of MDMA on social decision-making depends on the context of the other person's behavior.