Long-term neurocognitive side effects of MDMA in recreational ecstasy users following sustained abstinence: A systematic review and meta-analysis

Little is known about whether 3,4-methylenedioxy-N-methamphetamine (MDMA) neurocognitive side effects improve with sustained abstinence. This study aimed to systematically review and synthesise the existing literature on the long-term neurocognitive side effects of recreational MDMA use after a minimum of 6 months of abstinence. We searched relevant databases utilising terms related to (1) MDMA and (2) neurocognition. A qualitative synthesis of study findings was organised with reference to the neurocognitive domains defined in the <i>Diagnostic and Statistical Manual of Mental Disorders Fifth Edition</i> (DSM5). Fourteen articles met the inclusion criteria, assessing learning and memory (<i>n</i> = 8), executive function (<i>n</i> = 10), complex attention (<i>n</i> = 5), language (<i>n</i> = 2) and perceptual motor function (<i>n</i> = 1). Meta-analysis and assessment of bias were undertaken only for the domain of 'learning and memory' and included five studies. People with current and previous MDMA use had poorer learning and memory performance compared to people who were MDMA-naïve (Hedges' <i>g</i> = -1.06 and -1.37, respectively); there was no significant difference between current and abstinent MDMA users (Hedges' <i>g</i> = 0.03). A longer period of abstinence did not demonstrate greater improvements or recovery in learning and memory. There was limited evidence to conclude that MDMA use is associated with neurocognitive impairments in other domains. Overall, these conclusions are based on low-quality findings.