Effects of (±) 3,4-Methylenedioxymethamphetamine (MDMA) on Sleep and Circadian Rhythms

Abusing stimulant drugs like MDMA disrupts sleep-wake patterns because they promote arousal and prevent sleep. MDMA can also damage brain serotonin neurons in animals and possibly humans, and serotonin helps regulate sleep and circadian rhythms. People with MDMA-induced serotonin damage may develop chronic sleep and circadian problems, which could contribute to other issues like memory disturbances seen in abstinent users. This review examines preclinical and clinical studies on how prior MDMA exposure affects sleep, circadian activity, and the circadian pacemaker, identifies knowledge gaps, and suggests future research directions.

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Abstract

Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA), may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic toward brain monoaminergic neurons involved in normal sleep regulation. In particular, MDMA has been found to damage brain serotonin (5-HT) neurons in a variety of animal species, including nonhuman primates, with growing evidence that humans are also susceptible to MDMA-induced brain 5-HT neurotoxicity. 5-HT is an important modulator of sleep and circadian rhythms and, therefore, individuals who sustain MDMA-induced 5-HT neurotoxicity may be at risk for developing chronic abnormalities in sleep and circadian patterns. In turn, such abnormalities could play a significant role in other alterations reported in abstinent in MDMA users (e.g., memory disturbance). This paper will review preclinical and clinical studies that have explored the effects of prior MDMA exposure on sleep, circadian activity, and the circadian pacemaker, and will highlight current gaps in knowledge and suggest areas for future research.