Effects of acute 3,4-methylenedioxymethamphetamine on sleep and daytime sleepiness in MDMA users: a preliminary study.

3, 4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) IS THE PRIMARY ACTIVE INGREDIENT IN THE RECREATIONAL DRUG “ECSTASY.” MDMA HAS BOTH stimulant and hallucinogenic properties and is structurally similar to both amphetamine and mescaline.1–3 Chronic MDMA use in humans causes a significant serotonergic hypoactivity evident by reductions in cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin (5-HT), and decreases 5-HT in transporters and 5-HT uptake sites in various brain regions.4–7 According to DSM-IVTR, symptoms of chronic MDMAuse are defined by compulsive drug seeking and drug use leading to functional and molecular changes in the brain. Serotonin is among the monoamine neurotransmitters that play a role in the mediation of sleep and daytime sleepiness. In addition, MDMA acts as a releaser and reuptake inhibitor of dopamine and norepinephrine, and other monoamines important to sleep and daytime alertness.3,8 Given the pharmacologic profile of MDMA, it is not surprising that MDMA users report having trouble sleeping.9–11 Using a self-report 90-item Symptom CheckList (SCL-90), heavy MDMA users report having restless/disturbed sleep.12 Insomnia has been reported 2 years after MDMA use stopped,13 suggesting that the effects of MDMA may be prolonged. In sleep laboratory studies, MDMA users have significantly less total sleep time and less non-rapid eye movement (NREM) time than control subjects.11 They also have less stage 2 sleep and more stage 1 sleep in comparison with control subjects.11,14 In these studies, MDMA users were defined as those who stated that they had used MDMA on more than 20 occasions. However, these studies did not clearly verify the absence or concurrent use of other drugs of abuse and time allotted for sleep. In addition, the acute effects of MDMA on sleep have not been studied in the sleep laboratory under placebo-controlled conditions. Sleep laboratory studies of other stimulant drugs suggest that, beyond shortening sleep, MDMA may also disrupt the normal NREM-rapid eye movement (REM) sleep-stage cycling. Presleep administration of amphetamine specifically increases REM sleep latency and reduces REM sleep time, in addition to increasing sleep latency and wake time during the sleep period.15 Similarly, methylphenidate administered before sleep reduces REM time and increases REM latency, as well as reducing sleep time.16 Evening insufflations of cocaine reduce sleep time and REM time.17 Finally, presleep administration of methylenedioxyamphetamine, which is structurally related to MDMA, disrupts sleep and completely suppresses REM sleep.18 However, the effect of MDMA on REM sleep under similar laboratory conditions has not been evaluated. Reduced sleep time in healthy control subjects results in daytime sleepiness. As little as a 2-hour sleep loss (6 hour vs 8 hour time in bed) produces sleepiness and impaired performance.19 Thus, any sleep loss associated with MDMA use may cause daytime sleepiness, which may also contribute to impairments in cognition and mood associated with MDMA use. Further, the contributory role of a REM sleep disturbance to the cognitive and mood impairments of MDMA users is unknown. The current study was designed to establish the effect of acute MDMA administration on sleep and daytime sleepiness. It was hypothesized that MDMA would decrease sleep time, resulting in daytime sleepiness, and decrease REM sleep. A positive control, sleep restriction of 4 hours, was included to provide a metric to compare sleep loss and consequent sleepiness associated with MDMA use. To assess the extent of sleep disturbance in MDMA users, their baseline sleep and alertness were compared with those of an age-matched control group.