ReviewMDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational ‘Ecstasy’ users
Section snippets
MDMA and serotonergic neurotoxicity: general introduction
The methamphetamine derivative MDMA (3,4-methylenedioxymethamphetamine), has a particular affinity for the serotonin transporter, and by reversing its normal reuptake actions, causes a massive efflux of serotonin into the synaptic cleft (Berger et al., 1992). Hence an acute dose of MDMA can release around 80% of available serotonin (5-hydroxytryptamine, 5-HT) into the synaptic cleft (Green et al., 1995). In laboratory animals, repeated dosing with MDMA can damage the serotonergic
Serotonergic neurotoxicity in laboratory animals: pre-clinical findings
Serotonergic neurotoxicity following MDMA is a robust empirical phenomenon in many laboratory species. Single high doses of MDMA, or repeated administrations of lower doses, can lead to a pronounced reduction in markers for serotonin across higher brain regions, along with other indices of serotonergic change. The first studies to reveal this were undertaken in the mid-1980s (Ricaurte et al., 1985, Schmidt, 1987, Stone et al., 1987). Subsequent research has confirmed those early findings, and
Psychobiological functions with a serotonergic input: brief overview
As noted earlier, Jacobs and Fornal (1995) stated that serotonin was ‘implicated in virtually everything’ but ‘responsible for nothing’. Their review concluded that serotonin had a regulatory role (my italics) for many different psychobiological functions, including sleep, aggression, sex, pain, mood state, cardiovascular activity, respiratory control, nutrient intake, and psychomotor output. All these areas therefore need to be empirically studied in abstinent Ecstasy/MDMA users. One important
Neuroimaging studies with neurocognitive assessments
This section will review studies of brain activity (EEG, ERP, or neuroimaging) which involved parallel psychological assessments. As noted earlier, McCann et al. (2008) and Kish et al. (2010) found significant SERT reductions in their fMRI studies of abstinent Ecstasy/MDMA users. In relation to neurocognition, McCann et al. (2008) showed that memory task performance was inversely associated with SERT binding levels, in the dorso-lateral prefrontal cortex, orbitofrontal cortex, and parietal
Seeking help for Ecstasy/MDMA related problems
Comparatively few Ecstasy/MDMA users seek professional help for drug-related problems. Gunnarsson et al. (2004) surveyed 104 18 year-old high school students in Sweden, where 25% reported taking illicit recreational drugs, mostly amphetamine or Ecstasy. Amongst these stimulant users, 38% reported psychiatric symptoms which they attributed to drug usage, including low spiritedness and depression, anxiety/worry, and feelings of unreality. Yet none of them had sought medical help for their mental
MDMA and serotonergic neurotoxicity: early theoretical proposals
The notion that the functional problems of Ecstasy/MDMA users reflect serotonergic neurotoxicity, was proposed in the first human study. Peroutka (1989) surveyed 100 recreational users, and reported that with repeated usage, there was a tendency for the good effects of MDMA to diminish, and the negative drug effects to increase. It was reported that: ‘freshman love it, sophomores like it, juniors are ambivalent, and seniors are afraid of it’. Peroutka (1989) commented that these initial
Acknowledgements
This article was written during a sabbatical period at the Centre for Human Psychopharmacology, Swinburne University, in Melbourne, Australia.
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