Mood disorders and serotonin transporter density in ecstasy users—the influence of long-term abstention, dose, and gender

Win, Maartje M. L. de; Reneman, Liesbeth; Reitsma, Johannes B.; Heeten, Gerard J. den; Booij, Jan; Brink, Wim van den

doi:10.1007/s00213-003-1723-4

Cited by 75 publications

(77 citation statements)

References 44 publications

(60 reference statements)

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“…The purpose of the present study was to produce robust depletions in order to evaluate the long-term behavioral consequences for those heavy users who do experience serotonin depletion rather than model typical human use patterns. An emerging literature in humans and animals does suggest that humans who are heavy MDMA users experience measurable loss of serotonergic markers (Buchert et al 2004;De Win et al 2004;Ricaurte et al 2000;Semple et al 1999), although recovery in these markers may occur (Buchert et al 2004;De Win et al 2004) and the mediating mechanisms are still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Several clinical studies report greater loss of serotonin terminal markers in women than in men (Buchert et al 2004;De Win et al 2004;McCann et al 1994). These differences in humans could reflect the average greater dose women ingest due to the fixed dose that most human users receive rather than a specific vulnerability to serotonin depletion in women.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, men experience greater increases in blood pressure (Liechti et al 2001). Sex differences in the persevering effects of MDMA are more poorly understood, although greater reductions in the density of 5-HT transporters and the levels of 5-HIAA in women have been reported (Buchert et al 2004;De Win et al 2004;McCann et al 1994). Although these reports suggest that the effects of MDMA are not equivalent in men and women, a number of factors affect this conclusion.…”

mentioning

confidence: 98%

“…This second phase is characterized by decreases in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), tryptophan hydroxylase activity, and the density of 5-HT reuptake sites (see review by Lyles and Cadet 2003). Although the patterns of exposure are quite different in rodent exposure models and typical human use and mediating mechanisms might be different, similar MDMAinduced decrements in 5-HT systems are reported in heavy MDMA users, including decreased concentrations of 5-HT and 5-HIAA in cerebrospinal fluid (McCann et al 1994) and a decrease in the number of 5-HT transporter binding (Buchert et al 2004;De Win et al 2004;Ricaurte et al 2000;Semple et al 1999).…”

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confidence: 99%

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Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

et al. 2006

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Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute toxicities and persistent depletion of the neurotransmitter serotonin (5-HT). Objectives This study investigates whether sex differences in the acute and long-term effects of MDMA exist. Methods Male and female rats received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored on days 1 and 4. Locomotor activity was measured in a second cohort of animals on days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in a plus maze task and brain levels of serotonin (5-HT) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort of animals 2 weeks after the last MDMA treatment. Results Locomotor activity and temperature increased after MDMA administration on day 1. The drug-induced increases in temperature but not locomotion attenuated with repeated MDMA administration. Male and female MDMA-treated rats spent less time in the open arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions 2 weeks after the end of treatment. Temperature effects of MDMA and persistent effects on plus maze and brain serotonin content were similar in males and females. In contrast, females exhibited markedly greater locomotor stimulation after acute MDMA and also showed sensitization to an acute challenge 2 weeks later. Conclusions MDMA elicits substantially greater locomotor activation in female rats than in males, but persistent effects on anxiety and serotonin content were similar in males and females.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

et al. 2006

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“…However, there has been an over-reliance on recruitment of ecstasy users using purposive or snowballing techniques. A number of such studies comparing ecstasy users to both drug naive controls (Gerra et al 2000;Gerra et al 2002;Milani et al 2004) and cannabis or polydrug control groups (de Win et al 2004;Lamers et al 2006;Morgan et al 2002;Soar et al 2006) have reported poorer mental health, assessed via self-report measures of depressive and/or anxiety symptoms, among ecstasy users relative to non-users.…”

Section: Introductionmentioning

confidence: 99%

Are ecstasy users biased toward endorsing somatic mental health symptoms? Results from a general community sample

2010

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Rationale: Whether the reported poorer mental health of ecstasy users is due to a bias in endorsement of somatic symptoms has been postulated, but rarely examined.Objectives: To investigate whether levels of ecstasy use were associated with differential probabilities of endorsing somatic mental health symptoms.Methods: Current ecstasy users aged 24-30 years (n = 316) were identified from a population-based Australian study. Measures included frequency of ecstasy, meth/amphetamine and cannabis use and the Goldberg anxiety/depression symptom scales.Results: Multiple indicator, multiple cause (MIMIC) models demonstrated no bias towards endorsing somatic symptoms with higher ecstasy use, both with and without adjustment for gender, cannabis and meth/amphetamine use. Conclusions:Other studies using alternate measures of mental health should adopt this approach to determine if there is a bias in the endorsement of somatic symptoms among ecstasy users.

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Evidence for Chronically Altered Serotonin Function in the Cerebral Cortex of Female 3,4-Methylenedioxymethamphetamine Polydrug Users

Iorio

Watkins²,

Dietrich³

et al. 2012

Arch Gen Psychiatry

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Context MDMA (ecstasy) is a popular recreational drug that produces loss of serotonin (5-HT) axons in animal models. Whether MDMA produces chronic reductions in 5-HT signaling in humans remains controversial. Objective To determine if MDMA use is associated with chronic reductions in serotonin signaling in female human cerebral cortex as reflected by increased 5-HT2A receptors. Design Cross sectional case-control study comparing 5-HT2A receptor levels in abstinent female MDMA polydrug users to MDMA-naive females; within-group design assessing the association of lifetime MDMA use and 5-HT2A receptors. Subjects had at least 90 days abstinence from MDMA use as verified by hair sampling. Cortical 5-HT2A receptor levels were assayed with the 5HT2A-specific Positron Emission Tomography (PET) radioligand [18F]setoperone. Setting Academic Medical Center Research Laboratory. Participants Volunteer female MDMA users (N=14) and MDMA-naive controls (N=10). Main exclusion criteria were non-drug-related DSM-IV axis I psychiatric disorders and general medical illness. Main Outcome Measure Cortical 5-HT2A receptor non-displaceable binding potential (5-HT2ABPND). Results MDMA users had increased 5-HT2ABPND in occipital-parietal (19.7%), temporal (20.5%), occipito-temporal-parietal (18.3%), frontal (16.6%), and fronto-parietal (18.5%) regions (p<0.05; corrected). Lifetime MDMA use associated positively with 5-HT2ABPND in fronto-parietal (β=0.665;p=0.007), occipito-temporal (β=0.798;p=0.002), fronto-limbic (β=0.634;p=0.024), and frontal (β=0.691;p=0.008) regions. In contrast, there were no regions in which MDMA use was inversely associated with receptor levels. There were no statistically significant effects of the duration of MDMA abstinence on 5-HT2ABPND. Conclusions Human recreational MDMA use is associated with long-lasting increases in 5-HT2A receptor density. 5-HT2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These results suggest that MDMA produces chronic 5-HT neurotoxicity in humans. Given the broad role of 5-HT in human brain function, the possibility for therapeutic MDMA use, and the widespread recreational popularity of this drug, these results have critical public health implications.

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Mood disorders and serotonin transporter density in ecstasy users—the influence of long-term abstention, dose, and gender

Cited by 75 publications

References 44 publications

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

Are ecstasy users biased toward endorsing somatic mental health symptoms? Results from a general community sample

Evidence for Chronically Altered Serotonin Function in the Cerebral Cortex of Female 3,4-Methylenedioxymethamphetamine Polydrug Users

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