Potential Human Neurotoxicity of MDMA (‘Ecstasy’): Subjective Self-Reports, Evidence from an Italian Drug Addiction Centre and Clinical Case Studies

Schifano, Fabrizio

doi:10.1159/000026667

Cited by 78 publications

(94 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One dose of 10 mg/kg MDMA (i.p., 3 h), identical to that used under our experimental conditions, was found to increase 5-HT turnover in mouse brain (Steele et al, 1989). Few studies indicate that MDMA exerts an effect on food consumption in humans (anorectic or bulimic effects) (Shulgin, 1986;Rochester and Kirchner, 1999;Schifano, 2000), as would be expected from its 'substrate-type 5-HT releaser' activity. Furthermore, only one study reports its hypophagic effect in rats (Frith et al, 1987).…”

Section: Discussionsupporting

confidence: 62%

3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

Conductier

Crosson

Hen

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

3,4-Methylenedioxy-N-methamphetamine (MDMA or 'ecstasy') is a psychoactive substance, first described as an appetite suppressant in humans, inducing side effects and even death. MDMA increases serotonin (5-HT) levels, and 5-HT inhibits food intake, but the 5-HT receptors involved in MDMA-induced changes in feeding behavior are unknown. We examined whether a systemic MDMA injection would reduce the physiological drive to eat in starved mice and tested if the inactivation of 5-HT 1B or 5-HT 2C receptors could restore this response. Our results indicate that in starved mice, MDMA (10 mg/kg) provoked an initial hypophagia for 1 h (À77%) followed by a period of hyperphagia (studied between 1 and 3 h). This biphasic feeding behavior due to MDMA treatment was maintained in 5-HT 1B receptornull mice or in animals treated with the 5-HT 1B/1D receptor antagonist GR127935 (3 or 10 mg/kg). In contrast, MDMA-induced hypophagia (for the first 1 h period) was suppressed when combined with the 5-HT 2C receptor antagonist RS102221 (2 mg/kg). However, RS102221 did not alter MDMA-induced hyperphagia (for the 1-3 h period) but did exert a stimulant effect, when administered alone, during that period. We have previously shown that MDMA or 5-HT 1A/1B receptor agonist RU24969 fails to stimulate locomotor activity in 5-HT 1B receptor-null mice. Our present data indicate that the 5-HT 2C receptor antagonist RS102221 suppresses MDMA-induced hyperlocomotion. These findings provide the first evidence that the inactivation of 5-HT 2C receptors may reduce hypophagia and motor response to MDMA, while a genetic deficit or pharmacological inactivation of 5-HT 1B receptors was insufficient to alter the feeding response to MDMA.

show abstract

Section: Discussionsupporting

confidence: 62%

3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

Conductier

Crosson

Hen

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Fox et al (2001) found that significantly more Ecstasy users took amphetamine, cocaine, or LSD, in comparison with cannabis-user controls. Other studies have similarly noted that multiple psychoactive drug use is a typical characteristic of Ecstasy users Morgan, 1999;Parrott et al, 2000Parrott et al, , 2001Pedersen & Skrondal, 1999;Schifano, 2000;Topp et al, 1999). These findings are consistent with the notion of thresholds, that drug escalation follows a characteristic progression, from legal drugs, to cannabis, then other illicit Table 3 Normal Ecstasy dose per occasion and maximum number of Ecstasy tablets taken in 1 week, reported by novice, moderate, and heavy Ecstasy/MDMA users (1 -9, 10 -99, and + 100 lifetime occasions; N = 109, 136, and 37, respectively) drugs.…”

Section: Discussionmentioning

confidence: 89%

“…Around 5% of schoolchildren in the Netherlands have used it, as have 13% of British university students (Spruit, 2001;Webb, Ashton, Kelly, & Kamali, 1996). Its use is strongly associated with the dance club and rave scene, with 59% of Italian disco clubbers and 81% of Dutch ravers having experienced it, and 64% of the Dutch sample stating that they had taken Ecstasy the previous night (Schifano, 2000;Spruit, 2001). In the United States, its availability has also increased dramatically in recent years, so that it is now one of the most frequently used recreational drugs (Chang, 2001;Schensul, 2001).…”

Section: Introductionmentioning

confidence: 99%

Increased intensity of Ecstasy and polydrug usage in the more experienced recreational Ecstasy/MDMA users: A WWW study

Scholey

Parrott

Buchanan

et al. 2004

Addictive Behaviors

146

119

View full text Add to dashboard Cite

Recreational Ecstasy/MDMA (3,4-methylenedioxymethamphetamine) users often take a variety of psychoactive drugs, but there is little empirical data on how these drug consumption patterns change with greater experience of Ecstasy. The aim of this study was to compare the polydrug usage patterns reported by non-Ecstasy users, novice Ecstasy users, moderate Ecstasy users, and heavy Ecstasy users. In a WWW study of 763 unpaid volunteers, 481 had never taken Ecstasy, whereas 282 reported they had taken it. The Ecstasy users comprised 109 novice users (1-9 occasions), 136 moderate Ecstasy users (10 -99 occasions), and 36 heavy Ecstasy users ( + 100 occasions). Each participant also reported their experience with a range of other psychoactive drugs. The Ecstasy users reported significantly greater psychoactive drug usage than the nonEcstasy users. The novice, moderate, and heavy Ecstasy users also differed significantly from each other in the use of cocaine, amphetamine, LSD, and psilocybin mushrooms, but not of alcohol, cannabis, or cigarettes/nicotine. Experienced Ecstasy users also took significantly more MDMA tablets on each occasion, and reported a higher maximum weekly intake. The increased use of Ecstasy is associated with more intensive patterns of Ecstasy/MDMA intake, and the greater use of illicit CNS stimulants and hallucinogens, but not of alcohol, nicotine, or cannabis. These results are discussed in the context of cross-tolerance and drug predisposition/preference.

show abstract

“…Many previous studies reported increased levels of depression (Sumnall and Cole, 2005), impulsivity (Morgan, 1998;Parrott et al, 2000;Tuchtenhagen et al, 2000;Daumann et al, 2001Daumann et al, , 2004bBond et al, 2004;Butler and Montgomery, 2004), and sensation/novelty seeking (Gerra et al, 1998;Tuchtenhagen et al, 2000;Schifano, 2000;Dughiero et al, 2001) in ecstasy users, although it is unclear whether these associations reflect a causal relationship, that is whether ecstasy use causes changes in mood, impulsivity, and sensation seeking or whether depression, impulsivity, and sensation seeking increase the probability of (heavy) ecstasy use (see also De Win et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

Win

Reneman

Jager

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (42 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy ( 1 H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.873.1 years) in two sessions before and after first ecstasy use (1.871.3 tablets). Interval between baseline and follow-up was on average 8.176.5 months and time between last ecstasy use and follow-up was 7.774.4 weeks. Using 1 H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (À6.2%), dorsolateral frontal cortex (À4.0%), and superior parietal cortex (À3.0%) (all significant at po0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity ( + 3.7% on the Barratt Impulsiveness Scale) and decreased depression (À28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that incidental ecstasy use leads to extensive axonal damage. However, sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas, although it is not known whether this effect is permanent. Additional studies are needed to replicate these findings.

show abstract

Potential Human Neurotoxicity of MDMA (‘Ecstasy’): Subjective Self-Reports, Evidence from an Italian Drug Addiction Centre and Clinical Case Studies

Cited by 78 publications

References 31 publications

3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

Increased intensity of Ecstasy and polydrug usage in the more experienced recreational Ecstasy/MDMA users: A WWW study

A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

Contact Info

Product

Resources

About