Caveat Emptor Editors Beware

Vollenweider, Franz X.; Baggott, Matthew J.

doi:10.1016/s0893-133x(00)00170-6

Cited by 30 publications

(28 citation statements)

References 18 publications

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“…The validity of animal data for the human situation has been questioned, however, because MDMA is usually administered to animals in higher dosages than generally used by humans. Some authors do not support the suggestion that a single oral dose at 1.7 mg/kg is likely to produce neurotoxic effects in humans (Lieberman and Aghajanian, 1999;Vollenweider et al, 1999Vollenweider et al, , 2001). On the other hand, it has been advocated that these dosages in animals are equivalent to typical recreational dosages in humans according to the principles of interspecies scaling McCann and Ricaurte, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…These studies have led to ongoing discussion on safety and ethics of administration of potentially neurotoxic drugs to healthy humans. Several authors objected to administering a potential neurotoxic drug to humans for the purpose of science (Gijsman et al, 1999;McCann and Ricaurte, 2001), while others supported these experiments (Lieberman and Aghajanian, 1999;Vollenweider et al, 1999Vollenweider et al, , 2001.…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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Section: Introductionmentioning

confidence: 99%

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

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“…1a) has generally been criticized on two major grounds: the lack of a consistent definition for the term itself, and the questionable validity of interspecies dose scaling procedures used to equate experimental drug regimens in laboratory animals with recreational MDMA use in humans (see, e.g., Saunders 1995;Grob 2000;Kalia 2000;Vollenweider et al 2001;Kish 2002;de la Torre and Farre 2004). With regard to the terminology dispute, there are at least three morphological criteria that are generally accepted as validated indicators of neural damage: frank cell loss, argyrophilia (silver staining), and reactive gliosis (O'Callaghan and Miller 1993).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, on its face, the widely used "binge dosing" procedure in laboratory primates seems quite unlike the typical drug exposure pattern observed in humans. However, application of some allometric interspecies scaling procedures indicate that this particular drug regimen may be analogous to human MDMA use in recreational settings (Morgan 2000), although convincing arguments to the contrary have also been advanced (Vollenweider et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?

Fantegrossi

2006

Psychopharmacology

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Rationale: Many animal models relevant to the persistent effects of drugs of abuse necessitate the application of interspecies dose scaling procedures to approximate drug administration regimens in humans, but drug self-administration procedures differ in that they allow animal subjects to control their own drug intake. Objectives: This report reviews the reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA), its enantiomers, and several structural analogs in rhesus monkeys, paying particular attention to the pharmacological mechanisms of such reinforcing effects, the development of structure activity relationships among these compounds, the stability of MDMA self-administration behavior over time, and the persistent effects of selfadministered MDMA on monoamines. Results: The methylenedioxy amphetamine congeners MDMA, 3, 4-methylenedioxyamphetamine, N-ethyl-3,4-methylenedioxyamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine function as reinforcers in rhesus monkeys, maintaining self-administration behavior greater than that engendered by contingent saline but less than that engendered by traditional psychostimulants. These findings are remarkable as structurally distinct serotonergic hallucinogen-like drugs do not maintain reliable selfadministration in laboratory animals. During prolonged MDMA self-administration, MDMA-maintained responding progressively weakens, and MDMA eventually fails to maintain significant self-administration. The neurochemical correlates of this effect have not yet been identified. Conclusions: Procedures in which MDMA and related compounds are self-administered can be established in rhesus monkeys. These techniques can be used to engender contingent MDMA exposure without resorting to controversial methods of interspecies dose scaling. As such, further application of self-administration methods may provide important new insights into the persistent effects of MDMA on brain and behavior in nonhuman primates.

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“…A preliminary brain imaging study by Vollenweider, Jones and Baggott (2001) administered a moderate dose of MDMA (1.5-1.7 mg/kg) to Ecstasy-naive volunteers and found no changes in serotonin transporter densities (using PET) from pre-drug baseline to one month after MDMA administration. A related study found no changes in memory and cognitive performance at one month post-MDMA treatment (Ludewig et al, 2003).…”

Section: Conclusion: Do We Want Ecstasy To Cause Brain Damage?mentioning

confidence: 98%

Recreational ecstasy use and the neurotoxic potential of MDMA: current status of the controversy and methodological issues

Lyvers

2006

Drug and Alcohol Review

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The controversy over possible MDMA‐induced serotonergic neurotoxicity in human recreational ecstasy users is examined critically in light of recent research findings. Although the designs of such studies have improved considerably since the 1990s, the evidence to date remains equivocal for a number of reasons, including (1) inconsistent findings on the existence and reversibility of persistent ecstasy‐related serotonergic and cognitive deficits; (2) lack of clear association between changes in brain imaging measures and functional deficits attributed to MDMA‐induced neurotoxicity; (3) the contribution of concomitant cannabis or other drug use to both brain imaging abnormalities and cognitive deficits; (4) methodological shortcomings such as failure to adequately match samples of ecstasy users and controls; (5) the questionable relevance of animal models of MDMA‐induced neurotoxicity to typical human patterns of ecstasy use; and (6) the potential role of inherent pre‐drug deficits in serotonergic systems, impulse control and executive cognitive function that may predispose to excessive use of drugs including ecstasy. Given the retrospective nature of nearly all studies of ecstasy users to date, the controversy over whether MDMA has ever caused neurotoxicity or cognitive deficit in human ecstasy users is likely to continue for some time without resolution.

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Caveat Emptor Editors Beware

Cited by 30 publications

References 18 publications

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

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

Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?

Recreational ecstasy use and the neurotoxic potential of MDMA: current status of the controversy and methodological issues

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