Human Research on MDMA (3,4-Methylene- dioxymethamphetamine) Neurotoxicity: Cognitive and Behavioural Indices of Change

Abstract

Laboratory animals can develop serotonergic neurotoxicity after repeated doses of 3,4-methylenedioxymethamphetamine (MDMA) or ‘Ecstasy’. If similar neural damage occurs in humans, this may be evident in cognitive or behavioural impairments. In a review of the behavioural skills shown by drug-free recreational Ecstasy users, three aspects of cognitive performance are often affected: reduced memory for new information (Rivermead Behavioral Memory, supraspan word recall), impaired higher executive processing (Wisconsin Card Sort, Tower of London), and heightened impulsivity (Impulsiveness, Venturesomeness and Empathy Questionnaire, Matching Familiar Figures test). Performance on other more basic cognitive functions is generally unimpaired (simple reaction time, choice reaction time, number vigilance, Stroop, trail making). Some Ecstasy users also complain of poor memories and/or concentration difficulties, which they attribute to MDMA use. There are many methodological problems and uncertainties with research in this field: non-random allocation of subjects to drug conditions, the deleterious effects of other psychoactive drugs, and the possibility that these adverse profiles reflect pre-existing personality characteristics in Ecstasy users. However, this particular pattern of cognitive decrements in humans, is consistent with the animal data on those brain areas showing serotonergic damage following MDMA: the frontal cortex (impulsivity and higher cognitive impairments), and hippocampus (memory deficits). Finally, this profile of cognitive deficits is also consistent with a hypothetical integrative construct: namely reduced cortical inhibition.

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

“…Studies of MDMA users report no effect, increases, or decreases in selfperceptions of anxiety (Liester et al 1992;Morgan 1998;Parrott 2000;Verkes et al 2001;Wareing et al 2000). These diverse results suggest that MDMA influences on anxiety levels are likely dependent upon the total exposure to MDMA, the time of abstinence from the drug, use of other drugs, and the type of anxiety assessed.…”

“…Some human MDMA users have also reported increased levels of anxiety that can persist even after periods of abstinence from the drug (Gamma et al 2000;Parrott 2000;Verkes et al 2001;Wareing et al 2000). Animals treated with brief, high-dose regimens also exhibit persistent increases in anxiety-like behaviors, even without long-term serotonin depletion (Clemens et al 2004;Fone et al 2002;Gurtman et al 2002;McGregor et al 2003).…”

Acute Effects of 3,4-Methylenedioxymethamphetamine (MDMA) on Behavioral Measures of Impulsivity: Alone and in Combination with Alcohol

“…Studies that have examined the effect of MDMA on impulsivity in abstinent MDMA users have provided conflicting results. McCann et al (1994) reported a decrement in impulsivity ratings of MDMA users as measured by the Multidimensional Personality Questionnaire, whereas others reported elevated scores of impulsivity in heavy MDMA users, using different subjective measures of impulsivity (Butler and Montgomery, 2004;Morgan, 1998Morgan, , 2000Parrott, 2000). Elevated levels of impulsiveness have been associated with lower levels of 5HT and CSF-5HIA (Linnoila et al, 1983(Linnoila et al, , 1993 and with dopaminergic activation in the prefrontal cortex leading to a reduction in 'inhibitory control' over behavioral functions (Jentsch and Taylor, 1999).…”

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

“…There is also evidence that the popular recreational drug ecstasy (3,4-methelenedioxymethamphetamine, MDMA) causes damage to the 5-HT axons both in animals (eg Hatzidimitriou et al, 1999;Ricaurte et al, 2000) and humans (Gerra et al, 1998;Kish et al, 2000). The use of ecstasy is associated with decreased memory function and increased symptoms of depression (Parrott, 2000;Verbaten, 2003; Thomasius et al, 2003).…”