The NeXT Study; The Netherlands XTC Toxicity Study
Condition: Ecstasy (Drug); N-Methyl-3,4-Methylenedioxymethamphetamine; Psychopathology
Study type: Observational

Summary: 
      The purpose of this study is to investigate the possible neurotoxic effects of the party-drug
      Ecstasy (MDMA)on brain and brain function in humans. Main research questions concern the
      causality, course and clinical relevance of the neurotoxicity of ecstasy
    

Detailed description: 
      The study aims to investigate the causality, course and clinical relevance of the observed
      neurotoxicity in het human brain among users of the popular recreational drug
      3,4-methylenedioxymethamphetamine (MDMA). Studies in animals and non-human primates suggest
      that MDMA is toxic toward brain serotonin neurons at doses that overlap those used by humans.
      Much less is known about the effects of this drug on the human brain. Recent studies,
      however, suggest that MDMA might also be neurotoxic to 5-HT neurons in humans, and that it is
      associated with functional consequences, such as memory impairment and depression. However,
      these studies have been retrospective and potentially vulnerable to selection bias and
      confounding. Clearly, only a prospective study can ascertain that recreational XTC is
      neurotoxic in humans. However, given the existing data such a study is ethically not
      acceptable. In the present project, therefore, we have chosen a naturalistic study using a
      combination of prospective and retrospective approaches: a prospective study among 200 XTC
      naive subjects with a high-risk profile for first XTC use with a two-year follow up of 50
      incident-, and 50 continuously XTC naive subjects, and a retrospective design of 25 subjects
      with and 25 subjects without prior exposure to XTC selected from a large representative
      cohort (N=1600) that was prospectively followed from the age of 12. In addition, a cross
      sectional design is used of 70 subjects with variation in type and amount of drugs used,
      besides a history of frequent XTC use. Among the 50 incident cases and the sample of 50
      continuously XTC-naive subjects in the prospective cohort, indicators of neurotoxicity
      (SPECT,1H-MRS), markers of neuronal injury (fMRI, Perfusion MRI), and clinical assessments of
      memory, mood and personality prior to any XTC use will be compared with the same parameters
      two years later, i.e. after XTC user has taken place in the incident cases. In the
      retrospective cohort, subjects with lifetime XTC exposure will be compared with XTC naive
      subjects on the same neurotoxicity, neural injury and psychopathology parameters, controlling
      for potential confounders that were assessed prior to the first use of XTC. In the cross
      sectional cohort, all subjects will be assessed on the same neurotoxicity, neural injury and
      psychopathology parameters, controlling for the confounding effects of the use of other
      psychoactive drugs besides XTC. The combined results will result in conclusions that can be
      validly used in prevention messages, clinical decision making and the development op a
      national XTC policy.
    

Observational model: Defined Population
Time perspective: Other
Keywords: Ecstasy; MDMA; Cognition; Brain function; Neuroimaging