Original Article

Neuropsychopharmacology (1999) 20, 565–581. doi:10.1016/S0893-133X(98)00089-X

Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG

Euphrosyne Gouzoulis-Mayfrank MD1, Mathias Schreckenberger MD2,3, Osama Sabri MD2, Christoph Arning2, Bernhard Thelen MD1, Manfred Spitzer MD, Ph.D2,3, Karl-Artur Kovar Ph.D4, Leopold Hermle MD5, Udalrich Büll MD2 and Henning Sass MD1

  1. 1Department of Psychiatry and Psychotherapy, University of Technology (RWTH), Aachen, Germany
  2. 2Department of Nuclear Medicine, University of Technology (RWTH), Aachen, Germany
  3. 3Department of Psychiatry, University of Ulm, Ulm, Germany
  4. 4Pharmaceutical Institute, University of Tübingen, Tübingen, Germany
  5. 5Psychiatric and Neurological Hospital Christophsbad, Göppingen, Germany

Correspondence: E. Gouzoulis-Mayfrank, M.D., Department of Psychiatry and Psychotherapy, University of Technology (RWTH), Pauwelsstrasse 30, D-52074 Aachen, Germany

Received 14 March 1998; Accepted 20 July 1998



The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2–0.4 mg/kg) and the drugs’ interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation: word association) within 2–4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.


Psilocybin; MDE; Ecstasy; Methamphetamine; Model psychosis; FDG-PET; Activation study

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