Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers - A double-blind, placebo-controlled PET study with [F-18]FDG

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the s timulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interaction s with a prefrontal activation task were investigated in a double-blind, pl acebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomogr aphicPET 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 reg ions, particularly in the anterior cingulate and decreased rMRGlu in the th alamus. Both MDE and METH induced cortical hypometabolism and cerebellar hy permetabolism. In the MDE group, cortical hypometabolism was more pronounce d in frontal regions, with the exception of the right anterior cingulate, w hich tended to be hyperactive. Cognitive activation-related increases in le ft frontocortical regions were attenuated under all three psychoactive subs tances, but less so under MDE. Taking into account performance data and sub jective 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, bm t 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. (C) 1999 American College of Neuropsychophar macology. Published by Elsevier Science Inc.