976 BIOL PSYCHIATRY 1992;32:976-991 Mescaline-Induced Psychopathological, Neuropsychological, and Neurometabolic Effects in Normal Subjects: Experimental Psychosis as a Tool for Psychiatric Research Leo Hermle, Matthias Ftinfgeld, Godehard Oepen, Hanno Botsch, Dieter Borchardt, Euphrosyne Gouzoulis, Rose A. Fehrenbach, and Manfred Spitzer The psychological, neuropsychological, and neurometubolic effects of the hallucinogenic agent mescaline were investigated in 12 normal men who were volunteers. Mescaline produced an acute psychotic state 3½-4 hr after drug intake, as measured by the Brief Psychiatric Rating Scale (BPRS) and Paranoid Depression Scale (PDS). The Assessment of Altered States of Consciousness (APZ) questionnaire revealed specific effects of mes- caline in the visual system. Neuropsychological effects were studied with a face/ttonface decision task with known right-hemisphere advantage, in which mescaline induced a decrease of functioning of the right hemisphere. In functional brain imaging using single photon emission computed tomography (SPECT), mescaline produced a "hyperfrontai" pattern with an emphasis on the right hemisphere, which was correlated with mescaline- induced psychotic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for schizophrenic symptomatology. The study of psy- choactive substances under controlled laboratory conditions has the methodological ad- vantage of intraindividual control, and hence, minimal variability of data. Introduction Hallucinogenic drugs produce qualitative and quantitative alterations of consciousness. In particular, the psychopathological effects of mescaline have been described by Beringer as early as 1927. In the 1950s and 1960s hallucinogens, such as 3,4,5- trimethoxy- phenethylamine (mescaline), lysergic acid diethylamide (LSD), PCP, etc. were widely used to produce changes of perception, thought and mood, which were thought to resemble schizophrenia to some extent (Hermle et al 1988). Advantages of the investigation of From the Department of Psychiatry, Christophsbad, G6ppingen, Germany (LH); Department of Psychiatry, University of Freiburg (MF. DH, EG, RAF); Department of Psychiatry, Harvard Medical School, Cambridge, MA (GO); St. Josefs- Hospital, Freiburg, Germany (HB); and the Department of Psychiatry, University of Heidelberg, Germany (MS). Address reprint requests to Dr. Leo Hermle, Department of Psychiatry, Christophsbad, Faurndauerstrasse 16, D-7320 G6p- pingen, Germany. Received February 18, 1992; revised June 17, 1992. © 1992 Society of Biological Psychiatry 0006-3223/92/$05.00