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Vollenweider Hasler

Fakultäten » Medizinische Fakultät » Psychiatrische Universitätsklinik » Psychiatrie, Psychotherapie und Psychosomatik, Klinik für » Prof. Dr. Daniel Hell (emeritiert) » Vollenweider Hasler

Completed research project

Title / Titel Investigation of the Role of 5-HT2A Receptors in the Mediation of Cognitive and Perceptive Alterations in the Psilocybin Model of Psychosis. A PET study with [18F]-Altanserin.
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung Evidence from animal and human studies suggest that the integrity of 5-HT2 and 5-HT1 receptor function is crucial in the mediation of perception, mood, and cognition. Several lines of evidence including the pharmacodynamic mechanisms of action of atypical neuroleptics suggest that 5-HT2A receptors are also involved in the pathophysiology of schizophrenia.

The classic hallucinogen psilocybin is a mixed 5-HT2A/5-HT1A agonist. In healthy subjects, psilocybin produces a number of psychosis-like symptoms and cognitive deficits that resemble positive symptoms and cognitive deficits seen in incipient and acute stages of schizophrenic episodes. However, it is completely unknown where and to what extent psilocybin interacts with 5-HT2A receptors in the human brain.

Primary aim of this study is to localise and quantify 5-HT2A receptor occupancy in the brain following administration of psilocybin to healthy subjects by means of Positron Emission Tomography (PET) and the 5-HT2A receptor specific radioligand [18F]-altanserin. A further aim is to investigate whether 5-HT2A receptor occupancy during psilocybin challenge correlates with psilocybin-induced cognitive alterations, perceptual disturbances, or positive symptoms.

During 2005/2006, radiochemical synthesis of [18F]-altanserin was established at the PET-laboratory of the Department of Nuclear Medicine of the University Hospital Zürich in close collaboration with Mrs. Olga Kuznetsova from the Institute for the Human Brain in St. Petersburg, Russia. Validation procedures of tracer synthesis and analytical methods have been completed according to GMP guidelines.

To date (November 2008), eleven study subjects received [18F]-altanserin PET scans under both placebo and psilocybin condition. In our controlled clinical setting, the administration of psilocybin was well tolerated by all subjects without adverse effects. Also the PET scanning procedure of 90 min duration was not reported to be experienced stressfully. Preliminary PET data analysis revealed a strong and consistent decrease (≥ 30%) of distribution volume of [18F]-altanserin in the psilocybin condition as compared to placebo. Alterations in [18F]-altanserin binding were most pronounced in cortical regions and less change in tracer binding was seen in the basal ganglia. We also found that the subjective experience of altered states of consciousness induced by psilocybin is correlated with 5-HT2A receptor activation in the anterior cingulate and medial prefrontal cortex.
Publications / Publikationen Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Babler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport. 1998;9:3897-3902.
Keywords / Suchbegriffe Psilocybin, Serotonin, Altanserin, 5-HT2A, Positron Emission Tomography, PET, Receptor Mapping, Human Study, Model Psychosis, Cognition, Schizophrenia
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. F.X. Vollenweider (Project Leader) vollen@bli.uzh.ch
Dr. F. Hasler (Project Leader) fehasler@bli.uzh.ch
Prof. Dr. A.P. Schubiger  
Dr. B.B. Quednow quednow@bli.uzh.ch
Funding source(s) /
Unterstützt durch
Foundation
Heffter Research Insitute, Santa Fe, New Mexico, USANARSAD Young Investigator Award Program, USA
In collaboration with /
In Zusammenarbeit mit
Olga Kuznetsova, Institute for the Human Brain, St. Petersburg, Russia Russia
Prof. Trevor Robbins, Department of Experimental Psychology, University of Cambridge, Great Britain United Kingdom
Prof. P.A. Schubiger, PET Zentrum USZ und PSI Switzerland
Duration of Project / Projektdauer Aug 2003 to Jun 2009