Clinical NeuroscienceElevated endogenous cannabinoids in schizophreniaLeweke, F M.1,4,6; Giuffrida, A2,6; Wurster, U3; Emrich, H M.1; Piomelli, D2,5Author Information 1Department of Clinical Psychiatry and Psychotherapy, Medizinische Hochschule Hannover, D-30623 Hannover, Germany 3Department of Neurology, Medizinische Hochschule Hannover, D-30623 Hannover, Germany 2Department of Pharmacology, 360 Med Surge II, University of California, Irvine, CA 92697-4625, USA 4Present address:Department of Psychiatry, Heinrich Heine University, D-40629 Düsseldorf, Germany 5Corresponding Author: D. Piomelli 6These authors contributed equally to this study ACKNOWLEDGEMENTS: Funded by grants from the National Institute of Drug Abuse (DA 12447 and DA 12431) and Roche Bioscience to D.P. We thank Drs I. W. Lipkin, M. Hornig, N. Stella and F. Rodríguez de Fonseca for critical reading of the manuscript and Dr M. A. Schuckit for helpful comments. We are grateful to Dr U. Schneider for discussion and practical support of the clinical part of the study. Dr U. Sprick gave us helpful logistic support. Received 17 March 1999; accepted 30 March 1999 NeuroReport: June 3rd, 1999 - Volume 10 - Issue 8 - p 1665-1669 Buy Abstract EVIDENCE suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/massspectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls (p < 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The findings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia. © 1999 Lippincott Williams & Wilkins, Inc.