Clinical Neuroscience: Elevated endogenous cannabinoids in schizophrenia

CACorresponding Author These authors contributed equally to this study 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 ̄uid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were puri®ed from cerebrospinal ̄uid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quanti®ed by isotope dilution gas-chromatography/massspectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were signi®cantly 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 ®ndings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal ̄uid of schizophrenic patients may re ̄ect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia. NeuroReport 10:1665±1669 # 1999 Lippincott Williams & Wilkins.