Towards a Cannabinoid Hypothesis of Schizophrenia: Cognitive Impairments Due to Dysregulation of the Endogenous Cannabinoid System

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also by an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes. Herein, the perceptual abnormalities induced by psychotogenic agents play a major role as tools for the understanding of model psychoses. The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulator system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses. Neuropsychological results (three-dimensional inversion illusion) in delta 9-tetrahydrocannabinol-intoxicated normal volunteers exhibit strong similarities with data acquired from patients suffering from productive schizophrenic psychoses, regarding disturbances in internal regulation of perceptual processes. The relevance of this finding to a general cognitive dysfunction concept of schizophrenic psychosis is discussed.