The endogenous cannabinoid system in schizophrenia

Abstract

The human endogenous cannabinoid system is an appealing target in the investigation of schizophrenia. This is both because of clinical studies supporting the association between cannabis use and schizophrenia as well as the capacity of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) to induce psychotic symptoms in non-psychotic individuals (see Chapters 3–5). Only since the recent elucidation of the endogenous cannabinoid system have direct investigations into its potential role in schizophrenia and other neuropsychiatric disorders become possible. The endocannabinoid system contains the cannabinoid CB 1 , CB 1A and CB 2 receptors; the endogenous cannabinoids (most importantly, anandamide, 2-arachidonylglycerol (2-AG) and palmitoylethanolamide), their respective synthetic and degradative enzymes and a transport process. This chapter provides an overview of the human endogenous cannabinoid system, focusing specifically on those aspects relevant to schizophrenia (see also Chapters 1 and 2 for a broader overview), and then reviews studies concerning this system in schizophrenia. The human endogenous cannabinoid system The Cannabinoid CB 1 receptor in the brain The first component of the human endogenous cannabinoid system to be identified was the CB 1 receptor (Herkenham et al. , 1990). The gene for this receptor is located on region q14–q15 of chromosome 6 (Hoehe et al. , 1991) and encodes for a 472-amino-acid protein (Matsuda et al. , 1990). This receptor has seven trans -membrane-spanning domains and interacts with guanine nucleotide-binding proteins (G proteins) as part of its signal transduction mechanism, placing it within the superfamily of G protein-coupled receptors.