Postmortem studies of the brain cannabinoid system in schizophrenia

As outlined elsewhere in this book epidemiological, clinical and genetic approaches have linked cannabis to schizophrenia from aetiological, contributory and exacerbating perspectives. These studies implicate cannabis use as deleterious in schizophrenia either in increasing its incidence, precipitating illness onset or worsening its outcomes. This suggests that inhaled or ingested components of cannabis may interact directly with biological systems relevant to schizophrenia. Much work has focussed on the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC), which appears to induce psychotic symptoms in both healthy controls and those with schizophrenia (D’Souza et al., 2005). However, there are at least 60 other bioactive components that could mediate the effects of cannabis in humans (Mechoulam and Hanus, 2000; and see Chapters 2 and 3). Hence, one explanation for the association of cannabis with schizophrenia is that the human endocannabinoid (eCB) system (ECS) may be disrupted in vulnerable individuals, predisposing them to the risk of developing, precipitating or exacerbating schizophrenia when exposed to cannabis. The human ECS is detailed elsewhere (see Chapter 3) and consists of a number of eCBs, their synthetic, degradative and transport pathways and the receptors to which they bind, principally the cannabinoid CB1 and CB2 receptors. The two major endocannabinoids are anandamide and 2-arachidonoyl glycerol (2-AG), with the latter predominating in the human central nervous system (CNS) (Piomelli, 2003). In addition to the CB1 and CB2 receptors, the endocannabinoids also activate other receptors in the CNS, including vanilloid (VR1), peroxisome proliferator-activated receptors, orphan G-protein coupled receptors (e.g. GPR55) and transmitter-gated ion channels (Pertwee, 2010). Although it is possible that any component of the ECS may be altered in individuals vulnerable to developing schizophrenia, methodological constraints have restricted investigation to a number of key elements.