Title:The Endocannabinoid System and Schizophrenia: Integration of Evidence
VOLUME: 18 ISSUE: 32
Author(s):Erica Zamberletti, Tiziana Rubino and Daniela Parolaro
Affiliation:Department of Theoretical and Applied Sciences, Biomedical Division, and Neuroscience Center, University of Insubria, via A. da Giussano 10, 21052 Busto Arsizio (VA), Italy.
Keywords:Cannabinoid, cannabis, endocannabinoid system, psychosis, schizophrenia, animal models, human studies, CNS, dysregulation, controlled trials.
Abstract:Cannabis derivatives produce their CNS effect through activation of the endocannabinoid system, a recently discovered signalling
system comprising specific receptors, their intrinsic lipid ligands and the associated enzymatic machinery (transporters, biosynthetic
and degradative enzymes). This review provides the latest preclinical and clinical breakthroughs on the endocannabinoid system's role in
psychotic disorders such as schizophrenia. Data reported so far clearly indicate the presence of a dysregulation in the endocannabinoid
system (both in term of cannabinoid receptors and endocannabinoid ligands) in animal models of psychosis as well as in schizophrenic
patients. Based on these observations, the pharmacological modulation of the endocannabinoid system has been taken into account as a
new therapeutic possibility for psychotic disorders. However, preclinical studies have not provided straightforward results, with both
agonists and antagonists exhibiting positive, negative or even no effect. At human level, only cannabidiol, a non psychotropic phytocannabinoid,
and the antagonist/inverse agonist rimonabant were tested, however additional controlled trials are required to confirm the
therapeutic exploitation of these compounds. Another important aspect in studying the relationship between the endocannabinoid system
and schizophrenia is the impact of Cannabis consumption on psychotic disorders, especially when this occurs at vulnerable ages such as
adolescence. In fact literature from animal models support adolescence as a highly vulnerable age for the consequences of cannabis exposure
on different domains (such as cognition and social behaviour) that are altered in psychotic disorders.
