Is the highest density of CB1 receptors in paranoid schizophrenia a correlate of endocannabinoid system functioning?

Abstract

Evaluation of: Dalton VS, Long LE, Weickert CS, Zavitsanou K. Paranoid schizophrenia is characterized by increased CB(1) receptor binding in the dorsolateral prefrontal cortex. Neuropsychopharmacology 36(8), 1620–1630 (2011).

Increased binding of type 1 cannabinoid (CB1) receptor ligands in the dorsolateral prefrontal cortex and other areas has been shown in post-mortem studies, although there are some inconsistent results. The study by Dalton et al. employed a more rigorous control for potentially confounding variables and investigated whether the density of CB1 receptors and their mRNA expression were different in subtypes of schizophrenia patients. They observed an increased density of CB1 receptors in paranoid schizophrenia as compared with nonparanoid schizophrenia patients and controls. This finding strengthens the evidence for the involvement of endocannabinoids in schizophrenia. However, it is difficult to reconcile with previous observations of increased levels of anandamide in the cerebrospinal fluid in paranoid schizophrenia, since CB1 receptor agonists were shown to induce the downregulation of these receptors. The precise role of the endocannabinoid system in the pathophysiology of schizophrenia remains far from understood.

Keywords::

• CB1 receptor
• endocannabinoid system
• paranoid schizophrenia
• pathophysiology
• post-mortem

Financial & competing interests disclosure

Antonio Waldo Zuardi, Fransisco Silveira Guimarães, Jaime Eduardo C Hallak and José Alexandre S Crippa are recipients of Conselho Nacional de Pesquisa (CNPq) Productivity Awards. This study was partially funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and CNPq. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.