Measuring Disturbance of the Endocannabinoid System in Psychosis

Abstract

Importance: The endocannabinoid system (ECS) is a lipid-based endogenous signaling system. Its relevance to psychosis is through the association between cannabis use and the onset and course of illness and through the antipsychotic properties of cannabidiol, a potential ECS enhancer. Objective: To conduct a systematic review and meta-analysis of the blood and cerebrospinal fluid (CSF) measures of the ECS in psychotic disorders. Data Sources: Web of Science and PubMed were searched from inception through June 13, 2018. The articles identified were reviewed, as were citations to previous publications and the reference lists of retrieved articles. Study Selection: Original articles were included that reported blood or CSF measures of ECS activity in patients with psychotic illnesses and in healthy controls. Data Extraction and Synthesis: PRISMA guidelines, independent extraction by multiple observers, and random-effects meta-analysis were used. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results. Main Outcomes and Measures: The clinical relevance of ECS modifications in psychotic disorders was investigated by (1) a quantitative synthesis of the differences in blood and CSF markers of the ECS between patients and healthy controls, and (2) a qualitative synthesis of the association of these markers with symptom severity, stage of illness, and response to treatment. Results: A total of 18 studies were included. Three individual meta-analyses were performed to identify the differences in ECS markers between people with schizophrenia and healthy controls. Five studies, including 226 patients and 385 controls, reported significantly higher concentrations of anandamide in the CSF of patients than controls (standardized mean difference [SMD], 0.97; 95% CI, 0.67-1.26; P