Peripheral Endogenous Cannabinoid Levels Are Increased in Schizophrenia Patients Evaluated in a Psychiatric Emergency Setting.

Stéphane Potvin,Alexandra Furtos,Marjolaine Chicoine,Roxane Assaf,Louiza Mahrouche,Roger Godbout,Charles-Édouard Giguère

doi:10.3389/fpsyt.2020.00628

Abstract

BackgroundThe endogenous cannabinoid system mediates the psychoactive effects of cannabis in the brain. It has been argued that this system may play a key role in the pathophysiology of schizophrenia. While some studies have consistently shown that the levels of anandamide, an endogenous cannabinoid ligand, are increased in the cerebrospinal fluid of schizophrenia patients, inconsistent results have been observed in studies measuring anandamide levels in the periphery. Here, we sought to determine if the assessment of peripheral anandamide levels in patients evaluated in a psychiatric emergency setting would show robust increases.MethodsOne hundred seven patients with a schizophrenia-spectrum disorder from the psychiatric emergency settings of the Institut Universitaire en Santé Mentale de Montréal and 36 healthy volunteers were included in the study. A subsample of thirty patients were assessed at two time points: at the emergency and at their discharge from the hospital. Anxious and depressive symptoms, sleep and substance use were assessed using self-report questionnaires. In addition to anandamide, the levels of oleoylethanolamide (OEA), an anorexigenic fatty-acid ethanolamide, were also measured, since the prevalence of the metabolic syndrome is increased in schizophrenia. Plasma levels of anandamide and OEA were measured using liquid chromatography and mass spectrometry.ResultsPlasma anandamide and OEA levels were significantly increased in schizophrenia patients, relative to controls (Cohen’s d=1.0 and 0.5, respectively). Between-group differences remained significant after controlling for metabolic measures. No differences were observed between schizophrenia patients with and without a comorbid substance use disorder at baseline. Importantly, the levels of both endocannabinoids significantly decreased after discharge from the emergency setting.ConclusionThe current results add to the growing body of evidence of endocannabinoid alterations in schizophrenia. The strong elevation of plasma anandamide levels in schizophrenia patients assessed in the psychiatric emergency setting suggests that anandamide and OEA area potential biomarkers of the psychological turmoil associated with this context.

Highlights

Schizophrenia is a complex psychiatric disorder, and its pathophysiology is not fully understood
The primary objective of the current study is to show that peripheral levels of anandamide are increased in schizophrenia patients evaluated in a psychiatric emergency setting
Anandamide levels were strongly increased in schizophrenia patients, relative to controls, with a large effect size (Cohen’s d=0.9; p < 0.001) (Table 1 and Figure 2)

Summary

Introduction

Schizophrenia is a complex psychiatric disorder, and its pathophysiology is not fully understood. Several experimental studies have shown that the administration of delta-9-tetrahydrocannabinol to healthy volunteers produces transient effects that are similar to the psychiatric symptoms and cognitive deficits seen in schizophrenia [3, 4]. These findings have fueled interest in examining the potential role of the endogenous cannabinoid system, which mediates the psychoactive effects of cannabis in the brain, in the pathophysiology of schizophrenia [5, 6]. The endogenous cannabinoid (ECB) system is complex and is composed of two primary natural ligands, namely anandamide and 2-arachidonoylglycerol (2-AG), and two primary receptors, CB1 and CB2 [7]. We sought to determine if the assessment of peripheral anandamide levels in patients evaluated in a psychiatric emergency setting would show robust increases

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Conclusion