The endocannabinoid system and brain function
Evaluating cannabinoid 1 (CB1) receptor availability in schizophrenia: an [11C]-MePPEP PET study
King's College London
Schizophrenia is a complex brain disorder associated with significant disability and mortality which affects approximately 1% of the population. Genetic alterations in combination with diverse environmental insults are likely to result in the brain abnormalities underlying schizophrenia, though the precise pathophysiology is not completely understood. Several neurotransmitters systems, including dopaminergic, glutamatergic, and gamma-aminobutyric acid (GABA) are dysregulated in schizophrenia and it has been established that metabolic abnormalities occur prior to the use of antipsychotics. Recent studies indicate that first episode psychosis is associated with an increase in inflammatory markers.
The Endocannabinoid system (ECS) is a complex system which plays a role in the modulation of neurotransmitters, metabolism and inflammation. There are two cannabinoid receptors, CB1 located in the brain and CB2 located in cells of the immune system. The main psychoactive component of cannabis (∆9-tetrahydrocannabinol) can induce psychotic symptoms in healthy individuals and increases the rate of conversion to psychosis in those at risk of developing psychosis.
Previous studies have demonstrated an increase in CB1 receptor availability in schizophrenia, however this study will be the first to investigate the CB1 receptor in different stages of psychosis. The aim of this study is to investigate CB1 receptor availability using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) in people at risk of psychosis (N=25), in people with psychosis (N=25) and in healthy controls (N=25). This information will be correlated with inflammatory markers, metabolic markers, endocannabinoids, and genetic markers.
The information acquired about the ECS in this study will advance the understanding of the pathophysiology of schizophrenia and offers potential as both a biomarker and a therapeutic target for schizophrenia.
London - Camberwell St Giles Research Ethics Committee
Date of REC Opinion
4 Aug 2014
Further Information Favourable Opinion