Association between cannabinoid 1 receptor availability and glutamate levels in healthy controls and drug-free patients with first episode psychosis: a multi-modal PET and 1H-MRS study.

Cannabinoid 1 receptor and glutamatergic dysfunction have both been implicated in the pathophysiology of schizophrenia. However, it remains unclear if cannabinoid 1 receptor alterations shown in drug-naïve/free patients with first episode psychosis may be linked to glutamatergic alterations in the illness. We aimed to investigate glutamate levels and cannabinoid 1 receptor levels in the same region in patients with first episode psychosis. Forty volunteers (20 healthy volunteers, 20 drug-naïve/free patients with first episode psychosis diagnosed with schizophrenia/schizoaffective disorder) were included in the study. Glutamate levels were measured using proton magnetic resonance spectroscopy. CB1R availability was indexed using the distribution volume (V (ml/cm)) of [C]MePPEP using arterial blood sampling. There were no significant associations between ACC CB1R levels and ACC glutamate levels in controls (R = - 0.24, p = 0.32) or patients (R = - 0.10, p = 0.25). However, ACC glutamate levels were negatively associated with CB1R availability in the striatum (R = - 0.50, p = 0.02) and hippocampus (R = - 0.50, p = 0.042) in controls, but these associations were not observed in patients (p > 0.05). Our findings extend our previous work in an overlapping sample to show, for the first time as far as we're aware, that cannabinoid 1 receptor alterations in the anterior cingulate cortex are shown in the absence of glutamatergic dysfunction in the same region, and indicate potential interactions between glutamatergic signalling in the anterior cingulate cortex and the endocannabinoid system in the striatum and hippocampus.