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.2021 Jun;271(4):677-687.
doi: 10.1007/s00406-020-01191-2. Epub 2020 Sep 28.

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

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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

Faith Borgan et al. Eur Arch Psychiatry Clin Neurosci.2021 Jun.

Abstract

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 (VT (ml/cm3)) of [11C]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.

Keywords: Cannabinoid; Cannabinoid 1 receptor; Endocannabinoid system; Glutamate; Schizophrenia.

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Conflict of interest statement

FB became an employee at COMPASS Pathways Plc after the completion of this work. This work is unrelated to COMPASS Pathways Plc., M.V., and T. M. reported no potential conflicts of interest. O.H. reported receiving investigator-initiated research funding from or participating in advisory or speaker meetings organized by AstraZeneca, Autifony, Bristol-Myers Squibb, Eli Lilly, Heptares, Janssen, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, RAND, and Roche. J.H. reported speaker fees in meetings organized by Orion Pharma, Lundbeck, and Otsuka.

Figures

Fig. 1
Fig. 1
Coronal (left), axial (middle), and sagittal (right) planes depicting the placement of the voxel over the anterior cingulate during the proton magnetic resonance spectroscopy scan. The placement of the anterior cingulate voxel was based on the midline sagittal localizer with the centre of the 20 mm × 20 mm × 20 mm voxel placed 13 mm above the anterior portion of the genu of the corpus callosum, perpendicular to the anterior commissure–posterior commissure line to minimize the inclusion of white matter and cerebral spinal fluid
Fig. 2
Fig. 2
Scatter plot showing no association was detected between anterior cingulate cortex glutamate levels (ppm) and anterior cingulate cortex cannabinoid 1 receptor availability, indexed using the VT of [11C]MePPEP ina healthy volunteers controls (R = − 0.24,p = 0.32) orb patients (R = − 0.10,p = 0.25)
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