Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis

Abstract

KeywordsCannabinoid receptor type 1; endocannabinoid system; first-episode psychosis; positron emission tomography. AbstractThere is an established, albeit poorly-understood link between psychosis and metabolic abnormalities such as altered glucose metabolism and dyslipidemia, which often precede the initiation of antipsychotic treatment. It is known that obesity-associated metabolic disorders are promoted by peripheral activation of the endocannabinoid system (ECS). Our recent data suggest that ECS dysregulation may also play a role in psychosis. With the aim of characterizing the involvement of the central and peripheral ECSs and their mutual associations, here we performed a combined neuroimaging and metabolomic study in patients with first-episode psychosis (FEP) and healthy controls (HC). Regional brain cannabinoid receptor type 1 (CB1R) availability was quantified in two, independent samples of patients with FEP (n=20 and n=8) and HC (n=20 and n=10), by applying 3D positron emission tomography (PET), using two radiotracers, [ 11 C]MePPEP and [ 18 F]FMPEP-d2. Ten endogenous endocannabinoids or related metabolites were quantified in serum, drawn from these individuals during the same imaging session. Circulating levels of arachidonic acid and oleyl ethanolamide were reduced in FEP individuals, but not in those who were predominantly medication-free. In HC, there was an inverse association between levels of circulating arachidonoyl glycerol, anandamide, oleyl ethanolamide and palmitoyl ethanolamide, and CB1R availability in the posterior cingulate cortex. This phenomenon was, however, not observed in FEP patients. Our data thus provide evidence of cross-talk and dysregulation between peripheral endocannabinoids and central CB1R availability in FEP.

Association Between Circulating Lipids and Future Weight Gain in Individuals With an At-Risk Mental State and in First-Episode Psychosis

“…Our positron emission tomography (PET) imaging data suggest that the brain ECS is dysregulated in FEP, including in drug-naïve patients [38]. Brain CB1R availability, as measured by PET imaging, associates with changes in peripheral endocannabinoid levels [39]. Furthermore, there is a large body of literature suggesting that the ECS modulates energy intake [40], and that the development of NAFLD is promoted by peripheral activation of the ECS [41].…”

Structural correlates of sensorimotor dysfunction in heavy cannabis users

“…Cannabis does not contribute directly (through cannabis intoxication) to the development of NSS but rather by modulating the endocannabinoid system, which regulates the mesolimbic dopamine release, and inducing a sensorimotor dysfunction within the CCTCC. Future research requires carefully designed longitudinal MRI studies, preferably combining information from positron‐emission‐tomography (e.g., [ 18 F]FMPEP‐d2 or [ 11 C]MePPEP PET tracers, 69 as much as careful consideration of further demographic and clinical characteristics; e.g., persons at high clinical risk for psychosis and individuals with first‐episode psychosis with comorbid cannabis use) to elucidate the full spectrum of sensorimotor dysfunction of HCU in more detail.…”

Circulating lipids associate with future weight gain in individuals with an at-risk mental state and in first-episode psychosis

“…Our positron emission tomography (PET) imaging data suggest that the brain ECS is dysregulated in FEP, including in drug-naïve patients [38]. Brain CB1R availability, as measured by PET imaging, associates with changes in peripheral endocannabinoid levels [39]. Furthermore, there is a large body of literature suggesting that the ECS modulates energy intake [40], and that the development of NAFLD is promoted by peripheral activation of the ECS [41].…”