Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET

Abstract

Brain cannabinoid 1 receptors (CB1Rs) contribute importantly to the regulation of autonomic tone, appetite, mood and cognition. Inconsistent results have been reported from positron emission tomography (PET) studies using different radioligands to examine relationships between age, gender and body mass index (BMI) and CB1R availability in healthy individuals. In this study, we examined these variables in 58 healthy individuals (age range: 18-55 years; 44 male; BMI=27.01±5.56), the largest cohort of subjects studied to date using the CB1R PET ligand [¹¹C]OMAR. There was a significant decline in CB1R availability (V_T) with age in the pallidum, cerebellum and posterior cingulate. Adjusting for BMI, age-related decline in V_T remained significant in the posterior cingulate among males, and in the cerebellum among women. CB1R availability was higher in women compared to men in the thalamus, pallidum and posterior cingulate. Adjusting for age, CB1R availability negatively correlated with BMI in women but not men. These findings differ from those reported using [¹¹C]OMAR and other radioligands such as [¹⁸F]FMPEP-d₂ and [¹⁸F]MK-9470. Although reasons for these seemingly divergent findings are unclear, the choice of PET radioligand and range of BMI in the current dataset may contribute to the observed differences. This study highlights the need for cross-validation studies using both [¹¹C]OMAR and [¹⁸F]FMPEP-d₂ within the same cohort of subjects.

Keywords: Age effect; Body-mass index; Cannabinoid 1 receptor; Gender effect; Healthy humans; Positron Emission Tomography; [(11)C]OMAR.