Resting State Brain Networks under Inverse Agonist versus Complete Knockout of the Cannabinoid Receptor 1.
ACS Chemical Neuroscience April 17, 2024 Hui Li, Qiong Ye, Da Wang et al.
Suppressing the cannabinoid receptor 1 (CB1) has been proposed as a treatment for conditions like obesity and Parkinson's disease, but a clinical trial produced unanticipated psychological side effects. Using in vivo imaging in mice, the authors show that complete genetic knockout of the CB1 gene (cnr1-/-) alters white matter structure and functional directional uniformity (in male mice) across the brain while largely preserving network activity. In contrast, the CB1 inverse agonist rimonabant alters network activity in cortical regions known to be affected by THC but does not affect directional uniformity. Chronic loss of cnr1 differs substantially from short-term pharmacological suppression, which may explain why pathological CB1 mutations do not predict side effects of CB1-suppressing drugs.