Negative allosteric modulation of CB₁ cannabinoid receptor signaling suppresses opioid-mediated reward.

ABSTRACT: Blockade of cannabinoid type 1 (CB₁)-receptor signaling decreases the rewarding properties of many drugs of abuse and has been proposed as an anti-addiction strategy. However, psychiatric side-effects limit the clinical potential of orthosteric CB₁ antagonists. Negative allosteric modulators (NAMs) represent a novel and indirect approach to attenuate CB₁ signaling by decreasing affinity and/or efficacy of CB₁ ligands. We hypothesized that a CB₁-NAM would block opioid reward while avoiding the unwanted effects of orthosteric CB₁ antagonists. GAT358, a CB₁-NAM, failed to elicit cardinal signs of direct CB₁ activation or inactivation when administered by itself. GAT358 decreased catalepsy and hypothermia b

SUBMITTER: Iyer V 

PROVIDER: S-EPMC9948526 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature