Genetic deletion of NAPE-PLD induces context-dependent dysregulation of anxiety-like behaviors, stress responsiveness, and HPA-axis functionality in mice.

Unlabelled: The endocannabinoid (eCB) system regulates stress responsiveness and hypothalamic-pituitary-adrenal (HPA) axis activity. The enzyme -acyl phosphatidylethanolamine phospholipase-D (NAPE-PLD) is primarily responsible for the synthesis of the endocannabinoid signaling molecule anandamide (AEA) and other structurally related lipid signaling molecules known as -acylethanolamines (NAEs). However, little is known about how activity of this enzyme affects behavior.

Negative allosteric modulation of CB cannabinoid receptor signaling suppresses opioid-mediated tolerance and withdrawal without blocking opioid antinociception.

The direct blockade of CB cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB negative allosteric modulators (NAMs) represent an indirect approach to decrease the affinity and/or efficacy of orthosteric cannabinoid ligands or endocannabinoids at CB. We recently reported that GAT358, a CB-NAM, blocked opioid-induced mesocorticolimbic dopamine release and reward via a CB-allosteric mechanism of action.

Negative allosteric modulation of cannabinoid CB receptor signaling suppresses opioid-mediated tolerance and withdrawal without blocking opioid antinociception.

Unlabelled: The direct blockade of CB cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB negative allosteric modulators (NAMs) represent an indirect approach to decrease the affinity and/or efficacy of orthosteric cannabinoid ligands or endocannabinoids at CB . We recently reported that GAT358, a CB -NAM, blocked opioid-induced mesocorticolimbic dopamine release and reward via a CB -allosteric mechanism of action.