Negative allosteric modulation of CB1 cannabinoid receptor signalling decreases intravenous morphine self-administration and relapse in mice.

ABSTRACT: The endocannabinoid system interacts with the reward system to modulate responsiveness to natural reinforcers, as well as drugs of abuse. Previous preclinical studies suggested that direct blockade of CB1 cannabinoid receptors (CB1R) could be leveraged as a potential pharmacological approach to treat substance use disorder, but this strategy failed during clinical trials due to severe psychiatric side effects. Alternative strategies have emerged to circumvent the side effects of direct CB1 binding through the development of allosteric modulators. We hypothesized that negative allosteric modulation of CB1R signalling would reduce the reinforcing properties of morphine and decrease behaviours associated with opioid misuse. By employing intravenous self-administration in mice, we studied the

SUBMITTER: Oliva I 

PROVIDER: S-EPMC11304470 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature