Critical interactions between opioid and cannabinoid receptors during tolerance and physical dependence development to opioids in the murine gastrointestinal tract: proof of concept.

Introduction: Tolerance (TOL) and physical dependence (PD) constitute important limitations of opioid therapy. The aim of our study was to validate research tools to investigate TOL and PD and to characterize the interactions between opioid (OR) and cannabinoid (CB) receptors in these processes in the GI tract.

Methods: TOL was assessed through the comparison of morphine ability to inhibit electrically evoked smooth muscles contractility in the mouse ileum that was previously incubated with/without morphine for 1 h.

Novel orally available salvinorin A analog PR-38 protects against experimental colitis and reduces abdominal pain in mice by interaction with opioid and cannabinoid receptors.

Background: Salvinorin A (SA) is a potent anti-inflammatory diterpene isolated from the Mexican plant S. divinorum. Recently we showed that the novel SA analog, PR-38 has an inhibitory effect on mouse gastrointestinal (GI) motility mediated by opioid and cannabinoid (CB) receptors.