|Title||Cannabinoid-2 Agonism with AM2301 Mitigates Morphine-Induced Respiratory Depression.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Wiese BM, Liktor-Busa E, Levine A, Couture SA, Nikas SP, Ji L, Liu Y, Mackie K, Makriyannis A, Largent-Milnes TM, Vanderah TW|
|Journal||Cannabis Cannabinoid Res|
|Date Published||2020 Nov 13|
An escalating number of fatalities resulting from accidental opioid overdoses typically attributed to respiratory depression continue to define the opioid epidemic. Opioid respiratory depression results from a decrease in reflexive inspiration within the preBötzinger complex in the brainstem. Cannabinoid receptor agonism is reported to enhance opioid analgesia, yet whether cannabinoids enhance or inhibit opioid-induced respiratory depression is unknown. Studies herein sought to define the roles of cannabinoid-1 receptor (CB1R) and cannabinoid-2 receptor (CB2R) on respiratory depression using selective agonists alone and in combination with morphine in male mice. Using whole body plethysmography, the nonselective CB1R and CB2R agonist (Δ-tetrahydrocannabinol) and the CB1R synthetic cannabinoid, AM356, induced respiratory depression, whereas the well-published selective CB2 agonist, JWH 133, and the novel CB2 agonist (AM2301) did not. Moreover, a selective CB2R agonist (AM2301) significantly attenuated morphine sulfate-induced respiratory depression. Notably, findings suggest that attenuation of opioid-induced respiratory depression relies on CB2R activation, supporting selective CB2R agonism as an opioid adjunct therapy.
|Alternate Journal||Cannabis Cannabinoid Res|
Cannabinoid-2 Agonism with AM2301 Mitigates Morphine-Induced Respiratory Depression.
Faculty Member Reference:
Erika Liktor-Busa, PhD, PharmD
Tally Largent-Milnes, PhD
Todd Vanderah, PhD