{"doi":"10.1089/can.2020.0076","title":"Cannabinoid-2 Agonism with AM2301 Mitigates Morphine-Induced Respiratory Depression","abstract":"Introduction: 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. Objective: Cannabinoid receptor agonism is reported to enhance opioid analgesia, yet whether cannabinoids enhance or inhibit opioid-induced respiratory depression is unknown. Methods: 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. Results: Using whole body plethysmography, the nonselective CB1R and CB2R agonist (Δ 9 -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. Conclusion: Notably, findings suggest that attenuation of opioid-induced respiratory depression relies on CB2R activation, supporting selective CB2R agonism as an opioid adjunct therapy.","journal":"Cannabis and Cannabinoid Research","year":2020,"id":78320,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":408275,"name":"Erika Liktor‐Busa","orcid":null,"position":1,"is_corresponding":false},{"id":407430,"name":"Aidan A. Levine","orcid":"0000-0003-1808-5228","position":2,"is_corresponding":false},{"id":408276,"name":"Sarah Couture","orcid":null,"position":3,"is_corresponding":false},{"id":407431,"name":"Spyros P. Nikas","orcid":"0000-0001-5052-5292","position":4,"is_corresponding":false},{"id":407432,"name":"Lipin Ji","orcid":"0000-0001-9956-3855","position":5,"is_corresponding":false},{"id":407433,"name":"Yingpeng Liu","orcid":"0000-0002-2752-2947","position":6,"is_corresponding":false},{"id":227564,"name":"Ken Mackie","orcid":"0000-0001-8501-6199","position":7,"is_corresponding":false},{"id":407434,"name":"Alexandros Makriyannis","orcid":"0000-0003-3272-3687","position":8,"is_corresponding":false},{"id":407435,"name":"Tally M. Largent‐Milnes","orcid":"0000-0001-7599-102X","position":9,"is_corresponding":false},{"id":407436,"name":"Todd W. Vanderah","orcid":"0000-0003-0406-4354","position":10,"is_corresponding":false},{"id":407429,"name":"Beth M. Wiese","orcid":"0000-0003-4111-295X","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T21:49:40.769098Z","pmid":"33998869","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}