{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T20:10:49Z","timestamp":1782591049652,"version":"3.54.5"},"reference-count":50,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cannabis &amp; Cannabinoid Research"],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>Cannabis acceptance and use continues to rise despite the gaps in knowledge regarding the mechanisms of cannabinoids and the endocannabinoid system in many physiological functions, including respiratory influence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>With recent evidence of cannabinoid receptor 1 (CB1R) presence in the collection of respiratory neurons in the brainstem, as well as in the peripheral lung tissue, it is vital that the mechanisms involved in central and peripheral CB1R modulation of respiratory function be delineated. In this study we sought to define the roles of central versus peripheral CB1R activation on respiratory depression alone and in combination with morphine using whole body plethysmography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We show that the peripherally restricted CB1 agonist (4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3yl]ethyl}morpholine [PrNMI] 0.3, 0.6, and 1\u2009mg\/kg) does not induce respiratory depression, while our previous studies showed that a central penetrating synthetic cannabinoid does induce respiratory depression. Significantly, the combination of morphine with the peripheral CB1 agonist, PrNMI, attenuated morphine-induced respiratory depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>These studies support that a peripherally restricted CB1R agonist may be a unique strategy to attenuate the respiratory depression associated with opioid therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/can.2021.0090","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:27:03Z","timestamp":1640168823000},"page":"621-627","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Brain Penetrant, but not Peripherally Restricted, Synthetic Cannabinoid 1 Receptor Agonists Promote Morphine-Mediated Respiratory Depression"],"prefix":"10.1177","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-295X","authenticated-orcid":false,"given":"Beth M.","family":"Wiese","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Arizona, Tucson, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Liktor-Busa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona, Tucson, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Couture","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona, Tucson, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros P.","family":"Nikas","sequence":"additional","affiliation":[{"name":"Chemistry and Chemical Biology, Bouve College Health Sciences\u2014Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lipin","family":"Ji","sequence":"additional","affiliation":[{"name":"Chemistry and Chemical Biology, Bouve College Health Sciences\u2014Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingpeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Chemistry and Chemical Biology, Bouve College Health Sciences\u2014Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Makriyannis","sequence":"additional","affiliation":[{"name":"Chemistry and Chemical Biology, Bouve College Health Sciences\u2014Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Spigelman","sequence":"additional","affiliation":[{"name":"Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd W.","family":"Vanderah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona, Tucson, Arizona, USA."},{"name":"Comprehensive Pain and Addiction Center, University of Arizona, Health Sciences, Tucson, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tally M.","family":"Largent-Milnes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona, Tucson, Arizona, USA."},{"name":"Comprehensive Pain and Addiction Center, University of Arizona, Health Sciences, Tucson, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"e_1_3_4_2_2","unstructured":"National Academies of Sciences E Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. The National Academies Press: Washington DC 2017."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001278"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000364"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/can.2017.0012"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/1744806917728227"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/PR9.0000000000000897"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00355"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/can.2020.0076"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmcr.2017.07.011"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/cap.2011.0122"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-003-0787-3"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/PEC.0000000000001970"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-003-0755-y"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040576"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2015.1110590"},{"key":"e_1_3_4_17_2","unstructured":"Abuse NIoD. Synthetic Cannabinoids (K2\/Spice) Unpredictable Danger. https:\/\/www.drugabuse.gov\/related-topics\/trends-statistics\/infographics\/synthetic-cannabinoids-k2spice-unpredictable-danger Accessed March23 2020."},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2018.00162"},{"key":"e_1_3_4_19_2","author":"Darke S","year":"2019","unstructured":"Darke S, , Duflou J, , Farrell M, et al. Characteristics and circumstances of synthetic cannabinoid-related death. Clin Toxicol (Phila). 2019:1\u20137.","journal-title":"Clin Toxicol (Phila)"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2019.02.009"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/08897077.2013.846288"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2017.00052"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00611"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","unstructured":"Selwood D. The cannabinoid receptors. In: Howlett AC Padgett LW Shim JY eds. Cannabinoid agonist and inverse agonist regulation of g protein coupling. In the cannabinoid receptors Humana Press; Totowa NJ 2009:173\u2013202.","DOI":"10.1007\/978-1-59745-503-9_7"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00516"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00773-X"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.172866"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.07.002"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-020-01425-3"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1089\/can.2018.0022"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945010790980312"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1686-13.2013"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.10.043"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.08.027"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00187"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02655-5"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.632757"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.159.2.208"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-004-1825-7"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945010790980367"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.11.023"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000201"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.03.038"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2012.10.002"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01948.x"},{"key":"e_1_3_4_46_2","first-page":"588","article-title":"International Union of Basic and Clinical Pharmacology","volume":"62","author":"Pertwee RG","year":"2010","unstructured":"Pertwee RG, , Howlett AC, , Abood ME, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB(1) and CB(2). Pharmacol Rev. 2010; 62:588\u2013631.","journal-title":"LXXIX. Cannabinoid receptors and their ligands: beyond CB(1) and CB(2). Pharmacol Rev"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)22135-8"},{"key":"e_1_3_4_48_2","first-page":"257","volume-title":"International review of neurobiology","author":"Sagheddu C","year":"2015","unstructured":"Sagheddu C, , Muntoni AL, , Pistis M, et al. Chapter seven\u2014endocannabinoid signaling in motivation, reward, and addiction: influences on mesocorticolimbic dopamine function. In: Parsons L, , Hill M, eds. International review of neurobiology, Vol. 125. Academic Press: London, UK, 2015:257\u2013302."},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)89665-3"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2018.0266"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3109\/09687637.2016.1158239"}],"container-title":["Cannabis &amp; Cannabinoid Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/can.2021.0090","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/can.2021.0090","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/can.2021.0090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:11:25Z","timestamp":1777385485000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/can.2021.0090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,10,1]]}},"alternative-id":["10.1089\/can.2021.0090"],"URL":"https:\/\/doi.org\/10.1089\/can.2021.0090","relation":{},"ISSN":["2578-5125","2378-8763"],"issn-type":[{"value":"2578-5125","type":"print"},{"value":"2378-8763","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}