https://m2.mtmt.hu/ eng 2026-10-25 14:05 JournalArticle 35928581 ADMIN_APPROVED true 0 false 2026-10-02T10:13:48.513+0000 2026-10-02T10:10:06.803+0000 2025-03-15T12:18:01.790+0000 true 10063958 Horváth Eszter /api/admin/10063958 Admin true 10063958 2026-10-02T10:10:07.836+0000 2026-10-02T10:10:07.836+0000 2026-05-20T08:56:25.495+0000 true 10025544 Lévayné Deseő Katalin /api/admin/10025544 Admin true 10025544 Admin 10025544 /api/admin/10025544 Lévayné Deseő Katalin true 10025544 true 2026-05-20T07:50:09.894+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Watkins, Joshua CB1 cannabinoid receptor agonists induce acute respiratory depression in awake mice true true /api/journal/3622 REVIEWED true false 3622 false 3622 true 1043-6618 1096-1186 Journal FOREIGN 214 107682 107682 20 2025 Recreational use of synthetic cannabinoid agonists (i.e., “spice compounds”) that target the cannabinoid type 1 receptor (CB1) can cause acute respiratory failure in humans. However, Δ9-tetrahydrocannabinol (Δ9-THC), the major psychoactive phytocannabinoid in cannabis, is not traditionally thought to interact with the brain respiratory system, based largely upon sparse labeling of CB1 receptors in the medulla and relative safety suggested by widespread human use. Here we used whole body plethysmography and RNAscope in situ hybridization in mice to reconcile this conflict between conventional wisdom and human data. We examined the respiratory effects of the synthetic CB1 full agonist CP55,940 and Δ9-THC in male and female mice. CP55,940 and Δ9-THC potently and dose-dependently suppressed minute ventilation and tidal volume, decreasing measures of respiratory effort (i.e., peak inspiratory and expiratory flow). Both cannabinoids reduced respiratory frequency, decreasing inspiratory and expiratory time while markedly increasing inspiratory and expiratory pause. Respiratory suppressive effects were fully blocked by the CB1 antagonist AM251, were minimally impacted by the peripherally-restricted CB1 antagonist AM6545, and occurred at doses lower than those that produce cardinal behavioral signs of CB1 activation. Using RNAscope in situ hybridization, we also demonstrated extensive coexpression of Cnr1 (encoding the CB1 receptor) and Oprm1 (encoding the µ-opioid receptor) mRNA in respiratory cells in the medullary pre-Bötzinger complex, a critical nucleus of respiratory control. Our results show that mRNA for CB1 is present in respiratory cells in a medullary brain region essential for breathing and demonstrate that cannabinoids produce respiratory suppression via activation of central CB1 receptors. Funding 2066484 /api/funding/2066484 false true Funding 2066485 /api/funding/2066485 false true Funding 2066486 /api/funding/2066486 false true Funding 2066487 /api/funding/2066487 false true 2025 true true true false true false GOLD 2026-10-02 true https://doi.org/10.1016/j.phrs.2025.107682 6 0 6 4 0 6 6 5 6 6 6 4 4 4 2 0 6 4 6 4 0 0 0 Folyóiratcikk Journal Article 24 6 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2025 0 2 2 2 2 2026 0 4 2 4 2 D1 false false false false 2025-06-13T11:26:36.332+0000 Molekuláris Neurobiológiai Kutatócsoport (HRN KOKI); Élettani Intézet (SE / AOK / I) 2 17 2 7 0 true 10025544 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 124500298 /api/authorship/124500298 1 0.14285715 true false false Watkins Joshua true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 124500299 /api/authorship/124500299 2 0.143 false false false Author 10066933 /api/author/10066933 Aradi Petra true true Aradi Petra true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 124500300 /api/authorship/124500300 3 0.14285715 false false false Hahn Rachel true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 124500301 /api/authorship/124500301 4 0.14285715 false false false Makriyannis Alexandros true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 124500302 /api/authorship/124500302 5 0.14285715 false false false Mackie Ken true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 124500303 /api/authorship/124500303 6 0.143 false false false Author 10011502 /api/author/10011502 Katona István true 10011502 true Katona Istvan true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 124500304 /api/authorship/124500304 7 0.14285715 false true false Hohmann Andrea G. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PublicationIdentifier 28866891 /api/publicationidentifier/28866891 PlainSource 6 /api/publicationsource/6 PublicationSourceType 10001 /api/publicationsourcetype/10001 true true true DOI DOI https://doi.org/@@@ true true 6 true GOLD true IDENTICAL 10.1016/j.phrs.2025.107682 https://doi.org/10.1016/j.phrs.2025.107682 false true 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/api/classificationexternal/3004 true 3004 true D1 DIRECT true true /api/publication/35928581 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <div class="autype autype0"> <span class="author-name" >Watkins Joshua </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10066933"><a href="/gui2/?type=authors&mode=browse&sel=10066933" target="_blank">Aradi Petra (<span class="authorship-author-name">Aradi Petra</span> <span class="authorAux-mtmt"> Élettan</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Physiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Hahn Rachel </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Makriyannis Alexandros </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Mackie Ken </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10011502"><a href="/gui2/?type=authors&mode=browse&sel=10011502" target="_blank">Katona Istvan (<span class="authorship-author-name">Katona István</span> <span class="authorAux-mtmt"> Neurobiológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Molekuláris Neurobiológiai Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Hohmann Andrea G. </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;35928581" target="_blank">CB1 cannabinoid receptor agonists induce acute respiratory depression in awake mice</a></div> <div> <span class="journal-title">PHARMACOLOGICAL RESEARCH</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1043-6618">1043-6618</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1096-1186">1096-1186</a>)</span>: <span class="journal-volume">214</span> <span class="page"> Paper 107682. 20 p. </span> <span class="year">(2025)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1016/j.phrs.2025.107682" target="_blank" href="https://doi.org/10.1016/j.phrs.2025.107682"> DOI </a> </span> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:black" title="243170" target="_blank" href="https://real.mtak.hu/243170"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="001449640200001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001449640200001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="86000538330" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-86000538330"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="40064359" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=40064359&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_NONE" title=" None "> <a style="color:black" title="https://www.sciencedirect.com/science/article/pii/S1043661825001070" target="_blank" href="https://www.sciencedirect.com/science/article/pii/S1043661825001070"> Other URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Pharmacology&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 6</span> | Independent citation: 4 | Self citation: 2 | Unknown citation: 0 | Number of citations in WoS: 5 | Number of citations in Scopus:&nbsp;6 | WoS/Scopus assigned:&nbsp;6 | Number of citations with DOI:&nbsp;6 </div> <div class="mtid"><span class="long-pub-mtid">Publication: 35928581</span> | <span class="status-data status-ADMIN_APPROVED"> Admin approved </span> Core | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">RIS-Egyéb</span> </div> <div class="funder"> Drug Abuse(DA009158), Drug Abuse(DA047858), Indiana Clinical and Translational Sciences(ULTR002529), Predoctoral Training(DA024628.) </div> <div class="lastModified">Last Modified: 2026.10.02. 12:10 Rita Csernyik (MTMT központi admin) </div> <div class="lockedBy">Centrally managed 2026.05.20. 09:50 Katalin Lévayné Deseő (MTMT Központi admin) </div> </div></div>