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SCs-based products are responsible for several intoxications in humans. Cardiac toxicity is among the main side effects observed in emergency departments: SCs intake induces harmful effects such as hypertension, tachycardia, chest pain, arrhythmias, myocardial infarction, breathing impairment, and dyspnea. This study aims to investigate how cardio-respiratory and vascular JWH-018 (6 mg\/kg) responses can be modulated by antidotes already in clinical use. The tested antidotes are amiodarone (5 mg\/kg), atropine (5 mg\/kg), nifedipine (1 mg\/kg), and propranolol (2 mg\/kg). The detection of heart rate, breath rate, arterial oxygen saturation (SpO2), and pulse distention are provided by a non-invasive apparatus (Mouse Ox Plus) in awake and freely moving CD-1 male mice. Tachyarrhythmia events are also evaluated. Results show that while all tested antidotes reduce tachycardia and tachyarrhythmic events and improve breathing functions, only atropine completely reverts the heart rate and pulse distension. These data may suggest that cardiorespiratory mechanisms of JWH-018-induced tachyarrhythmia involve sympathetic, cholinergic, and ion channel modulation. Current findings also provide valuable impetus to identify potential antidotal intervention to support physicians in the treatment of intoxicated patients in emergency clinical settings.<\/jats:p>","DOI":"10.3390\/ijms24087515","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T03:25:11Z","timestamp":1681961111000},"page":"7515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions?"],"prefix":"10.3390","volume":"24","author":[{"given":"Beatrice","family":"Marchetti","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrine","family":"Bilel","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9337-9184","authenticated-orcid":false,"given":"Micaela","family":"Tirri","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-2446","authenticated-orcid":false,"given":"Giorgia","family":"Corli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7590-5363","authenticated-orcid":false,"given":"Elisa","family":"Roda","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2154-5897","authenticated-orcid":false,"given":"Carlo Alessandro","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0221-6000","authenticated-orcid":false,"given":"Elena","family":"Cavarretta","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Roma, Italy"},{"name":"Mediterrranea Cardiocentro, 80122 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"De-Giorgio","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Health Care Surveillance and Bioetics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8751-2882","authenticated-orcid":false,"given":"Matteo","family":"Marti","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Collaborative Center for the Italian National Early Warning System, Department of Anti-Drug Policies, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","first-page":"152","article-title":"Novel psychoactive substances (NPS)-knowledge and expe riences of drug users from Hungary, Poland, the UK and the USA","volume":"21","author":"Pisarska","year":"2019","journal-title":"Neuropsychopharmacol. 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