Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions?
JWH-018 is the most known compound among synthetic cannabinoids (SCs) used for their psychoactive effects. 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 suc...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7515 |
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| author | Beatrice Marchetti Sabrine Bilel Micaela Tirri Giorgia Corli Elisa Roda Carlo Alessandro Locatelli Elena Cavarretta Fabio De-Giorgio Matteo Marti |
| author_facet | Beatrice Marchetti Sabrine Bilel Micaela Tirri Giorgia Corli Elisa Roda Carlo Alessandro Locatelli Elena Cavarretta Fabio De-Giorgio Matteo Marti |
| author_sort | Beatrice Marchetti |
| collection | DOAJ |
| description | JWH-018 is the most known compound among synthetic cannabinoids (SCs) used for their psychoactive effects. 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. |
| first_indexed | 2024-03-11T04:54:56Z |
| format | Article |
| id | doaj.art-46b9072ec959464393997c0db3cefe84 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:54:56Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-46b9072ec959464393997c0db3cefe842023-11-17T19:41:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248751510.3390/ijms24087515Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions?Beatrice Marchetti0Sabrine Bilel1Micaela Tirri2Giorgia Corli3Elisa Roda4Carlo Alessandro Locatelli5Elena Cavarretta6Fabio De-Giorgio7Matteo Marti8Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, ItalyLaboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS Pavia, 27100 Pavia, ItalyLaboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS Pavia, 27100 Pavia, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Roma, ItalySection of Legal Medicine, Department of Health Care Surveillance and Bioetics, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyDepartment of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, ItalyJWH-018 is the most known compound among synthetic cannabinoids (SCs) used for their psychoactive effects. 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.https://www.mdpi.com/1422-0067/24/8/7515JWH-018synthetic cannabinoidcardiovascularrespiratoryatropineamiodarone |
| spellingShingle | Beatrice Marchetti Sabrine Bilel Micaela Tirri Giorgia Corli Elisa Roda Carlo Alessandro Locatelli Elena Cavarretta Fabio De-Giorgio Matteo Marti Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions? International Journal of Molecular Sciences JWH-018 synthetic cannabinoid cardiovascular respiratory atropine amiodarone |
| title | Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions? |
| title_full | Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions? |
| title_fullStr | Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions? |
| title_full_unstemmed | Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions? |
| title_short | Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions? |
| title_sort | acute cardiovascular and cardiorespiratory effects of jwh 018 in awake and freely moving mice mechanism of action and possible antidotal interventions |
| topic | JWH-018 synthetic cannabinoid cardiovascular respiratory atropine amiodarone |
| url | https://www.mdpi.com/1422-0067/24/8/7515 |
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