{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:17:13Z","timestamp":1760059033551,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Recent drug enforcement activities have possibly suggested the presence of some calcium channel blocker antihypertensives in association with cocaine. The seizure revealed the possibility that the two drugs might have been used together for some unknown reasons. Methods: Hence, this study aimed at investigating the nature and frequency of adverse drug reactions (ADRs) reported in association with the concomitant use of calcium channel blockers (CCBs) and cocaine, using data from the FDA Adverse Event Reporting System (FAERS). Results: After removing duplicate reports, a total of 67 cases involving concomitant use of cocaine and CCBs were analyzed and were stratified into three groups based on the CCB involved: verapamil (n = 19), diltiazem (n = 30), and amlodipine (n = 18). Logistic regression analysis identified \u201cproduct use for unknown indication\u201d (\u03b2 = 0.33) as the strongest predictor of fatal outcomes. Age revealed a modest negative association with fatal outcome (\u03b2 = \u22120.93, intercept = 4.07). Concomitant substance use was reported in over 84% of cases. Frequently co-used substances included opioids, benzodiazepines, antidepressants, antihistamines, and alcohol. Poly-drug use was most pronounced in the diltiazem group, which exhibited the highest burden of opioid and alcohol co-exposure. Conclusions: It is here suggested that clinicians should exercise caution when managing individuals who use cocaine, due to the potential for increased toxicity and lethality when CCBs are co-used, either as part of a prescribed treatment or if CCBs are present as adulterants in cocaine.<\/jats:p>","DOI":"10.3390\/jcm14103461","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T08:56:55Z","timestamp":1747299415000},"page":"3461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adverse Drug Reactions Associated with Concomitant Use of Calcium Channel Blockers and Cocaine: An Analysis of FDA Adverse Events Reporting System Data"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-1540","authenticated-orcid":false,"given":"Stefania","family":"Chiappini","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Department of Psychiatry, UniCamillus University of Medical Sciences, Via di S. Alessandro 8, 00131 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-1398","authenticated-orcid":false,"given":"Alessio","family":"Mosca","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Imaging, and Clinical Sciences, University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duccio G.","family":"Papanti Pelletier","sequence":"additional","affiliation":[{"name":"Cividale Community Mental Health Centre, ASUFC Mental Health Department, Friuli Venezia Giulia, 33100 Udine, Italy"},{"name":"Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, University of Hertfordshire, Hertfordshire AL10 9AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-817X","authenticated-orcid":false,"given":"John M.","family":"Corkery","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, University of Hertfordshire, Hertfordshire AL10 9AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8255-0660","authenticated-orcid":false,"given":"Amira","family":"Guirguis","sequence":"additional","affiliation":[{"name":"Pharmacy, Swansea University Medical School, Swansea University, Wales SA28PP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-0595","authenticated-orcid":false,"given":"Davide","family":"Arillotta","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, University of Hertfordshire, Hertfordshire AL10 9AB, UK"},{"name":"Department of Pharmacology and Toxicology, University of Florence Medical School, 50134 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-2341","authenticated-orcid":false,"given":"Giovanni","family":"Martinotti","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Imaging, and Clinical Sciences, University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-5401","authenticated-orcid":false,"given":"Fabrizio","family":"Schifano","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, University of Hertfordshire, Hertfordshire AL10 9AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","unstructured":"ANSA.it (2025, April 04). Con la Droga Sequestrati Anti-Ipertensivi, Allarme a Cuneo. 2 March 2025. Available online: https:\/\/www.ansa.it\/piemonte\/notizie\/2025\/03\/02\/con-la-droga-sequestrati-anti-ipertensivi-allarme-a-cuneo_29d72eb9-3a22-45b0-a340-f1d6133724ba.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/bs.apha.2021.10.007","article-title":"Substance abuse and neurotransmission","volume":"93","author":"Davis","year":"2022","journal-title":"Adv. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6583","DOI":"10.1523\/JNEUROSCI.1544-06.2006","article-title":"Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction","volume":"26","author":"Volkow","year":"2006","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1151\/spp05314","article-title":"The neurobiology of cocaine addiction","volume":"3","author":"Nestler","year":"2005","journal-title":"Sci. Pract. Perspect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1177\/1074248416681644","article-title":"\u03b2-Blockers, Cocaine, and the Unopposed \u03b1-Stimulation Phenomenon","volume":"22","author":"Richards","year":"2017","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jchemneu.2017.06.001","article-title":"Cocaine adulteration","volume":"83\u201384","author":"Kudlacek","year":"2017","journal-title":"J. Chem. Neuroanat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3928\/02793695-20231109-02","article-title":"Xylazine: The Drug Taking the World By Storm: What You Need to Know","volume":"61","author":"Mumba","year":"2023","journal-title":"J. Psychosoc. Nurs. Ment. Health Serv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11916-024-01211-z","article-title":"Xylazine: A Drug Adulterant of Clinical Concern","volume":"28","author":"Edinoff","year":"2024","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1081\/CLT-100102437","article-title":"Insulin-Glucose as Adjunctive Therapy for Severe Calcium Channel Antagonist Poisoning","volume":"37","author":"Yuan","year":"1999","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.3109\/15563650.2010.543906","article-title":"2009 Annual Report of the American Association Of Poison Control Centers\u2019 National Poison Data System (NPDS): 27th Annual Report","volume":"48","author":"Bronstein","year":"2010","journal-title":"Clin. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"911","DOI":"10.3109\/15563650.2012.746424","article-title":"2011 Annual Report of the American Association of Poison Control Centers\u2019 National Poison Data System (NPDS): 29th Annual Report","volume":"50","author":"Bronstein","year":"2012","journal-title":"Clin. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3109\/15563650.2013.863906","article-title":"2012 Annual Report of the American Association of Poison Control Centers\u2019 National Poison Data System (NPDS): 30th Annual Report","volume":"51","author":"Mowry","year":"2013","journal-title":"Clin. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1080\/15563650.2019.1677022","article-title":"2018 Annual Report of the American Association of Poison Control Centers\u2019 National Poison Data System (NPDS): 36th Annual Report","volume":"57","author":"Gummin","year":"2019","journal-title":"Clin. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1080\/15563650.2016.1245421","article-title":"2015 Annual Report of the American Association of Poison Control Centers\u2019 National Poison Data System (NPDS): 33rd Annual Report","volume":"54","author":"Mowry","year":"2016","journal-title":"Clin. Toxicol."},{"key":"ref_15","unstructured":"UNODC (2024). World Drug Report 2024 (United Nations Publication, 2024), UNODC."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chiappini, S., and Schifano, F. (2020). What about \u201cPharming\u201d? Issues Regarding the Misuse of Prescription and Over-the-Counter Drugs. Brain Sci., 10.","DOI":"10.3390\/brainsci10100736"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chiappini, S., Vickers-Smith, R., Guirguis, A., Corkery, J.M., Martinotti, G., and Schifano, F. (2022). A Focus on Abuse\/Misuse and Withdrawal Issues with Selective Serotonin Reuptake Inhibitors (SSRIs): Analysis of Both the European EMA and the US FAERS Pharmacovigilance Databases. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050565"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2478\/10004-1254-62-2011-2086","article-title":"Nifedipine lowers cocaine-induced brain and liver enzyme activity and cocaine urinary excretion in rats","volume":"62","author":"Vitcheva","year":"2011","journal-title":"Arh. Za Hig. Rada I Toksikol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0022-3565(25)24488-3","article-title":"Calcium channel blockers antagonize some of cocaine\u2019s cardiovascular effects, but fail to alter cocaine\u2019s behavioral effects","volume":"272","author":"Schindler","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0278-5846(01)00281-0","article-title":"Nifedipine potentiates the toxic effects of cocaine in mice","volume":"26","author":"Ansah","year":"2002","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/0735-6757(89)90246-5","article-title":"Potentiation of cocaine toxicity with calcium channel blockers","volume":"7","author":"Derlet","year":"1989","journal-title":"Am. J. Emerg. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s11906-001-0094-7","article-title":"Central sympathoinhibitory effects of calcium channel blockers","volume":"3","author":"Leenen","year":"2001","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1046\/j.1365-2125.2001.01386.x","article-title":"Inhibitory effects of verapamil and diltiazem on simvastatin metabolism in human liver microsomes","volume":"51","author":"Yeo","year":"2001","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1161\/CIRCULATIONAHA.107.188950","article-title":"Management of cocaine-associated chest pain and myocardial infarction: A scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology","volume":"117","author":"McCord","year":"2008","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Alawo\u00e8, C., Chapet, N., Roubille, F., Peyri\u00e8re, H., and Eiden, C. (2024). Narrative Review of Heart Failure Related to Cocaine Consumption and Its Therapeutic Management. J. Clin. Med., 13.","DOI":"10.3390\/jcm13237275"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/dar.13581","article-title":"Clinical characteristics of fatal cocaine toxicity in Australia, 2000\u20132021","volume":"42","author":"Darke","year":"2023","journal-title":"Drug Alcohol Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.amjcard.2006.10.044","article-title":"Cardiac arrest in patients who smoke crack cocaine","volume":"99","author":"Hsue","year":"2007","journal-title":"Am. J. Cardiol."},{"key":"ref_28","unstructured":"(2025, May 07). Verapamil. Available online: https:\/\/www.medicines.org.uk\/emc\/product\/10613\/smpc."},{"key":"ref_29","unstructured":"(2025, May 07). Diltiazem. Available online: https:\/\/www.medicines.org.uk\/emc\/product\/7583\/smpc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.2174\/1570159X19666210113151136","article-title":"The Benzydamine Experience: A Systematic Review of Benzydamine Abuse","volume":"19","author":"Chiappini","year":"2021","journal-title":"Curr. Neuropharmacol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:33:17Z","timestamp":1760031197000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":30,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14103461"],"URL":"https:\/\/doi.org\/10.3390\/jcm14103461","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,5,15]]}}}