{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:09:30Z","timestamp":1778882970337,"version":"3.51.4"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022606","name":"Almirall","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014114","name":"GW Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014114","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cannabinoids may be useful to treat pain, epilepsy and spasticity, although they may bear an increased risk of cardiovascular events. This study aims to evaluate the cardiovascular safety of nabiximols, a cannabis-based drug, in patients with spasticity following stroke, thus presenting an increased cardiovascular risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is an ancillary study stemming from the SativexStroke trial: a randomized double-blind, placebo-controlled, crossover study aimed at assessing the effect of nabiximols on post-stroke spasticity. Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Only the phase with the active treatment was considered for each patient who completed the study. The average values of blood pressure (diastolic, systolic, differential) and heart rate from the first 5 days of the phase (lowest nabiximols dosage) were compared to the average values recorded during the last 5 days at the end of the phase (highest nabiximols dosage). Baseline comparisons between gender, stroke type and affected side and correlation between age and blood pressure and heart rate were performed. The study was registered with the EudraCT number 2016-001034-10.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty-four patients completed the study and were included in the analysis. Thirty-one were taking antihypertensive drugs and, among these, 12 were taking beta-blockers. During the study, no arrhythmic events were recorded, blood pressure and heart rate did not show pathological fluctuations, and no cardiovascular or cerebrovascular events occurred. At baseline blood pressure and heart rate were comparable concerning gender, stroke type and affected side. A significant direct correlation emerged between differential blood pressure and age and an inverse correlation between diastolic blood pressure and age. No correlation emerged between systolic blood pressure or heart rate and age. Blood pressure and heart rate did not change during nabiximols treatment compared to the baseline condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This ancillary study adds evidence that, in patients who already underwent a cerebrovascular accident, nabiximols does not determine significant blood pressure and heart rate variation or cardiovascular complications. These data support the cardiovascular safety of nabiximols, encouraging more extensive studies involving cannabinoids characterized by slow absorption rates.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.990188","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T10:02:55Z","timestamp":1666951375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled study"],"prefix":"10.3389","volume":"9","author":[{"given":"Gian Marco","family":"Rosa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Puce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Curr\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Fattapposta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Italo","family":"Porto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola Luigi","family":"Bragazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Trompetto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucio","family":"Marinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1038\/sj.npp.1300496","article-title":"The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis.","volume":"29","author":"D\u2019Souza","year":"2004","journal-title":"Neuropsychopharmacology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1001\/archpsyc.57.6.547","article-title":"Marijuana and medicine: assessing the science base: a summary of the 1999 institute of medicine report.","volume":"57","author":"Watson","year":"2000","journal-title":"Arch Gen Psychiatry."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1111\/j.1468-1331.2010.03328.x","article-title":"A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex\u00ae), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis: Sativex for refractory spasticity in MS.","volume":"18","author":"Novotna","year":"2011","journal-title":"Eur J Neurol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.009099","article-title":"Cannabinoids, the heart of the matter.","volume":"7","author":"Alfulaij","year":"2018","journal-title":"J Am Heart Assoc."},{"key":"B5","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/sj.bjp.0705313","article-title":"Endocannabinoids protect the rat isolated heart against ischaemia.","volume":"139","author":"L\u00e9picier","year":"2003","journal-title":"Br J Pharmacol."},{"key":"B6","first-page":"1030","article-title":"Cannabinoid-induced hypotension and bradycardia in rats mediated by CB1-like cannabinoid receptors.","volume":"281","author":"Lake","year":"1997","journal-title":"J Pharmacol Exp Ther."},{"key":"B7","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1042\/bj3460835","article-title":"Functional CB1 cannabinoid receptors in human vascular endothelial cells.","volume":"346","author":"Liu","year":"2000","journal-title":"Biochem J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"466","DOI":"10.23736\/S2724-5683.20.05497-3","article-title":"Marijuana influence on cardiac modulation and heart rate: novel hypotheses and gaps in evidence.","volume":"69","author":"Iannaccone","year":"2021","journal-title":"Minerva Cardiol Angiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.amjcard.2013.09.042","article-title":"Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.","volume":"113","author":"Thomas","year":"2014","journal-title":"Am J Cardiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1136\/emj.2004.014969","article-title":"Cardiovascular complications induced by cannabis smoking: a case report and review of the literature.","volume":"22","author":"Fisher","year":"2005","journal-title":"Emerg Med J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1213\/01.ANE.0000131505.03006.74","article-title":"The procoagulatory effects of delta-9-tetrahydrocannabinol in human platelets.","volume":"99","author":"Deusch","year":"2004","journal-title":"Anesth Analg."},{"key":"B12","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1093\/cvr\/cvp240","article-title":"CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages.","volume":"84","author":"Han","year":"2009","journal-title":"Cardiovasc Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1111\/j.1365-2125.2012.04351.x","article-title":"Is the cardiovascular system a therapeutic target for cannabidiol?","volume":"75","author":"Stanley","year":"2013","journal-title":"Br J Clin Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/j.1600-0447.1992.tb03247.x","article-title":"Middle cerebral artery velocity during upright posture after marijuana smoking.","volume":"86","author":"Mathew","year":"1992","journal-title":"Acta Psychiatr Scand."},{"key":"B15","doi-asserted-by":"publisher","first-page":"58S","DOI":"10.1002\/j.1552-4604.2002.tb06004.x","article-title":"Cardiovascular system effects of marijuana.","volume":"42","author":"Jones","year":"2002","journal-title":"J Clin Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/nrcardio.2017.130","article-title":"Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly.","volume":"15","author":"Pacher","year":"2018","journal-title":"Nat Rev Cardiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1002\/dta.1898","article-title":"Coronary thrombosis and marijuana smoking: a case report and narrative review of the literature.","volume":"8","author":"Marchetti","year":"2016","journal-title":"Drug Test Anal."},{"key":"B18","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.tcm.2019.08.003","article-title":"Marijuana use and acute myocardial infarction: a systematic review of published cases in the literature.","volume":"30","author":"Patel","year":"2020","journal-title":"Trends Cardiovasc Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1080\/15563650.2019.1601735","article-title":"Cannabis use and acute coronary syndrome.","volume":"57","author":"Richards","year":"2019","journal-title":"Clin Toxicol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.1161\/01.cir.103.23.2805","article-title":"Triggering myocardial infarction by marijuana.","volume":"103","author":"Mittleman","year":"2001","journal-title":"Circulation."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9061925","article-title":"The impact of marijuana on the cardiovascular system: a review of the most common cardiovascular events associated with marijuana use.","volume":"9","author":"Latif","year":"2020","journal-title":"JCM."},{"key":"B22","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s40119-017-0102-x","article-title":"Cardiovascular complications of marijuana and related substances: a review.","volume":"7","author":"Singh","year":"2018","journal-title":"Cardiol Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1002\/cbdv.200790152","article-title":"Human cannabinoid pharmacokinetics.","volume":"4","author":"Huestis","year":"2007","journal-title":"Chem Biodivers."},{"key":"B24","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/j.2042-7158.1980.tb12966.x","article-title":"Identification in human urine of delta 9-tetrahydrocannabinol-11-oic acid glucuronide: a tetrahydrocannabinol metabolite.","volume":"32","author":"Williams","year":"1980","journal-title":"J Pharm Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1111\/j.2042-7158.1988.tb05272.x","article-title":"Prolonged apparent half-life of delta 1-tetrahydrocannabinol in plasma of chronic marijuana users.","volume":"40","author":"Johansson","year":"1988","journal-title":"J Pharm Pharmacol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1017\/S1461145709990605","article-title":"A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL\/6JArc mice.","volume":"13","author":"Long","year":"2010","journal-title":"Int J Neuropsychopharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.pbb.2009.04.010","article-title":"Cannabidiol reverses the reduction in social interaction produced by low dose Delta (9)-tetrahydrocannabinol in rats.","volume":"93","author":"Malone","year":"2009","journal-title":"Pharmacol Biochem Behav."},{"key":"B28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/clpt.1980.139","article-title":"Metabolic and psychophysiologic studies of cannabidiol-hexobarbital interaction.","volume":"28","author":"Benowitz","year":"1980","journal-title":"Clin Pharmacol Ther."},{"key":"B29","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/BF01059266","article-title":"Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man.","volume":"9","author":"Hunt","year":"1981","journal-title":"J Pharmacokinet Biopharm."},{"key":"B30","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00213-011-2495-x","article-title":"Interaction between cannabidiol (CBD) and \u0394(9)-tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids.","volume":"219","author":"Zuardi","year":"2012","journal-title":"Psychopharmacology."},{"key":"B31","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/clpt.2010.318","article-title":"Subjective and physiological effects after controlled Sativex and oral THC administration.","volume":"89","author":"Karschner","year":"2011","journal-title":"Clin Pharmacol Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1373\/clinchem.2010.152439","article-title":"Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.","volume":"57","author":"Karschner","year":"2011","journal-title":"Clin Chem."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-016843","article-title":"A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity.","volume":"7","author":"Marinelli","year":"2017","journal-title":"BMJ Open."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.892165","article-title":"Cannabinoid effect and safety in spasticity following stroke: a double-blind randomized placebo-controlled study.","volume":"13","author":"Marinelli","year":"2022","journal-title":"Front Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.cpr.2011.12.002","article-title":"Tobacco and marijuana use among adolescents and young adults: a systematic review of their co-use.","volume":"32","author":"Ramo","year":"2012","journal-title":"Clin Psychol Rev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"341","DOI":"10.4140\/TCP.n.2017.341","article-title":"Marijuana use in the elderly: implications and considerations.","volume":"32","author":"Mahvan","year":"2017","journal-title":"Consult Pharm."},{"key":"B37","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/S1474-4422(18)30406-X","article-title":"Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.","volume":"18","author":"Riva","year":"2019","journal-title":"Lancet Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1212\/WNL.0b013e3182762448","article-title":"Toward an epidemiology of poststroke spasticity.","volume":"80","author":"Wissel","year":"2013","journal-title":"Neurology."},{"key":"B39","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1080\/14737175.2021.1935879","article-title":"Safety and tolerability of nabiximols oromucosal spray: a review of more than 15 years\u201d accumulated evidence from clinical trials.","volume":"21","author":"Prieto Gonz\u00e1lez","year":"2021","journal-title":"Expert Rev Neurother."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.990188\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T10:03:00Z","timestamp":1666951380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.990188\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,28]]},"references-count":39,"alternative-id":["10.3389\/fcvm.2022.990188"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.990188","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,28]]},"article-number":"990188"}}