{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:35:22Z","timestamp":1786588522962,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T00:00:00Z","timestamp":1517356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>\u22069-Tetrahydrocannabinol (THC) has complex effects on the cardiovascular system. We aimed to systematically review studies of THC and haemodynamic alterations. PubMed, Medline, and EMBASE were searched for relevant studies. Changes in blood pressure (BP), heart rate (HR), and blood flow (BF) were analysed using the Cochrane Review Manager Software. Thirty-one studies met the eligibility criteria. Fourteen publications assessed BP (number, n = 541), 22 HR (n = 567), and 3 BF (n = 45). Acute THC dosing reduced BP and HR in anaesthetised animals (BP, mean difference (MD) \u221219.7 mmHg, p &lt; 0.00001; HR, MD \u221253.49 bpm, p &lt; 0.00001), conscious animals (BP, MD \u221212.3 mmHg, p = 0.0007; HR, MD \u221230.05 bpm, p &lt; 0.00001), and animal models of stress or hypertension (BP, MD \u221261.37 mmHg, p = 0.03) and increased cerebral BF in murine stroke models (MD 32.35%, p &lt; 0.00001). Chronic dosing increased BF in large arteries in anaesthetised animals (MD 21.95 mL\/min, p = 0.05) and reduced BP in models of stress or hypertension (MD \u221222.09 mmHg, p &lt; 0.00001). In humans, acute administration increased HR (MD 8.16 bpm, p &lt; 0.00001). THC acts differently according to species and experimental conditions, causing bradycardia, hypotension and increased BF in animals; and causing increased HR in humans. Data is limited, and further studies assessing THC-induced haemodynamic changes in humans should be considered.<\/jats:p>","DOI":"10.3390\/ph11010013","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T12:41:24Z","timestamp":1517402484000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Systematic Review and Meta-Analysis of the In Vivo Haemodynamic Effects of \u03949-Tetrahydrocannabinol"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9981-6138","authenticated-orcid":false,"given":"Salahaden","family":"Sultan","sequence":"first","affiliation":[{"name":"Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby DE22 3DT, UK"},{"name":"Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1318-7671","authenticated-orcid":false,"given":"Sophie","family":"Millar","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saoirse","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-8584","authenticated-orcid":false,"given":"Timothy","family":"England","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1021\/ja01062a046","article-title":"Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish","volume":"86","author":"Gaoni","year":"1964","journal-title":"J. Am. Chem. Soc."},{"key":"ref_2","first-page":"1","article-title":"Pharmacological actions of cannabinoids","volume":"20","author":"Pertwee","year":"2005","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/sj.bjp.0707460","article-title":"The orphan receptor GPR55 is a novel cannabinoid receptor","volume":"152","author":"Ryberg","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1111\/j.1476-5381.2011.01497.x","article-title":"Delta(9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells","volume":"165","author":"McHugh","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2006.02.001","article-title":"Cannabinoids in medicine: A review of their therapeutic potential","volume":"105","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.nbd.2004.11.009","article-title":"Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: Relevance to Parkinson\u2019s disease","volume":"19","author":"Ramos","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.jep.2010.11.035","article-title":"Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis","volume":"133","author":"Buccellato","year":"2011","journal-title":"J Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1001\/jama.2015.6358","article-title":"Cannabinoids for Medical Use: A Systematic Review and Meta-analysis","volume":"313","author":"Whiting","year":"2015","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"487","DOI":"10.6004\/jnccn.2012.0048","article-title":"Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting","volume":"10","author":"Todaro","year":"2012","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/cpt.108","article-title":"Cannabis in cancer care","volume":"97","author":"Abrams","year":"2015","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/sj.bjp.0702381","article-title":"Inhibition of the production of endothelium-derived hyperpolarizing factor by cannabinoid receptor agonists","volume":"126","author":"Fleming","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1523\/JNEUROSCI.22-11-04720.2002","article-title":"\u03949Tetrahydrocannabinol and Cannabinol Activate Capsaicin-Sensitive Sensory Nerves via a CB1 and CB2 Cannabinoid Receptor-Independent Mechanism","volume":"22","author":"Zygmunt","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/sj.bjp.0706218","article-title":"The effects of \u0394(9)-tetrahydrocannabinol in rat mesenteric vasculature, and its interactions with the endocannabinoid anandamide","volume":"145","author":"Kendall","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ejphar.2004.11.056","article-title":"Vascular effects of delta 9-tetrahydrocannabinol (THC), anandamide and N-arachidonoyldopamine (NADA) in the rat isolated aorta","volume":"507","author":"Kendall","year":"2005","journal-title":"Eur. J. Pharmacol"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.bbrc.2005.09.121","article-title":"Novel time-dependent vascular actions of Delta9-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma","volume":"337","author":"Tarling","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.2042-7158.1975.tb09507.x","article-title":"The evidence of the release of prostaglandin-like material from rabbit kidney and guinea-pig lung by (minus)-trans-delta9-tetrahydrocannabinol","volume":"27","author":"Kaymakcalan","year":"1975","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1124\/jpet.104.067587","article-title":"Characterization of cannabinoid modulation of sensory neurotransmission in the rat isolated mesenteric arterial bed","volume":"311","author":"Duncan","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_18","first-page":"253","article-title":"Vasoconstriction induced by delta 9-tetrahydrocannabinol on the perfused rabbit ear artery","volume":"252","author":"Barbosa","year":"1981","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/0014-2999(74)90172-1","article-title":"The effect of (\u2212)-\u03949-trans-tetrahydrocannabinol on myocardial contractility and venous return in anesthetized dogs","volume":"29","author":"Cavero","year":"1974","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/S0022-3565(25)29788-9","article-title":"The influence of delta 9-tetrahydrocannabinol on cardiovascular and subcutaneous microcirculatory systems in the bat","volume":"188","author":"Brown","year":"1974","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1476-5381.2008.00010.x","article-title":"Effect of delta9-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans","volume":"156","author":"Beaumont","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/0024-3205(77)90015-7","article-title":"\u03949-tetrahydrocannabinol and dimethylheptylpyran induced tachycardia in the conscious rat","volume":"21","author":"Osgood","year":"1977","journal-title":"Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0021-5198(19)31450-7","article-title":"Effects of delta-9-tetrahydrocannabinol on the cardiovascular system, and pressor and behavioral responses to brain stimulation in rats","volume":"30","author":"Kawasaki","year":"1980","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0014-2999(79)90305-4","article-title":"The triple effect induced by delta 9-tetrahydrocannabinol on the rat blood pressure","volume":"58","author":"Siqueira","year":"1979","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0014-2999(72)90201-4","article-title":"Effects of (\u2212)-\u03949-trans-tetrahydrocannabinol on regional blood flow in anesthetized dogs","volume":"20","author":"Cavero","year":"1972","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0014-2999(73)90078-2","article-title":"Hemodynamic and myocardial effects of (\u2212)-\u03949-trans-tetrahydrocannabinol in anesthetized dogs","volume":"24","author":"Cavero","year":"1973","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0014-2999(73)90025-3","article-title":"Studies on the bradycardia induced by (\u2212)-delta9-trans-tetrahydrocannabinol in anesthetized dogs","volume":"22","author":"Cavero","year":"1973","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","first-page":"121","article-title":"Action of delta 9 tetrahydrocannabinol on the central cardiovascular regulation: Mechanism and localization","volume":"1","author":"Daskalopoulos","year":"1975","journal-title":"Lencephale"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0022-3565(25)30459-3","article-title":"Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat","volume":"196","author":"Adams","year":"1976","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_30","first-page":"201","article-title":"Effects of chronic administration of delta9-tetrahydrocannabinol on the heart rate of mongrel dogs","volume":"14","author":"Jandhyala","year":"1976","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_31","first-page":"593","article-title":"Autonomic and cardiovascular effects of chronic delta9-tetrahydrocannabinol administration in mongrel dogs","volume":"16","author":"Jandhyala","year":"1977","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_32","first-page":"489","article-title":"Effects of prolonged administration of delta 9-tetrahydrocannabinol on the autonomic and cardiovascular function and regional hemodynamics in mongrel dogs","volume":"20","author":"Jandhyala","year":"1978","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S0022-3565(25)31361-3","article-title":"A study of the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on mammalian salivary flow","volume":"206","author":"McConnell","year":"1978","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0024-3205(81)90019-9","article-title":"Potentials evoked in the intermediolateral column by hypothalamic stimulation\u2014Suppression by \u03949-tetrahydrocannabinol","volume":"29","author":"Schmeling","year":"1981","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0024-3205(87)90559-5","article-title":"Cardiovascular effects of delta 9- and delta 9(11)-tetrahydrocannabinol and their interaction with epinephrine","volume":"41","author":"Estrada","year":"1987","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0014-2999(99)00165-X","article-title":"Delta9-tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB1 receptors","volume":"371","author":"Krowicki","year":"1999","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1159\/000136550","article-title":"Lack of tolerance to the bradycardic effect of delta 9-trans-tetrahydrocannabinol in rats","volume":"12","author":"Kaymakcalan","year":"1974","journal-title":"Pharmacology"},{"key":"ref_38","first-page":"663","article-title":"Cannabidiol interaction with delta9-tetrahydrocannabinol","volume":"7","author":"Borgen","year":"1974","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0361-9230(87)90087-6","article-title":"delta 9-Tetrahydrocannabinol: EEG changes, bradycardia and hypothermia in the rhesus monkey","volume":"19","author":"Matsuzaki","year":"1987","journal-title":"Brain Res. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1111\/j.1471-4159.2007.04565.x","article-title":"Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism","volume":"102","author":"Hayakawa","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.neuropharm.2006.11.005","article-title":"Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance","volume":"52","author":"Hayakawa","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/BF00429307","article-title":"\u03949-Tetrahydrocannabinol: A hypotensive effect in rats","volume":"28","author":"Williams","year":"1973","journal-title":"Psychopharmacologia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1476-5381.1973.tb08236.x","article-title":"Reduction by 9-tetrahydrocannabinol in the blood pressure of hypertensive rats bearing regenerated adrenal glands","volume":"48","author":"Birmingham","year":"1973","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","first-page":"76","article-title":"Antihypertensive effects of delta9-tetrahydrocannabinol","volume":"233","author":"Kosersky","year":"1978","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1159\/000136375","article-title":"Comparative Studies in Man and in Laboratory Animals on \u03948-and \u03949-trans-Tetrahydrocannabinol","volume":"9","author":"Karniol","year":"1973","journal-title":"Pharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1159\/000136944","article-title":"Effects of delta9-tetrahydrocannabinol and cannabinol in man","volume":"13","author":"Karniol","year":"1975","journal-title":"Pharmacology"},{"key":"ref_47","first-page":"1614","article-title":"Changes of simple somatic parameters by delta-9-trans-tetrahydrocannabinol (delta-9-THC) in a double-blind-study. Short communication","volume":"26","author":"Zimmer","year":"1976","journal-title":"Arzneimittelforschung"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/sj.npp.1301243","article-title":"Opioid antagonism of cannabinoid effects: Differences between marijuana smokers and nonmarijuana smokers","volume":"32","author":"Haney","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1365-2982.2010.01587.x","article-title":"The cannabinoid receptor agonist delta-9-tetrahydrocannabinol does not affect visceral sensitivity to rectal distension in healthy volunteers and IBS patients","volume":"23","author":"Klooker","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/S0022-3565(24)36714-X","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":"ref_51","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1177\/0269881108089870","article-title":"Modelling of the concentration\u2014Effect relationship of THC on central nervous system parameters and heart rate\u2014Insight into its mechanisms of action and a tool for clinical research and development of cannabinoids","volume":"22","author":"Strougo","year":"2008","journal-title":"J. Psychopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/jat\/bks044","article-title":"Psychomotor performance, subjective and physiological effects and whole blood Delta(9)-tetrahydrocannabinol concentrations in heavy, chronic cannabis smokers following acute smoked cannabis","volume":"36","author":"Schwope","year":"2012","journal-title":"J. Anal. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","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":"ref_54","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/0006-3223(92)90019-V","article-title":"Changes in middle cerebral artery velocity after marijuana","volume":"32","author":"Mathew","year":"1992","journal-title":"Biol. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/bcp.12071","article-title":"Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Delta9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans","volume":"76","author":"Klumpers","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/npp.2009.184","article-title":"Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology","volume":"35","author":"Bhattacharyya","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3389\/fpsyt.2013.00130","article-title":"Does Cannabidiol Protect Against Adverse Psychological Effects of THC?","volume":"4","author":"Niesink","year":"2013","journal-title":"Front. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0014-2999(74)90129-0","article-title":"Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man","volume":"28","author":"Karniol","year":"1974","journal-title":"Eur. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Stroke Therapy Academic Industry Roundtable (1999). Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke, 30, 2752\u20132758.","DOI":"10.1161\/01.STR.30.12.2752"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/jcbfm.2014.218","article-title":"Cannabinoids in experimental stroke: A systematic review and meta-analysis","volume":"35","author":"England","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3389\/fphar.2017.00081","article-title":"A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol","volume":"8","author":"Sultan","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1097\/ALN.0b013e31818e435c","article-title":"Sympathetic nervous system: Evaluation and importance for clinical general anesthesia","volume":"109","author":"Neukirchen","year":"2008","journal-title":"Anesthesiology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/11\/1\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:53:16Z","timestamp":1760194396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/11\/1\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,31]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["ph11010013"],"URL":"https:\/\/doi.org\/10.3390\/ph11010013","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,31]]}}}