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Preparations often contain mixtures of drugs, including multiple synthetic cathinones or synthetic cathinones and caffeine. Little is known about the interactions of \u2018bath salts\u2019 constituents and adverse effects often reported by users.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>This study used adult male Sprague\u2013Dawley rats to characterise the cardiovascular effects, locomotor effects and pharmacokinetics of methylone, methylenedioxypyrovalerone (MDPV) and caffeine, administered alone and as binary mixtures. Dose\u2010addition analyses were used to determine the effect levels of a strictly additive interaction for dose pairs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Methylone, MDPV and caffeine increased heart rate (HR) and locomotion, with methylone producing the largest increase in HR, MDPV producing the largest increase in locomotor activity and caffeine being the least effective in stimulating HR and locomotor activity. MDPV and caffeine increased mean arterial pressure (MAP), with caffeine being more effective than MDPV. The nature of the interactions between methylone and MDPV tended towards sub\u2010additivity for all endpoints, whereas interactions between MDPV or methylone and caffeine tended to be additive or sub\u2010additive for cardiovascular endpoints, and additive or supra\u2010additive for increases in locomotion. No pharmacokinetic interactions were observed between individual constituents, but methylone appeared to display nonlinear pharmacokinetics at the largest dose evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>These findings demonstrate that \u2018bath salts\u2019 preparations can impact both cardiovascular and locomotor effects and suggest that interactions among constituent drugs could contribute to the \u2018bath salts\u2019 toxidrome reported by human users.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17444","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T02:14:32Z","timestamp":1737598472000},"page":"1836-1855","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cardiovascular and locomotor effects of binary mixtures of common \u2018bath salts\u2019 constituents: Studies with methylone, methylenedioxypyrovalerone and caffeine in rats"],"prefix":"10.1111","volume":"182","author":[{"suffix":"Jr","given":"Robert W.","family":"Seaman","sequence":"first","affiliation":[{"name":"Department of Pharmacology The University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Galindo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin T.","family":"Stinson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Sulima","sequence":"additional","affiliation":[{"name":"Drug Design and Synthesis Section, Molecular 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