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Background and Purpose: The use of 'bath salts' drug preparations has been associated with high rates of toxicity and death. Preparations often contain mixtures of drugs, including multiple synthetic cathinones or synthetic cathinones and caffeine. Little is known about the interactions of 'bath salts' constituents and adverse effects often reported by users., Experimental Approach: This study used adult male Sprague-Dawley rats to characterise the cardiovascular effects, locomotor effects and pharmacokinetics of methylone, methylenedioxypyrovalerone (MDPV) and caffeine, administered alone and as binary mixtures. Dose-addition analyses were used to determine the effect levels of a strictly additive interaction for dose pairs., Key Results: 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-additivity for all endpoints, whereas interactions between MDPV or methylone and caffeine tended to be additive or sub-additive for cardiovascular endpoints, and additive or supra-additive for increases in locomotion. No pharmacokinetic interactions were observed between individual constituents, but methylone appeared to display nonlinear pharmacokinetics at the largest dose evaluated., Conclusion and Implications: These findings demonstrate that 'bath salts' preparations can impact both cardiovascular and locomotor effects and suggest that interactions among constituent drugs could contribute to the 'bath salts' toxidrome reported by human users., (© 2025 British Pharmacological Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

With recent evolution of cannabis legalization around the world and multiplication of cannabis derived products, identifying and qualifying cannabis consumption has a proven interest. Although blood, plasma, and urine are common matrices widely used in toxicology laboratories, oral fluid presents specific advantages. In the context of doping tests, addiction consultation or roadside checks, where other matrices are impractical to collect or can be adulterated, oral fluid is a promising matrix that allows a non-invasive, rapid, and monitored self-sampling. However, available devices required a consequent volume of oral fluid, more than 250 µL, sometimes difficult to collect. We present here a fully optimized quantitative method for seven cannabinoids, including four metabolites, in oral fluid, Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol; cannabidiol, 7-hydroxy and 7-carboxycannabidiol; and cannabinol. After self-collection of 20 µL using an accurate and precise volumetric absorptive microsampling device (VAMS ® ), cannabinoids were derivatized with 2-fluoro-1-methylpyridinium p-toluenesulfonate to increase sensitivity. The successive steps of the proposed method, including biosampling, 1 h sample preparation with derivatization, and acquisition by ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry, were fully optimized. A limit of quantification of 0.5 ng/mL (≈10 pg per sampling) was thus targeted, adapted to the legal threshold required by the authorities and to clinical monitoring. Applied to six cannabis consumers, the proposed method made it possible to quantify in 20 µL oral fluid samples, Δ9-tetrahydrocannabinol ranging from 0.5 to 6236 ng/mL, cannabidiol from 0.6 to 190 ng/mL and cannabinol from 0.5 to 118 ng/mL., Competing Interests: Declarations. Ethics approval: The observational study was conducted in accordance with ethical guidelines established in the Declaration of Helsinki and the French legislation. Our ethics internal review board examined and approved the study design in a meeting on August 4 2023. The decision mentioned that the study did not fell within the scope of Loi Jardé (arrêté du 3 mai 2017 fixant la liste des recherches mentionnées au 2° de l’article L. 1121–1 du code de la santé publique) because it was a secondary analysis of a previous collection. The previously collected urinary and salivary samples were collected in non-treatment seeking healthy volunteers, who gave a written informed consent and were recruited among University of Paris students by word of mouth. Informed consent: Informed consent was obtained from all volunteers. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)