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Clephedrone and methylone were investigated using a non-controlled, prospective observational design in eight healthy volunteers, with baseline and 5-hour follow-up of vital signs and subjective effects. Oral fluid concentrations of clephedrone and cortisol were measured, and prior pilot data for methylone were included. 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Clinical Pharmacology and Biochemistry, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTiP-IGTP), Carretera de Canyet S/N, 08916 Badalona, Spain; [lpoyatos@igtp.cat](lpoyatos@igtp.cat) (L.P.); [nmmelani@gmail.com](nmmelani@gmail.com) (M.N.-M.); ohladun.germanstrias@gencat.cat (O.H.);  \ngrosalo.germanstrias@gencat.cat (G.D.l.R.); [smartins.mn.ics@gencat.cat](smartins.mn.ics@gencat.cat) (S.M.);  \nsvidelac.germanstrias@gencat.cat (S.V.); smartinezcou.germanstrias@gencat.cat (S.M.-C.);  \n[cperezm.mn.ics@gencat.cat](cperezm.mn.ics@gencat.cat) (C.P.-M.); [epapaseit@researchmar.net](epapaseit@researchmar.net) (E.P.)  \n2 Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), 08193 Cerdanyola del Vallés, Spain  \n3 Energy Control, Associació Benestar i Desenvolupament, Carrer de la Independència 384, 08041 Barcelona, Spain; [mireia@energycontrol.org](mireia@energycontrol.org)  \n4 National Center On Addiction and Doping, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy; [nunzia.lamaida@iss.it](nunzia.lamaida@iss.it) (N.L.M.); annagiulia.ditrana@iss.it (A.D.T.); [simona.pichini@iss.it](simona.pichini@iss.it) (S.P.)  \n5 Department of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, 60121 Ancona, Italy; [f.busardo@univpm.it](f.busardo@univpm.it)  \n6 Drug Addiction Unit, Parc de Salut Mar, Hospital del Mar Research Institute, 08003 Barcelona, Spain; [mtorrens@researchmar.net](mtorrens@researchmar.net)  \n* [Correspondence: magi.farre@uab.cat](Correspondence: magi.farre@uab.cat)[ ](Correspondence: magi.farre@uab.cat)† These authors contributed equally to this work.  \n‡ These authors share senior position.  \nAbstract  \nSynthetic cathinones represent the second most frequently reported group of new psychoactive substances identified annually, according to the United Nations. It remains unknown whether specific derivatives differ in the onset of effects related to absorption kinetics. Clephedrone (4-chloromethcathinone, 4-CMC) has been among the most frequently seized cathinones in recent years; however, available data on its pharmacology and abuse potential remain scarce. A non-controlled, prospective, observational study was conducted involving eight healthy volunteers (six women) who self-administered a single oral dose of clephedrone (100 or 150 mg) . Study variables were assessed at baseline and over a 5-h period following administration, including vital signs and subjective effects. Oral fluid concentrations of clephedrone and cortisol were determined. For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects. Results indicated that both clephedrone and methylone produced stimulant-like subjective effects. However, clephedrone exhibited a delayed onset and peak of effects compared with methylone, indicating a clinically relevant pharmacokinetic difference. Both substances were detected in oral fluid, with peak concentrations","cbCaibNlq6BSQVsK","https://ap.wps.com/l/cbCaibNlq6BSQVsK","pdf",1474630,"English","# Introduction\n## Synthetic cathinones as new psychoactive substances\n## First-generation compounds and regulatory responses\n## Second-generation compounds and chemical modification","[{\"question\":\"What was the study design for clephedrone in humans?\",\"answer\":\"A non-controlled, prospective, observational study involved eight healthy volunteers who self-administered a single oral dose of clephedrone (100 or 150 mg). Outcomes were assessed at baseline and over 5 hours, including vital signs and subjective effects.\"},{\"question\":\"How did clephedrone’s effects compare with methylone?\",\"answer\":\"Both compounds produced stimulant-like subjective effects, but clephedrone had a delayed onset and delayed peak compared with methylone. This difference aligned with later peak oral-fluid concentrations for clephedrone.\"},{\"question\":\"Which biomarkers were measured in oral fluid?\",\"answer\":\"The article reports oral fluid concentrations of clephedrone and cortisol. Oral-fluid measurements were used to evaluate concentration-time profiles and relate them to the observed pharmacodynamic timing.\"}]","Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans | PDF",1790762656]