22ae86c0fd7269ebef7b9e09e6ef98f4 ijms-27-00089-v2.pdf e96b94a67e22f5491eaed2706983be1beedfb194 ijms-27-00089-v2.pdf b8b8bc909b5bde9592791a30bacd3fd612fb8e5f8be794dd6f13a11bc7d88214 ijms-27-00089-v2.pdf Title: Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans Subject: Synthetic 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 For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects.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 occurring later following clephedrone administration, consistent with its delayed pharmacodynamic profile. 40pt Keywords: pharmacology; new psychoactive substances; synthetic cathinones; clephedrone; 4-chloromethcathinone; 4-CMC; methylone; subjective effects Author: Lourdes Poyatos, Melani Núñez-Montero, Olga Hladun, Georgina De la Rosa, Soraya Martín, Sebastian Videla, Silvia Martínez-Couselo, Mireia Ventura, Nunzia La Maida, Annagiulia Di Trana, Francesco Paolo Busardò, Marta Torrens, Simona Pichini, Clara Pérez-Mañá, Magí Farré and Esther Papaseit Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Mon Dec 22 09:49:41 2025 CET ModDate: Mon Dec 22 09:57:23 2025 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1474630 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLFTRW+VnURWPalladioL-Bold Type 1 Custom yes yes yes 120 0 PJYQQB+VnURWPalladioL Type 1 Custom yes yes yes 121 0 YUXDTD+URWPalladioL-Bold Type 1 Custom yes yes yes 122 0 GDYCQP+URWPalladioL-Roma Type 1 Custom yes yes yes 123 0 OCRTEQ+URWPalladioL-Ital Type 1 Custom yes yes yes 124 0 QDCWHF+EURM10 Type 1 Builtin yes yes yes 166 0 FNGJBE+PalatinoLinotype TrueType WinAnsi yes yes no 192 0 TRXZTX+CMSY10 Type 1 Builtin yes yes yes 254 0 RAMSXI+wasy9 Type 1 Builtin yes yes yes 255 0 MPUDFL+PazoMath Type 1 Builtin yes yes yes 256 0 FNGJBG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 247 0 FNGJBE+PalatinoLinotype TrueType WinAnsi yes yes no 248 0 FNGJBG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 290 0 FNGJBE+PalatinoLinotype TrueType WinAnsi yes yes no 291 0 FNGJBG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 326 0 FNGJBE+PalatinoLinotype TrueType WinAnsi yes yes no 327 0 FNGJBG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 318 0 FNGJBE+PalatinoLinotype TrueType WinAnsi yes yes no 319 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-01-23 03:08:16 CET RepresentationInformation: ijms-27-00089-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-01-22 12:43:36 CET Size: 1474630 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 600 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Results Children: Item: Title: Participants Item: Title: Physiological Effects Item: Title: Subjective Effects Item: Title: Oral Fluid Concentrations Item: Title: Discussion Item: Title: Materials and Methods Children: Item: Title: Study Design Item: Title: Procedures Item: Title: Drugs Item: Title: Physiological Effects Item: Title: Subjective Effects Item: Title: Oral Fluid Concentrations Item: Title: Statistical Analysis Item: Title: Conclusions Item: Title: References Info: Title: Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans Author: Lourdes Poyatos, Melani Núñez-Montero, Olga Hladun, Georgina De la Rosa, Soraya Martín, Sebastian Videla, Silvia Martínez-Couselo, Mireia Ventura, Nunzia La Maida, Annagiulia Di Trana, Francesco Paolo Busardò, Marta Torrens, Simona Pichini, Clara Pérez-Mañá, Magí Farré and Esther Papaseit Subject: Synthetic 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. 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