Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans

Poyatos, Lourdes; Núñez-Montero, Melani; Hladun, Olga; Rosa, Georgina De la; Martín, Soraya; Videla, Sebastian; Martínez-Couselo, Silvia; Ventura, Mireia; La Maida, Nunzia; Trana, Annagiulia Di; Busardò, Francesco Paolo; Torrens, Marta; Pichini, Simona; Pérez-Mañá, Clara; Farré, Magí; Papaseit, Esther

doi:10.3390/ijms27010089

Open AccessArticle

Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans

by

Lourdes Poyatos

^1,†

,

Melani Núñez-Montero

^1,2,†,

Olga Hladun

^1,2

,

Georgina De la Rosa

^1,2,

Soraya Martín

¹

,

Sebastian Videla

^1,2,

Silvia Martínez-Couselo

¹,

Mireia Ventura

³

,

Nunzia La Maida

⁴

,

Annagiulia Di Trana

⁴

,

Francesco Paolo Busardò

⁵,

Marta Torrens

⁶,

Simona Pichini

^4,‡,

Clara Pérez-Mañá

^1,2,‡

,

Magí Farré

^1,2,*,‡

and

Esther Papaseit

^1,2,6,‡

¹

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

²

Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), 08193 Cerdanyola del Vallés, Spain

³

Energy Control, Associació Benestar i Desenvolupament, Carrer de la Independència 384, 08041 Barcelona, Spain

⁴

National Center On Addiction and Doping, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy

⁵

Department of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, 60121 Ancona, Italy

⁶

Drug Addiction Unit, Parc de Salut Mar, Hospital del Mar Research Institute, 08003 Barcelona, Spain

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors share senior position.

Int. J. Mol. Sci. 2026, 27(1), 89; https://doi.org/10.3390/ijms27010089

Submission received: 15 November 2025 / Revised: 16 December 2025 / Accepted: 18 December 2025 / Published: 21 December 2025

(This article belongs to the Special Issue Molecular Advances in Forensic Toxicology: Innovative Approaches in Detection of New Psychoactive Substances)

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Abstract

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.

Keywords: pharmacology; new psychoactive substances; synthetic cathinones; clephedrone; 4-chloromethcathinone; 4-CMC; methylone; subjective effects

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MDPI and ACS Style

Poyatos, L.; Núñez-Montero, M.; Hladun, O.; Rosa, G.D.l.; Martín, S.; Videla, S.; Martínez-Couselo, S.; Ventura, M.; La Maida, N.; Trana, A.D.; et al. Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans. Int. J. Mol. Sci. 2026, 27, 89. https://doi.org/10.3390/ijms27010089

AMA Style

Poyatos L, Núñez-Montero M, Hladun O, Rosa GDl, Martín S, Videla S, Martínez-Couselo S, Ventura M, La Maida N, Trana AD, et al. Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans. International Journal of Molecular Sciences. 2026; 27(1):89. https://doi.org/10.3390/ijms27010089

Chicago/Turabian Style

Poyatos, Lourdes, Melani Núñez-Montero, Olga Hladun, Georgina De la Rosa, Soraya Martín, Sebastian Videla, Silvia Martínez-Couselo, Mireia Ventura, Nunzia La Maida, Annagiulia Di Trana, and et al. 2026. "Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans" International Journal of Molecular Sciences 27, no. 1: 89. https://doi.org/10.3390/ijms27010089

APA Style

Poyatos, L., Núñez-Montero, M., Hladun, O., Rosa, G. D. l., Martín, S., Videla, S., Martínez-Couselo, S., Ventura, M., La Maida, N., Trana, A. D., Busardò, F. P., Torrens, M., Pichini, S., Pérez-Mañá, C., Farré, M., & Papaseit, E. (2026). Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans. International Journal of Molecular Sciences, 27(1), 89. https://doi.org/10.3390/ijms27010089

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Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans

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