title: Human Pharmacology of Mephedrone in Comparison with MDMA.
abstract: Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users.
authors.affiliation: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program IMIM-Hospital del Mar Medical Research Institute, Parc de Salut Mar, Barcelona, Spain.|Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol (IGTP), Badalona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Papaseit
authors.affiliation: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program IMIM-Hospital del Mar Medical Research Institute, Parc de Salut Mar, Barcelona, Spain.|Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Pérez-Mañá
authors.affiliation: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program IMIM-Hospital del Mar Medical Research Institute, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Julián-Andrés
authors.initials: JA
authors.lastname: Mateus
authors.affiliation: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program IMIM-Hospital del Mar Medical Research Institute, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Mitona
authors.initials: M
authors.lastname: Pujadas
authors.affiliation: Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|Institut de Neuropisquiatria i Adiccions. Addiction Unit and IMIM, Barcelona, Spain.
authors.forename: Francina
authors.initials: F
authors.lastname: Fonseca
authors.affiliation: Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|Institut de Neuropisquiatria i Adiccions. Addiction Unit and IMIM, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Torrens
authors.affiliation: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program IMIM-Hospital del Mar Medical Research Institute, Parc de Salut Mar, Barcelona, Spain.|Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Olesti
authors.affiliation: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program IMIM-Hospital del Mar Medical Research Institute, Parc de Salut Mar, Barcelona, Spain.|Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain.|CIBER de Fisiopatología de la Obesidad y Nutrición (CB06/03), CIBEROBN, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.affiliation: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program IMIM-Hospital del Mar Medical Research Institute, Parc de Salut Mar, Barcelona, Spain.|Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol (IGTP), Badalona, Spain.
authors.forename: Magí
authors.initials: M
authors.lastname: Farré
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006213:Hallucinogens / Q000097:blood / Q000494:pharmacology*; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D013997:Time Factors; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D006213:Hallucinogens; D008694:Methamphetamine; C548233:mephedrone; D018817:N-Methyl-3,4-methylenedioxyamphetamine