Pharmacological effects of methylone and MDMA in humans
In a randomised, double‑blind, placebo‑controlled crossover trial in 17 experienced psychostimulant users, a single oral dose of methylone (200 mg) produced sympathomimetic effects and stimulant/entactogenic subjective effects similar to MDMA (100 mg) but with a faster onset and shorter duration. These results indicate methylone’s acute pharmacological profile and abuse potential in humans are comparable to those of MDMA.
Authors
- Magí Farré
- Benjamin Kelmendi
- Marta Torrens
Published
Abstract
Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a β-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone remains scarcely explored in humans. Herein, we aimed to evaluate the acute pharmacological effects of methylone and its abuse potential in humans when compared with that of MDMA following oral administration under controlled conditions. Seventeen participants of both sexes (14 males, 3 females) with a previous history of psychostimulant use completed a randomized, double-blind, placebo-controlled, crossover clinical trial. Participants received a single oral dose of 200 mg of methylone, 100 mg of MDMA, and a placebo. The variables included physiological effects (blood pressure, heart rate, oral temperature, pupil diameter), subjective effects using visual analog scales (VAS), the short form of the Addiction Research Center Inventory (ARCI), the Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire (VESSPA-SSE), and the Sensitivity to Drug Reinforcement Questionnaire (SDRQ), and psychomotor performance (Maddox wing, psychomotor vigilance task). We observed that methylone could significantly increase blood pressure and heart rate and induce pleasurable effects, such as stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone exhibited an effect profile similar to MDMA, with a faster overall onset and earlier disappearance of subjective effects. These results suggest that abuse potential of methylone is comparable to that of MDMA in humans.
Research Summary of 'Pharmacological effects of methylone and MDMA in humans'
Introduction
Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone that emerged as a new psychoactive substance and is commonly used as a substitute for MDMA because of its similar chemical structure and reported effects. Preclinical data indicate that methylone acts as a substrate at dopamine, norepinephrine and serotonin transporters and evokes monoamine release, but human pharmacology has been sparsely characterised; available human information has largely come from user reports and a small observational naturalistic study. Important uncertainties therefore remain about methylone’s acute physiological, subjective and psychomotor effects in controlled conditions and about its abuse potential relative to MDMA. [Poyatos] and colleagues set out to address this gap by conducting a randomised, double-blind, placebo-controlled, crossover clinical trial that directly compared single oral doses of methylone and MDMA with placebo under controlled laboratory conditions. The primary aim was to evaluate acute cardiovascular, subjective and psychomotor effects and indicators of abuse potential following 200 mg methylone versus 100 mg MDMA and placebo in experienced recreational users.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Poyatos, L., Pérez-Mañá, C., Hladun, O., Núñez-Montero, M., de la Rosa, G., Martín, S., Barriocanal, A. M., Carabias, L., Kelmendi, B., Taoussi, O., Busardò, F. P., Fonseca, F., Torrens, M., Pichini, S., Farré, M., & Papaseit, E. (2023). Pharmacological effects of methylone and MDMA in humans. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1122861
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Wolfson, P. E., Andries, J., Feduccia, A. A. et al. · Scientific Reports (2020)
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Schmidt, E. F., Warner-Schmidt, J., Stogniew, M. et al. · Frontiers in Neuroscience (2024)
Heifets, B. D., Olson, D. E. · Neuropsychopharmacology (2023)
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