Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans

This double-blind placebo-controlled trial (n=12) assessed the pharmacokinetics (movement of drugs in the body) of varying doses of methylone (50-200mg) and MDMA in healthy volunteers. Plasma concentrations of methylone increased dose-dependent and quickly reached peak concentration levels. The method used here offers a fast and effective way to assess the kinetics of methylone, MDMA and their metabolites.

Abstract

“The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d₅, MDA-d₅ and methylone-d₃ internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0–24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 h·ng/mL and T_1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10–14-fold lower and an AUC0–24 value that was 21–29-fold lower. Methylone pharmacokinetics was linear across 50–200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50–200 mg.”

Authors: Lourdes Poyatos, Alfredo Lo Faro, Diletta Beradinelli, Giorgia Sprega, Sara Malaca, Simona Pichini, Marilyn A. Huestis, Esther Papaseit, Clara Perez-Mana, Francesco P. Busardo & Magi Farre

Summary of Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans

Synthetic cathinones are similar to cathinone, a naturally occurring psychoactive molecule from Catha edulis plants. They were placed into schedule I of the Controlled Substances Act in 2011.

3,4-methylenedioxy-methcathinone, also known as methylone or MDMC, is a designer drug of the phenethylamine class that was first identified in 2009. It has pharmacological effects similar to MDMA, including inhibition of neuronal reuptake of the monoamines dopamine and serotonin and increasing monoamine concentrations in the synaptic cleft.

This research aims to define methylone’s and HMMC’s human pharmacokinetics and evaluate whether or not non-linear pharmacokinetics occur following controlled administration.

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