A Comparison of Acute Pharmacological Effects of Methylone and MDMA Administration in Humans and Oral Fluid Concentrations as Biomarkers of Exposure.

Abstract

Simple SummaryMethylone is a synthetic cathinone that is usually used as a substitute for conventional psychostimulants, such as MDMA. Chemically, methylone is considered the β-keto analogue of MDMA, with which it presumably shares similar pharmacological effects. To date, the available data about the human pharmacology of methylone in humans are very scarce and are mainly derived from user experiences, published in internet forums or intoxication reports. Thus, an observational–naturalistic study was conducted to evaluate the acute pharmacological effects and determine biomarkers of exposure in oral fluid of methylone after oral self-administration in comparison to MDMA. Methylone induced the prototypical psychostimulant and empathogenic effects commonly associated with MDMA, although they were of lower intensity. Oral fluid concentrations of methylone can be considered a suitable biomarker of acute exposure, and oral fluid has been proven to be a useful biological matrix of detection.Considered the β-keto analogue of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-Methylenedioxymethcathinone (methylone) is a synthetic cathinone. Over the years, methylone has been used as a substitute for conventional psychostimulants, such as MDMA. To date, little is known about the human pharmacology of methylone; the only available information has been provided by surveys or published intoxication reports. In the present observational–naturalistic study, we evaluate the acute subjective and physiological effects of methylone after oral self-administration in comparison to MDMA in healthy poly-drug users. Fourteen participants (10 males, 4 females) selected their single oral doses of methylone from 100 to 300 mg (n = 8, mean dose 187.5 mg) or MDMA from 75 to 100 mg (n = 6, mean dose 87.5 mg) based on their experience. Study variables were assessed at 0, 1, 2, and 4 h (h) and included vital signs (non-invasive blood pressure, heart rate, cutaneous temperature) and subjective effects using visual analogue scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI) short form, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) questionnaire. Additionally, oral fluid concentrations of methylone and MDMA were determined. Acute pharmacological effects produced by methylone followed the prototypical psychostimulant and empathogenic profile associated with MDMA, although they were less intense. Methylone concentrations in oral fluid can be considered a useful biomarker to detect acute exposure in oral fluid. Oral fluid concentrations of MDMA and methylone peaked at 2 h and concentrations of MDMA were in the range of those previously described in controlled studies. Our results demonstrate that the potential abuse liability of methylone is similar to that of MDMA in recreational subjects.