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

Abstract

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.

Abuse Potential of Cathinones in Humans: A Systematic Review

“…These include euphoria, stimulation, perception alteration, energy increase, and sociability, although to a lesser extent. The results suggest that methylone induced a similar profile of effects to its non-β-analogue MDMA and mephedrone [62,63], both of which were also administered in naturalistic conditions but showed lower intensity of effects.…”

“…Overall, in terms of pharmacological effects, cathinone, diethylpropion, mephedrone, and methylone shared a similar stimulant profile to other recreational substances, such as MDMA and amphetamine [57,63,75]. These substances commonly produce an increase in cardiovascular effects and body temperature as well as stimulant and euphorigenic effects.…”

“…Only one study concerning methylone administration in humans was found in the literature (Table 3) [63]. This observational study was carried out in naturalistic settings, where eight participants selected their oral methylone doses from between 100 to 300 mg (mean dose 187.5 mg) according to their experience with psychostimulant use (Poyatos, 2021). A total of six participants self-administered a single oral dose of 75 or 100 mg of MDMA.…”

3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs

“…In 1978, Alexander Shulgin, a Californian chemist, synthesized and tested the drug, being the first to describe that MDMA was a psychoactive drug in humans. MDMA induces changes in mood, lowering emotional defensiveness and increasing the ability to open to others, breaking boundaries in communication and increasing empathy and self-acceptance without producing marked hallucinogenic effects ( 64 , 65 ). Therefore, it is not a “classic” psychedelic drug, but an “entactogen,” producing a gentler and easily tolerated state compared to LSD.…”

Identifying new psychoactive substances (NPS) using drug checking services: An innovative observational study design

“…This information was never given to the researchers outside the screening surveys. This observational and non-interventionist approach was based on previously published research developed in our institution (52)(53)(54)(55).…”