# Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans

## TL;DR

This study compares the effects and absorption of clephedrone and methylone in humans, finding that clephedrone has a delayed onset and peak effect compared to methylone.

## Contribution

The study provides new pharmacokinetic and subjective effect data for clephedrone and compares it with methylone in a human observational setting.

## Key findings

- Clephedrone and methylone both produce stimulant-like effects in humans.
- Clephedrone has a delayed onset and peak of effects compared to methylone.
- Oral fluid concentrations of clephedrone peak later than those of methylone.

## Abstract

Synthetic cathinones represent the second most frequently reported group of new psychoactive substances identified annually, according to the United Nations. It remains unknown whether specific derivatives differ in the onset of effects related to absorption kinetics. Clephedrone (4-chloromethcathinone, 4-CMC) has been among the most frequently seized cathinones in recent years; however, available data on its pharmacology and abuse potential remain scarce. A non-controlled, prospective, observational study was conducted involving eight healthy volunteers (six women) who self-administered a single oral dose of clephedrone (100 or 150 mg). Study variables were assessed at baseline and over a 5-h period following administration, including vital signs and subjective effects. Oral fluid concentrations of clephedrone and cortisol were determined. For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects. Results indicated that both clephedrone and methylone produced stimulant-like subjective effects. However, clephedrone exhibited a delayed onset and peak of effects compared with methylone, indicating a clinically relevant pharmacokinetic difference. Both substances were detected in oral fluid, with peak concentrations occurring later following clephedrone administration, consistent with its delayed pharmacodynamic profile.