Melani Núñez-Montero

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 For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects.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.

Background: Synthetic cathinones (SCs) are the second most representative class of New Psychoactive Substances, with more than 100 analogues identified in the illicit drug market up to 2024. According to the United Nations Office on Drugs and Crimes, N-ethylhexedrone (NEH) and N-ethyl-nor-pentedrone (NEP) were identified among the most frequently seized SCs worldwide. However, still, little is known with regard to their pharmacological effects in humans. Methods: For the first time, we conducted a naturalistic, prospective observational study in 16 participants (7 women and 9 men) with a previous history of psychostimulant recreational use. They intranasally self-administered a single dose of NEP (n = 8, 20–40 mg) or NEH (n = 8, 20–40 mg). The physiological effects (systolic and diastolic blood pressure, heart rate, and temperature) and subjective effects (visual analogue scales, Addiction Research Center Inventory questionnaire and Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire) were assessed up to 4 h after the self-administration at different time points (0, 20 and 40 min and 1, 1.5, 2, 3 and 4 h). Results: Despite several differences, both NEP and NEH produced significant effects within 20 min, with a return to baseline 3–4 h after self-administration. In general, NEP showed a faster onset and a more rapid disappearance of subjective effects than NEH. Moreover, intranasal self-administration of NEH and NEP in experienced recreational drug users, within a non-controlled setting, induces a constellation of psychostimulant-like effects. Conclusion: NEH and NEP showed similar pharmacological properties after insufflation, with typical effects of SCs