Pharmacokinetic disposition in oral fluid, excretion profile, and subjective and physiological responses following oral and intranasal administration of Clophedrone (3-CMC)
Abstract
<b>Background and Purpose:</b> Clophedrone (3-chloromethcathinone, 3-CMC) belongs to the methcathinone subclass of ring-substituted cathinones, a prominent group of new psychoactive substances (NPS) present in the illicit drug market. To date no studies have assessed concentrations and acute effects of 3-CMC in humans after self-administration. <b>Experimental Approach:</b> A total of 16 psychostimulant users self-administered 3-CMC by oral (OR, 100-150 mg, N=8) or intranasal route (IN, 60-80 mg, N=8). Physiological and subjective effects were assessed alongside collection of oral fluid, urine, and sweat samples for 3-CMC quantification at predetermined time points over 5 hours. Subjective effects were evaluated using visual analog scales, Addiction Research Center Inventory and the Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire Cortisol concentrations were additionally measured in oral fluid. <b>Key Results:</b> Intranasal administration produced earlier peak oral fluid concentrations (40-60 min) and a shorter concentration-time profile than oral administration, which reached peak concentrations at 1-3 h and remained quantifiable beyond 5 h. Route-dependent differences in urinary excretion were observed, with greater glucuronide formation following oral administration. 3-CMC was detected in nearly all sweat samples and showed higher concentrations after intranasal use. 3-CMC increased blood pressure, heart rate, and cortisol concentrations, and induced marked stimulant, drug-liking and prosocial effects, which appeared earlier with the IN route than with the OR route. Desire for redosing was greater following IN administration. <b>Conclusion and Implications:</b> 3-CMC produces a mixed psychostimulant and empathogen profile similar to that of other ring-substituted cathinones and MDMA. Intranasal administration may be associated with greater abuse liability than oral use. Oral fluid concentrations could be a useful biomarker of recent 3-CMC exposure, while the N-glucuronide metabolite may help identify oral administration. These findings provide novel insights into human pharmacology, disposition, and excretion of 3-CMC and may support clinical, forensic, and toxicological assessments.
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