Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in Humans

Abstract

Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100–200 mg; mean 150 mg) or intranasally (n = 5, 50–100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.

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

“…The study was designed as a non-controlled prospective observational study in a naturalistic setting with methylone and MDMA self-administration. The methodology, including procedures and evaluations, coincides with previous observational–naturalistic studies aimed at evaluating the acute effects of other NPS [ 38 , 39 , 40 ]. Six subjects (5 M, 1 F) self-administered MDMA and 8 subjects (5 M, 3 F) self-administered methylone.…”

“…Pills containing methylone and MDMA were analyzed by gas chromatography associated with mass spectrometry (GC/MS), a technique that traces the presence of the most frequent drugs of abuse, such as MDMA, cocaine, heroin, amphetamine and methamphetamine, LSD, and multiple NPS (methylone, mephedrone, and other synthetic cathinones, synthetic cannabinoids, tryptamines, among others). The testing of the pills showed a more than 95% purity of methylone and MDMA, as well as the absence of toxic components or adulterants [ 38 , 39 , 40 ].…”

“…Visual analogue scales (100 mm, from “not at all” to “extremely”) contained 30 items that subjects were asked to rate, such as: intensity, stimulated, high, good effects, liking, happiness, drunkenness, changes in colors, changes in shapes, changes in lights, hallucinations (seeing lights or spots), hallucinations (seeing of animals), changes in hearing, hallucinations (hearing sounds or voices), different or changed body feeling, unreal body feeling, changes in distances, different surroundings, unreal surroundings, confusion, fear, depression or sadness, drowsiness, dizziness, bad effects, headache, sickness, vertigo, shortness of breath, and face flushing [ 38 , 39 , 40 ].…”

“…The standardized ARCI 49-item short form is a true/false questionnaire used to evaluate the subjective effects of drugs of abuse. This inventory includes five subscales that assess pentobarbital–chlorpromazine–alcohol-like effects (PCAG, sedation), morphine–benzedrine-like effects (MBG, euphoria), lysergic acid diethylamide-like effects (LSD, dysphoria), benzedrine-like effects (BG, intellectual efficiency), and amphetamine-like effects (A, increased energy) [ 38 , 39 , 40 ].…”

“…The VESSPA-SSE is a questionnaire sensitive to subjective effects related to stimulants such as MDMA that includes six subscales: sedation (S), psychosomatic anxiety (ANX), changes in perception (CP), pleasure and sociability (SOC), activity and energy (ACT), and psychotic symptoms (PS) [ 38 , 39 , 40 ].…”