Mephedrone Concentrations in Cases of Clinical Intoxication

Background: Mephedrone (4-methylmethcathinone, 4-MMC), a ring-substituted synthetic cathinone derivative has become established as a permanent illicit drug in the dynamic new psychoactive substances (NPS) scene. Objective: This review summarizes current knowledge on mephedrone concentrations in biological samples from cases of acute intoxications (fatal and non-fatal), pharmacokinetics studies, wastewater and anonymous pooled urine analysis in order to provide an overview of the reliable scientific knowledge on toxicokinetics of mephedrone in humans. Method: The PubMed® database complemented with Google Scholar® was systematically searched to find published cases of mephedrone intoxications. The searches were done using the keyword “mephedrone OR 4- methylmethcathinone” in association to each of the following strategies: i) “intoxication OR poisoning”; ii) “(blood OR serum OR plasma”) OR “urine” OR (“saliva OR oral fluid”) OR “hair”; iii) “forensic toxicology samples”; iv) “wastewater OR sewage OR pooled urine” and v) “toxicity OR death OR fatal”. Results: Since 2010, a total of 97 fatal cases and 57 non-fatal intoxication cases were identified that presented mephedrone concentrations in human biological matrices attributed directly or indirectly to mephedrone. Typical subjects involved were young male with concomitant use of other drugs (psychostimulants, cannabis, alcohol and other depressants). Mephedrone mean blood concentration from fatal cases was 2,663 ng/mL (range 51-22,000 ng/mL), from non-fatal cases was 166 ng/mL (range, 13-412 ng/mL), that resulted in a similar range from data found in controlled studies with no acute toxicity associated (135 ng/mL, range 52-218 ng/mL). Forensic epidemiology studies based on wastewater and anonymous pooled urine analysis point towards similar variations in use (nightclub scene) to those self-reported in surveys and questioners. Conclusion: Mephedrone blood concentrations in cases of fatal intoxications were higher than in non-fatal cases. In both cases, great variability in mephedrone concentration potentially attributable to interindividual differences in pharmacokinetics-pharmacodynamics and poly-drug use complicates the interpretation of the forensic toxicological analysis.