Mephedrone (4-Methylmethcathinone)-Related Deaths

Maskell, Peter; Paoli, Giorgia De; Seneviratne, C; Pounder, Derrick J.

doi:10.1093/anatox/35.3.188

Cited by 165 publications

(91 citation statements)

References 12 publications

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“…These results are consistent with previous studies in animal models, reporting that, it induces substantial increases in blood pressure, heart rate, and cardiac contractility (Meng et al, 2012), in addition to acute cardiovascular toxicity characterized by hypertension and tachycardia (Sivagnanam et al, 2013;Nicholson et al, 2010;Regan et al, 2011;Maskell et al, 2011;Wood et al, 2010). Moreover, mephedrone consistently results in mydriasis, a specific and acute effect also observed after MDMA and amphetamine administration de la Torre et al, 2000de la Torre et al, , 2004Mas et al, 1999), although slighter in comparison with MDMA.…”

Section: Discussionsupporting

confidence: 93%

Human Pharmacology of Mephedrone in Comparison with MDMA

Papaseit

Pérez‐Mañá

Mateus

et al. 2016

Neuropsychopharmacol

133

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Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users.

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Section: Discussionsupporting

confidence: 93%

Human Pharmacology of Mephedrone in Comparison with MDMA

Papaseit

Pérez‐Mañá

Mateus

et al. 2016

Neuropsychopharmacol

133

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“…There are two reported fatalities in the European Union in which mephedrone appears to be the sole cause of death and there are at least another 37 deaths in which mephedrone have been detected in post-mortem samples (Maskell et al 2011). Mephedrone was the first cathinone derivative to be 'risk-assessed' by the extended Scientific Committee of the EMCDDA (European Monitoring Centre for Drugs and Drug Addiction).…”

Section: Introductionmentioning

confidence: 99%

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

et al. 2013

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Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine.Objective The major aims were to investigate the pharmacokinetics and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. MethodsMephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min.Results Mephedrone plasma concentrations after i.v. administration fit to a twocompartment model (α=10.23 h -1 and β=1.86 h -1 ). After oral administration, peak mephedrone concentrations were achieved between 0.5-1 h, and declined to undetectable levels at 9 h. Absolute bioavailability of mephedrone was of about 10% and the percentage of mephedrone protein binding was of 21.59 ± 3.67%. We have identified five Phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85 ± 0.08.Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. ConclusionsWe suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

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“…Urine drug screening in another series found that 16 of 17 specimens were positive for other drugs of abuse [13]. Postmortem toxicology testing has also revealed that concurrent use of other substances is common [32][33][34] Adverse Clinical Effects of Synthetic Cathinones Cardiac, psychiatric, and neurological signs and symptoms are the most common adverse effects reported in synthetic cathinone users who require medical care. There are four series detailing clinical effects of cathinones.…”

Section: Subjective User Effectsmentioning

confidence: 99%

The Toxicology of Bath Salts: A Review of Synthetic Cathinones

2011

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Synthetic cathinones have recently emerged and grown to be popular drugs of abuse. Their dramatic increase has resulted in part from sensationalized media attention as well as widespread availability on the Internet. They are often considered "legal highs" and sold as "bath salts" or "plant food" and labeled "not for human consumption" to circumvent drug abuse legislation. Cathinone is a naturally occurring beta-ketone amphetamine analogue found in the leaves of the Catha edulis plant. Synthetic cathinones are derivatives of this compound. Those that are being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3-and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone. Synthetic cathinones are phenylalkylamines derivatives, and are often termed "bk-amphetamines" for the beta-ketone moiety. They may possess both amphetaminelike properties and the ability to modulate serotonin, causing distinct psychoactive effects. Desired effects reported by users of synthetic cathinones include increased energy, empathy, openness, and increased libido. Cardiac, psychiatric, and neurological signs and symptoms are the most common adverse effects reported in synthetic cathinone users who require medical care. Deaths associated with use of these compounds have been reported. Exposure to and use of synthetic cathinones are becoming increasingly popular despite a lack of scientific research and understanding of the potential harms of these substances. The clinical similarities to amphetamines and MDMA specifically are predictable based on the chemical structure of this class of agents. More work is necessary to understand the mechanisms of action, toxicokinetics, toxicodynamics, metabolism, clinical and psychological effects as well as the potential for addiction and withdrawal of these agents.

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Mephedrone (4-Methylmethcathinone)-Related Deaths

Cited by 165 publications

References 12 publications

Human Pharmacology of Mephedrone in Comparison with MDMA

Human Pharmacology of Mephedrone in Comparison with MDMA

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

The Toxicology of Bath Salts: A Review of Synthetic Cathinones

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