Analysis of Synthetic Cathinones Commonly Found in Bath Salts in Human Performance and Postmortem Toxicology: Method Development, Drug Distribution and Interpretation of Results
ABSTRACT To date, the Toxicology Section of the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory has identified six synthetic cathinones, commonly found in bath salt products, in 43 cases. Thirty-two cases will be reviewed here, including all of the postmortem cases, all of the human performance cases that had blood specimens submitted, and one urine-only human performance case. The following compounds have been confirmed: 3,4-methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), pyrovalerone, pentylone, alpha-pyrrolidinopentiophenone (alpha-PVP) and methedrone. The method also screens for mephedrone, butylone and 3-fluoromethcathinone. Case demographics show 42 white males and females ranging in age from 19 to 53 years. The remaining case was that of a 34-year-old Hispanic male. The 43 cases represent 17 driving under the influence, two domestic violence, four suicides, 12 overdoses, six accidents, one drug-facilitated assault and one homicide. Data will be presented on the distribution of some of these cathinones in various matrices. After review, blood concentration does not appear to predict outcome regarding fatalities or impairment. The highest MDPV concentration occurred in a suicide by hanging and the highest methylone concentration was in a driver. The confirmation method is a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in multiple reaction monitoring mode.
- SourceAvailable from: Matthias E Liechti
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- "All these cathinones are characterized by a pyrrolidine ring structure, making them different structurally and possibly also pharmacologically from other synthetic cathinones (Marusich et al., 2014; Simmler et al., 2013). Among the pyrovalerone cathinones, MDPV is currently the most widely detected and used, both in the EU (European Monitoring Center for Drugs and Drug Addiction, 2014b; Helander et al., 2014; Zuba and Byrska, 2013) and US (Leffler et al., 2014; Marinetti and Antonides, 2013; Spiller et al., 2011). In fact, MDPV has become the most frequently detected and used of all cathinones ( " bath salts " ) in some EU countries (Helander et al., 2014; Zuba and Byrska, 2013) and the US (Leffler et al., 2014). "
ABSTRACT: The pharmacology of novel psychoactive substances is mostly unknown. We evaluated the transporter and receptor interaction profiles of a series of para-(4)-substituted amphetamines and pyrovalerone cathinones. We tested the potency of these compounds to inhibit the norepinephrine (NE), dopamine (DA), and serotonin (5-HT) transporters (NET, DAT, and SERT, respectively) using human embryonic kidney 293 cells that express the respective human transporters. We also tested the substance-induced efflux of NE, DA, and 5-HT from monoamine-loaded cells, binding affinities to monoamine receptors, and 5-HT2B receptor activation. Para-(4)-substituted amphetamines, including 4-methylmethcathinone (mephedrone), 4-ethylmethcathinone, 4-fluoroamphetamine, 4-fluoromethamphetamine, 4-fluoromethcatinone (flephedrone), and 4-bromomethcathinone, were relatively more serotonergic (lower DAT:SERT ratio) compared with their analogs amphetamine, methamphetamine, and methcathinone. The 4-methyl, 4-ethyl, and 4-bromo groups resulted in enhanced serotonergic properties compared with the 4-fluoro group. The para-substituted amphetamines released NE and DA. 4-Fluoramphetamine, 4-flouromethamphetamine, 4-methylmethcathinone, and 4-ethylmethcathinone also released 5-HT similarly to 3,4-methylenedioxymethamphetamine. The pyrovalerone cathinones 3,4-methylenedioxypyrovalerone, pyrovalerone, α-pyrrolidinovalerophenone, 3,4-methylenedioxy-α-pyrrolidinopropiophenone, and 3,4-methylenedioxy-α-pyrrolidinobutiophenone potently inhibited the NET and DAT but not the SERT. Naphyrone was the only pyrovalerone that also inhibited the SERT. The pyrovalerone cathinones did not release monoamines. Most of the para-substituted amphetamines exhibited affinity for the 5-HT2A receptor but no relevant activation of the 5-HT2B receptor. All of the cathinones exhibited reduced trace amine-associated receptor 1 binding compared with the non-β-keto-amphetamines. In conclusion, para-substituted amphetamines exhibited enhanced direct and indirect serotonergic agonist properties and are likely associated with more MDMA-like effects. The pharmacological profile of the pyrovalerone cathinones predicts pronounced stimulant effects and high abuse liability.European Neuropsychopharmacology 01/2015; 25(3). DOI:10.1016/j.euroneuro.2014.12.012 · 5.40 Impact Factor
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- "Chemical analyses of numerous bath salts products have identified that the main active ingredients are usually analogues of the amphetaminelike stimulant cathinone (National Drug Intelligence Center, 2011). The presence of synthetic cathinone analogues was confirmed by toxicology screening and post mortem analysis of patients who had presented with bath salts intoxication (Coppola & Mondola, 2012; Marinetti & Antonides, 2013). Synthetic cathinone analogues first started to appear in Japan, Australia, and several European countries as early as 2006 and in the United States in 2009 (Camilleri et al., 2010; Bronstein et al., 2011; Gunderson et al., 2013; Zawilska & Wojcieszak, 2013). "
ABSTRACT: Several novel synthetic amphetamines have been marketed worldwide as "bath salts." The use of bath salts is associated with severe medical consequences resulting in a US federal ban over the last 3 years on the more common substances found in this group. Bath salts intoxication has a relatively nonspecific presentation, and urine toxicology confirmation in emergency departments (EDs) is impractical because the turnaround time is several days. Emergency clinicians must therefore rely heavily on patients' self-reports to verify the diagnosis. We performed an online survey of emergency clinicians to determine their degree of exposure to bath salts-intoxicated patients, the clinically relevant features of such patients, and the typical emergency management. We invited 124 physicians and physician assistants in 7 Cleveland Clinic EDs to participate in an online survey. From a total of 43 of the 124 respondents, 77% did not specifically ask patients about bath salts use. Sixty percent had encountered a bath salts-intoxicated individual. Most respondents reported that the majority of patients were male, were between 19 and 29 years old, and used other drugs in addition to bath salts. Agitation, aggression/violence, and hallucinations were reported to be the most common presentations, and intravenous/intramuscular tranquilization was reported as the most often used management. Most patients were discharged home from the ED. Despite the lack of toxicology screening in EDs, about two thirds of the surveyed emergency clinicians encountered bath salts-intoxicated individuals. Our study demonstrates the need for increased screening of bath salts intoxication in EDs, especially in agitated patients.Journal of Addiction Medicine 12/2014; DOI:10.1097/ADM.0000000000000094 · 1.71 Impact Factor
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- "Severe cases of acute toxicity and fatalities have been reported (Maskell et al. 2001; Gustavsson & Escher 2009; Torrance & Cooper 2010; Wood et al. 2010a; 2010b; Lusthof et al. 2011; Wong & Holt 2011; Wood et al. 2011), but in many cases the presence of multiple drugs of abuse contributed to greater monoamine toxicity (Maskell et al. 2011; Coppola & Mondola 2012; Aromatario et al. 2012; Schifano et al. 2012; Prosser & Nelson 2012). Bizarre at-risk behaviors, such as hangings, stabbings, and self-mutilation, have also been reported amongst synthetic cathinone users (Schifano et al. 2012; Marinetti & Antonides 2013). Despite these incurred user consequences, use of synthetic cathinones is increasingly embedded in contemporary drug culture, whether through blending in existing street-available drugs such as MDMA and cocaine, or through chemical restructuring of compounds (Van Hout & Brennan 2011a; 2010b; 2012). "
ABSTRACT: Abstract A synthetic cathinone called 4-methylethcathinone (4-MEC) emerged online in 2010, and was cyber-marketed to be a replacement for mephedrone. The study aimed to present user experiences of 4-MEC as reported on the Internet, with a focus on user profiles, sourcing and product characteristics, routes of administration, dosage, positive and undesirable effects, and comparisons to mephedrone. Twenty-three individual, anonymous trip reports of the sole use of 4-MEC, and 112 screenshots of general 4-MEC user discussion boards, were taken from a purposeful sample of public drug-related sites. A content textual analysis was conducted on extracted qualitative information and produced 41 categories compiled into five general themes: "Type of 4-MEC user"; "Sourcing, informed decision making, product characteristics, and quality assurance"; "Routes of administration, gauging of dosage, and consumption of other drugs"; "Time course effects and outcomes"; and "Comparisons with mephedrone." 4-MEC is sold as white beads, crystalline shards, or green balls. User motives centered on curiosity, pricing, and ease of web sourcing. Oral, nasal, injecting, eyeball, and rectal routes of administration were described. Testing for purity, "allergy testing," and gauging of dosage were common. Users described euphoric but short-lived effects, with little comedown. Continued research is vital to inform harm reduction.Journal of psychoactive drugs 09/2014; 46(4):273-286. DOI:10.1080/02791072.2014.934979 · 1.10 Impact Factor