methylone and Substance-Related-Disorders

The synthetic cathinones are a class of designer drugs of abuse that share a common core scaffold. The pharmacokinetic profiles of the synthetic cathinones vary based on the substitutions to the core scaffold.. To provide a summary of the literature regarding the pharmacokinetic characteristics of the synthetic cathinones, with a focus on the impact of the structural modifications to the pharmacokinetics.. In many, but not all, instances the pharmacokinetic characteristics of the synthetic cathinones can be reasonably predicted based on the substitutions to the core scaffold. Mephedrone and methylone are chemically alike and have similar T. Continued research will lead to a better understanding of the pharmacokinetic changes associated with structural modifications to the cathinone scaffold, and potentially in the long range, enhanced overdose and addiction therapy. Additionally, the areas of polydrug use and pharmacogenetics have been largely overlooked with regard to synthetic cathinones.

Topics: Alkaloids; Amphetamines; Animals; Designer Drugs; Humans; Methamphetamine; Substance-Related Disorders; Synthetic Drugs

Synthetic cathinones, more commonly known as "bath salts", are synthetic drugs chemically related to cathinone, a psychostimulant found in the khat plant. They are the first most consumed products among new psychoactive substances, which cause psychostimulant and hallucinogenic effects determining a number of fatalities worldwide.  In this paper, we have systematically reviewed cases of synthetic cathinones-related fatalities analytically confirmed, which have occurred in the last few years.. Relevant scientific articles were identified in Medline, Cochrane Central, Scopus, Web of Science and Institutional/government websites up to November 2017 using the following keywords: synthetic cathinones, mephedrone, methylenedioxypyrovalerone, MDPV, methylone, ethylone, buthylone, fatal intoxication, fatalities and death.. In total, 20 citations met the criteria for inclusion, representing several fatal cases with analytically confirmed synthetic cathinones in biological sample/s of the deceased. The death was attributed to hyperthermia, hypertension, cardiac arrest and more in general to the classic serotonin syndrome. Only rarely did the concentration of the parent drug causing fatality overcome the value of 1 mg/L in post-mortem biological fluids.. Abuse of synthetic cathinones still represents a serious public health issue. Systematic clinical studies on both the animal and human model are lacking; therefore, the only available data are from the users who experience the possible hazardous consequences. Analytical methodologies for the identification of parent compounds and eventual metabolites both in ante-mortem and post-mortem cases need to be developed and validated. Analytical data should be shared through different communication platforms with the aim of stopping this serious health threat for drug users.

Topics: Alkaloids; Autopsy; Central Nervous System Stimulants; Death; Fever; Heart Arrest; Humans; Methamphetamine; Substance-Related Disorders

Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These "synthetic cathinones" include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. This Review will thus detail (i) historical context of cathinone use and the rise of "dark" synthetic derivatives, (ii) structural features and mechanisms of synthetic cathinones, (iii) behavioral effects observed clinically and in animals under controlled laboratory conditions, and (iv) neurotransmitters and circuits that may be targeted to manage synthetic cathinone abuse in humans.

Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Body Temperature; Catha; Central Nervous System Stimulants; Dopamine; History, 21st Century; History, Medieval; Humans; Locomotion; Methamphetamine; Pyrrolidines; Serotonin; Substance-Related Disorders; Synaptic Transmission; Synthetic Cathinone

Animal models of drug self-administration are currently the gold standard for making predictions regarding the relative likelihood that a recreational drug substance will lead to continued use and addiction. Such models have been found to have high predictive accuracy and discriminative validity for a number of drug classes including ethanol, nicotine, opioids, and psychostimulants such as cocaine and methamphetamine. Members of the entactogen class of psychostimulants (drugs that produce an "open mind state" including feelings of interpersonal closeness, intimacy and empathy) have been less frequently studied in self-administration models. The prototypical entactogen 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") supports self-administration but not with the same consistency nor with the same efficacy as structurally related drugs amphetamine or methamphetamine. Consistent with these observations, MDMA use is more episodic in the majority of those who use it frequently. Nevertheless, substantial numbers of MDMA users will meet the criteria for substance dependence at some point in their use history. This review examines the currently available evidence from rodent self-administration studies of MDMA and two of the new and emerging psychoactive substances (NPS) that produce entactogen type neuropharmacological responses - mephedrone (4-methylmethcathinone; 4MMC; "meow meow") and methylone (3,4-methylenedioxymethcathinone). Overall, the current evidence predicts that these NPS entactogens have enhanced abuse liability compared with MDMA.

Topics: Animals; Behavior, Animal; Methamphetamine; Models, Animal; N-Methyl-3,4-methylenedioxyamphetamine; Psychotropic Drugs; Rats; Self Administration; Substance-Related Disorders

New psychoactive substances have drastically modified the world drug scene. An increasingly popular class comprises synthetic or substituted cathinones (legal highs, research chemicals, bath salts). Among the most common psychoactive constituents of bath salts are mephedrone and methylone. Recent reports on the abuse of novel synthetic cathinone derivatives call attention to the serious physical and psychological risks resulting from their consumption, thereby emphasizing the growing use of these drugs might constitute an important public health issue. In this paper, we will review the available data regarding the use and effects of mephedrone and methylone in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were "mephedrone", "methylone", "new psychoactive substances", "synthetic cathinones", "substituted cathinones", "substance abuse", "substance use disorder", "adverse effects", "fatalities". The literature search was limited to years 2005-2015 and led to the identification of 71 potentially relevant articles. To date, the actual prevalence rates of their use remains difficult to estimate. Important health-related issues have emerged in relation to the somatic, psychiatric, and addictive consequences of their use. The potential chronic health effects of their prolonged use remain to date unknown (e.g., reproductive toxicity, genotoxicity and carcinogenic potential). Treatment for patients with prolonged exposure to synthetic cathinones should ideally include a drug management plan coupled with psychotherapy taking place in a structured program of care.

Topics: Animals; Central Nervous System Stimulants; Databases, Bibliographic; Humans; Methamphetamine; Substance-Related Disorders

"Bath salts" is one street name for a family of synthetic cathinones that display pharmacological effects resembling cocaine and commonly abused amphetamines. Despite extensive legislation aimed at the criminalization of bath salts, several designer cathinones are gaining a foothold in the illicit drug scene; for example, in the United Kingdom, mephedrone (4-methylmethcathinone, MEPH) is highly popular among drug abusers whereas, in the United States, MDPV (methylenedioxypyrovalerone) and methylone are highly prevalent. To date, knowledge about the hazards of designer cathinones is based mostly on hospital reports and anecdotal evidence derived from online surveys. Despite the paucity of preclinical studies directed toward designer cathinones, a number of invaluable findings arising from those studies are enabling scientists to develop their neuropharmacological profiles. Despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce different behavioral effects, including unique effects on locomotor activity, learning, anxiety, thermoregulation, and abuse liability. The present review will discuss the behavioral effects of MEPH, MDPV, and methylone and compare those effects to established psychostimulant drugs. The rise in the use of designer cathinones in the United States and abroad justifies further investigations into these compounds, both for a greater understanding of the danger that "bath salts" pose to the public, and to provide insight into replacement cathinones as they emerge onto the market.

Topics: Alkaloids; Animals; Benzodioxoles; Central Nervous System Stimulants; Designer Drugs; Drug Evaluation, Preclinical; Humans; Illicit Drugs; Methamphetamine; Pyrrolidines; Substance-Related Disorders; Synthetic Cathinone

Designer drugs belong to a group of legally or illegally produced substances that are structurally and pharmacologically very similar to illicit drugs. In the past, designer drugs were often used during all-night dance parties, but they are now consumed in multiple settings from college bars to parks to private house parties. Most of these club drugs can be bought on legal websites and home-delivered for private parties. Recently, legal highs have once again become a burning media issue across the world. Our review will focus on GHB and synthetic cathinones. Literature searches were conducted for the period from 1975 to July 2010 using PubMed, EMBASE, PsycInfo, Internet underground and governmental websites using the following keywords alone or in combination: designer drugs, club drugs, party drugs, GHB, synthetic cathinones, mephedrone, methylone, flephedrone, MDAI, and MDVP. Available epidemiological, neurobiological, and clinical data for each compound are described. There is evidence that negative health and social consequences may occur in recreational and chronic users. The addictive potential of designer drugs is not weak. Non-fatal overdoses and deaths related to GHB/GBL or synthetic cathinones have been reported. Clinicians must be careful with GBL or synthetic cathinones, which are being sold and used as substitutes for GHB and MDMA, respectively. Interventions for drug prevention and harm reduction in response to the use of these drugs should be implemented on the Internet and in recreational settings. Prevention, Information, Action, and Treatment are the main goals that must be addressed for this new potentially addictive problem.

Topics: Alkaloids; Animals; Designer Drugs; Humans; Illicit Drugs; Indans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Sodium Oxybate; Substance-Related Disorders

Polydrug use is well documented in synthetic cathinone users, although the consequences of such use are not well characterized. In pre-clinical research, a pre-exposure to a drug has been reported to attenuate the aversive effects of other drugs which has implications for their abuse potential. The goal of the present study was to investigate the impact of pre-exposure to the synthetic cathinone methylone on the aversive effects of MDPV and MDMA.. Male and female Sprague-Dawley rats were exposed to 10 mg/kg of methylone every 4th day (for a total of five injections) prior to taste avoidance training with 1.8 mg/kg of MDPV or 1 mg/kg of MDMA.. MDPV and MDMA induced taste avoidance in males and females (all p's < 0.05). In males, methylone pre-exposure attenuated the avoidance induced by MDPV and MDMA (all p's < 0.05) with the attenuation greater with MDPV. In females, methylone pre-exposure attenuated avoidance induced by MDPV (all p's < 0.05), but it had no effect on those induced by MDMA (all p's > 0.05).. The effects of exposure to methylone on taste avoidance induced by MDPV and MDMA were drug- (MDPV > MDMA) and sex- (MDMA only in males) dependent. The attenuating effects of methylone pre-exposure on MDPV and MDMA were discussed in terms of their shared neurochemical action. These findings suggest that a history of methylone use may reduce the aversive effects of MDPV and MDMA which may have implications for polydrug use involving the synthetic cathinones.

Topics: Animals; Benzodioxoles; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Female; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Pyrrolidines; Rats; Rats, Sprague-Dawley; Substance-Related Disorders

This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in "Ecstasy" formulations, these data indicate that adulterated "Ecstasy" formulations may drive more compulsive drug use than those containing only MDMA.

Topics: Animals; Benzazepines; Central Nervous System Stimulants; Conditioning, Operant; Disease Models, Animal; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins; Drug Combinations; Hallucinogens; HEK293 Cells; Humans; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Serotonin; Substance-Related Disorders

Hundreds of new psychoactive substances (NPS) have emerged in the drug market over the last decade. Few drug surveys in the USA, however, ask about use of NPS, so prevalence and correlates of use are largely unknown. A large portion of NPS use is unintentional or unknown as NPS are common adulterants in drugs like ecstasy/Molly, and most NPS are rapidly eliminated from the body, limiting efficacy of urine, blood and saliva testing. We utilized a novel method of examining prevalence of NPS use in a high-risk population utilizing hair-testing. Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography-tandem mass spectrometry. Eighty samples collected from different parts of the body were analyzed, 57 of which detected positive for at least one substance-either a traditional or new drug. Among these, 26 samples tested positive for at least one NPS-the most common being butylone (25 samples). Other new drugs detected include methylone, methoxetamine, 5/6-APB, α-PVP and 4-FA. Hair analysis proved a powerful tool to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use. Such testing can be used actively or retrospectively to validate survey responses and inform research on consumption patterns, including intentional and unknown use, polydrug-use, occasional NPS intake and frequent or heavy use.

Topics: Cyclohexanones; Cyclohexylamines; Hair; Humans; Illicit Drugs; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Pentanones; Prevalence; Psychotropic Drugs; Pyrrolidines; Substance Abuse Detection; Substance-Related Disorders

To define the characteristics of synthetic cathinone users admitted to hospital including clinical and laboratory parameters and the complications of use.. Retrospective single-center study of patients treated for acute cathinone intoxication and complications of cathinone use between January 2010 and January 2016.. A specialized clinical toxicology unit at an academic tertiary care center in Southern Germany serving a population of about 4 million.. 81 consecutive patients with laboratory-confirmed use of cathinones who presented for acute intoxication or complications of cathinone use were retrospectively analyzed.. The patients were predominantly male (64%, 52/81) with a median age of 34 years. 60 were admitted for signs of acute intoxication while 21 suffered from complications of cathinone use. 70% of acutely intoxicated patients had an increased creatinine phosphokinase. Only a minority of patients presented with a sympathomimetic toxidrome. Three patients had infectious complications, 10 prolonged psychosis, 6 rhabdomyolyses and/or kidney failure, and two patients died. Based on presentations, cathinone use has increased with the first cases seen in 2010. Opiates/opioids are the main co-ingested drugs of abuse. The pattern of cathinone use shifted from methylone in 2010/2011 to 3,4-methylenedioxypyrovalerone (MDPV) and 3-methylmethcathinone (3-MMC) in 2014/2015. We conclude that in our setting "typical" cathinone users are males in their thirties. They are seldom drug naïve and regularly co-ingest illicit drugs. Preventive measures have to be tailored to these difficult to reach patients. Present efforts to educate young clubbers in their late teens may fail to reach the pertinent demographic.

Topics: Academic Medical Centers; Adolescent; Adult; Alkaloids; Benzodioxoles; Female; Germany; Hospitalization; Humans; Illicit Drugs; Male; Methamphetamine; Middle Aged; Pyrrolidines; Retrospective Studies; Substance-Related Disorders; Synthetic Cathinone; Young Adult

Methylone is a synthetic derivative of cathinone. It is sold principally on the Internet in powder form under the name «bath salts». Deaths following consumption are very rare. This report details the first case of a death in France (a 21-year-old man), following ingestion of methylone during an evening with friends. Anoxia was observed at the time of autopsy. Toxicological analyses highlighted a consumption of methylone and cannabis. However, biological analyses showed an absence of ethanol, cocaine, amphetamines, and opiate derivatives. Likewise, no medications were found. High concentrations of methylone were found in the peripheral blood (3.13 mg/L) and in the central blood (6.64 mg/L). Its presence in the gastric contents provides evidence that the substance was taken orally. The dosage of δ9-tetrahydrocannabinol (THC) suggests a recent cannabis consumption (THC 12.9 μg/L, THC-COOH 29.3 μg/L, 11-OH-THC 4.9 μg/L). This case illustrates that the consumption of methylone, which has a reputation of being less «powerful» than ecstasy, is not without its dangers.

Topics: Administration, Oral; Bile; Central Nervous System Stimulants; Chromatography, High Pressure Liquid; Dronabinol; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Gastrointestinal Contents; Humans; Male; Methamphetamine; Psychotropic Drugs; Substance-Related Disorders; Vitreous Body; Young Adult

Ecstasy (MDMA) in the US is commonly adulterated with other drugs, but research has not focused on purity of ecstasy since the phenomenon of "Molly" (ecstasy marketed as pure MDMA) arose in the US.. We piloted a rapid electronic survey in 2015 to assess use of novel psychoactive substances (NPS) and other drugs among 679 nightclub/festival-attending young adults (age 18-25) in New York City. A quarter (26.1%) of the sample provided a hair sample to be analyzed for the presence of select synthetic cathinones ("bath salts") and some other NPS. Samples were analyzed using fully validated UHPLC-MS/MS methods. To examine consistency of self-report, analyses focused on the 48 participants with an analyzable hair sample who reported lifetime ecstasy/MDMA/Molly use.. Half (50.0%) of the hair samples contained MDMA, 47.9% contained butylone, and 10.4% contained methylone. Of those who reported no lifetime use of "bath salts", stimulant NPS, or unknown pills or powders, about four out of ten (41.2%) tested positive for butylone, methylone, alpha-PVP, 5/6-APB, or 4-FA. Racial minorities were more likely to test positive for butylone or test positive for NPS after reporting no lifetime use. Frequent nightclub/festival attendance was the strongest predictor of testing positive for MDMA, butylone, or methylone.. Results suggest that many ecstasy-using nightclub/festival attendees may be unintentionally using "bath salts" or other NPS. Prevention and harm reduction education is needed for this population and "drug checking" (e.g., pill testing) may be beneficial for those rejecting abstinence.

Topics: Adolescent; Adult; Alkaloids; Animals; Drug Users; Female; Hair; Humans; Illicit Drugs; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; New York City; Self Report; Substance-Related Disorders; Surveys and Questionnaires; Tandem Mass Spectrometry; Young Adult

The abuse of synthetic cathinones, formerly marketed as "bath salts", has emerged over the last decade. Three common drugs in this class include 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). An LC-MS/MS method has been developed and validated for the simultaneous quantification of MDPV, mephedrone, and methylone in brain tissue. Briefly, MDPV, mephedrone, methylone, and their deuterium-labeled analogs were subjected to solid phase extraction (SPE) and separated using an HILIC Silica Column. The HPLC was coupled to a Shimadzu IT-TOF (ion trap-time of flight) system with the electrospray source running in positive mode (+ESI). The method was validated for precision, accuracy, and extraction efficiency. All inter-day and intra-day % RSD (percent relative standard deviation) and % error values were less than 15% and extraction efficiency exceeded 80%. These conditions allowed for limits of detection of 1ng/mL for MDPV, and 5 ng/mL for both mephedrone and methylone. The limits of quantification were determined to be 5ng/mL for MDPV and 10 ng/mL for mephedrone and methylone. The method was utilized to evaluate the pharmacokinetics of these drugs in adult male rats following administration of a drug cocktail including MDPV, mephedrone, and methylone. All three compounds reached peak concentrations in the brain within 15 min. Although methylone and mephedrone were administered at the same dose, the peak concentration (C

Topics: Alkaloids; Animals; Area Under Curve; Benzodioxoles; Brain; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Half-Life; Male; Methamphetamine; Pyrrolidines; Rats; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization; Substance-Related Disorders; Synthetic Cathinone; Tandem Mass Spectrometry

The name `bath salts', for an emerging class of synthetic cathinones, is derived from an attempt to evade prosecution and law enforcement. These are truly illicit drugs that have psychoactive CNS (central nervous system) stimulant effects and they have seen a rise in abuse as recreational drugs in the last few years since first having been seen in Japan in 2006. The ease of synthesis and modification of specific functional groups of the parent cathinone make these drugs particularly difficult to regulate. MDPV (3,4-methylenedioxypyrovalerone) is commonly encountered as its hydrochloride salt (C16H21NO3·HCl), in either the hydrated or the anhydrous forms. This `bath salt' has various names in the US, e.g. `Super Coke', `Cloud Nine', and `Ivory Wave', to name just a few. We report here the structures of two forms of the HCl salt, one as a mixed bromide/chloride salt, C16H22NO3(+)·0.343Br(-)·0.657Cl(-) [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide/chloride (0.343/0.657)], and the other with the H7O3(+) cation, as well as the HCl counter-ion [systematic name: hydroxonium 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one dichloride, H7O3(+)·C16H22NO3(+)·2Cl(-)]. This is one of a very few structures (11 to be exact) in which we have a new example of a precisely determined hydroxonium cation. During the course of researching the clandestine manufacture of MDPV, we were surprised by the fact that a common precursor of this illicit stimulant is known to be the fragrant species piperonal, which is present in the fragrances of orchids, most particularly in the case of the vanilla orchid. We found that MDPV can be made by a Grignard reaction of this heliotropin. This may also explain the unexpected appearance of the bromide counter-ion in some of the salts we encountered (C16H21NO3·HBr), one of which is presented here [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide, C16H22NO3(+)·Br(-)]. Complexation of MDPV with a forensic crystallizing reagent, HAuCl4, yields the tetrachloridoaurate salt of this drug, (C16H22NO3)[AuCl4]. The heavy-metal complexing agent HAuCl4 has been used for over a century to identify common quarternary nitrogen-containing drugs via microscopic identification. Another street drug, called ethylone (3,4-methylenedioxyethylcathinone), is regularly sold and abused as its hydrochloride salt (C12H15NO3·HCl), and its structure is herein described

Topics: Alkaloids; Benzaldehydes; Benzodioxoles; Central Nervous System Stimulants; Crystallography, X-Ray; Designer Drugs; Drug Combinations; Humans; Illicit Drugs; Japan; Lidocaine; Methamphetamine; Psychotropic Drugs; Pyrrolidines; Salts; Substance-Related Disorders; Synthetic Cathinone

Abuse of synthetic cathinones, popularized as "bath salts," has increased dramatically in the USA since their debut in 2010. Preclinical behavioral studies may clarify determinants of the abuse-related effects produced by these compounds.. This study examined behavioral effects of (±)-methcathinone, (±)-3,4-methylenedioxypyrovalerone (MDPV), (±)-3,4-methylenedioxymethcathinone (methylone), and (±)-4-methylmethcathinone (mephedrone) in rats using intracranial self-stimulation (ICSS).. Male Sprague-Dawley rats (n = 18) with electrodes targeting the medial forebrain bundle responded for multiple frequencies of brain stimulation and were tested in two phases. First, dose-effect curves for methcathinone (0.1-1.0 mg/kg), MDPV (0.32-3.2 mg/kg), methylone (1.0-10 mg/kg), and mephedrone (1.0-10 mg/kg) were determined. Second, time courses were determined for effects produced by the highest dose of each compound.. Methcathinone produced dose- and time-dependent facilitation of ICSS. MDPV, methylone, and mephedrone produced dose- and time-dependent increases in low rates of ICSS maintained by low brain stimulation frequencies, but also produced abuse-limiting depression of high ICSS rates maintained by high brain stimulation frequencies. Efficacies to facilitate ICSS were methcathinone ≥ MDPV ≥ methylone > mephedrone. Methcathinone was the most potent compound, and MDPV was the longest acting compound.. All compounds facilitated ICSS at some doses and pretreatment times, which is consistent with abuse liability for each of these compounds. However, efficacies of compounds to facilitate ICSS varied, with methcathinone displaying the highest efficacy and mephedrone displaying the lowest efficacy to facilitate ICSS.

Topics: Animals; Benzodioxoles; Brain; Conditioning, Operant; Data Interpretation, Statistical; Designer Drugs; Dose-Response Relationship, Drug; Electric Stimulation; Injections; Male; Methamphetamine; Propiophenones; Pyrrolidines; Rats; Rats, Sprague-Dawley; Self Administration; Self Stimulation; Substance-Related Disorders; Synthetic Cathinone

This is the first reported case of α-pyrrolidinovalerophenone (α-PVP), methylone and ethylone in a suspected impaired driving case in the state of Washington. An initial traffic stop by law enforcement was made of a driver due to poor navigation of the roadway. The drug recognition expert (DRE) officer observed slurred speech, bloodshot watery eyes, dilated pupils, involuntary muscle movements and an elevated pulse and blood pressure. The DRE deduced that the driver was likely under the influence of central nervous system (CNS) stimulants, specifically 'bath salts'. Routine testing of the blood did not reveal the presence of alcohol or common drugs of abuse. Upon further review of the officer's report and the unconfirmed identification of α-PVP, blood was sent to NMS Labs in Willow Grove, PA, USA for bath salts and stimulant designer drugs testing. Analysis was conducted by liquid chromatography-time-of-flight mass spectrometry with the following results: 63 ng/mL α-PVP, 6.1 ng/mL methylone and positive for ethylone. These results are consistent with the DRE opinion of driving performance being impaired by a CNS stimulant.

Topics: Adult; Automobile Driving; Central Nervous System Stimulants; Chromatography, Liquid; Designer Drugs; Humans; Male; Mass Spectrometry; Methamphetamine; Pyrrolidines; Substance Abuse Detection; Substance-Related Disorders; Washington

Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs.

Topics: Adolescent; Adult; Alcohol Drinking; Cocaine; Dancing; Emergency Service, Hospital; Female; Holidays; Humans; Illicit Drugs; Male; Methamphetamine; Music; N-Methyl-3,4-methylenedioxyamphetamine; New York City; Substance-Related Disorders; Young Adult

The rise in popularity of "bath salts" as safe alternatives to MDMA (3,4-methylenedioxymethamphetamine), methamphetamine, and other illicit substances has resulted in increased scrutiny of the contents and toxicology associated with these products. We report a case of sudden death related to the synthetic cathinone methylone (3,4-methylenedioxy-N-methylcathinonmethylone) in a previously healthy 19-year-old man. Although several fatal case reports have been published involving methylone and other synthetic cathinones, this is the first reported case of sudden cardiac death associated with methylone use. Although lack of published data prevented a comparison of blood methylone concentrations between our case and existing reports, the amount of methylone we detected postmortem (0.07 mg/dL) is below those reported in MDMA-related fatalities. Our report suggests that methylone toxicity has been greatly underestimated by users of this synthetic cathinone.

Topics: Alkaloids; Central Nervous System Stimulants; Death, Sudden, Cardiac; Designer Drugs; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Male; Methamphetamine; Molecular Structure; Substance-Related Disorders; Young Adult

The study aimed to collect information concerning the increasing use of new psychoactive substances, commonly sold through online shops as 'Internet drugs' or 'legal highs', or in terms of masked products such as 'bath salts' and 'plant food'.. The Karolinska Institutet and Karolinska University Laboratory and the Swedish Poisons Information Centre have initiated a project called 'STRIDA' aiming to monitor the occurrence and trends of new psychoactive substances in Sweden, and collect information about their clinical symptoms, toxicity and associated health risks. A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-component method has been developed, currently allowing for the determination of > 80 novel psychoactive compounds or metabolites thereof. This study focused mainly on the particular drug substances identified and the population demographics of the initial STRIDA cases.. In urine and/or blood samples obtained from 103 consecutive cases of admitted or suspected recreational drug intoxications in mostly young subjects (78% were ≤ 25 years, and 81% were males) presenting at emergency departments all over the country, psychoactive substances were detected in 82%. The substances comprised synthetic cannabinoids ('Spice'; JWH analogues), substituted cathinones ('bath salts'; e.g. butylone, MDPV and methylone) and tryptamines (4-HO-MET), plant-based substances (mitragynine and psilocin), as well as conventional drugs-of-abuse. In 44% of the cases, more than one new psychoactive substance, or a mixture of new and/or conventional drugs were detected.. The initial results of the STRIDA project have documented use of a broad variety of new psychoactive substances among mainly young people all over Sweden.

Topics: Adolescent; Adult; Amphetamines; Benzodiazepines; Cannabinoid Receptor Agonists; Female; Humans; Illicit Drugs; Indoles; Male; Methamphetamine; Middle Aged; Psilocybin; Psychotropic Drugs; Secologanin Tryptamine Alkaloids; Substance-Related Disorders; Sweden; Tryptamines; Young Adult

New designer drugs such as K2, Spice, and "bath salts" present a formidable challenge for law enforcement and public health officials. The following report summarizes a three-year study of 1320 law enforcement cases involving over 3000 products described as vegetable material, powders, capsules, tablets, blotter paper, or drug paraphernalia. All items were seized in Arkansas from January 2010 through December 2012 and submitted to the Arkansas State Crime Laboratory for analysis. The geographical distribution of these seizures co-localized in areas with higher population, colleges, and universities. Validated forensic testing procedures confirmed the presence of 26 synthetic cannabinoids, 12 designer stimulants, and 5 hallucinogenic-like drugs regulated by the Synthetic Drug Prevention Act of 2012 and other state statutes. Analysis of paraphernalia suggests that these drugs are commonly used concomitantly with other drugs of abuse including marijuana, MDMA, and methamphetamine. Exact designer drug compositions were unpredictable and often formulated with multiple agents, but overall, the synthetic cannabinoids were significantly more prevalent than all the other designer drugs detected. The synthetic cannabinoids JWH-018, AM2201, JWH-122, JWH-210, and XLR11 were most commonly detected in green vegetable material and powder products. The designer stimulants methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy-N-methylcathinone (methylone), and α-methylamino-valerophenone (pentedrone) were commonly detected in tablets, capsules, and powders. Hallucinogenic drugs were rarely detected, but generally found on blotter paper products. Emerging designer drug products remain a significant problem and continued surveillance is needed to protect public health.

Topics: Benzodioxoles; Cannabinoids; Capsules; Central Nervous System Stimulants; Designer Drugs; Dronabinol; Hallucinogens; Humans; Indoles; Methamphetamine; Methylamines; Molecular Structure; Naphthalenes; Paper; Pentanones; Powders; Pyrrolidines; Substance-Related Disorders; Synthetic Cathinone; Tablets

Abuse of psychogenic substances sold as "bath salts" and "plant food" has escalated in recent years in the United States (USA). Previous reports suggest regional differences in the primary active β-keto phenylalkylamines found in these products and the corresponding signs and symptoms reported after exposure. Currently, there are only limited studies describing the clinical effects associated with reported "bath salts" exposure in the USA. This study describes the clinical effects associated with "bath salt" and "plant food" exposures as reported to the poison center serving the state of North Carolina (Carolinas Poison Center). We performed a retrospective review of the Carolinas Poison Center database for all cases of reported human exposure to "bath salt" and "plant food" products from 2010 to 2011 with specific attention to clinical effects and routes of exposure. Additionally, we reviewed therapies used, trended the volume of exposure cases reported over the study period, and evaluated the distribution of calls within state counties using descriptive statistics. Carolinas Poison Center received 485 total calls and 409 reported exposure calls regarding "bath salt" or "plant food" products between January of 2010 and December of 2011. The peak of reported exposures occurred in May of 2011. Clinical effects commonly reported in the exposure cases generated from these calls included tachycardia (53.3 %, n = 218), agitated/irritable (50.4 %, n = 206), hallucination/delusions (26.7 %, n = 109), and hypertension (25.2 %, n = 103). In addition to intravenous fluids, common therapies included benzodiazepines (46.0 %, n = 188), sedation (13.4 %, n = 55), alkalinization (3.90 %, n = 16), antihistamine (4.16 %, n = 17), and intubation (3.67 %, n = 15). Haloperidol was the antipsychotic agent used most often to treat agitation (n = 40). Serious complications associated with reported exposure to "bath salt" and "plant food" products included rhabdomyolysis, renal failure, excited delirium syndrome, and death. While treatments have not been empirically determined, sedation with benzodiazepines, aggressive cooling for hyperthermic patients, and use of small doses of antipsychotics for choreoathetoid movements not controlled with benzodiazepines are not likely to be harmful.

Topics: Adult; Baths; Benzodioxoles; Databases, Factual; Designer Drugs; Dietary Supplements; Female; Humans; Illicit Drugs; Male; Methamphetamine; Middle Aged; North Carolina; Phenethylamines; Plant Preparations; Poison Control Centers; Psychotropic Drugs; Pyrrolidines; Retrospective Studies; Substance Abuse Detection; Substance-Related Disorders; Synthetic Cathinone; Young Adult

Psychoactive bath salts are a relatively new group of designer drugs sold as tablets, capsules, or powder and pur-chased in places such as tobacco and convenience stores, gas stations, head shops, and the Internet. Bath salts are stimulant agents that mimic cocaine,lysergic acid diethylamide, methamphetamine, or methylenedioxymethamphetamine (ecstasy). The most common bath salts are the cathinone derivatives 3,4-methylenedioxypyrovalerone(MDPV), 4-methylmethcathinone(mephedrone), and 3,4-methylenedioxy-N-methylcathinone (methylone). The drugs cause intense stimulation, eu-phoria, elevated mood, and a pleasurable "rush" Tachycardia, hypertension,peripheral constriction, chest pain, hallucinations, paranoia, erratic behavior,inattention, lack of memory of substance use, and psychosis have been observed in those who have used bath salts. The U.S. Drug Enforcement Administration recently exercised an emergency authority to name three key ingredients in bath salts as Schedule I, thereby making them illegal to possess or sell in the United States. Nursing implications related to both clinical and educational settings are discussed.

Topics: Benzodioxoles; Central Nervous System Stimulants; Cross-Sectional Studies; Designer Drugs; Drug and Narcotic Control; Female; Humans; Illicit Drugs; Male; Methamphetamine; Middle Aged; Paranoid Disorders; Psychoses, Substance-Induced; Pyrrolidines; Substance Abuse Detection; Substance-Related Disorders; Synthetic Cathinone

The use of "Head Shop" compounds has received much media attention lately. There is very little research in the current literature with regard to the extent of the usage of these substances amongst the drug using population in Ireland. We conducted a study to examine the extent of the usage of Mephedrone, Methylone and BZP amongst attendees of Methadone maintenance programs at the DTCB. Two hundred and nine samples in total were tested. The results showed significant usage of these compounds amongst this cohort of drug users, with 29 (13.9%) of samples tested being positive for Mephedrone, 7 (3.3%) positive for Methylone and 1 (0.5%) positive for BZP.

Topics: Chromatography, Liquid; Female; Humans; Illicit Drugs; Ireland; Male; Mass Screening; Mass Spectrometry; Methamphetamine; Piperazines; Substance Abuse Treatment Centers; Substance-Related Disorders

Many psychotropic substances are easily available in Japan via the Internet, thus the spread of drug abuse is becoming more serious problem. To avoid drug abuse, 32 substances have been controlled in Japan since April in 2007 by the Pharmaceutical Affairs Law as designated substances (Shitei-Yakubutsu, classified as 11 tryptamines, 11 phenethylamines, 2 piperazines, 6 alkyl nitrites, 1 diterpene and 1 plant). Although the distributions of these drugs have been decreased through this regulation, new designer drugs are still being found. In this study, we detected 7 designer drugs in 15 products, which purchased just before the amendment of the law, by NMR, GC-MS and LC-MS analyses. Three methylone derivertives (1-(3,4-methylenedioxyphenyl-2-(pyrrolidin-1-yl)-1-pentanone: MDPV, 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one: bk-MBDB, 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one): bk-MDEA, a MDMA derivative (N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane: N-OH MDMA), a methamphetamine derivative (N-methyl-1-(4-fluorophenyl)propan-2-amine: N-Me-4-FMP), a tryptamine derivative (5-methoxy-N-ethyl-N-isopropyltryptamine: 5-MeO-EIPT) and indan-2-amine were detected. 5-MeO-EIPT was newly identified in this study.

Topics: Chromatography, Liquid; Designer Drugs; Drug and Narcotic Control; Gas Chromatography-Mass Spectrometry; Japan; Magnetic Resonance Spectroscopy; Mass Spectrometry; Methamphetamine; Substance-Related Disorders; Time Factors; Tryptamines

Although preclinical studies suggest that methylone (2-methylamino-1-[3,4-methylenedioxyphenyl]propan-1-one) and 5-MeO-MIPT (5-methoxy-N-methyl,N-isopropyl tryptamine) may have psychostimulant properties, the scientific reports about the clinical effects of these agents are scant. We describe a 27-year-old male patient with substance intoxication after a single ingestion of the mixture of methylone and 5-MeO-MIPT. Though he bought the drug as pure methylone powder via an internet order, our chemical analyses indicated that the drug was composed of about 60% methylone (120 mg) and 38% 5-MeO-MIPT (76 mg). This case report suggests that clinicians should be alert to the possibility of the emergence of methylone or 5-MeO-MIPT intoxication, and substance-related mental disorder may be complicated by combined use of other psychoactive drugs.

Topics: Adult; Akathisia, Drug-Induced; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Humans; Male; Methamphetamine; Psychoses, Substance-Induced; Substance-Related Disorders; Tryptamines

Recently, two new ecstasy-like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4-methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called 'Explosion'. mCPP (meta-chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4-methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.

Topics: Adrenergic Uptake Inhibitors; Biogenic Monoamines; Cross-Sectional Studies; Designer Drugs; Humans; Illicit Drugs; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Netherlands; Piperazines; Receptors, Serotonin; Serotonin Receptor Agonists; Substance-Related Disorders