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Stimulants
Published in G. Hussein Rassool, Alcohol and Drug Misuse, 2017
Synthetic cathinones, more commonly known as “bath salts,” are synthetic drugs chemically related to cathinone, one of the principal psychoactive components in khat. Synthetic cathinones are included “New Psychoactive Substances” can be much stronger than the natural product and, in some cases, very dangerous (Baumann 2014). The synthetic cathinones include mephedrone and methylone and are used as a recreational drug and can be addictive. The synthetic drugs are in the form of a white or brown crystal-like powder and are sold in small plastic or foil packages. These products sold as “Molly” (MDMA) often contain synthetic cathinones. These psychoactive substances are marketed “not for human consumption” as plant food or household cleaners. Most users tend to snort (insufflate) mephedrone but most of the cathinones are ingested. These psychoactive substances are sometimes injected because they are soluble in water. Mephedrone or substituted cathinone drugs can be smoked but it is not a “cost-effective” way of consuming them.
Marvin the Paranoid Android and Alice in Wonderland
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Pierluigi Simonato, Attilio Negri, Marco Solmi, Rita Santacroce
The most important change in this scenario happened in 2005, when the diffusion of cathinone derivatives as NPS via online drug markets exploded. The first substituted cathinone, methylone, was reported to the European Monitoring Centre on Drugs and Drugs Addiction (EMCDDA), shortly followed by warnings for 4-methylmethcathinone (mephedrone) (EMCDDA, 2007). Since then, a wide number of variously substituted synthetic cathinones has flooded the market, e.g., naphyrone, 3,4 methylenedioxypyrovalerone (MDPV), and α-pyrrolidinopentiophenone (alpha-PVP) (UNODC, 2013). As new compounds hit the streets in rapid succession, posing significant risks for users, and scientific literature began to report their pharmacological prophile (Schifano et al., 2011; Coppola & Mondola, 2012; Dunne, Jaffar, & Hashmi, 2015; Germanm, Fleckenstein, & Hanson, 2014), regulation amendments have been slow to follow. In recent years, 118 new SC were detected, including 14 reported for the first time in 2016 (EMCDDA, 2017b). According to EMCDDA, the five most commonly seized cathinones in 2015 were alpha-PVP, 3-methylmethcathinone (3-MMC), ethylone, 4-chloromethcathinone (4-CMC) and pentedrone; some of these, such as 3-MMC, were not under international control at the time of the seizures. As new analogues (formally legal to possess until a proper ban by drug authorities takes place) are synthetized in low-cost laboratories and then marketed (Archer et al., 2014), the governments of several countries faced the need for new strategies of control. Cathinone and methcatinone are listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances, while amfepramone and pyrovalerone are listed in Schedule IV. In Europe, the legal framework for the control of new psychoactive substances dates back to 2005 and is currently under revision, in order to establish more effective policies and limit the harms related to synthetic cathinones. At a national level, many countries in Europe responded by using consumer safety legislation and subsequently extending or adapting existing drug laws to incorporate NPS, as was done for mephedrone in the United Kingdom, Belgium, Denmark, Germany, Estonia, Ireland, France, Italy, Lithuania, Romania, Sweden, Croatia, and Norway (EMCDDA, 2018; Advisory Council on the Misuse of Drugs, 2010).
Intoxication as a Risk Factor
Published in Burkhard Madea, Asphyxiation, Suffocation,and Neck Pressure Deaths, 2020
Chest compression may also be a factor in sudden deaths associated with subdual of violent persons by the police, guards, paramedics or healthcare professionals. The actions taken may involve both restraint and chest compression. In many cases, positional asphyxia has also been suggested to have played an important role in these deaths. A large number of violent persons resisting arrest or emergency care are under the influence of alcohol, yet sudden deaths during apprehension and subdual of drunk subjects is rare. It was observed relatively early that many of the sudden deaths in custody comprised subjects with an altered mental status, and Wetli and Fishbain in 1985 [45] linked many of these deaths with cocaine-induced psychosis, today called ‘excited delirium’. A large number of case reports and case series were subsequently published. In parallel, many reports dealt with positional asphyxia as a competing cause for these in-custody deaths, and a number of experimental studies on human subjects were performed to evaluate the effects of various restraint measures and body positions on respiratory and circulatory parameters [7,8,33]. However, the limitation of these studies was that all volunteers were healthy subjects and were not under the influence of drugs. During the last two decades, a fairly large number of papers have been published reporting on sudden in-custody deaths associated with excited delirium. Most commonly, the excited delirium cases have been associated with cocaine abuse, but the syndrome has also been described in association with use of methamphetamine, MDMA, alpha-PVP, methylone and ephedrine [22,23,29]. Virtually all drugs associated with excited delirium are psychostimulants that result in an increase in extracellular dopamine levels in critical brain regions. The main pathophysiological explanation for the clinical symptoms is a dopaminergic overdrive, due to a failure of the affected person to upregulate the dopamine transporter protein [22], although a general depression of the cholinergic system in the brain probably contributes to the delirious state. The severity of this acute condition is well recognized today. In the acute phase, death may be caused by cardiac ischaemia due to a tremendous increase in energy demand during extraordinary exertion and sympatico-mimetic overdrive. Hyperthermia is almost always recorded, and may cause death after a while, if unrecognized, or left uncontrolled. Subjects surviving these phases may die later due to massive rhabdomyolysis. The problem is that many of these deaths occur early and unexpectedly during a violent fight, and hence before any medical examination is possible. Postmortem examination of the dopamine transporter protein in ventral striatum and expression of the HSPA1B gene and its product HSP70 in the temporal cortex has been suggested as with markers of excited delirium [23]. However, even if this condition has been observed to cause death in the absence of any intervention [36], in most cases restraints, chest compression and abnormal body position are factors that the pathologist needs to consider when evaluating the case.
Emergency department visits due to new psychoactive substances and other illicit drugs in Taiwan: preliminary results of the Taiwan Emergency Department Drug Abuse Surveillance (TEDAS) project
Published in Clinical Toxicology, 2022
Chih-Chuan Lin, Te-I Weng, Chip-Jin Ng, Chia-Pang Shih, Jui Hsu, Yuan-Chun Liao, Chen-Chang Yang, Cheng-Chung Fang
The clinical features associated with NPS group and other illicit drug group were different in this study. Younger patients and women were more likely to have NPS detected in their urine samples. Fattore et al. revealed that men were more likely than women to use all types of drugs; in addition, women may be more susceptible to drug toxicity, especially NPS [32]. Exposure to methylone or cathinone was found to induce higher anxiety-related behavior in female rats than in male rats [33,34]. Females are more susceptible than males to ketamine withdrawal symptoms and adverse effects, such as anxiety, dysphoria, and tremors [4]. We propose that female NPS users may visit the ED more frequently due to the adverse effects from NPS use. Patients in NPS group presented with more instances of tachycardia, chest pain, and suicide attempt/self-injury than patients in other illicit drug group. Since “NPS” refers to a mixture of drug classes with different clinical effects owing to variable receptor interactions and varying potencies at these receptors, further investigations are required to explore the clinical features of each NPS drug class.
Gender differences in tolerance to the hyperthermia mediated by the synthetic cathinone methylone
Published in Temperature, 2019
Robert Goldsmith, Sudhan Pachhain, Sayantan Roy Choudhury, Vipa Phuntumart, Ray Larsen, Jon E. Sprague
The hyperthermia induced by synthetic cathinones (“bath salts”) has been linked to acute kidney injury, rhabdomyolysis, and ultimately death [1,2]. Methylone, the β-keto analog of 3,4-methylenedioxymethamphetamine (MDMA), continues to be commonly seen in forensic laboratories [3]. We have previously demonstrated that methylone is the most potent thermogen of the synthetic cathinones [4]. Both males and females demonstrate an increase in plasma norepinephrine levels following MDMA treatment; however, males display a significantly greater acute increase in norepinephrine levels relative to female animals [5]. Additionally, skeletal muscle uncoupling protein 3 (UCP3) expression is 80% less in females than in males. This depressed expression level is dependent upon estrogen levels and correlates with a reduced thermogenic response in the female rats following acute MDMA treatment [5]. UCP1 and UCP3 play complementary roles in the onset (UCP1) and maintenance (UCP3) of sympathomimetic-induced hyperthermia [6].
Identification of three new phase II metabolites of a designer drug methylone formed in rats by N-demethylation followed by conjugation with dicarboxylic acids
Published in Xenobiotica, 2018
Monika Židková, Igor Linhart, Marie Balíková, Michal Himl, Veronika Dvořáčková, Eva Lhotková, Tomáš Páleníček
Methylone is one of the most commonly available synthetic cathinone derivatives, which are used as an alternative to controlled stimulant drugs such as amphetamines and MDMA. Its metabolism in rats and humans has been rather extensively studied. Therefore, in this study on rats the attention was focussed on a new type of amidic conjugates with three dicarboxylic acids, which were originally identified in the case of another frequently abused synthetic cathinone, mephedrone (Linhart et al., 2016; Pozo et al., 2015). Like for mephedrone, three amidic conjugates of the demethylated parent compound, i.e. MDC-SC, MDC-GL and MDC-AD were identified in the urine of rats dosed with methylone. In both cases, the succinic acid amide strongly predominated and adipamide was the least abundant. Interestingly, neither mephedrone nor methylone formed any N-acetylated metabolite. Therefore, we hypothesise that dicarboxylic acid conjugation is probably an alternative pathway coming into operation if a compound is not a substrate for N-acetyltransferases. Succinamide conjugate of normehedrone was identified also in the urine of human volunteers dosed with mephedrone (Pozo et al., 2015). Although data on either on amidic conjugates of MDC or glutaric and adipic acid conjugate of normephedrone in humans has not been, to our knowledge, published as yet, it is likely that these phase II metabolites are formed also in humans.