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European Review For Medical and... Oct 2015Synthetic cathinones are an emerging class of designer drugs abused of due to their psychostimulant and hallucinogenic effects, similar to those of cocaine,... (Review)
Review
OBJECTIVE
Synthetic cathinones are an emerging class of designer drugs abused of due to their psychostimulant and hallucinogenic effects, similar to those of cocaine, methylenedioxymethamphetamine (MDMA), amphetamines and methamphetamines. Mephedrone is a cathinone analogue (4-methyl aromatic analogue of methcathinone) that was reported to be implicated in several fatalities in the media across Europe, but only a few have actually resulted in mephedrone cited as the cause of death. In this paper, we aim to systematically review analytically confirmed cases of mephedrone-related fatalities.
MATERIALS AND METHODS
Relevant scientific articles were identified from Medline, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar, through May 2015 using the following keywords: "Mephedrone", "fatal intoxication," "fatalities", "acute intoxication" and "death".
RESULTS
In total, 10 citations met the criteria for inclusion, representing 18 fatal cases with analytically confirmed mephedrone in biological sample/s of the deceased. The death was attributed to mephedrone intoxication in 9 cases (range of post-mortem blood mephedrone concentration: 1.33-22 mg/L), whereas multiple drug toxicity, involving mephedrone was cited as cause of death in 6 cases (range of post-mortem blood mephedrone concentration: 0.04-1.3 mg/L).
CONCLUSIONS
Data suggest that the abuse of mephedrone remains to be a public health issue. Mephedrone appears to have a rather narrow therapeutic window that makes its use dangerous. Dosages which supposedly fall within recreational use limits could also lead to death when combined with other drugs in certain circumstances. Forensic Toxicology laboratories must assess their testing procedures to ensure they can achieve both an appropriate screening regime and targeted quantitative analysis for the detection of mephedrone in various biological matrices.
Topics: Alkaloids; Central Nervous System Stimulants; Death; Designer Drugs; Humans; Methamphetamine; Substance-Related Disorders
PubMed: 26502870
DOI: No ID Found -
Analytical Methods : Advancing Methods... Nov 2023This study was focused on the development of a sensitive, reliable, and efficient extraction procedure for the determination of amphetamine and methamphetamine utilized...
Simultaneous derivatization and extraction of amphetamine and methamphetamine using dispersive liquid-liquid microextraction prior to their analysis using GC-FID in creatine supplements.
This study was focused on the development of a sensitive, reliable, and efficient extraction procedure for the determination of amphetamine and methamphetamine utilized in the adulteration of creatine sports supplements. The separation and detection of the analytes were conducted using the gas chromatography-flame ionization detection method. In this study, the analytes were extracted from a supplement powder into a proper solvent by sonication. Then, the extract was mixed with butyl chloroformate to obtain their butylated derivatives and then concentrated by a dispersive liquid-liquid microextraction procedure. The method was performed in a short time. Under optimized extraction conditions, a linear range of 2.01-500 ng g was obtained by a coefficient of determination ≥0.996. Low detection (0.22 ng g and 0.61 ng g for amphetamine and methamphetamine, respectively) and quantification (0.73 ng g and 2.01 ng g for amphetamine and methamphetamine, respectively) limits, good precision (relative standard deviations ≤8.2%), and high extraction recoveries (79% and 86% for amphetamine and methamphetamine, respectively) were achieved. The usefulness of the method in the analysis of the target compounds was confirmed by studying the matrix effect and analysis of the analytes in different real samples.
Topics: Methamphetamine; Amphetamine; Creatine; Liquid Phase Microextraction; Chromatography, Gas
PubMed: 37987503
DOI: 10.1039/d3ay00828b -
Addiction Science & Clinical Practice Aug 2023We examined acceptability of and preferences for potential medications for treating methamphetamine use disorder (MUD) among people who use methamphetamine and examined...
INTRODUCTION
We examined acceptability of and preferences for potential medications for treating methamphetamine use disorder (MUD) among people who use methamphetamine and examined how benefits and drawbacks of methamphetamine use affect perceived acceptability and preferences.
METHODS
We conducted qualitative interviews as part of a larger study in 2019-2020. The interview assessed patterns of substance use (including methamphetamine), benefits and drawbacks of methamphetamine use, and interest in a medication to treat MUD. Analysis used an inductive thematic approach, guided by three primary questions: (1) would participants be interested in taking a potential medication for MUD?; (2) what effects would they would like from such a medication?; and (3) what would their ideal treatment route and schedule be (e.g. daily pill, monthly injection)?.
RESULTS
We interviewed 20 people reporting methamphetamine use in the past 3 months (10 from Reno, Nevada, USA and 10 from Rio Arriba County, New Mexico, USA). Seven used exclusively methamphetamine, while thirteen used other substances in addition to methamphetamine. Most were enthusiastic about a potential medication to treat MUD. Of those who were not interested (n = 5), all indicated no current concerns about their methamphetamine use. Perceived functional benefits of methamphetamine use (i.e., energy, counteracting opioid sedation, and improved social and emotional wellbeing) informed preferences for a replacement-type medication that would confer the same benefits while mitigating drawbacks (e.g., psychosis, hallucinations, withdrawal). Opinions on preferred dosing varied, with some preferring longer acting medications for convenience, while others preferred daily dosing that would align with existing routines.
CONCLUSION
Participants were excited about a potential for a medication to treat MUD. Their preferences were informed by the functional role of methamphetamine in their lives and a desire to maintain the stimulant effects while mitigating harms of illicit methamphetamine. Treatment outcomes that emphasize functioning and wellbeing, rather than abstinence, should be explored.
Topics: Humans; Methamphetamine; Qualitative Research; Analgesics, Opioid; Emotions
PubMed: 37587515
DOI: 10.1186/s13722-023-00401-1 -
Chemical & Pharmaceutical Bulletin 2023We have developed a fluorescence detection-liquid chromatography (HPLC-FL) method that involves sample pretreatment by solid-phase dispersive extraction (SPDE) and...
We have developed a fluorescence detection-liquid chromatography (HPLC-FL) method that involves sample pretreatment by solid-phase dispersive extraction (SPDE) and solid-phase fluorescence derivatization for the simple and rapid analysis of methamphetamine (MA) in urine. This method uses a reversed-phase polymeric solid-phase gel to clean up analytes in SPDE, followed by fluorescence derivatization with 9-fluorenylmethyl chloroformate (FMOC) in the solid-phase. The optimal conditions for SPDE and solid-phase fluorescence derivatization were obtained when J-SPEC PEP was used as the solid-phase gel and 0.5 mmol/L FMOC in 50 mmol/L borate buffer solution (pH 10) was used as the fluorescence derivatization reagent. The recovery experiment of MA in urine yielded a clean chromatogram with no interfering peaks, demonstrating the validity of our method; the recoveries were 83.6% when spiked at a low concentration level (100 ng/mL) and 80.7% when spiked at a high concentration level (1000 ng/mL). Compared with the conventional liquid-phase method, the reaction product (FMOC-MA) of solid-phase fluorescence derivatization had higher stability. Reaction rate constants were calculated by changing the temperature conditions, and physicochemical parameters, including activation energy and activation entropy involved in the degradation reaction, were obtained from the Arrhenius plot and analyzed thermodynamically. Taken together, our results suggest that the HPLC-FL method with SPDE and solid-phase fluorescence derivatization for sample pretreatment provides a simple and rapid means of analyzing MA in urine samples.
Topics: Methamphetamine; Chromatography, High Pressure Liquid; Chromatography, Liquid
PubMed: 36596509
DOI: 10.1248/cpb.c22-00216 -
Journal of Burn Care & Research :... Jul 2023Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of...
Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements.
Topics: Humans; Methamphetamine; Retrospective Studies; Burns; Fluid Therapy; Ethanol; Resuscitation
PubMed: 37227949
DOI: 10.1093/jbcr/irad077 -
Archives of Pharmacal Research Apr 2017Clinical and preclinical studies have indicated that chronic methamphetamine (MA) use is associated with extensive neurodegeneration, psychosis, and cognitive... (Review)
Review
Clinical and preclinical studies have indicated that chronic methamphetamine (MA) use is associated with extensive neurodegeneration, psychosis, and cognitive impairment. Evidence from animal models has suggested a considerable role of excess dopamine or glutamate, oxidative stress, neuroinflammation, and apoptosis in MA-induced neurotoxicity, and that protein kinase Cδ might mediate the interaction among these factors. In addition, the relatively long-lasting and recurrent nature of MA psychosis has been reproduced in animals treated with various dosing regimens of MA, which have shown behavioral sensitization, sociability deficits, and impaired prepulse inhibition. Genetic predisposition as well as dopaminergic and glutamatergic alterations might be important in the development of MA psychosis. Neuroimaging studies have identified functional and morphological changes related to the cognitive dysfunction shown in chronic MA users. Failure in the task-evoked phosphorylation of extracellular signal-related kinase likely underlies MA-induced memory impairment. Recent progress has suggested certain roles of oxidative stress and neuroinflammation in the psychosis and cognitive deficits induced by repeated low doses of MA. This review provides a comprehensive description of pertinent findings from human and animal studies, with an emphasis on the current understanding of the underlying mechanisms of MA neuropsychotoxicity and its relevance to Parkinson's disease or schizophrenia.
Topics: Animals; Central Nervous System Stimulants; Dopamine; Humans; Methamphetamine
PubMed: 28243833
DOI: 10.1007/s12272-017-0897-y -
Current Neuropharmacology 2017Mephedrone is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and... (Review)
Review
BACKGROUND
Mephedrone is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties as well as for their abuse potential.
OBJECTIVE
The aim of this review was to examine the emerging scientific literature on the possible mephedrone-induced neurotoxicity, yet not well defined due to the limited number of experimental studies, mainly carried on animal models.
MATERIALS AND METHODS
Relevant scientific articles were identified from international literature databases (Medline, Scopus, etc.) using the keywords: "Mephedrone", "4-MMC," "neurotoxicity," "neuropharmacology", "patents", "monoamine transporters" and "neurochemical effects".
RESULTS
Of the 498 sources initially found, only 36 papers were suitable for the review. Neurotoxic effect of mephedrone on 5-hydroxytryptamine (5-HT) and dopamine (DA) systems remains controversial. Although some studies in animal models reported no damage to DA nerve endings in the striatum and no significant changes in brain monoamine levels, some others suggested a rapid reduction in 5-HT and DA transporter function. Persistent serotonergic deficits were observed after binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve endings at high ambient temperature. Oxidative stress cytotoxicity and an increase in frontal cortex lipid peroxidation were also reported. In vitro cytotoxic properties were also observed, suggesting that mephedrone may act as a reductant agent and can also determine changes in mitochondrial respiration. However, due to the differences in the design of the experiments, including temperature and animal model used, the results are difficult to compare.
CONCLUSIONS
Further studies on toxicology and pharmacology of mephedrone are therefore necessary to establish an appropriate treatment for substance abuse and eventual consequences for public health.
Topics: Animals; Central Nervous System Stimulants; Databases, Bibliographic; Humans; Methamphetamine; Neurotoxicity Syndromes
PubMed: 27908258
DOI: 10.2174/1570159X14666161130130718 -
Medicina (Kaunas, Lithuania) Mar 2024Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older... (Review)
Review
Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older generations of these compounds, new formulations appeared on the drug market. One of them is metaphedrone (3-methylmethcathinone, 3-MMC), a structural isomer of 4-methylmethcathinone and a psychostimulant drug. Metaphedrone became popular in a large number of countries in a short period of time. The collection, analysis, and review of relevant research on the subject of metaphedrone in order to present information about the pharmacological, clinical, and toxicological profile of this compound. An assessment of the significance and role of metaphedrone in consumption patterns of novel psychoactive substances among recreational drug users. By using search engines like Google Scholar and PubMed, the relevant literature on metaphedrone was looked for and analyzed. The search was not limited to a specific period of time. All information regarding the compound of interest was analyzed and presented. All novel psychoactive substances are abused due to their pronounced stimulatory, hallucinogenic, dissociative, and euphoric and/or relaxing characteristics. Users of 3-methylmethcathinone usually opt for this substance for recreational purposes and/or sexual stimulation. Metaphedrone has the potential to cause a psychological dependence to the users. It was determined in relevant studies that most users are from 17 to 50 years of age. Older users usually administer metaphedrone intravenously, while younger ones usually choose snorting and oral ingestion of the drug. In Serbia, metaphedrone is a legally controlled substance. The pharmacodynamic properties make metaphedrone similar to classical recreational drugs. The method of administration, mainly repeated administration in a single session, could be explained using the pharmacokinetic profile of the drug. The most reported symptoms of intoxication were those of a sympathomimetic nature, such as tachycardia, chest pain, hypertension, diaphoresis, and agitation. Most intoxications and fatal outcomes occurred to users who combined several psychoactive substances. The correlation between measured blood concentrations of the drug and outcomes of intoxication was not found. The mechanisms of metaphedrone's toxicity are not fully understood. There is an increasing trend of abuse of metaphedrone among recreational drugs users. Future studies should focus on pharmacological and toxicological effects of metaphedrone on animals and humans.
Topics: Humans; Animals; Illicit Drugs; Hypertension; Serbia; Methamphetamine
PubMed: 38541192
DOI: 10.3390/medicina60030466 -
Current Problems in Cardiology Jan 2023The use of methamphetamines is growing worldwide with cardiovascular disease as the leading cause of mortality and morbidity. Long-term use of methamphetamines is... (Review)
Review
The use of methamphetamines is growing worldwide with cardiovascular disease as the leading cause of mortality and morbidity. Long-term use of methamphetamines is associated with malignant hypertension, myocardial ischemia, pulmonary hypertension, and methamphetamines-associated cardiomyopathy. These effects are noted to be dose-dependent and potentially reversible with discontinuation of methamphetamines in the early stages when there is limited or no myocardial fibrosis. This review aims to (1) summarize the available data from epidemiologic studies, (2) describe pathophysiological mechanisms and clinical presentation, (3) Management of methamphetamines induced cardiomyopathy and potential complications associated with it, and (4) Strategies to reduce methamphetamines abuse and related hospitalization.
Topics: Humans; Methamphetamine; Cardiomyopathies; Cardiovascular Diseases; Hypertension, Pulmonary
PubMed: 34780869
DOI: 10.1016/j.cpcardiol.2021.101042 -
Journal of the American Heart... Aug 2022Background Methamphetamine misuse affects 27 million people worldwide and is associated with cardiovascular disease (CVD); however, risk factors for CVD among users...
Background Methamphetamine misuse affects 27 million people worldwide and is associated with cardiovascular disease (CVD); however, risk factors for CVD among users have not been well studied. Methods and Results We studied hospitalized patients in California, captured by the Healthcare Cost and Utilization Project database, between 2005 and 2011. We studied the association between methamphetamine use and CVD (pulmonary hypertension, heart failure, stroke, and myocardial infarction). Among 20 249 026 persons in the Healthcare Cost and Utilization Project, 66 199 used methamphetamines (median follow-up 4.58 years). Those who used were more likely younger (33 years versus 45 years), male (63.3% versus 44.4%), smoked, misused alcohol, and had depression and anxiety compared with nonusers. Methamphetamine use was associated with the development of heart failure (hazard ratio [HR], 1.53 [95% CI, 1.45-1.62]) and pulmonary hypertension (HR, 1.42 [95% CI, 1.26-1.60]). Among users, male sex (HR, 1.73 [95% CI, 1.37-2.18]) was associated with myocardial infarction. Chronic kidney disease (HR, 2.38 [95% CI, 1.74-3.25]) and hypertension (HR, 2.26 [95% CI, 2.03-2.51]) were strong risk factors for CVD among users. When compared with nonuse, methamphetamine use was associated with a 32% significant increase in CVD, alcohol abuse with a 28% increase, and cocaine use with a 47% increase in CVD. Conclusions Methamphetamine use has a similar magnitude of risk of CVD compared with alcohol and cocaine. Prevention and treatment could be focused on those with chronic kidney disease, hypertension, and mental health disorders.
Topics: Cardiovascular Diseases; Cocaine; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Male; Methamphetamine; Myocardial Infarction; Renal Insufficiency, Chronic; Risk Factors
PubMed: 35912709
DOI: 10.1161/JAHA.121.023663