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European Review For Medical and... Jan 2018Synthetic cathinones, more commonly known as "bath salts", are synthetic drugs chemically related to cathinone, a psychostimulant found in the khat plant. They are the... (Review)
Review
OBJECTIVE
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.
MATERIALS AND METHODS
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.
RESULTS
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.
CONCLUSIONS
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
PubMed: 29364498
DOI: 10.26355/eurrev_201801_14129 -
Current HIV Research 2021Antiretroviral therapy (ART) non-adherence and methamphetamine use are associated with higher HIV drug resistance prevalence. How they affect drug resistance mutations...
BACKGROUND
Antiretroviral therapy (ART) non-adherence and methamphetamine use are associated with higher HIV drug resistance prevalence. How they affect drug resistance mutations accumulation is less studied.
OBJECTIVE
We assessed factors associated with drug resistance mutations accumulation.
METHODS
We evaluated HIV chronically-infected patients from a clinic-based research cohort on first-line ART regimens with genotype results within 30 days of baseline. Methamphetamine use and ART adherence were self-reported at each study visit. High ART adherence was defined as 0-5% missed doses in the last 30 days.
RESULTS
One-hundred twenty-five patients contributed 496 study visits. At baseline, 81% of patients reported high ART adherence; 90% reported no methamphetamine use in the prior 4 months, 8% used monthly or less and 2% used daily or weekly. Methamphetamine users and non-users had similarly high ART adherence (p=0.93). Adjusted incidence rate ratio (aIRR) of drug resistance mutations accumulation was 2.04 (95% CI 0.64, 6.46) for daily/weekly users and 1.71 (95% CI 0.66, 4.42) for patients with monthly or less users, compared to non-users. aIRR was 0.71 (95% CI 0.44, 1.15) with >5-10% missed ART doses and 1.21 (95% CI 0.80, 1.83) with >10% missed doses compared to 0-5% missed doses.
CONCLUSION
We found no strong evidence for the effect of methamphetamine use and ART adherence on drug resistance mutations accumulation. Research cohort patients may have been more engaged in care and treatment adherent than non-cohort patients. Our findings suggest methamphetamine use might not lead to treatment failure among HIV patients who are otherwise engaged in care.
Topics: Anti-HIV Agents; Drug Resistance; HIV Infections; HIV Seropositivity; HIV-1; Humans; Medication Adherence; Methamphetamine; Mutation
PubMed: 34176462
DOI: 10.2174/1570162X19666210625103902 -
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 -
Proceedings of the National Academy of... Jul 2023The serotonin transporter (SERT) is a member of the SLC6 neurotransmitter transporter family that mediates serotonin reuptake at presynaptic nerve terminals. SERT is the...
The serotonin transporter (SERT) is a member of the SLC6 neurotransmitter transporter family that mediates serotonin reuptake at presynaptic nerve terminals. SERT is the target of both therapeutic antidepressant drugs and psychostimulant substances such as cocaine and methamphetamines, which are small molecules that perturb normal serotonergic transmission by interfering with serotonin transport. Despite decades of studies, important functional aspects of SERT such as the oligomerization state of native SERT and its interactions with potential proteins remain unresolved. Here, we develop methods to isolate SERT from porcine brain (pSERT) using a mild, nonionic detergent, utilize fluorescence-detection size-exclusion chromatography to investigate its oligomerization state and interactions with other proteins, and employ single-particle cryo-electron microscopy to elucidate the structures of pSERT in complexes with methamphetamine or cocaine, providing structural insights into psychostimulant recognition and accompanying pSERT conformations. Methamphetamine and cocaine both bind to the central site, stabilizing the transporter in an outward open conformation. We also identify densities attributable to multiple cholesterol or cholesteryl hemisuccinate (CHS) molecules, as well as to a detergent molecule bound to the pSERT allosteric site. Under our conditions of isolation, we find that pSERT is best described as a monomeric entity, isolated without interacting proteins, and is ensconced by multiple cholesterol or CHS molecules.
Topics: Animals; Swine; Serotonin Plasma Membrane Transport Proteins; Cryoelectron Microscopy; Detergents; Serotonin; Central Nervous System Stimulants; Cocaine; Methamphetamine
PubMed: 37436958
DOI: 10.1073/pnas.2304602120 -
Cell Reports. Medicine Jan 2024Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and...
Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and reliable biomarkers for monitoring craving and diagnosing MUD. Here, we seek to identify a neurobiological signature of craving based on individual-level functional connectivity pattern differences between healthy control and MUD subjects. We train high-density electroencephalography (EEG)-based models using data recorded during the resting state and then calculate imaginary coherence features between the band-limited time series across different brain regions of interest. Our prediction model demonstrates that eyes-open beta functional connectivity networks have significant predictive value for craving at the individual level and can also identify individuals with MUD. These findings advance the neurobiological understanding of craving through an EEG-tailored computational model of the brain connectome. Dissecting neurophysiological features provides a clinical avenue for personalized treatment of MUD.
Topics: Humans; Methamphetamine; Craving; Electroencephalography; Brain
PubMed: 38151021
DOI: 10.1016/j.xcrm.2023.101347 -
MMWR. Morbidity and Mortality Weekly... Mar 2020Methamphetamine is a highly addictive central nervous system stimulant. Methamphetamine use is associated with a range of health harms, including psychosis and other...
Methamphetamine is a highly addictive central nervous system stimulant. Methamphetamine use is associated with a range of health harms, including psychosis and other mental disorders, cardiovascular and renal dysfunction, infectious disease transmission, and overdose (1,2). Although overall population rates of methamphetamine use have remained relatively stable in recent years (3), methamphetamine availability and methamphetamine-related harms (e.g., methamphetamine involvement in overdose deaths and number of treatment admissions) have increased in the United States* (4,5); however, analyses examining methamphetamine use patterns and characteristics associated with its use are limited. This report uses data from the 2015-2018 National Surveys on Drug Use and Health (NSDUHs) to estimate methamphetamine use rates in the United States and to identify characteristics associated with past-year methamphetamine use. Rates (per 1,000 adults aged ≥18 years) for past-year methamphetamine use were estimated overall, by demographic group, and by state. Frequency of past-year use and prevalence of other substance use and mental illness among adults reporting past-year use were assessed. Multivariable logistic regression examined characteristics associated with past-year use. During 2015-2018, the estimated rate of past-year methamphetamine use among adults was 6.6 per 1,000. Among adults reporting past-year methamphetamine use, an estimated 27.3% reported using on ≥200 days, 52.9% had a methamphetamine use disorder, and 22.3% injected methamphetamine. Controlling for other factors, higher adjusted odds ratios for past-year use were found among men; persons aged 26-34, 35-49, and ≥50 years; and those with lower educational attainment, annual household income <$50,000, Medicaid only or no insurance, those living in small metro and nonmetro counties, and those with co-occurring substance use and co-occurring mental illness. Additional efforts to build state and local prevention and response capacity, expand linkages to care, and enhance public health and public safety collaborations are needed to combat increasing methamphetamine harms.
Topics: Adolescent; Adult; Amphetamine-Related Disorders; Female; Humans; Male; Mental Disorders; Methamphetamine; Middle Aged; Risk Factors; Socioeconomic Factors; Substance Abuse, Intravenous; United States; Young Adult
PubMed: 32214077
DOI: 10.15585/mmwr.mm6912a1 -
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 -
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 -
Cells Nov 2022a significant percentage of methamphetamine (MA) dependent patients develop psychosis. The associations between oxidative pathways and MA-induced psychosis (MIP) are not...
BACKGROUND
a significant percentage of methamphetamine (MA) dependent patients develop psychosis. The associations between oxidative pathways and MA-induced psychosis (MIP) are not well delineated.
OBJECTIVE
the aim of this study is to delineate whether acute MA intoxication in MA dependent patients is accompanied by increased nitro-oxidative stress and whether the latter is associated with MIP.
METHOD
we recruited 30 healthy younger males and 60 acutely intoxicated males with MA dependence and assessed severity of MA use and dependence and psychotic symptoms during intoxication, and serum oxidative toxicity (OSTOX) biomarkers including oxidized high (oxHDL) and low (oxLDL)-density lipoprotein, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO), and antioxidant defenses (ANTIOX) including HDL-cholesterol, zinc, glutathione peroxidase (GPx), total antioxidant capacity (TAC), and catalase-1.
RESULTS
a large part (50%, n = 30) of patients with MA dependence could be allocated to a cluster characterized by high psychosis ratings including delusions, suspiciousness, conceptual disorganization and difficulties abstract thinking and an increased OSTOX/ANTIOX ratio. Partial Least Squares analysis showed that 29.9% of the variance in MIP severity (a first factor extracted from psychosis, hostility, excitation, mannerism, and formal thought disorder scores) was explained by HDL, TAC and zinc (all inversely) and oxLDL (positively). MA dependence and dosing explained together 44.7% of the variance in the OSTOX/ANTIOX ratio.
CONCLUSIONS
MA dependence and intoxication are associated with increased oxidative stress and lowered antioxidant defenses, both of which increase risk of MIP during acute intoxication. MA dependence is accompanied by increased atherogenicity due to lowered HDL and increased oxLDL and oxHDL.
Topics: Male; Humans; Lipid Peroxidation; Methamphetamine; Antioxidants; Psychotic Disorders; Zinc
PubMed: 36429122
DOI: 10.3390/cells11223694 -
International Journal of Environmental... Sep 2020The experience of craving via exposure to drug-related cues often leads to relapse in drug users. This study consolidated existing empirical evidences of cue reactivity... (Review)
Review
The experience of craving via exposure to drug-related cues often leads to relapse in drug users. This study consolidated existing empirical evidences of cue reactivity to methamphetamine to provide an overview of current literature and to inform the directions for future research. The best practice methodological framework for conducting scoping review by Arkey and O'Malley was adopted. Studies that have used a cue paradigm or reported on cue reactivity in persons with a history of methamphetamine use were included. Databases such as Medline, EMBASE, PsycINFO and CINAHL were searched using key terms, in addition to citation check and hand search. The search resulted in a total of 32 original research articles published between 2006 to 2020. Three main themes with regard to cue reactivity were identified and synthesized: (1) effects of cue exposure, (2) individual factors associated with cue reactivity, and (3) strategies that modulate craving or reactivity to cues. Exposure to methamphetamine-associated cues elicits significant craving and other autonomic reactivity. Evidence suggests that drug cue reactivity is strongly associated with indices of drug use and other individual-specific factors. Future studies should focus on high quality studies to support evidence-based interventions for reducing cue reactivity and to examine cue reactivity as an outcome measure.
Topics: Craving; Cues; Humans; Methamphetamine; Recurrence; Substance-Related Disorders
PubMed: 32906716
DOI: 10.3390/ijerph17186504