Impact of reduced sampling frequency of illicit drug wastewater monitoring in the Netherlands.

Drug consumption estimates are traditionally based on surveys or information from police seizures. Alternatively, residues of illicit drugs in untreated wastewater (influent) can be used to calculate mass loads and subsequently estimate drug consumption in the community throughout the week. For this purpose, wastewater is commonly sampled for seven consecutive days within the Sewage analysis CORe group Europe (SCORE), while other sampling schemes may be implemented in long-term studies outside this consortium. The current study demonstrates how sampling frequency of illicit drug residues in the influent of wastewater treatment plants (WWTPs) affects the derived weekly average. Thirty WWTPs were sampled over the course of 12 years and influents were analyzed for five drugs (metabolites): 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, amphetamine, benzoylecgonine (a metabolite of cocaine), and 11-nor-9-Carboxy tetrahydrocannabinol (THC-COOH). Subsequently, small and large WWTPs were grouped with a threshold of 100,000 inhabitants. After data curation, standardized loads were calculated (mg/d per 1000 inhabitants). Weekly averages of loads of the drug residues were calculated based on six scenarios (sampling one to six weekdays) and compared to the weekly average in the control situation (sampling seven weekdays) in a Monte Carlo simulation. Results indicate that drug residues with more dynamic loads over a week require more frequent sampling. The analysis illustrates that a decreased sampling frequency (4 or 5 days per week) still leads to a representative weekly average for all drugs tested when a deviation up to a factor of 1.25 is deemed acceptable. However, knowledge on typical levels is necessary to define outliers. We therefore recommend to study dynamics in drug residue loads for WWTPs before reducing sampling frequency in long term monitoring programs.

Reasons for using methamphetamine: Systematic review.

BACKGROUND AND OBJECTIVES: Use of methamphetamine has increased in the last decade. The reasons for using methamphetamine vary according to the characteristics of the users. The literature includes review studies on methamphetamine use; however, no systematic review on the reasons for using methamphetamine was found. This study aims to determine the reasons for methamphetamine use through a systematic review of the literature. METHOD: The data from a systematic review of the literature review were reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Science Direct, Ovid-Medline, and Google Scholar databases were scanned using the keywords "methamphetamine", "crystal", "meth", "addiction", "reason for use", and "motivation to use". The articles (n = 25,004) were reviewed based on the inclusion and exclusion criteria, and 21 articles were finally selected for this study. RESULTS: The reasons for using methamphetamine included improving performance, staying awake, increasing sexual performance and impulses, reducing the effects of withdrawal from other substances, coping with problems, socializing, having fun, and coping with pain and discomfort. DISCUSSION AND CONCLUSIONS: Methamphetamine users typically take this drug to provide performance enhancement and cope with problems in different areas. It is recommended to inform the users correctly about methamphetamine, to teach effective methods of coping with withdrawal, and to carry out supply prevention studies. SCIENTIFIC SIGNIFICANCE: This is the first systematic literature review to reveal the reasons why people take methamphetamine. Revealing these causes is very important in terms of intervention (basic, primary, secondary, and tertiary protection) strategies.

A methamphetamine vaccine using short monoamine and diamine peptide linkers and poly-mannose.

Methamphetamine (METH) substance use disorder is a long-standing and ever-growing public health concern. Efforts to develop successful immunotherapies are ongoing with vaccines that generate strong antibody responses are an area of significant research interest. Herein, we describe the development of a METH Hapten conjugate vaccine comprised of either two short-length peptides as linkers and mannan as an immunogenic delivery carrier. Initially, Hapten 1 (with a monoamine linker) and Hapten 2 (with a diamine linker) were synthesised. Each step of the Hapten synthesis were characterized by LC-MS and purified by Flash Chromatography and the identity of the purified Haptens were confirmed by 1H NMR. Haptens were conjugated with mannan (a polymannose), and conjugation efficiency was confirmed by LC-MS, TLC, 1H NMR, and 2,4 DNPH tests. The immunogenic potential of the two conjugated vaccines were assessed in mice with a 3-dose regimen. Concentrations of anti-METH antibodies were measured by enzyme-linked immunosorbent assay. All the analytical techniques confirmed the identity of Hapten 1 and 2 during the synthetic phase. Similarly, all the analytical approaches confirmed the conjugation between the Haptens and mannan. Mouse immunogenicity studies confirmed that both vaccine candidates were immunogenic and the vaccine with the monoamine linker plus adjuvants induced the highest antibody response after the second booster.

Role of MARK4 in methamphetamine-induced acute kidney injury. / MARK4在甲基苯丙胺诱导急性肾损伤中的作用.

OBJECTIVES: Methamphetamine (METH) is an illicit psychoactive substance that can damage various organs, with the urinary system being one of its significant targets. This study aims to explore the role of microtubule affinity-regulating kinase 4 (MARK4) in METH-induced acute kidney injury (AKI). METHODS: A total of 10 healthy adult male C57BL/6 mice were randomly divided into a control group and a METH group, 5 mice in each group. The METH group was administered METH (20 mg/kg, intraperitoneally, once daily for 3 consecutive days), while the control group received an equal volume of physiological saline. The mice were executed 24 hours after the final injection, and the success of the AKI model was detected by blood serum creatinine, blood urea nitrogen, and renal HE staining. Proteins differentially expressed between kidney tissues with METH-induced AKI and normal kidney tissues were screened by proteomics techniques and subjected to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and bioinformatics analysis. The accuracy of proteomic data was validated using Western blotting, and the expression levels of MARK4 and cleaved caspase-3 in mouse kidneys were measured. We further explored the role of MARK4 in METH-induced AKI. Firstly, a METH toxicity model was established in BUMPT cells to screen the appropriate concentration and time of METH treatment; the viability of BUMPT cells after METH treatment and the expression of cleaved caspase-3 were detected by interfering with MARK4 expression through inhibitors. RESULTS: The proteomic analysis of kidney tissues from METH and control groups screened for a total of 17 differentially expressed proteins, of which 11 were up-regulated and 6 were down-regulated (all P<0.05). The expression levels of MARK4 and cleaved caspase-3 were elevated in the kidneys of METH-treated mice (both P<0.05). The activity of BUMPT cells gradually decreased with increasing METH treatment concentration (all P<0.05), where the viability of BUMPT cells decreased to about 60% after METH treatment at 4 mmol/L. Compared with the control group, expression levels of MARK4 and cleaved caspase-3 were increased with higher METH concentrations and longer exposure times in a concentration- and time-dependent manner (all P<0.05). Inhibition of MARK4 expression improved METH-induced decrease in BUMPT cell activity, down-regulated the expression of cleaved caspase-3, and decreased the apoptosis of BUMPT cells induced by METH. CONCLUSIONS: MARK4 is highly expressed in a mouse model of METH-induced AKI, and MARK4 mediates METH-induced AKI by regulating cell apoptosis.

Structural and Functional Dysregulation of the Brain Endothelium in HIV Infection and Substance Abuse.

Blood-brain barrier (BBB) injury and dysfunction following infection with the human immunodeficiency virus (HIV) enables viral entry into the brain, infection of resident brain cells, neuronal injury and subsequent neurodegeneration leading to HIV-associated neurocognitive disorders (HAND). Although combination antiretroviral therapy has significantly reduced the incidence and prevalence of acquired immunodeficiency syndrome and increased the life expectancy of people living with HIV, the prevalence of HAND remains high. With aging of people living with HIV associated with increased comorbidities, the prevalence of HIV-related central nervous system (CNS) complications is expected to remain high. Considering the principal role of the brain endothelium in HIV infection of the CNS and HAND, the purpose of this manuscript is to review the current literature on the pathobiology of the brain endothelium structural and functional dysregulation in HIV infection, including in the presence of HIV-1 and viral proteins (gp120, Tat, Nef, and Vpr). We summarize evidence from human and animal studies, in vitro studies, and associated mechanisms. We further summarize evidence of synergy or lack thereof between commonly abused substances (cocaine, methamphetamine, alcohol, tobacco, opioids, and cannabinoids) and HIV- or viral protein-induced BBB injury and dysfunction.

Analysis of methamphetamine in urine by GC/MS coupled with solid-phase dispersive extraction and solid-phase derivatization.

In this study, we investigated a solid-phase dispersive extraction (SPDE) method and solid-phase derivatization method using the same solid-phase gel to extract methamphetamine (MA) from urine samples more efficiently and perform trifluoroacetic acid (TFA) derivatization for MA analysis by gas chromatography/mass spectrometry (GC/MS). N-Methylbenzylamine (NMe-BA) was added to the urine sample as a surrogate, and MA was extracted by SPDE using Oasis® HLB gel as a solid-phase agent. After drying the solid-phase gel of the SPDE, anhydrous TFA was added to the MA-absorbed HLB gel in order to derivatize MA with TFA on the solid-phase, followed by elution of the TFA derivative from this gel using ethyl acetate. As a validation of the analytical method, the limit of detection (S/N = 3) and the limit of quantification (S/N > 10) of MA were 0.002 µg/mL and 0.01 µg/mL, respectively. And the average recovery rate was 97.6-100.1%, repeatability was 5.6-10.7%, and intermediate precision was 10.1-11.4% for low (0.02 µg/mL), intermediate (0.1 µg/mL), and high (1 µg/mL) concentrations of MA added in urine. The developed pretreatment method enabled continuous extraction, cleanup, and TFA derivatization of urinary MA on the same solid-phase. Thus, urinary MA can be analyzed easily, rapidly, and with high sensitivity and accuracy.

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial protocol.

Background: While most pregnant individuals with methamphetamine use disorder (MUD) achieve abstinence, the postpartum period remains a vulnerable time for return to methamphetamine use (MU). Promising data from human and animal models, including three randomized controlled trials, suggest that micronized progesterone may prevent postpartum return to cocaine and nicotine use by reducing cravings. The primary objective of this study is to assess feasibility of enrollment and randomization of postpartum individuals with MUD to micronized progesterone to prevent return to MU. The secondary objectives are to evaluate safety, establish a preliminary estimate of efficacy, and characterize the association between allopregnanolone levels and methamphetamine cravings. Methods: This is a pilot double-blind placebo randomized controlled trial. We plan to enroll 40 postpartum individuals with MUD over 24-months. Individuals, stratified by opioid use disorder (OUD), are randomized 1:1-400 mg oral micronized progesterone daily or placebo and attend weekly study sessions for 12 weeks. Feasibility is measured by achieving 80 % of enrollment goal. Safety is evaluated by side effect frequency, mental health status changes, lactation and medical complications. Efficacy is assessed by comparing proportion of participants with return to MU and time to return to MU based on self-report or urine testing between treatment and control groups. Salivary allopregnanolone levels and methamphetamine cravings are compared between the groups. Conclusion: Study results will provide a first critical step towards potential intervention for prevention of return to MU among postpartum individuals. Completion of this trial will set the stage for a large-scale efficacy trial.

Decreased consumption of natural rewards in rhesus monkeys with prolonged methamphetamine abstinence.

Rationale: Relapse to drug use is a major clinical challenge in the treatment of addictive disorders, including psychostimulant use and may be exacerbated by reduced sensitivity to natural, non-drug reward. Given the relatively limited set of outcomes, and short withdrawal time in rodent studies, we conducted a more detailed assessment of the response to natural rewards in methamphetamine (METH) naive versus exposed monkeys during long-term abstinence. Methods: This study introduced an improved sucrose preference test (iSPT) to assess natural reward seeking and consumption in monkeys with long-term abstinence after methamphetamine (METH) use. The test was administered to sixteen naive monkeys and five METH exposed monkeys that had been abstinent for at least 3 months. Results: METH exposed monkeys showed a lower sucrose preference score in both the iSPT (z = -2.10, p = 0.036) and the sucrose preference test (z = -2.61, p = 0.009). The sucrose preference score was significantly correlated with the latency of the establishment of stable sucrose-preference (r = -0.76, df = 46, p < 0.001) but not with the other variables. Furthermore, water-sucrose switch latency and switch times were significantly negatively correlated (r = -0.50, df = 20, p = 0.02). Conclusion: These results show reductions in natural reward consumption during long-term methamphetamine abstinence.

The development and validation of a knowledge, attitude, and practice questionnaire of methamphetamine use.

Methamphetamine is a synthetic psychostimulant that is showing a rising trend of usage among adolescents and youths. Its harmful side effects and high risk of developing addiction is a public health problem. Recognizing the knowledge, attitudes, and practices (KAP) on methamphetamine is critical in the planning of an intervention strategy. Currently there is a lack of KAP questionnaires on methamphetamine. The study aims to develop and validate a KAP questionnaire on methamphetamine-use for use among Malaysian adolescents. Following an extensive literature review, face and content validity were carried out among healthcare workers, the public, students, and local subject matter experts. A pilot study was conducted amongst 50 students to assess the test-retest reliability. The questionnaire was then distributed to two groups of 269 and 331 individuals for the Exploratory (EFA) and Confirmatory Factor Analysis (CFA), respectively. The internal reliability was also assessed among these groups. The content validation consisting of Item Content Validity Index (I-CVI, ranging from 0.875 to 1.00), and Scale Content Validity Index (S-CVI/Ave = 0.941) both showed good validation scores. Test-retest reliability showcased an Intraclass Correlation Coefficient (ICC) of > 0.7, indicating its reliability. The model was constructed via the EFA resulting in four constructs, and the model's goodness of fit was confirmed with CFA. An internal reliability was calculated with Cronbach's Alpha and showed acceptable reliability (α-values > 0.6) for all constructs. The KAP questionnaire of methamphetamine use is a valid and reliable tool that can be used among Malaysian adolescents. The model arising from this study, can also be used as a guide for future intervention models for adolescent methamphetamine-use disorder.

Methamphetamine and Ecstasy-Induced Acute Reversible Cerebellar Neurotoxicity in a 3-Year-Old Child: A Case Report.

The prevalence of substance use disorders is increasing among children and adolescents. We present a case of a 3-year-old girl who was admitted to our hospital with complaints of acute onset difficulty walking and speaking. Neurological examination revealed dysarthria, truncal ataxia, hypotonia, and hyporeflexia. Brain magnetic resonance imaging, cerebrospinal fluid analysis, and routine blood and urine analyses were normal. Urine drug testing revealed positive results for ecstasy and methamphetamine. The patient's symptoms improved during hospitalization. To our knowledge, this is the youngest reported case of methamphetamine and ecstasy-induced acute reversible cerebellar neurotoxicity. It is essential to carefully monitor acute reversible neurological symptoms related to methamphetamine and ecstasy.

A Confirmatory Factor Analysis of the NIH Emotions Toolbox Among People Living with HIV and Who May Use Methamphetamine.

The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) was developed to provide researchers and clinicians with a concise tool for measuring emotional health. The NIHTB-EB has been validated and normed in English and Spanish-speaking populations in the United States. However, its application in certain groups, such as people living with HIV (PWH) and who may use methamphetamine has not been tested. This paper evaluates the factor structure in a sample of people without HIV and PWH who may or may not use methamphetamine. The sample included 773 adults ages 18 to 87. The factorial structure of the NIHTB-EB was examined using confirmatory factor analysis (CFA) in the full sample and among four subgroups based on HIV status and methamphetamine use. The CFA confirmed a three-factor structure that mirrors the previously validated structure with latent factors measuring negative affect, social relationships, and psychological well-being for three subgroups. While each latent factor was confirmed in all groups, we could not confirm, with confidence, the full battery in the smallest subgroup (HIV-seronegative participants who use methamphetamine). The three-factor NIHTB-EB is appropriate for use among PWH who may use methamphetamine, but further examination with larger samples is warranted.

Correlates of Current Methamphetamine Use and Opioid Co-Use Among Latina Women in a Low-Income Community.

Using data from Proyecto SALTO, a 15-year follow-up study of a cohort of Mexican American women in a low-income community in San Antonio, Texas, this study examines emerging patterns of current methamphetamine (MA) use, including opioid co-use, among this understudied population. A bivariate analysis compared individuals with and without current MA use and identified sociodemographic correlates and co-occurring mental health and substance use. A secondary analysis compared those with current MA use, opioid use, and concurrent MA and opioid use. Nineteen percent of the sample had current MA use. MA use was associated with having a lower income (OR = 7.04-1.93, SE = 1.59-5.46), residential instability (OR = 5.19, SE = 1.99), and suicidal ideation (OR = 2.62, SE = 0.93). Participants with MA use had more than four times the odds of using opioids than those without MA use. Women with concurrent MA and opioid use differed in sociodemographics and behavioral risks compared to those with only MA or only opioid use. These findings explore the social, mental health, and structural inequities that exacerbate risks and harms associated with high-risk substance use among marginalized Latino populations. Prevention and intervention strategies should adopt a holistic approach that considers and addresses polysubstance use, mental health, and the sociocultural contexts in which individuals live.

Death Due to Caffeine and Methamphetamine Toxicity: A Case Report.

Caffeine (1,3,7-trimethylxanthine) is an over-the-counter psychostimulant that, when used in appropriate amounts, is generally considered safe. However, excessive use can cause various symptoms and, in severe cases, can even be life-threatening. A 34-year-old man with a reported history of psychiatric disorders was found unresponsive at his girlfriend's house and transported to an emergency department. He was presumed to have taken several caffeine pills and was pronounced dead approximately six hours later. There was no evidence of trauma or natural diseases at autopsy. Toxicology testing on hospital blood samples revealed toxic levels of caffeine and methamphetamine. After investigation of the circumstances surrounding the death and accounting for the autopsy and toxicology findings, the cause and manner of death were certified as combined caffeine and methamphetamine toxicity and accident, respectively. Lethal levels of caffeine have been reported when blood concentration exceeds 80 mg/L. Caution is needed to avoid excessive caffeine intake, especially when consumed in concentrated forms like tablets or powders. Caffeine should be used with care not only in cases of cardiovascular disease or genetic vulnerability but also for those with psychiatric disorders. Although deaths from caffeine are rare, they are consistently reported, necessitating attention and caution in its use.

Cross sectional analysis of an addiction consultation service, substance co-use patterns, and receipt of medications for opioid use disorder during hospitalization.

INTRODUCTION: Despite effective medications for opioid use disorder (MOUD), treatment engagement remains low. As the overdose crisis is increasingly characterized by opioids co-used with other substances, it is important to understand whether existing models effectively support treatment for patients who use multiple substances. Hospital-based addiction consultation services (ACS) have shown promise at increasing MOUD initiation and treatment engagement, but the effectiveness for patients with specific co-use patterns remains unknown. METHODS: Using 2016-2023 admissions data from a large safety net hospital, we estimated a random-effects logistic regression model to determine whether specific co-use (methamphetamine, cocaine, alcohol, sedative, and other) moderated the effect of being seen by ACS on the receipt of MOUD. Adjusting for patient sociodemographic, health, and admission characteristics we estimated the proportion of patients who received MOUD across specific co-use groups. RESULTS: Of 7679 total admissions indicating opioid use, of which 5266 (68.6 %) indicated co-use of one or more substances and 2387 (31.1 %) were seen by the ACS. Among admissions not seen by the ACS, a smaller proportion of admissions with any co-use received MOUD (23.5 %; 95 % CI: 21.9-25.1) compared to admissions with opioid use alone (34.0 %; 95 % CI: 31.9-36.1). However, among admissions seen by the ACS a similar proportion of admissions with any co-use received MOUD (57.8 %; 95 % CI: 55.5-60.1) as admissions with opioid use alone (56.2 %; 95 % CI: 52.2-60.2). The increase in proportion of admissions receiving MOUD associated with being seen by the ACS was larger for admissions with methamphetamine (38.6 percentage points; 95 % CI: 34.6-42.6) or cannabis co-use (39.0 percentage points; 95 % CI: 32.9-45.1) compared to admissions without methamphetamine (25.7 percentage points; 95 % CI: 22.2-29.2) or cannabis co-use (29.1 percentage points; 95 % CI: 26.1-32.1). CONCLUSIONS: The ACS is an effective hospital-based treatment model for increasing the proportion of admissions which receive MOUD. This study shows that ACSs are also able to support increased receipt of MOUD for patients who use other substances in addition to opioids. Future research is needed to further understand what transition strategies best support treatment linkage for patients who use multiple substances.

A synergistic effect of herb and acupuncture on the methamphetamine.

Background: Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)'s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH. Methods: Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data. Results: Locomotor activity and USV calls were increased by METH (P < 0.05) and these increases were inhibited by JGJ (P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ (P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA (P < 0.05), and MSG mimicked JGJ (P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data (P < 0.05). Conclusion: Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect.

Pharmacological Treatments for Methamphetamine Use Disorder: Current Status and Future Targets.

The illicit use of the psychostimulant methamphetamine (METH) is a major concern, with overdose deaths increasing substantially since the mid-2010s. One challenge to treating METH use disorder (MUD), as with other psychostimulant use disorders, is that there are no available pharmacotherapies that can reduce cravings and help individuals achieve abstinence. The purpose of the current review is to discuss the molecular targets that have been tested in assays measuring the physiological, the cognitive, and the reinforcing effects of METH in both animals and humans. Several drugs show promise as potential pharmacotherapies for MUD when tested in animals, but fail to produce long-term changes in METH use in dependent individuals (eg, modafinil, antipsychotic medications, baclofen). However, these drugs, plus medications like atomoxetine and varenicline, may be better served as treatments to ameliorate the psychotomimetic effects of METH or to reverse METH-induced cognitive deficits. Preclinical studies show that vesicular monoamine transporter 2 inhibitors, metabotropic glutamate receptor ligands, and trace amine-associated receptor agonists are efficacious in attenuating the reinforcing effects of METH; however, clinical studies are needed to determine if these drugs effectively treat MUD. In addition to screening these compounds in individuals with MUD, potential future directions include increased emphasis on sex differences in preclinical studies and utilization of pharmacogenetic approaches to determine if genetic variances are predictive of treatment outcomes. These future directions can help lead to better interventions for treating MUD.

Melatonin Regulates Neuronal Synaptic Plasticity in the Supramammillary Nucleus and Attenuates Methamphetamine-Induced Conditioned Place Preference and Sensitization in Mice.

Methamphetamine (METH) is an addictive drug that threatens human health. The supramammillary nucleus (SuM) and its neural circuits play key roles in the regulation of spatial memory retrieval, and hippocampal contextual or social memory. Melatonin (MLT), a pineal hormone, can regulate hypothalamic-neurohypophysial activity. Our previous study showed that MLT attenuates METH-induced locomotor sensitization. However, whether MLT regulates SuM function and participates in METH-induced contextual memory retrieval remains unclear. Using a mouse model of METH-conditioned place preference (CPP) and sensitization, we found that METH activated c-Fos expression and elevated calcium (Ca²âº) levels in SuM neurons. Chemogenetic inhibition of SuM attenuates CPP and sensitization. Pretreatment with MLT decreased c-Fos expression and Ca2+ levels in the SuM and reversed METH-induced addictive behavior, effects that were blocked with the selective MT2 receptors antagonist 4P-PDOT and the MT1 receptors antagonist S26131. Furthermore, MLT reduced SuM synaptic plasticity, glutamate (Glu) release, and neuronal oscillations caused by METH, which were blocked by 4P-PDOT. In conclusion, our data revealed that MLT regulates neuronal synaptic plasticity in the SuM, likely through the MLT receptors (MTs), and plays a role in modulating METH-addictive behavior.

Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse.

PURPOSE: Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach. METHODS: 38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid-liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument. RESULTS: Significantly, altered metabolites were identified by the fold analysis and Welch's test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body. CONCLUSION: It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups.

Naloxone Administration and Survival in Overdoses Involving Opioids and Stimulants: An Analysis of Law Enforcement Data from 63 Pennsylvania Counties.

Background: In consideration of rising deaths from opioid-stimulant-involved overdoses in the United States, this study explored rates of naloxone administration and survival in opioid overdoses with versus without stimulants co-involved. Methods: The study used data from the Pennsylvania Overdose Information Network, focusing on 26,635 suspected opioid-involved overdose events recorded by law enforcement and other first responders in 63 Pennsylvania counties from January 2018 to July 2024. Relative frequencies and chi-square tests were first used to compare suspected opioid overdoses with, versus without, stimulants (cocaine or methamphetamine) co-involved. Next, mediation analyses tested naloxone administration as a mediator of the association between stimulant co-involvement (in opioid overdoses) and survival. Results: Naloxone was reportedly administered in 72.2% of the opioid-no-cocaine overdoses, compared to 55.1% of the opioid-cocaine-involved overdoses, and 72.1% of the opioid-no-methamphetamine overdoses vs. 52.4% of the opioid-methamphetamine-involved overdoses. With respect to survival rates, 18.0% of the opioid-no-cocaine overdoses ended in death, compared to 41.3% of the opioid-cocaine overdoses; 18.1% of the opioid-no-methamphetamine overdoses ended in death, versus 42.9% of the opioid-methamphetamine overdoses. In mediation analyses (adjusted for demographics, county, year, and other drug co-involvement), naloxone administration mediated 38.7% (95% Confidence Interval [CI], 31.3%-46.0%) of the association between cocaine co-involvement and survival and 39.2% (95% CI, 31.3%-47.1%) of the association between methamphetamine co-involvement and survival. Conclusions: Among suspected opioid overdose events recorded in the Pennsylvania Overdose Information Network, stimulant co-involvement was associated with lower naloxone administration and higher fatality, with naloxone partially mediating the association between stimulant co-involvement and death.