Amphetamine-type Stimulants Research Articles

Breaking the Cycle: A Scoping Review Exploring Non-Pharmacological Treatment Programs for Amphetamine-Type Stimulant Use for People in Contact with the Justice System

Breaking the Cycle: A Scoping Review Exploring Non-Pharmacological Treatment Programs for Amphetamine-Type Stimulant Use for People in Contact with the Justice System

Methamphetamine-induced cardiotoxicity: in search of protective transcriptional mechanisms.

Crystalline methamphetamine hydrochloride is an illegal drug with ahigh addictive potential, better known by its colloquial name "ice" or "crystal meth". The abuse of this drug has led to significant health problems worldwide. Like other amphetamine-type stimulants, chronic consumption of methamphetamine leads to direct toxic effects on the central nervous system, causing cognitive impairment, depressive behavior, and other severe neurological or psychiatric symptoms. Besides its neurotoxicity, the drug exhibits numerous deleterious effects on the cardiovascular system, including hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, and dilated cardiomyopathy with congestive heart failure and left ventricular dysfunction. The excessive release of catecholamines upon methamphetamine exposure causes vasoconstriction and vasospasm, which ultimately lead to hypertension, tachycardia, endothelial dysfunction, and cardiotoxicity. While numerous studies have focused on transcription factors expressed in the brain that cause the neurotoxic effects of the drug, much less is known about transcription factors involved in the development of methamphetamine-induced heart failure. In this article, we provide an overview of the Janus kinase-signal transducer and activator of transcription3 (JAK-STAT3) pathway involved in ischemia/reperfusion injury in the myocardium, which may be activated by the vasospasm-inducing action of the drug. However, much more work is needed to decipher the precise role of STAT protein family members, including the potentially cardioprotective STAT3, in the pathogenesis of methamphetamine-induced cardiotoxicity.

Analysis of Amphetamine-Type Stimulants (ATS) Drugs and their Metabolites in Hair Samples of Drug Abusers using GC-FID

Analysis of Amphetamine-Type Stimulants (ATS) Drugs and their Metabolites in Hair Samples of Drug Abusers using GC-FID

Carboxyl hybrid monolithic column in-tube solid-phase microextraction coupled with UPLC-QTRAP MS/MS for the determination of amphetamine-type stimulants

Carboxyl hybrid monolithic column in-tube solid-phase microextraction coupled with UPLC-QTRAP MS/MS for the determination of amphetamine-type stimulants

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

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. 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. 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. 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.

Unraveling how hydrogen-bonding networks affect the capture of amphetamine-type stimulants by polymerized deep eutectic solvent modified magnetic biochar: Coupling quantum chemical calculations with experiment

The abuse of amphetamine-type stimulants (ATSs) has caused irreversible harm to public safety and ecosystems. A novel polymerized deep eutectic solvent modified magnetic pomelo peel biochar (PMBC) was prepared, and the differences in adsorption of four abused amphetamine-type stimulants (ATSs: AMP, MAMP, MDA and MDMA) were due to varying hydrogen bonds quantities and strengths. PMBC showed excellent chemical reactivity to MDMA, with a maximum adsorption capacity of 926.13 μg g−1, which was 3.25, 2.52 and 1.15 times higher than that of AMP, MAMP and MDA, respectively. Modern spectral analysis showed that there were a series of active centers (-COOH, -NH2 and -OH) on the PMBC, which could form hydrogen bond networks with the nitrogen and oxygen functional groups of ATSs. In various chemical environments: pH level (4–11), inorganic ion and organic matter (humic acid), PMBC maintained high activity towards four ATSs. Additionally, the quantum chemical calculations revealed that the methylenedioxy bridge of ATSs can increase the active sites, and the -NH- and -NH2 groups had different hydrogen bond formation capabilities, which together resulted in the adsorption order of PMBC on the four ATSs: MDMA > MDA > MAMP > AMP. Moreover, the hydrogen-bonding binding energies of several common hydrogen-bonding types were compared, including O-H····O, N-H····O/O-H····N and N-H···N. This study laid an empirical and theoretical foundation for the efficient capture of ATSs in water and contributed to the innovative design of materials.

Mega-analysis of the brain-age gap in substance use disorder: An ENIGMA Addiction working group study.

The brain age gap (BAG), calculated as the difference between a machine learning model-based predicted brain age and chronological age, has been increasingly investigated in psychiatric disorders. Tobacco and alcohol use are associated with increased BAG; however, no studies have compared global and regional BAG across substances other than alcohol and tobacco. This study aimed to compare global and regional estimates of brain age in individuals with substance use disorders and healthy controls. This was a cross-sectional study. This is an Enhancing Neuro Imaging through Meta-Analysis Consortium (ENIGMA) Addiction Working Group study including data from 38 global sites. This study included 2606 participants, of whom 1725 were cases with a substance use disorder and 881 healthy controls. This study used the Kaufmann brain age prediction algorithms to generate global and regional brain age estimates using T1 weighted magnetic resonance imaging (MRI) scans. We used linear mixed effects models to compare global and regional (FreeSurfer lobestrict output) BAG (i.e. predicted minus chronological age) between individuals with one of five primary substance use disorders as well as healthy controls. Alcohol use disorder (β = -5.49, t = -5.51, p < 0.001) was associated with higher global BAG, whereas amphetamine-type stimulant use disorder (β = 3.44, t = 2.42, p = 0.02) was associated with lower global BAG in the separate substance-specific models. People with alcohol use disorder appear to have a higher brain-age gap than people without alcohol use disorder, which is consistent with other evidence of the negative impact of alcohol on the brain.

Determination of amphetamines in hair samples using microextraction by packed sorbent and gas chromatography-mass spectrometry.

Several protocols for the analysis of amphetamine-type stimulants (ATS) in hair have been developed over the years, with microextraction by packed sorbent (MEPS) being used for drugs like opiates, cocaine and ketamine. However, concerning ATS determination in hair samples, this approach has only been applied so far to amphetamine (AMP) and methamphetamine (MAMP). This study aimed at developing and validating a MEPS-based procedure for the determination in hair of not only AMP and MAMP but also of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 1-(1,3-benzodioxol-5-yl)propan-2-yl (ethyl)amine (MDE) and N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane (MBDB) as well. Hair, 50 mg, was incubated with 1M sodium hydroxide (NaOH) at 45°C overnight, neutralization with 10M hydrochloric acid (HCl) and centrifugation followed. The design of experiments approach was used for MEPS optimization, with the final optimized conditions including conditioning (250 μL methanol and deionized water), loading (18 × 100 μL) and elution (7× 100 μL 2% NH4OH in acetonitrile). The eluted extract was evaporated to dryness and underwent microwave-assisted derivatization with N-methyl-bis(trifluoroacetamide) (MBTFA), and it was afterwards injected onto the gas chromatography-mass spectrometer (GC-MS). The obtained recoveries ranged between 8% and 14% for AMP, 14% and 20% for MAMP, 10% and 15% for MDA, 18% and 28% for MDMA, 25% and 43% for MDE and 34% and 52% for MBDB, and the method was linear from 0.2 to 5.0ng/mg. Precision and accuracy were in accordance with international method validation guidelines. This novel method involving MEPS coupled to GC-MS offers a swift, eco-friendly and cost-effective alternative to traditional procedures for detecting these AMPs in hair samples.

Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Efficacité et innocuité du modafinil pour le traitement des troubles liés à l'usage de stimulants de type amphétamine : revue systématique et méta-analyse d'essais randomisés contrôlés par placebo.

Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD. A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables. Five RCTs (N = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p = 0.029). There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential.

The Effect of Chronic Administration of Amphetamine-Type Stimulants on Oxidative Stress and Inflammation in Wistar Rats

تهدف هذه الدراسة إلى تحديد تأثير التناول المزمن للمنشطات من نوع الأمفيتامين بجرعات متفاوتة على الالتهاب والإجهاد التأكسدي في فئران ويستار. تم إعطاؤهم ميثيلفينيديت وتم تقسيمهم إلى 4 مجموعات علاجية. علاوة على ذلك ، تم إجراء تجميع عشوائي بسيط لتقسيم العينات إلى 5 مجموعات ، تتكون كل مجموعة من 9 فئران. تضمنت هذه المجموعات الفئران التي أعطيت فقط الماء المقطر كعناصر تحكم ، بالإضافة إلى تلك التي أعطيت ميثيلفينيديت بجرعات 10 مجم / كجم من وزن الجسم ، و 20 مجم / كجم من وزن الجسم ، و 40 مجم / كجم من وزن الجسم لمدة 4 أسابيع كمجموعات تجريبية. ثم تم إجراء التحليل الإحصائي باستخدام GraphPad Prism لمقارنة تأثيرات الإجهاد التأكسدي والالتهاب الجهازي و BDNF والذاكرة المكانية لفئران Wistar. أدى الاستخدام المزمن للمنشطات إلى انخفاض كبير في مستويات الجلوتاثيون بيروكسيديز وكذلك زيادة في إطلاق IL-6 وعامل نخر الورم ألفا مقارنة بمجموعة التحكم. بناءً على النتائج ، لعبت المسارات المتورطة في الضعف الإدراكي ، والتي كانت مرتبطة باستخدام المنشطات من نوع الأمفيتامين ، دورًا في معالجة التأثير الضار لتعاطي المخدرات والأمراض المصاحبة لها.

Toxic Effects of Methamphetamine on Reproductive Systems, Embryo Development, and Newborns: An Evidence-Based Review.

Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the human body. Specifically, METH has a negative impact on the hypothalamic- pituitary-testicular axis, testicular structure, sperm function, ovarian folliculogenesis, oocyte quality, embryo development, and newborns. However, the mechanisms underlying these toxic effects have not yet been fully described. This study reviews the evidence concerning the impact of METH on male and female reproduction in the context of the testis, sperm, ovaries, oocytes, reproductive hormones, embryo development, and newborns, discussing the potential pathophysiological mechanisms in the reproductive toxicity induced by METH.

An Adaptation and Validation of Cocaine Craving Questionnaire for Malaysians Who Use Amphetamine-Type Stimulants.

Cases of amphetamine-type stimulants (ATS) use have been increasing over the past decade. Cravings are considered a causal factor for recurrent relapses in ATS use cases. The absence of questionnaires measuring cravings for ATS in the local population necessitates the creation of one, especially considering the rising number of cases. This study aimed to adapt and validate the Cocaine Cravings Questionnaire into a questionnaire suitable for measuring cravings for ATS in the local population. The original questionnaire was adapted by substituting "cocaine" with "ATS". The process involved a back-to-back translation, followed by a round of face and content validation. The participants included people who use drugs (PWUD) with a history of ATS use recruited from rehabilitation centers in Malaysia. A set of questionnaires consisting of demographic items and the adapted ATS Cravings Questionnaire (ATS-CQ) were given. This cross-sectional study recruited a total of 205 PWUD, mostly single men, with a mean age of 33.32 (s.d.=13.14). The mean age of ATS initiation was 22.89 (s.d.=9.39), with a median duration of ATS use of 60 months (IQR=24.00, 120.00). The adapted questionnaire received a good score for content validation. Unlike the original, this adapted version was found to have only three factors showing good internal consistency, ranging from 0.707 to 0.918 for all three factors. Test-retest reliability also showed good results, with an interclass correlation coefficient of 0.875 (95% CI=0.835, 0.905). The translated ATS-CQ has been finalized and deemed valid and reliable for use among Malaysian substance users to measure ATS cravings.

Responding to the global epidemic of amphetamine-type stimulant use compromising biomedical HIV prevention among men who have sex with men

Responding to the global epidemic of amphetamine-type stimulant use compromising biomedical HIV prevention among men who have sex with men

Model compounds for evaluating the reactivity of amphetamine-type stimulants

The use of controlled precursors for reaction optimisation is not always practical. One approach to limiting the use of controlled substances is to instead use ‘model compounds’. Herein, two model compounds resembling norephedrine and ephedrine were selected based on their (i) structural similarity (i.e., presence of key functional groups) and (ii) availability from multiple suppliers without restriction. Model compounds 2-amino-1-phenylethanol and 2-(methylamino)-1-phenylethanol (halostachine), were compared to norephedrine and pseudoephedrine by firstly subjecting them to transformations known in the synthesis of amphetamines, and secondly, comparing the compounds using colourimetric spot tests, FTIR and NMR.

Nrf2 expression, mitochondrial fission, and neuronal apoptosis in the prefrontal cortex of methamphetamine abusers and rats

Methamphetamine (MA), a representative amphetamine-type stimulant, is one of the most abused drugs worldwide. Studies have shown that MA-induced neurotoxicity is strongly associated with oxidative stress and apoptosis. While nuclear factor E2-related factor 2 (Nrf2), an antioxidant transcription factor, is known to exert neuroprotective effects, its role in MA-induced dopaminergic neuronal apoptosis remains incompletely understood. In the present study, we explored the effects of MA on the expression levels of Nrf2, dynamin-related protein 1 (Drp1), mitofusin 1 (Mfn1), cytochrome c oxidase (Cyt-c), and cysteine aspartate-specific protease 3 (Caspase 3), as well as the correlations between Nrf2 and mitochondrial dynamics and apoptosis. Brain tissue from MA abusers was collected during autopsy procedures. An MA-dependent rat model was also established by intraperitoneal administration of MA (10 mg/kg daily) for 28 consecutive days, followed by conditioned place preference (CPP) testing. Based on immunohistochemical staining and western blot analysis, the protein expression levels of Nrf2 and Mfn1 showed a decreasing trend, while levels of Drp1, Cyt-c, and Caspase 3 showed an increasing trend in the cerebral prefrontal cortex of both MA abusers and MA-dependent rats. Notably, the expression of Nrf2 was positively associated with the expression of Mfn1, but negatively associated with the expression levels of Drp1, Cyt-c, and Caspase 3. These findings suggest that oxidative stress and mitochondrial fission contribute to neuronal apoptosis, with Nrf2 potentially playing a critical role in MA-induced neurotoxicity.

Psychostimulants and social behaviors.

Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that the neural circuits underlying the regulation and expression of social behaviors are highly overlapped with those targeted by psychostimulants, which in most cases have strong rewarding and, consequently, addictive properties. In the present work, we provide an overview regarding the effects of illicit and prescription psychostimulants, such as cocaine, amphetamine-type stimulants, methylphenidate or modafinil, upon social behaviors such as social play, maternal behavior, aggression, pair bonding and social cognition and how psychostimulants in both animals and humans alter them. Finally, we discuss why these effects can vary depending on numerous variables such as the type of drug considered, acute versus long-term use, clinical versus recreational consumption, or the presence or absence of concomitant risk factors.

Patterns and Characteristics of Amphetamine-type Stimulant Use in a North-eastern State of India: A Cross-sectional Study

Background: South Asia generally reports low levels of amphetamine-type stimulant (ATS) use, with few studies on the pattern of ATS use. We assessed the pattern of ATS use and associated high-risk behavior in Manipur, a north-eastern state of India. Methods: 209 adult male ATS users (mean age 28.8 years) from three districts of Manipur were interviewed. Data were collected on the patterns of high-risk behavior with ATS use, health consequences, and help-seeking. The severity of use with various substances was assessed using the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Depression and anxiety were assessed by the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale, respectively. Results: The mean duration of ATS use was 3.7 years (SD 2.3). The majority used ATS almost daily (88%) and depended on ATS (77%). Methamphetamine (99.5%) was the most used ATS orally. Around 87% also suffered from opioid dependence. About 76% injected drugs, most commonly heroin. Almost three-fourths (78%) used ATS before their sexual intercourse, 31% of whom did not use condoms. Most reported physical problems with ATS and had above-cut-off scores on PHQ-9 and GAD-7. The majority (95%) reported that they could procure ATS easily. Also, the majority (93%) had thought of quitting ATS use. Discussion: Most ATS users start using ATS at a young age and have comorbid other drug use, including heroin. ATS use is associated with various physical and psychological problems. Focusing on ATS use in India and developing strategies to address this problem is essential.

Iraq's Meth Crisis: Prioritizing Research to Combat Suicidal Ideation

As dedicated readers of Al-Kindy College Medical Journal, we are writing to highlight a critical and profoundly concerning matter that requires urgent research attention: the alarming surge in suicidal ideation among users of Iraqi crystal methamphetamine. Expert psychiatrists at Baghdad Medical City and Ibn-Rushd Psychiatry Teaching Hospital have observed this worrisome trend. In tandem, previous studies regarding suicidal ideation among Iraqi medical students have revealed an unexpectedly high prevalence (64.9%). The escalating global trend in amphetamine-type stimulant (ATS) abuse and the distinct challenges posed by crystal meth addiction necessitate comprehensive investigation into the resultant psychological toll.According to the World Drug Report 2022, amphetamines' popularity and use, including methamphetamine, have surged globally, ranking as the second most commonly abused illicit substance after cannabis. This rise in ATS abuse has not spared Iraq, where illicit methamphetamine and captagon use have dramatically increased, notably in Al-Basrah governorate. The transition from opioid-related overdose deaths to the abuse of stimulants like methamphetamine signifies the urgency for novel strategies to monitor and combat this growing public health concern. As methamphetamine misuse becomes more prevalent, it is imperative to prioritize research that explores the mental health consequences of its abuse.

Dog and cat exposures to drugs of abuse identified by the California animal health and food safety laboratory system 2013-2023.

While known animal exposures to human "drugs of abuse" (DA) were previously considered relatively uncommon in veterinary medicine, the trends are changing. Marijuana and amphetamines are among the 20 toxicants most frequently consulted about with the Pet Poison Helpline. When such exposures occur, they are typically considered emergencies. This retrospective study describes confirmed cases of DA exposure in pets from the California Animal Health and Food Safety Laboratory System (CAHFS), 2013-2023. Fifty-seven samples tested positive for DA through liquid chromatography with tandem mass spectrometry analysis (qualitative method). In 75% (43/57) of the DA screen tests, the detected drugs included amphetamine-type stimulants and metabolites (methamphetamine, amphetamine, or both). In 47% (27/57) of cases, a combination of more than one drug group was found. Most cases were diagnosed from a urine specimen. In at least 32% (18/57) of cases, the samples were submitted due to suspicions of animal cruelty, and at least 41% (23/57) of the patients were deceased when the samples were submitted. More studies on the prevalence of illicit drugs in small animals, using confirmatory testing, are warranted to fully understand the significance of this emerging toxicological hazard in veterinary medicine.

Amphetamine increases vascular permeability by modulating endothelial actin cytoskeleton and NO synthase via PAR-1 and VEGF-R

Abuse of amphetamine-type stimulants is linked to cardiovascular adverse effects like arrhythmias, accelerated atherosclerosis, acute coronary syndromes and sudden cardiac death. Excessive catecholamine release following amphetamine use causes vasoconstriction and vasospasms, over time leading to hypertension, endothelial dysfunction or even cardiotoxicity. However, immediate vascular pathomechanisms related to amphetamine exposure, especially endothelial function, remain incompletely understood and were analyzed in this study. Pharmaco-pathological effects of acute d-amphetamine-sulfate (DAM) were investigated ex vivo using contraction–force measurements of rat carotid artery rings and in vitro using label-free, real-time electrochemical impedance spectroscopy (EIS) on endothelial and smooth muscle cells. Specific receptor and target blocking was used to identify molecular targets and to characterize intracellular signaling. DAM induced vasodilation represented by 29.3±2.5% decrease in vascular tone (p<0.001) involving vascular endothelial growth factor receptor (VEGF-R) and protease activated receptor 1 (PAR-1). EIS revealed that DAM induces endothelial barrier disruption (−75.9±1.1% of initial cellular impedance, p<0.001) also involving VEGF-R and PAR-1. Further, in response to DAM, Rho-associated protein kinase (ROCK) mediated reversible contraction of actin cytoskeleton resulting in endothelial barrier disruption. Dephosphorylation of Serine1177 (−50.8±3.7%, p<0.001) and Threonine495 (−44.8±6.5%, p=0.0103) of the endothelial NO synthase (eNOS) were also observed. Blocking of VEGF-R and PAR-1 restored baseline eNOS Threonine495 phosphorylation. DAM induced vasodilation, enhanced vascular permeability and actin cytoskeleton contraction and induced eNOS hypophosphorylation involving VEGF-R, PAR-1 and ROCK. These results may contribute to a better understanding of severe adverse cardiovascular effects in amphetamine abuse.