An intelligent cellulose-based sorbent (Cell-Azo) was developed by grafting azobenzene onto cellulose via atom-transfer radical polymerization, enabling the light-driven solid-phase extraction of amphetamine (AMP). Successful grafting was verified by FT-IR and XPS, with UV-vis spectroscopy demonstrating the rapid and reversible trans-cis isomerization upon alternating UV/visible light irradiation. Batch adsorption studies revealed a maximum capacity of 19.86 mg·g-1 at pH 9.0, governed by synergistic electrostatic, π-π stacking, and hydrogen-bonding interactions. The core functionality of the switch was demonstrated by triggering AMP release with UV light, achieving a high desorption efficiency of 90.54%, significantly surpassing the <35% observed in the dark. This light-controlled release is attributed to conformational change in azobenzene units, which disrupts the binding sites. A dispersive solid-phase extraction protocol coupled with HPLC-UV was developed, demonstrating wide linearity (0.05-2.00 mg·L-1), low LOD (7 μg·L-1) and LOQ (23.33 μg·L-1), and satisfactory precision (RSD < 5.1%). When applied to spiked urine samples, the method achieved recoveries of 69.53-75.68%, demonstrating the potential application of Cell-Azo as an efficient, green, and controllable alternative for trace AMP analysis in complex matrices.

As the synthetic abused drug with high addictive potential, methamphetamine (METH) and its major metabolite amphetamine (AMP) are chiral compounds. The S-enantiomer of METH is primarily abused because of its potent psychoactive effects, whereas the R-enantiomer may originate from the metabolism of selegiline, a prescription medication for Parkinson's disease. This research aimed to develop a robust and reliable analytical method to distinguish illicit METH abuse from legal selegiline therapy. A novel, simplified chiral stationary phase liquid chromatography-tandem mass spectrometry (CSP-LC-MS/MS) method was developed and validated for the rapid determination of R- and S-enantiomers of METH and AMP in human hair, eliminating the need for derivatization pretreatment. Employing an Agilent Chiral-V column under isocratic conditions, the developed CSP-LC-MS/MS method achieved efficient baseline separation (resolution ≥2) and rapid quantification of the R/S enantiomers of METH and AMP within 10 min. Analysis of hair samples from three METH abusers revealed a predominance of the S-enantiomers. Conversely, only the R-enantiomer was detected in the hair of a selegiline user. This research enables precise enantiomer differentiation, offering critical insights into drug metabolism and forensic discrimination between illicit METH abuse and legitimate selegiline treatment.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) affects 5-7% of children and 2.5% of adults worldwide [1]. Stimulant medications including methylphenidate (MPH) and amphetamines (AMP) remain first-line despite cardiovascular and psychiatric safety concerns [4]. Objective: Comprehensive assessment of long-term cardiovascular safety, psychiatric risk profile, and therapeutic efficacy utilizing population-based cohort data [5]. Methods: Systematic review 2010-2025 across major medical databases evaluating cardiovascular events, hemodynamic changes, psychosis incidence, and academic outcomes [14]. Results: 0.92 cardiac events and 3.08 cardiac symptoms per 1,000,000 treatment days [5]. Current stimulant use aOR 0.69 (95%CI 0.42-1.12) vs non-users[5]. MPH demonstrated no short/long-term psychosis risk elevation [8]. MTA 8-year: +12% GPA, 56% symptom remission [10]. Conclusion: Protocolized stimulant therapy exhibits favorable safety-efficacy balance [11].

Methamphetamine (METH) is typically characterized as a potent dependent psychostimulant. Various behavioral models have been used to study METH drug dependence. The objective of this study was to determine the time period during which the neuropharmacological effects of METH are most pronounced, through a combined study of pharmacodynamics and pharmacokinetics. The present study simultaneously investigated the pharmacodynamics and pharmacokinetics of METH and its metabolite amphetamine (AMP) in mice by measuring the locomotor activity level and the concentrations of METH and AMP in the blood and brain from 5min to 8h after administration. The pharmacodynamic analysis showed that the mice maintained a high level of activity from 5min to 1h after the administration, followed by a significant decrease in activity at 2h. The pharmacokinetic analysis showed that METH was rapidly absorbed into the blood, and its concentration reached the peak value at 5min. AMP concentration in blood increased and reached the peak value at 1h; the concentrations of METH and AMP in the brain both reached the peak value at 30min. In terms of pharmacodynamics and pharmacokinetics, the behavioral effects of METH on mice are most obvious within 1h, at most 2h, after administration, which can thus be considered a preferred time period to study the neuropharmacology effects of METH.

Comparative analysis of toxicokinetic profiles of methamphetamine and its metabolites at toxic and therapeutic doses in mice.

A rat model of oral hormonal contraception: Effects on drug preference and gonadal function.

The Wistar-Kyoto rat strain (WKY) is a model for treatment-resistant depression, exhibiting behaviors indicative of anhedonia. Although anhedonia is measured using the sucrose preference test (SPT), 50-kHz ultrasonic vocalizations (USVs) hold promise as a complementary assessment tool. This study aimed to detect whether 50-kHz USVs differ in the WKY rats compared to control Wistar (W) rats. First, WKY and W rats were compared for their basal 50-kHz calls. Then, rats were repeatedly treated with four administrations of either amphetamine (AMPH) or morphine (MORPH), and 50-kHz calls were recorded. In addition, the drug-evoked locomotor activity, sucrose consumption in the SPT, and the time spent in the drug- vs. saline-paired compartment in the conditioned place preference (CPP) test were collected. WKY rats emitted fewer basal calls and fewer calls following the first and the fourth AMPH administration. Contrary to controls, AMPH did not affect the number of calls in WKY rats following the first administration. WKY also displayed reduced AMPH-induced locomotor activity and sucrose consumption in the SPT. MORPH did not affect USVs or locomotion in either strain. The results highlight the benefits of 50-kHz calls as a complementary behavioral marker for assessing anhedonia in preclinical models of depression.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-27298-x.

Site-specific assessment of illicit drug consumption patterns in South Korea via wastewater-based epidemiology.

The establishment of new behaviors requires epigenetic modifications that regulate the expression of genes underlying neuroplasticity in relevant circuits. Dopamine plays a central role in many physiological and pathological behavioral changes, including learning, memory, and addictive behaviors. In this study, we explored the relationship between dopaminergic neurotransmission and the epigenetic enzyme lysine-specific demethylase 1 (LSD1, KDM1a). LSD1 has a neurospecific isoform (neuroLSD1) generated by alternative splicing, which acts as a dominant-negative regulator, counteracting the ubiquitous LSD1 (uLSD1) functions. Notably, neuroLSD1 regulates immediate early gene expression, neuroplasticity, learning, and memory, making it a candidate regulator of dopamine-dependent behaviors. Our findings show that mice lacking neuroLSD1 have greater interindividual differences in their locomotor response to acute and repeated amphetamine (AMPH) exposure compared with their wild-type littermates. The analysis of the neurochemical effect of this psychostimulant using fast-scan cyclic voltammetry and microdialysis showed a reduced dopamine efflux in the nucleus accumbens (NAc). On the other hand, while a single dose of the AMPH did not alter uLSD1 and neuroLSD1 isoforms' expression, repeated AMPH administration led to a transient increase followed by a reduction of neuroLSD1 transcripts' abundance in the striatum and hippocampus. In conclusion, our data reveal a critical interplay between dopaminergic neurotransmission and the expression of LSD1 isoforms in the brain, highlighting their potential role in modulating dopamine-dependent behaviors.

A proposed mechanism for amphetamine-induced behavioral sensitization involving the vesicular monoamine transporter.

Evaluation of emerging contaminants and biochemical parameters in the blood plasma of wild American alligators (Alligator mississippiensis).

Food restriction and amphetamine exposure synergistically enhance accumbal dopamine D1 receptor-mediated locomotor activity.

Neurochemical alterations in monoaminergic systems induced by excessive sucrose consumption from the juvenile period to adolescence in mice.

Urine methamphetamine-to-amphetamine ratio by LC-MS/MS to differentiate methamphetamine use from pharmaceutical impurity in patients prescribed amphetamine.

Exposure of human neuroblastoma SH-SY5Y cells to amphetamine-type stimulants leads to oxidative-antioxidative imbalance associated with DNA damage and acetylcholine antagonism.

GPR55 in the bed nucleus of stria terminalis modulates anxiety-like behavior, amphetamine self-administration and inflammatory response.

The expression of addictive behaviors is linked to the structural plasticity of dendritic spines in the nucleus accumbens (NAcc). While radixin is known to contribute to morphological changes in dendritic spines, its role in the NAcc, specifically in the structural plasticity of dendritic spines and related drug-induced behavioral changes, is not well understood. In the present study, we investigated the effects of radixin manipulation in the NAcc core on amphetamine (AMPH)-induced locomotor activity, both in association with and independent of a specific environment. Additionally, we examined the accompanying changes in dendritic spine density in this region. We used a phosphomimetic pseudo-active mutant form (Rdx-T564D) and wild-type (Rdx-WT) radixin in conditioning and context-independent sensitization models induced by AMPH (1mg/kg). We observed that Rdx-T564D in the NAcc core selectively inhibited the expression of non-associative locomotor sensitization induced by AMPH. Conversely, overexpression of Rdx-WT in this region inhibited both conditioned locomotor activity and context-specific locomotor sensitization. Spine analysis revealed that the increase in mature thin spine density observed in the context-paired group was specifically suppressed by Rdx-WT, but not by GFP or Rdx-T564D. This study revealed that associative and non-associative forms of AMPH-induced reward memory are differentially regulated by radixin manipulation in the NAcc core, suggesting a critical role of radixin in psychomotor stimulant addiction.

Schizophrenia, a profoundly impactful neuropsychiatric disorder, has been the subject of extensive research using animal models. However, certain important aspects remain understudied, including assumed long-term consequences of psychotic episodes on negative symptoms development and progression. Addressing these limitations, we proposed a novel animal model in male rats based on early postnatal immune activation triggered by lipopolysaccharide (LPS), serving as the predisposing factor (1st hit). As the 2nd hit, representing psychotic-like episodes, we implemented a multi-episodic co-treatment with dizocilpine (MK-801) and amphetamine (AMP), spanning multiple developmental periods. The animals were tested in two social behavioral assays in adolescence and adulthood to investigate whether a social deficit would arise. In addition, we evaluated the level of oxytocin (OT), a neuropeptide relevant to social behavior, in selected brain regions. In the social interaction test, when animals could freely interact in the open field and express their social behavioral profile entirely, social behavior decreased in adolescent experimental animals. In the social approach test in the Y maze, all animals, irrespective of treatment, preferred conspecific over an indifferent object and novel rat over a familiar rat. Further, the results revealed that the OT content in the hypothalamus increased with age. In the proposed model, social interaction in the open field was decreased in adolescent but not in adult rats, indicating that the pharmacological manipulations caused only transient age-dependent changes. The study was thus in certain aspects successful in creating a novel approach to model social deficit potentially relevant to schizophrenia; other findings require further investigation.

The utilization of urine testing for drugs of abuse has emerged as a valuable tool in discerning the evolving landscape of drug abuse patterns. The objective of this study was to determine the patterns of drug of abuse within the Pakistani population, incorporating demographic factors such as age, gender, and location. This observational study was conducted at the Department of Pathology and Laboratory Medicine, Aga Khan University from January 2008 to December 2022. A review of drugs of abuse screening data extracted from laboratory information system was carried out. The panel includes screening of common drugs, amphetamine (AMP), benzodiazepine (BZO), barbiturates (BAR), cannabinoids (THC), cocaine (COC), and opioids (OPI) as well as blood alcohol (ALC) levels. Mean, standard deviation, percentage and frequency were calculated by using STATA version 13.Over a period of 15 years, a total of 130, 859 tests were performed, with 89.5% being male and mean age of 32.4 ± 11.3 years, while seventy-seven percent of the specimens (n = 101, 648) came from the province of Sindh. Of the total 6270 (4.8%) were screened positive for at least one drug, THC (n = 3626, 57.8%) was the most frequently positive test, followed by OPI (n = 1000, 16%), ALC (n = 671, 10.7%), COC (n = 31, 0.5%), AMP (n = 45, 0.7%), BAR (n = 35, 0.6%) and BZO (n = 862, 13.7%). Yearly trend analysis shows an increasing number of THC tests requested over time, with THC exhibiting the highest positivity rate, followed by BZO, OPI, and ALC.The 15-year patterns depict the rising prevalence of drug consumption which is subsequently increasing the demand for drug screening tests. The study highlights Pakistan's growing drug prevalence and calls for targeted policies to address its use, including strengthened prevention programs, improved regulation and better management and rehabilitation access.

Forensic significance of quantitatively analyzing methamphetamine in male reproductive organs.