Background/Objectives: Prenatal methamphetamine exposure may adversely affect fetal and neonatal outcomes, but its contribution to fetal and infant death remains incompletely understood. This study aimed to describe six fetal or infant deaths in which methamphetamine and amphetamine were detected and maternal methamphetamine exposure was considered a possible contributing factor. Methods: After obtaining the necessary approvals, medico-legal records, autopsy findings, and toxicological results were retrospectively reviewed for six cases from Bursa (n = 3) and Şanlıurfa (n = 3). Results: One case occurred in 2019, one in 2020, and four in 2021. Five cases involved preterm delivery between 24 and 32 gestational weeks, whereas Case 4 was born at 37 gestational weeks. Three cases were stillbirths, two infants died on postnatal day 4, and the term-born infant died on postnatal day 17. Methamphetamine and amphetamine were detected in postmortem specimens from all cases. Blood samples were available in five cases, with methamphetamine concentrations ranging from 19 to 256 ng/mL and amphetamine concentrations ranging from 4 to 42 ng/mL. In one case, only decomposition fluid was available. The organ damage attributable to methamphetamine and its role in the pathophysiology of death could not be fully established. Stimulant exposure was considered the most probable cause of death in Case 3, methamphetamine exposure was classified as the direct cause of death in Case 6, and methamphetamine exposure was considered a predisposing factor in the remaining four cases. Conclusions: Although methamphetamine and amphetamine were detected in all cases, these findings alone do not establish a causal relationship with death. Larger studies are needed to clarify prenatal and postnatal exposure pathways and to establish interpretive toxicological reference ranges for methamphetamine in fetal and infant populations.

Surface-enhanced Raman scattering (SERS) is widely used for detecting various analytes; however, the transferability and comparability of spectral data are limited by the complex interplay between electromagnetic and chemical enhancement mechanisms. In particular, mode-selective chemical enhancement within narrow spectral intervals can significantly distort relative band intensities, complicating comparisons across different substrates and experimental platforms. In this study, we measured amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine molecules adsorbed on electrochemically prepared large-scale gold substrates and evaluated the related extent of narrow-interval chemical enhancement. Compared to colloidal gold nanoparticle substrates, large-scale substrates exhibit a substantially attenuated narrow-interval chemical enhancement response, which is attributed to hotspot heterogeneity and spatial signal averaging across the extended surface. To quantitatively describe and compare these effects, a modified narrow-interval chemical enhancement factor is introduced, enabling systematic evaluation of substrate-dependent chemical enhancement contributions. The results demonstrate that this factor can be extended beyond concentration-dependent analyses and employed as a methodological parameter for improving the robustness and transferability of SERS data. This approach provides a framework for more reliable cross-platform comparison of SERS spectra and supports the development of reproducible spectroscopic protocols for forensic applications.

Methamphetamine (meth) is an addictive psychostimulant that induces monoamine oxidase (MAO)-dependent mitochondrial oxidative stress and MAO-dependent degeneration of substantia nigra pars compacta (SNc) dopamine neurons in male mice, suggesting that meth-induced mitochondrial oxidative stress is necessary for degeneration. However, the impact of chronic in vivo meth administration on SNc mitochondria is unclear. We therefore examined the impact of chronic meth administration on the expression of mitochondrial fission 1 (FIS1) and Dynamin-related protein 1 (DRP1), proteins involved in mitophagy, as well as mitochondrial density and mitochondrial function in the SNc. Male C57BL/6J mice received saline or meth (5 mg/kg; i.p.) for 28 days; chronic meth administration decreased SNc expression of both DRP1 and FIS1 proteins, suggesting impaired mitophagy. Consistent with this, mitochondrial density in SNc dopamine neurons was also increased. Moreover, this increase in mitochondrial density was MAO-dependent, suggesting that chronic meth-induced SNc degeneration is associated with an increase in mitochondrial density. To determine whether mitochondria were functional, high-resolution respirometry assessments were conducted using SNc tissue from mice treated with either chronic meth or saline. Results indicate that chronic in vivo meth administration decreased mitochondrial complex I as well as complex I + II oxidative phosphorylation capacities and coupling efficiencies in the SNc. Presented data suggest that chronic in vivo meth administration results in an accumulation of functionally compromised mitochondria in the SNc, which is associated with and may potentially contribute to chronic meth-induced neurodegeneration.

Background: This cross-sectional study compared immunoassay urine drug screening with LC-MS/MS confirmation in individuals with substance use disorder undergoing probation monitoring, focusing on samples with results close to assay cutoff values. Methods: The study was conducted between January and March 2026 in Şanlıurfa, Türkiye, and included 110 individuals followed at an Addiction Treatment Center (AMATEM). Urine samples with at least one analyte result within ±20% of the cutoff value were analyzed. Immunoassay screening was performed using a Beckman Coulter AU480 analyzer, whereas confirmation was performed by LC-MS/MS using a SCIEX Triple Quad 5500+ system. Agreement was evaluated using Cohen's kappa and McNemar's test, while diagnostic performance was assessed using 2 × 2 contingency tables. Results: Agreement varied substantially among analyte groups. Buprenorphine showed the highest agreement (κ = 0.47), followed by amphetamines (κ = 0.33), whereas opioids showed very low agreement (κ = 0.081). Benzodiazepines, cocaine, and cannabinoids showed no meaningful agreement; however, benzodiazepine and cocaine findings were limited by very low numbers of positive cases. Immunoassay screening produced notable false-positive results for amphetamines and opioids and false-negative results for cannabinoids and opioids. Conclusions: Immunoassay performance was analyte-dependent and appeared limited in samples with results close to cutoff values. LC-MS/MS confirmation remains important for reliable toxicological interpretation in probation monitoring settings.

Studying how drugs act on neuronal circuits requires delivering them with temporal precision while behavior proceeds undisturbed, a combination that tethered infusion systems cannot provide. We developed WEARIT (W ireless E quipment for A utonomous R at I nfusion T asks), a wearable, tetherless infusion platform that gives freely moving rats intravenous access under either remote or closed-loop operant control. The device houses a reservoir, miniaturized pump, rechargeable battery and Bluetooth circuitry in a 3D-printed enclosure worn on the back. By measuring spontaneous locomotion, amphetamine-induced hyperlocomotion and food-reinforced operant responding, we show that WEARIT leaves these behaviors unchanged. Remotely triggered fentanyl infusions yielded reliable delivery with physiological responses confirmed by pulse oximetry, and self-administration acquisition and dose-response functions were comparable to conventional tethered systems. WEARIT removes a longstanding constraint on intravenous pharmacology, opening self-administration paradigms to naturalistic and enriched environments and to concurrent imaging or optogenetic manipulation of the circuits engaged by drug reinforcement.

Delusional infestation (DI) is a psychocutaneous disorder marked by sensations of crawling and perceived fibers or foreign materials on the skin. Traditionally viewed as psychiatric, evidence now suggests a multifactorial pathogenesis involving dermatologic, neurologic, endocrine, psychosocial, and pharmacologic factors-most notably, striatal dopamine dysregulation. This review explores DI through a multidimensional lens, highlighting elevated striatal dopamine as a mechanism influenced by factors such as medication (e.g., amphetamines, dopamine agonists), iron deficiency, estrogen status, substance use, and psychosocial stressors. Radioligand neuroimaging supports aberrant striatal dopamine activity as central to pathogenesis. It is also possible that genetic predispositions may intersect with these factors, implicating polymorphisms in dopamine transporter/receptor genes and, iron regulation pathways. Central and peripheral nervous system dysfunction-seen in spinal cord injury, fibromyalgia, and neuropathic itch-may contribute, as can dermatologic conditions like prurigo nodularis that share inflammatory and sensory processing pathways with DI. We propose a model of DI that extends beyond psychiatric classification, emphasizing integrated care. Addressing nutritional deficiencies, medication effects, hormonal status, neuroinflammation, and social determinants may improve patient outcomes. Such a multidisciplinary approach targets underlying biological and environmental contributors.

Independent forensic quantification of methamphetamine (MA) and amphetamine (AMP) remains challenging due to their near-identical structures and overlapping electrochemical signatures. We report an end-to-end AI-integrated MIP-ECL biosensing framework employing target-specific MIP-NP/MWCNT/Nafion/Ir(pq)2(acac)/SPCE platforms. The Ir(III) luminophore within an MWCNT/Nafion matrix produced markedly superior ECL emission over the [Ru(bpy)3][2+] benchmark (40 mM DBAE, pH 8.0). MIP nanoparticles conferred high selectivity against structurally related interferents, validated in saliva, urine, and blood plasma, achieving detection limits of 0.11 ng mL[-1] for MA and 0.28 ng mL[-1] for AMP. A structured explainable machine learning pipeline employing CatBoost with Group-K-Fold cross-validation eliminated data leakage and achieved test R[2] values of 0.9864 (MA) and 0.9675 (AMP). SHAP analysis confirmed that model predictions were consistent with known electrochemical kinetics. This modular framework establishes a generalizable paradigm for intelligent MIP-ECL biosensing with direct applicability in forensic toxicology and point-of-care diagnostics.

Novel psychoactive phenethylamines and phenidates are synthetically designed analogs of conventional substances such as 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, and methylphenidate, developed to circumvent existing drug regulations. In Korea, the abuse of these substances has increased, particularly among habitual users and newly addicted younger individuals. To address this issue, new substances are regulated through the analog legislation and the temporary narcotic designation system. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using solid-phase extraction (SPE) was developed and validated for the simultaneous determination of 13 substituted phenethylamines and 5 substituted phenidates in human urine. The target analytes included 5-MAPDB, BDB, 4-FEA, PMEA, 3-FPM, 25iP-NBOMe, 2C-N, 2C-TFM, 30C-NBOMe, 3C-P, 4-MMA-NBOMe, DOI, and 2C-H, as well as 4-MeTMP, 4F-EPH, 4F-MPH, IPPH, and HDEP-28. No interfering peaks were observed at the retention times of analytes and internal standards. Linearity was confirmed over analyte-specific concentration within the overall range of 0.1-100 ng/mL, with coefficient of determination (r2) exceeding 0.995. The limits of detection and quantification were 0.001-0.1 ng/mL and 0.1-0.2 ng/mL, respectively. Accuracy and precision, expressed as bias and coefficient of variation (CV), were within ±10% and <10%, respectively. The CVs for matrix effects and extraction efficiencies were approximately 10%, and the extraction efficiencies exceeded 70%, confirming the reliability of the method for forensic applications. The validated method enables simultaneous determination of substituted phenethylamines and phenidates in urine and facilitates prompt positive identification in forensic casework. In addition, the structural information, MRM conditions, and analytical method validation results presented in this study can serve as a basis for expanding research on substances with similar core structures, which is expected to strengthen regulatory responses to evolving drug trends.

Immune system activation contributes to the pathophysiology of multiple psychiatric disorders, including schizophrenia. A substantial subgroup of people with schizophrenia are characterised by increased central and peripheral cytokine levels, and a tendency towards more severe symptoms and dopamine-targeting antipsychotic treatment resistance. Previous studies have shown an association between inflammation and increased dopamine turnover as well as increased sensitivity to stimulants such as dextroamphetamine (DEX). However, thus far, no study has demonstrated that increased dopamine release is responsible for stimulant-induced psychosis-relevant behaviour during inflammatory states. This calls the role of dopamine in inflammatory schizophrenia into question. To test whether inflammation-exacerbated behavioural responses are driven by dopaminergic mechanisms, we used a multimodal approach in a mouse model combining intraperitoneally (i.p) administered DEX (0.5 mg kg[-1])-evoked open-field behaviour, in vivo dopamine monitoring, molecular and c-Fos profiling of dopamine-relevant brain regions using qPCR and immunostaining. We measured blood-brain barrier permeability and central DEX exposure in brain after DEX via fluorescein uptake and liquid chromatography-mass spectrometry. To induce inflammation, we administered two doses of lipopolysaccharide (LPS, 0.83 mg kg[-1]i.p.) or phosphate-buffered saline (PBS i.p.) to male C57BL/6J mice (n = 158) 24 h apart and measured neuro-behavioural outcomes from 72 to 74 h. Sickness responses, including body mass change, body condition, and inactivity, were assessed longitudinally to confirm resolution of LPS-induced sickness prior to DEX-evoked behavioural testing. In parallel, inflammatory and kynurenine pathway markers were measured in the ventral midbrain and striatum to determine whether persistent neuroinflammatory and metabolic alterations remained after sickness behaviours had subsided and could contribute to exaggerated psychosis-relevant behavioural responses. We found that LPS-treated mice exhibited significantly greater DEX-evoked locomotor activity than PBS-treated controls, despite no differences in whole-brain DEX concentrations. Neuronal activation, indexed by c-Fos[+] cell density, was significantly increased in both the dorsal and ventral striatum of LPS-treated mice. However, real-time ventral striatal dopamine dynamics assessed using fibre photometry, together with dopamine-related mRNA expression in the ventral midbrain and striatum, did not differ between treatment groups. In contrast, mRNA levels of inflammatory markers (IL-1β, TNF, NF-κB2) were upregulated. To explore alternative pathways through which behaviour may be affected, we measured mRNA levels of enzymes in the inflammation-induced kynurenine pathway. We found that dysregulation of mRNA levels of all three measured kynurenine pathway enzymes (TDO2, KAT II, KMO) was present in the LPS group following behavioural testing. Taken together, our findings suggest that while inflammation augments psychosis-relevant mouse behaviour, dopamine may not be the key driver.

Clandestine production of synthetic drugs like amphetamine generates tremendous amounts of chemical waste which may partly be disposed into the sewage system by the producers. Specific synthesis-related marker compounds present in the production waste thus enter wastewater after discharges. Hence, wastewater monitoring could be an additional tool for law enforcement agencies to localize clandestine laboratories that dispose production waste into the sewage system. For such a scenario, a programmable sampling unit may be useful, which can be installed in manholes to access the sewage line and which could provide time-resolved composite samples. In contrast to common sampling at wastewater treatment plants, this approach provides a higher spatial resolution. In this study, small volumes of amphetamine production waste were discharged into real sewage environments in combination with a progammable sampling unit for sample collection. Composite (time-proportional) and event-triggered sampling protocols were tested for the detection and time correlation of waste discharges. Analytes from these wastewater samples were extracted with polydimethylsiloxane rods in the laboratory which proved to be easy to use and effective passive sampling devices to extract relevant amphetamine synthesis markers from wastewater matrix. The controlled discharge experiments in the sewer system showed that clandestine discharges can be tracked and traced with composite (time-proportional) sampling. Furthermore, event-triggered sampling was enabled via continuous pH measurements due to the often extreme pH values of amphetamine production waste. In addition, the detection of synthesis markers from production waste discharges by direct wastewater sampling in the sewage line with polydimethylsiloxane rods was tested.