To examine patterns of stimulant ADHD medications to adults in Ireland between 2015 and 2024, under community drug schemes. We aimed to describe changes over time across age groups, demographic characteristics, and geographic areas.

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.

Benzylpiperazine (BZP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) are early‑appearing piperazine‑type new psychoactive substances (NPSs) frequently detected in ecstasy. Their combined use produces cardiovascular stimulation (hypertension and tachycardia) comparable to dextroamphetamine, yet data on their toxicokinetics and tissue distribution are scarce. We investigated the pharmacokinetics and tissue distribution of BZP and TFMPP after intraperitoneal injection (2 mg kg[-1]) in Wistar rats, both singly and in combination. Compared with single‑drug administration, combined dosing significantly altered t1/2 of BZP, mean residence time (MRT), and apparent volume of distribution (Vz/F), and reduced area under the curve (AUC) of TFMPP (p < 0.05). Apart from peak concentration (Cmax), the two compounds have similar toxicokinetic characteristics in some aspects. BZP and TFMPP were rapidly absorbed (Tmax 0.15-0.70 h). Elimination half‑lives were 0.36 h for BZP and 2.56 h for TFMPP. After a single dose, Cmax (173 ng/mL) of BZP was significantly lower than Cmax (284 ng/mL) of TFMPP. Twenty-four hours after administration, the tissue concentrations of BZP, whether given alone or in combination, ranked as follows: liver > kidney > lung > spleen > brain > heart. For TFMPP, the distribution pattern under combined administration was the same as that of BZP; however, when administered alone, its concentration in the brain was higher than that in the spleen. These findings indicate that co‑exposure to BZP and TFMPP can modify toxicokinetic behavior and tissue distribution, suggesting distinct poisoning dynamics from exposure to either compound alone.

Cannabigerol (CBG) is a phytocannabinoid present in the plant Cannabis sativa that, similar to cannabidiol (CBD), does not cause psychotomimetic effects. It has shown potential therapeutic effects for relieving pain, inflammation, and anxiety, and it possesses antioxidant and neuroprotective properties. To date, few studies have investigated the potential of CBG in animal models of schizophrenia. Previous studies have demonstrated the antipsychotic-like profile of CBD in clinical and preclinical studies, with a lower induction of side effects when compared to conventional therapy. Although the pharmacological properties of CBG partially resemble those of CBD, some important differences could result in distinct clinical potential. In the present work, we investigated whether CBG could also show an antipsychotic-like profile in animal models of schizophrenia. Male Swiss mice received intraperitoneal injections of CBG followed by d-amphetamine (AMPH) or MK-801 and were exposed to different behavioral assays, including the open field, novel object recognition (NOR), social interaction, and prepulse inhibition (PPI) tests. CBG attenuated the disruptive effects of AMPH in the PPI and open field tests. In addition, pre-treatment with this compound also attenuated the impairments in the social interaction test, NOR, and PPI induced by MK-801. These results suggest that CBG therapeutic profile in behavioral assays. Notably, these benefits were observed at reduced concentrations, indicating that this compound represents a promising candidate for future translational and clinical investigations.

Background: Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized among women of reproductive age. Little is known about time trends in maternal ADHD, and treatment utilization in this group.

Choosing a relatively large reward with a lower chance of payoff compared with a relatively small reward with a higher chance of payoff can be operationalized as a risky choice. Risky choices are often observed in humans through gambling. Gambling disorder is characterized by excessive gambling that results in detrimental personal, social, and financial outcomes. Clarifying mechanisms that contribute to perseverative gambling could help clarify why problem gambling may occur. The presentation of win-paired cues is suggested to contribute to excessive gambling because of a conditioned-reinforcing function. Stimulant drugs have been shown to enhance conditioned reinforcers and to increase risky choice under certain experimental conditions. The present study was designed to examine how the combined administration of d -amphetamine, a commonly prescribed psychomotor stimulant, and the presentation of win-paired cues on winning and losing trials would impact risky choice patterns in a probability-discounting procedure in Sprague-Dawley rats. d -Amphetamine produced dose-dependent increases in risky choice with or without win-paired cues. Win-paired cues alone did not alter absolute levels of risky choice, but the combination of d -amphetamine and win-paired cues promoted perseveration for the risk-associated response option. This effect was particularly evident following losing trials where the win-paired cue was presented. Results are discussed in the context of electronic gambling machine use, and suggestions for research with more commonly used stimulants are offered.

BACKGROUND Fatigue is common in multiple sclerosis (MS) and adversely affects function and quality of life. We examined clinical correlates of fatigue, its relationship with depression and sleepiness, and whether fatigue-related medications improve patient-reported outcomes. MATERIAL AND METHODS This single-center, longitudinal observational study retrospectively analyzed prospectively collected data from 203 veterans, categorized based on the presence or absence of fatigue. Primary outcomes were changes in the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Epworth Sleepiness Scale (ESS) from baseline to 12 months. Secondary outcomes included changes in the EuroQol 5-Dimension Questionnaire (EQ-5D), EQ visual analog scale (EQ-VAS), Total Functional Independence Measure (TFIM), Expanded Disability Status Scale (EDSS), 2-Minute Walk Test (2MWT), and Beck Depression Inventory (BDI). Medication exposure (amantadine, modafinil/armodafinil, methylphenidate/dextroamphetamine) was recorded. RESULTS Fatigue was present in 134 of 203 (66%) and associated with higher body mass index (30.1±5.5), hyperlipidemia (53.7%), diabetes (16.4%), higher BDI (4.58±4.36) and ESS (10.7±6.51), and worse EQ-5D VAS (all P<0.01). Strong positive correlations were observed among fatigue (FSS/MFIS), depression (BDI), sleepiness (ESS), and disability (EDSS) scales (P<0.05). Compared with no medication, fatigue-related medications did not improve FSS/MFIS or EQ-VAS scores; however, modest gains favored treated patients in TFIM change (P=0.04) and 2MWT distance (P=0.02). Post hoc comparisons across amantadine, modafinil/armodafinil, and amphetamine showed no between-drug differences in primary or secondary outcomes. CONCLUSIONS MS fatigue in veterans is highly prevalent and closely linked to metabolic comorbidities, depression, and sleep disturbance. Common fatigue medications provided no improvement in fatigue severity and quality of life.

Dextroamphetamine is a psychostimulant widely used in the treatment of attention-deficit/hyperactivity disorder and as a model compound in clinical toxicology and pharmacokinetic studies, and some studies report its use in cocaine dependence treatment. The present work describes the development and validation of a capillary electrophoresis (CE) method coupled with diode array (DAD) and capacitively coupled contactless conductivity (C4D) detectors for the simultaneous analysis of dextroamphetamine and its main urinary metabolites. Although phenylacetone is a key intermediate in the oxidative deamination pathway, this study focuses on the determination of 4-hydroxyamphetamine, norephedrine, hippuric acid, and benzoic acid in synthetic urine and spiked human samples. The method was optimized for background electrolyte composition, pH, and separation voltage, allowing efficient resolution and dual detection. Rapid separations were obtained, with migration times under 8 min. Linear responses were observed for all compounds within 1-200 μM (R2 ≥ 0.955), with LOD/LOQ ranging 0.32-32.2 μM and 1.07-97.6 μM, respectively. For dextroamphetamine, migration occurred at 3.64 min (DAD) and 3.41 min (C4D), with LOD/LOQ of 2.16/7.19 μM (DAD) and 8.58/28.60 μM (C4D). Intra- and inter-day repeatability tests demonstrated analytical precision with acceptable limits. The method was applied to spiked human urine samples using the standard addition technique for endogenous metabolites (hippuric acid and benzoic acid). This study demonstrates the feasibility of clinical and toxicological monitoring involving psychostimulant determination.

ADHD is a neurodevelopmental condition marked by persistent symptoms of inattention, hyperactivity, and impulsivity. The gold standard pharmacotherapy for the treatment of ADHD is CNS psychostimulants. However, a shortage of CNS psychostimulants used for the treatment of ADHD has persisted since 2022, and many patients have been forced to switch medications or have been unable to obtain medication at all, raising concerns about symptom management and quality of life. This case report describes a 30-year-old female who was unable to obtain lisdexamfetamine amid the shortage, found mixed amphetamine salts ineffective, but found success with immediate-release dextroamphetamine sulfate, a less frequently used amphetamine. This report serves to demonstrate that immediate-release dextroamphetamine sulfate may be a viable alternative stimulant to address the shortage; however, more research must be conducted to confirm these findings.