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Deficits in social cognition are seen in both people living with HIV (PWH) and people with a history of methamphetamine (METH) dependence. Dually affected individuals may experience additive negative effects on social cognition due to these conditions. We evaluated social cognition in 4 diagnostic groups (HIV-/METH-, HIV-/METH+, HIV+/METH-, HIV+/METH+). First, we used traditional social-emotional functioning assessments, the Difficulties in Emotion Regulation Scale and the Faux Pas Task, to determine any significant effects of METH dependence and HIV on social cognition. Next, we quantified social cognition using the Human Behavioral Pattern Monitor by evaluating social behavior represented by interaction with novel objects. METH dependence significantly affected social-emotional functions and HIV significantly affected on object interactions, however no significant additive effects were observed using these methods. The nuanced relationship between HIV and METH dependence suggests that other factors (i.e., adaptive life skills) likely mediate social cognition-related behaviors.

Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain of these neurons is highly complex, with a large subset of non-synaptic release sites and a smaller subset of synaptic terminals from which in addition to DA, glutamate or GABA are also released. The molecular mechanisms regulating the connectivity of DA neurons and their neurochemical identity are unknown. An emerging literature suggests that neuroligins, trans-synaptic cell adhesion molecules, regulate both DA neuron connectivity and neurotransmission. However, the contribution of their major interaction partners, neurexins (Nrxns), is unexplored. Here, we tested the hypothesis that Nrxns regulate DA neuron neurotransmission. Mice with conditional deletion of all Nrxns in DA neurons (DAT::NrxnsKO) exhibited normal basic motor functions. However, they showed an impaired locomotor response to the psychostimulant amphetamine. In line with an alteration in DA neurotransmission, decreased levels of the membrane DA transporter (DAT) and increased levels of the vesicular monoamine transporter (VMAT2) were detected in the striatum of DAT::NrxnsKO mice, along with reduced activity-dependent DA release. Strikingly, electrophysiological recordings revealed an increase of GABA co-release from DA neuron axons in the striatum of these mice. Together, these findings suggest that Nrxns act as regulators of the functional connectivity of DA neurons.

BackgroundEscalating misuse of amphetamine-type stimulants, mainly methamphetamine, has led to a staggering rise in associated overdose deaths and a pressing need to understand the basis of methamphetamine use disorder (MUD). MUD is characterized by disadvantageous decision-making, and people with MUD perform below controls on the Balloon Analogue Risk Task (BART), a laboratory test of decision-making under uncertainty. The BART presents a series of choices with progressively higher stakes-greater risk of loss and greater potential monetary reward. This research aimed to clarify whether impaired behavioral updating contributes to maladaptive performance on the BART.MethodsTwo groups (28 drug-abstinent participants with MUD and 16 healthy control participants) were compared on BART performance. Using a computational model, we deconstructed behavior into risk-taking and behavioral updating. A subset of participants (22 MUD, 15 healthy control) underwent [18F]fallypride positron emission tomography scans to measure dopamine D2-type receptor availability (BPND) in the striatum (caudate and accumbens nuclei and putamen) and the globus pallidus.ResultsParticipants with MUD exhibited slower behavioral updating than the healthy controls (p = 0.0004, d=1.77). BPND in all four bilateral volumes of interest were higher in the healthy control group (ps

It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non-randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2-4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal.

Background: Men who have sex with men (MSM) who use stimulants are at increased risk for HIV infection. Adherence to pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection. We evaluated the efficacy of the individualized Texting for Adherence Building (iTAB) intervention for PrEP adherence compared to standard of care (SoC) among 119 MSM who use stimulants (cocaine, methamphetamine and/or other amphetamine) from the California Collaborative Treatment Group 595 randomized control trial.Method: Three ordered levels of PrEP adherence (non-adherence, adequate adherence, and near-perfect adherence) were compared between intervention arms across study visits (weeks 12 and 48) using ordinal logistic regressions.Results: The effect of intervention arm was not significant in the final model; however, there was a 38% decrease in odds (OR = 0.62, p=.023) of having near-perfect adherence (versus non-adherence or adequate adherence) at week 48 compared to week 12, indicating a significant effect of time. In a follow-up analysis examining week 48 only, logistic regression examining PrEP adherence showed that receiving iTAB (compared to SoC) trended toward higher odds of near-perfect adherence relative to adequate adherence (OR = 2.48, p=.061). Higher HIV knowledge resulted in higher odds (OR = 1.72, p=.020) of near-perfect adherence (versus non-adherence or adequate adherence).Conclusion: HIV knowledge may influence PrEP adherence, and most notably, the iTAB intervention may support near-perfect adherence relative to adequate adherence.

ObjectiveThe combination of d-methylphenidate and guanfacine (an α-2A adrenergic agonist) may be an effective alternative to either agent as monotherapy in children with attention-deficit/hyperactivity disorder (ADHD). This study investigated the neural mechanisms underlying medication effects using cortical source analysis of electroencephalography (EEG) data.MethodA total of 172 children with ADHD (aged 7-14; 118 boys) completed an 8-week randomized, double-blind, comparative study with 3 treatment arms: d-methylphenidate, guanfacine, or their combination. EEG modulations of brain oscillations at baseline and end point were measured during a spatial working memory task from cortical sources localized within the anterior cingulate (midfrontal) and primary visual cortex (midoccipital), based on previously reported ADHD and control differences. Linear mixed models examined treatment effects on EEG and performance measures.ResultsCombined treatment decreased midoccipital EEG power across most frequency bands and task phases. Several midoccipital EEG measures also showed significantly greater changes with combined treatment than with monotherapies. D-methylphenidate significantly increased midoccipital theta during retrieval, while guanfacine produced only trend-level reductions in midoccipital alpha during maintenance and retrieval. Task accuracy improved with combined treatment, was unchanged with d-methylphenidate, and worsened with guanfacine. Treatment-related changes in midoccipital power correlated with improvement in ADHD severity.ConclusionThese findings show that combined treatment ameliorates midoccipital neural activity associated with treatment-related behavioral improvements and previously implicated in visuo-attentional deficits in ADHD. Both monotherapies had limited effects on EEG measures, with guanfacine further showing detrimental effects on performance. The identified midoccipital EEG profile may aid future treatment monitoring for children with ADHD.Clinical trial registration informationSingle Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); https://clinicaltrials.gov/; NCT00429273.Diversity & inclusion statementWe worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group.

Kleine Levin syndrome (KLS) is a rare entity. It presents with subacute onset episodic hypersomnia, cognitive decline, altered perception, and occasional hyperphagia and hypersexuality with full recovery during the interepisodic period. Five cases presented with episodic hypersomnia and met the diagnostic criteria of KLS. The majority of the cases were females (3/5) in whom KLS is even rarer. The initial presentation was in the age range of 10--25 years. Cognitive dysfunction (5/5), derealization (4/5), viral prodrome (3/5), hyperphagia (3/5), and hypersexuality (2/5) were other clinical presentations. A differential diagnosis of atypical depression is the major challenge, and thorough history taking would help in differentiation. Treatment with stimulants (modafinil) and mood stabilizers (lithium) proved effective. A high degree of suspicion should be kept for cases of episodic hypersomnolence for early diagnosis and management of KLS. [ABSTRACT FROM AUTHOR]

ADHD is associated with an increased risk of injury. Causal evidence for effects of pharmacological treatment on injuries is scarce. We estimated effects of ADHD medication on injuries using variation in provider preference as an instrumental variable (IV). Using Norwegian registry data, we followed 8051 patients who were diagnosed with ADHD aged 5 to 18 between 2009 and 2011 and recorded their ADHD medication and injuries treated in emergency rooms and emergency wards up to 4 years after diagnosis. Persons with ADHD had an increased risk of injuries compared to the general population (RR 1.35; 95% CI: 1.30–1.39), with higher risk in females (RR 1.47; 95% CI: 1.38–1.56) than males (RR 1.23; 95% CI: 1.18–1.28). The between-clinics variation in provider preference for ADHD medication was large and had a considerable impact on patients' treatment status. There was no causal evidence for protective effects of pharmacological treatment on injuries overall for young individuals with ADHD characterized by milder or atypical symptoms. However, there was an apparent effect of pharmacological treatment over time on the risk of injuries treated at emergency wards in this patient group. [ABSTRACT FROM AUTHOR]

Objectives: Disruptive mood dysregulation disorder (DMDD) is a relatively new diagnosis that comprises severe, nonepisodic irritability and recurrent outbursts of emotional instability in adolescents. This meta-analysis examined the efficacy of the available pharmacological and nonpharmacological interventions for DMDD. Methods: Literature searches were conducted in July 2023. To determine relevant articles, 330 abstracts were reviewed, and 39 articles were identified for full review. A random-effects model was used for the meta-analysis, and a subgroup analysis was performed to assess the effects of study design and intervention type. Results: Eleven studies were reviewed, including six pharmacological and five nonpharmacological. Despite high heterogeneity in effects (I2 = 85%), we showed statistically significant improvements in irritability symptoms following intervention. We showed statistically significant enhancements in symptoms of irritability following the intervention. The subgroup analysis revealed that, compared with randomized controlled trials (RCTs), open trials showed significant improvements in irritability. In addition, drug intervention significantly improved irritability compared to nondrug interventions. Atomoxetine (ATX), optimized stimulants, and stimulants combined with other drugs and behavioral therapy effectively improved irritability. Conclusions: With research indicating potential benefits for irritability from a combination of pharmacological interventions and therapy, including ATX, stimulants in conjunction with antipsychotic or antidepressant medications, and cognitive-behavioral techniques such as Dialectical Behavior Therapy for Children. Future large-scale RCTs are essential to further explore and refine these treatment approaches, especially focusing on the efficacy of combining pharmacological with effective nonpharmacological to improve irritability and overall outcomes in this population. [ABSTRACT FROM AUTHOR]

Background: Dental medicine should expand its scope to properly assess medical and psychosocial factors that might have an impact on patients' oral health. Based on previous literature and clinical experience, attention‐deficit/hyperactivity disorder and psychostimulant medications might represent factors associated with orofacial pain symptoms. Objective: The aim of the study was to assess whether common orofacial pain complaints such as jaw pain, jaw clicking, teeth clenching and headaches are more prevalent in dental patients who have an ADHD diagnosis and/or use psychostimulant medications. Methods: Orofacial pain symptoms prevalence was compared among four groups from a sample of new patients seeking dental care at Tufts University School of Dental Medicine (n = 11 699) based on ADHD diagnosis and psychostimulants intake: G1: no ADHD, no stimulants; G2: yes ADHD, yes stimulants; G3: yes ADHD, no stimulants; G4: no ADHD, yes stimulants. Results: In multivariable logistic regression models adjusting for age, gender, tobacco use, and alcohol consumption, significant differences were found for clenching (p <.0001), jaw pain (p <.0001), and headache (p <.0001). Compared to G1, two groups (G2 and G4) exhibited significantly higher odds of clenching and headaches, whereas only G2 exhibited significantly higher odds of jaw pain. Conclusions: In comparison with patients without ADHD and not taking psychostimulants medications, dental patients using psychostimulants with and without ADHD diagnosis report headaches and teeth clenching more frequently, while jaw pain is reported more frequently only by those taking psychostimulants with an ADHD diagnosis. Further research is necessary to assess the nature of these associations and their clinical relevance. [ABSTRACT FROM AUTHOR]

This review focused on the concept of dementia in the Unani system of medicine and comprehensive, updated information on Majoon Vaj about the phytochemistry, nootropic, CNS activities and provide insights into potential opportunities for future research. The classical literature on Majoon Vaj for its anti-dementic properties, and therapeutic uses were gathered from nearly thirteen classical Unani books including Unani Pharmacopoeia. The information of pharmacognosy, phytochemical and pharmacological activities of Majoon Vaj and its ingredient was collected by browsing the Internet (PubMed, ScienceDirect, Wiley online library, Google Scholar, ResearchGate). The relevant primary sources were probed, analysed, and included in this review. The keywords used to browse were Majoon Vaj, Dementia, Nootropic, Acorus calamus, Piper nigram, Zingiber officinalis, Nigella sativa, Carum carvi, Plumbago zeylanica, and β-asarone. Relevant Sources were gathered up to July 2021, and the chemical structures were drawn using ACD/ChemSketch software. The species name and synonyms were checked with WFO (2021): World Flora online (http://www.worldfloraonline.org) an updated version of 'The Plant List.' Majoon Vaj contains an excess of bioactive compounds e.g., alkaloids, phenols, flavonoids, tannins, diterpenes, coumarins, carbohydrates, and fixed oils and its ingredients possess broad pharmacological properties, including cognitive-enhancing, neuroprotective, anti-inflammatory, antioxidant and antimicrobial properties. The literature of Unani medicine is quite rich in discussing the pathophysiological basis of memory disorders. It argues that memory, retention, and retrieval are regulated by a complex process involving various faculties. Majoon Vaj seems to have great potential for therapeutic applications in the treatment of dementia and thus encourage more preclinical and clinical trials in this field. [ABSTRACT FROM AUTHOR]

Methamphetamine (meth) is a potent and addictive central nervous system stimulant with increasing use. Stroke is one severe possible complication of meth use. Due to high levels of manufacturing in Mexico, the western United States has experienced greater consequences of meth use. The literature reviewed herein is comprised of case studies and series, and it suggests that hemorrhagic stroke (including hypertensive-like intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage), as opposed to ischemic stroke, is the more common type of neurovascular complication of meth use. Meth-related strokes are a particular concern for younger patients with stroke and may be a partial explanation for increasing stroke rates in this age group. We describe two cases (one intraparenchymal hemorrhage and one ischemic stroke) in young patients (<50years old) with recent meth use to illustrate clinical characteristics and therapeutic considerations. There are several proposed pathophysiological explanations for meth-associated hemorrhagic stroke including an induced hypertensive surge, vasospasm, blood brain barrier breakdown, chronic hypertension, aneurysm development and rupture, and very rarely associated vasculitis. The increased risk of ischemic stroke related to meth use is less well supported in the literature, but this may, in part, be related to a lack of appropriately designed and powered research studies. Proposed mechanisms for ischemic stroke complications of meth use include those affecting blood vessels such as accelerated atherosclerosis, chronic hypertension, vasospasm, and vasculitis, plus mechanisms that affect the heart including cardiomyopathy, arrhythmias, and infective endocarditis (especially with injection drug use). Standard therapeutic interventions for acute stroke and approaches to secondary stroke prevention seem appropriate for meth-associated strokes, with the addition of abstinence from continued meth use. There is no evidence for any meth-specific stroke treatments. Finally, the prolonged duration of meth withdrawal is described. Larger, prospective studies of meth-related strokes are needed to allow for a better understanding and improved care for this often-devastating consequence of an increasingly prevalent cause of strokes in young patients. [ABSTRACT FROM AUTHOR]

Background and aims: Total abstinence has historically been the goal of treatment for substance use disorders; however, there is a growing recognition of the health benefits associated with reduced use as a harm reduction measure in stimulant use disorders treatment. We aimed to assess the validity of reduced stimulant use as an outcome measure in randomized controlled trials (RCTs) of pharmacological interventions for stimulant use disorder. Design: We conducted a secondary analysis of a pooled dataset of 13 RCTs. Setting and participants: Participants were individuals seeking treatment for cocaine or methamphetamine use disorders (N = 2062) in a wide range of treatment facilities in the United States. Measurements We validated reduced stimulant use against a set of clinical indicators drawn from harmonized measurements, including severity of problems caused by drug use, comorbid depression, global severity of substance use and improvement, severity of drug‐seeking behavior, craving and high‐risk behaviors, all assessed at the end of the trial, as well as follow‐up urine toxicology. A series of mixed effect regression models was conducted to validate reduction in frequency of use against no reduction in use and abstinence. Findings More participants reduced frequency of primary drug use than achieved abstinence (18.0% vs. 14.2%, respectively). Reduced use was significantly associated with decreases in craving for the primary drug [60.1%, 95% confidence interval (CI) = 54.3%–64.7%], drug seeking behaviors (41.0%, 95% CI = 36.6%–45.7%), depression severity (39.9%, 95% CI = 30.9%–48.3%), as well as multiple measures of global improvement in psychosocial functioning and severity of drug‐related problems, albeit less strongly so than abstinence. Moreover, reduced use was associated with sustained clinical benefit at follow‐up, as confirmed by negative urine tests (adjusted odds ratio compared with those with no reduction in use: 0.50, 95% CI = 0.35–0.71). Conclusion: Reduced frequency of stimulant use appears to be associated with meaningful improvement in various clinical indicators of recovery. Assessment of reduced use, in addition to abstinence, could broaden the scope of outcomes measured in randomized controlled trials of stimulant use disorders and facilitate the development of more diverse treatment approaches. [ABSTRACT FROM AUTHOR]

Purpose: In competitive sport, classic methods of measuring drug prevalence, such as doping controls or questionnaires, are challenging. Here we describe a novel urine sampling method to measure drug use in athletes. We hypothesize that the prevalence of drug use in ultramarathon runners is measured more accurately with our sampling method than randomized-response questionnaires. Methods: Urine samples and associated demographic data were collected from male participants using blind, automated urinals at the start ot ultramarathon races. Various nonprohibited and prohibited substances were subsequently screened. Concomitantly, 2931 male and female runners participating in the same ultramarathons completed an anonymized, randomized-response questionnaire regarding drug use. Results: Among 412 individual urine samples, 205 (49.8%) contained at least one substance, and 16.3% of the samples contained one or more prohibited substances. Substances detected in urine included nonsteroid anti-inflammatory drugs (NSAID) (22.1%), acetaminophen (15.5%), opioids (6.6%), diuretics (4.9%), hypnotics (4.4%), glucocorticoids (2.7%), beta-2 agonists (2.2%), cannabinoids (1.9%), and stimulants (1.2%). None of the samples contained erythropoietin-receptor agonists or suspicious testosterone. Drug use was not associated with the participants' characteristics or ranking. Respondents to the questionnaire reported using acetaminophen (13.6%) and NSAID (12.9%); however, no prohibited substances were declared. Conclusions: There was a high prevalence of drug use among male ultramarathon runners, in particular, NSAID and painkillers; however, performance-enhancing drugs were marginally used. Blind urine sampling highlighted prohibited drug use not declared in questionnaires, and it is useful to assess the prevalence of drug use and/or doping in competitive athletes. [ABSTRACT FROM AUTHOR]

Objective: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women. Methods: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups. Results: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p <.05) compared to no common mental disorder. Conclusions: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers. [ABSTRACT FROM AUTHOR]

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations. [ABSTRACT FROM AUTHOR]

A cohort study involving both publicly and commercially insured patients has found in adjusted analyses that exposure to stimulant medications during pregnancy did not significantly increase risk of childhood neurodevelopmental disorders. The investigators focused largely on children's risk of autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD). Study results were published online Jan. 24, 2024, in JAMA Psychiatry. [ABSTRACT FROM AUTHOR]

The article highlights the changes in safety labeling approved by the U.S. Food and Drug Administration (FDA) from October to December 2023. Topics mentioned include the life-threatening respiratory depression caused by opioid Actiq, the risks associated with the use of central nervous system depressant benzodiazepines, and the interaction of Actiq with cytochrome P450 3A4.

Purpose: Although attention deficit hyperactivity disorder (ADHD) has been associated with illicit stimulants use, less is known about their prospective association in university students. We aimed to examine the association between ADHD symptoms at inclusion and illicit stimulants use following 1 year among university students. Methods: The i-Share cohort recruited French students from February 2013 to July 2020. The study included 4270 participants. The Adult ADHD Self-Report Scale (ASRS) was used to evaluate ADHD symptoms at inclusion. Illicit stimulants use was assessed at inclusion and 1 year after inclusion. Multivariable logistic regressions were conducted to assess the association between ADHD symptoms at inclusion and illicit stimulants use following 1 year. Results: High levels of ADHD symptoms at inclusion were associated with a greater probability of illicit stimulants use following 1 year (adjusted OR: 2.42 (1.51–3.8)). The adjusted odds ratio was 2.7 (1.08–7.84) among participants who had used illicit stimulant at least once (continuation) and 2.25 (1.04–4.37) among participants who had never used illicit stimulants at inclusion (initiation). Conclusion: High levels of ADHD symptoms are a feature that may promote both initiation and continuation of illicit stimulants use among university students. Our findings suggest that university students with high levels of ADHD symptoms may benefit from screening to help identify those at risk of illicit stimulants use. [ABSTRACT FROM AUTHOR]

Background: Caffeine, a xanthine alkaloid compound, is a stimulant of the central nervous system and is mainly used in the pharmaceutical and food industries. Because caffeine is directly absorbed into the body, Chinese pharmacopeia has high requirements on the quality of caffeine products, and fluorescence has always been an important indicator to measure the quality of caffeine. In this study, a major fluorescent impurity affecting the appearance and purity of caffeine products was isolated for the first time, and the solubility, thermodynamic properties and dissociation constants of this impurity were studied. Results: (i) The fluorescent impurity affecting the appearance and purity of the product was successfully isolated from crude caffeine and theophylline sodium salt, and named as a blue fluorescent substance. The mass purity of the substance was 96.27%, and its structure was determined based on a comprehensive analysis of high‐resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy [hydrogen 1 (1H) NMR, carbon‐13 (13C) NMR, COSY, NOESY, HSQC, HMBC]. (ii) The solubility of blue fluorescent substance in four pure solvents was determined and the thermodynamic properties were calculated. (iii) The dissociation constants of the blue fluorescent substance in water at 298.15 K were determined by UV spectrophotometry. Conclusion: The results provide a theoretical basis for the crystallization separation of the blue fluorescent substance during the industrial production of caffeine, as well as basic data for the green synthesis process of caffeine. © 2024 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

This study presents a comprehensive examination of Pinus kesiya var. langbianensis (Pinus kesiya var. langbianensis), the primary resin-extraction tree species in Yunnan Province, China. In this study, we formulated different concentration gradients of 0.25%, 0.5%, 1%, and 2% of diquat solution as tapping stimulant to test the effect of different concentrations on the resin gain rate of Pinus kesiya, and analyzed the relationship between anatomical structure, major chemical composition of turpentine and resin yield by methods such as wood anatomy and chemical composition analysis of turpentine. The primary focus of the investigation was on exploring the interrelationships among resin-tapping stimulants, anatomical structures, turpentine components, and resin yield. Research findings demonstrate a significant enhancement in resin production due to the application of stimulants, with the highest increase rate reaching 55% in a specific group, while others achieved approximately 30% increments. Moreover, measurement data about resin duct dimensions indicate a noteworthy increase in resin duct area for the stimulant-treated group compared to the control group. However, it should be noted that the impact on resin duct area by varying stimulant concentrations was relatively minor. Furthermore, continuous observation of resin extraction from different resin-yield classes of P. kesiya revealed insignificant variation in resin yield over time for the low and moderate resin-yield groups. In contrast, the high resin-yield group exhibited a gradual increase in resin production. Interestingly, the high resin-yield group exhibited the smallest resin duct area, but the highest resin duct density, indicating an interconnectedness of resin duct-related data that influences resin yield. Additionally, correlative investigations between anatomical structures and resin yield demonstrate a positive correlation between resin duct area and resin yield, total resin production, and average resin yield. This underscores the importance of resin duct area as a significant factor in resin production. On the other hand, the influence of stimulant concentrations on the turpentine components was found to be negligible. Overall, the correlation results suggest that turpentine components cannot reliably predict or differentiate between high and low resin-yield trees. This study provides a comprehensive analysis of the interrelationships among stimulants, anatomical structures, and turpentine components, offering a theoretical foundation for the resin extraction and resin processing industries in Yunnan Province. [ABSTRACT FROM AUTHOR]

Introduction Viloxazine is an antidepressant medication classified as an SNRI (serotonin and norepinephrine reuptake inhibitor). In April 2021, it received FDA approval in the United States for the treatment of ADHD in children aged 6 to 17. Subsequently, in May 2022, it was also approved for the treatment of adults with ADHD [1]. Viloxazine, available in extendedrelease capsules, represents novel non-stimulant medication option for patients with ADHD. Aim of the study Our aim was to review the viloxazine in the fields of ADHD treatment, summarize current knowledge and analyze the first treatment results. Methods and materials A review of the literature available in the PubMed database was performed, using the key words: „Viloxazine"; „ADHD treatment"; „ADHD", „attention deficit hyperactivity disorder", „attention deficit hyperactivity disorder treatment"; „ADHD non-stimulant treatment"; „ADHD non-stimulant"; „ADHD non-stimulant drugs", „SPN-812" Conclusion Viloxazine presents a promising non-stimulant alternative for ADHD treatment with more favorable pharmacokinetics, new way of possible administration and fewer adverse effects, particularly within the cardiovascular system, than other available ADHD medication options. While these findings are encouraging, continual research is imperative to establish the longterm safety profile. [ABSTRACT FROM AUTHOR]

Over half of youth with attention-deficit/hyperactivity disorder (ADHD) have co-occurring psychiatric or medical conditions that present treatment challenges. Stimulants are the most effective pharmacologic treatment of ADHD for preschoolers to adults but questions about safety with co-occurring conditions frequently arise. In addition, stigma surrounding diagnosis and treatment can negatively impact care. This manuscript presents evidence-based practice pearls to guide treatment decisions for youth with ADHD and common coexisting psychiatric and medical conditions. Recommendations address specific stimulant adverse effects (i.e., anxiety, cardiac, growth, mania, psychosis) along with management strategies. Pearls were developed for the most common clinical questions, controversial topics, or therapeutic issues that may not be widely known. The goals of this manuscript are to: 1) provide a detailed resource for interprofessional teams regarding stimulant use in youth with ADHD, 2) improve therapeutic outcomes for youth with ADHD and co-occurring psychiatric and/or medical conditions through evidence-based recommendations, and 3) decrease stigma associated with stimulant use through education. [ABSTRACT FROM AUTHOR]

Contingency management (CM) is the only proven treatment for stimulant use disorder. It is based on paying people money for staying off stimulants, but the reward has to be much bigger than the $75 a year allowed under federal law (See Contingency management, best treatment for stimulants, essential with fentanyl; CPU April 2023; https://onlinelibrary.wiley.com/doi/10.1002/cpu.30761). In February, top researchers again called on the federal government to pay attention to this problem, raising the cap. Methamphetamine‐involved deaths increased from 545 in 1999 to 32,353 in 2021. Of the more than 100,000 illicit drug deaths in 2021, two‐thirds involved fentanyl, but almost half of the fentanyl‐involved deaths included the co‐use of methamphetamine, cocaine, or other stimulants.. [ABSTRACT FROM AUTHOR]

Purpose: Dopamine transporter (DAT) imaging is used to support the diagnosis of neurodegenerative parkinsonian disorders. Specific medications have been reported to confound the interpretation of [123I]I-FP-CIT SPECT scans, but there is limited data. The aim of the current study is to identify potential medication effects on the interpretation of [123I]I-FP-CIT SPECT scans in routine practice. Materials and methods: Consecutive patients undergoing a [123I]I-FP-CIT SPECT/CT scan on a 360° CZT camera between September 2019 and December 2022 were included. An exhaustive review of patient medications (antidepressants, antipsychotics, anti-epileptics, anti-parkinsonians, benzodiazepines, lithium, opioids, and stimulants) was performed. Two experienced nuclear physicians, blinded to the medication reports, interpreted the [123I]I-FP-CIT SPECT scans visually and a semi-quantitative analysis was performed using a local normal database. Results: The study included 305 patients (71.0 ± 10.4, 135 women) and 145 (47.5%) visually interpreted normal scans. In normal scans, the striatum/occiput radioligand uptake ratio was decreased by noradrenergic and specific serotonergic antidepressants (NASSAs) (n = 15, z-score of − 0.93) and opioid medication (tramadol, n = 6, z-score of − 0.85) and was associated with a younger age in the multivariate analysis. In the overall population, the striatum/occiput ratio was influenced by NASSAs and associated with consensual visual analysis, age, sex, and anti-parkinsonian medications related to the status of the disease. Conclusion: Our study confirms the potential impact of antidepressant (NASSA) and opioid (tramadol) medications on the semi-quantitative analysis of [123I]I-FP-CIT SPECT scans. However, when performing a visual analysis, only NASSAs significantly impacted the interpretation of [123I]I-FP-CIT SPECT scans. [ABSTRACT FROM AUTHOR]

Pubertal timing predicts a miscellany of negative mental and physical health outcomes. Prior work examining pubertal timing in youth with attention-deficit hyperactivity disorder (ADHD) has failed to investigate potential sex specificity of results. Therefore, we aim to extend past findings in a sample of female adolescents with ADHD. We compare pubertal timing (1) between females with and without carefully diagnosed ADHD and (2) between females with ADHD who do vs. do not have a history of stimulant medication use during childhood. We examine 127 adolescent females with childhood-diagnosed ADHD and 82 matched neurotypical peers (Mage: 14.2 years, range: 11.3–18.2) from the Berkeley Girls with ADHD Longitudinal Study (Wave 2). We measured pubertal timing using self-reported Tanner staging and age at menarche. Three strategies compared pubertal timing across groups: (1) χ 2 tests of Tanner Stages, (2) t tests of residuals of pubertal status regressed on age, and (3) t tests of age at menarche. Pubertal timing of girls with and without ADHD did not differ significantly across methods and measures. Yet females with ADHD who had received stimulant medication during childhood menstruated later than those without a stimulant history, potentially related to differences in BMI across groups. On the other hand, no significant differences between medicated vs. non-medicated participants emerged for the two Tanner staging indicators. Our findings extend prior work, suggesting that females with ADHD are developing physically at a similar time as their peers, which parallels findings from previous mixed-sex samples that did not examine effects separately by sex. [ABSTRACT FROM AUTHOR]

Background: Drinking commonly occurs in social settings and may bolster social reinforcement. Laboratory studies suggest that subjective effects and mood are mechanisms through which the social context influences alcohol consumption. Ecological momentary assessment (EMA) may be useful for extending these findings to the natural environment. This pre-registered secondary analysis of EMA data investigated the influence of the social environment on: (1) stimulating and sedating subjective effects of alcohol, (2) contentedness and negative affect, and (3) next-day evaluations of the drinking occasion. Methods: Nontreatment seeking adults reporting past-month heavy drinking (N = 131; Mage = 28.09; 42% female) completed 7 days of EMA (in the morning, at random, and following drinking prompts), which included questions on their social context (drinking in the presence of known others or alone), contemporaneous stimulating and sedating effects, contentedness and negative affect, alcohol consumption, and next-day evaluations of a prior day's drinking event (how satisfying/pleasant was drinking). We used multi-level models in SAS 9.4 M7 software to examine relations among the variables. Results: Contemporaneous subjective effects (stimulating or sedating), negative affect, and contentedness did not significantly depend on the social context. For next-day evaluations of pleasure/satisfaction from drinking, context effects were dependent on consumption totals. As the total number of standard drinks consumed increased, recollections of pleasure/satisfaction were higher when drinking had occurred with others, relative to alone. At lower consumption totals, next-day evaluations did not appear to depend on social context. Conclusions: When reported contemporaneously, subjective effects and affect do not appear dependent upon the presence of known others. However, heavier drinking events, relative to lighter drinking events, are appraised more favorably the following day when occurring within social contexts. [ABSTRACT FROM AUTHOR]

Recent research shows that co-use of stimulants and opioids appears to be increasing and injection of opioids and stimulants carries a risk for HIV transmission. This study examined stimulant injection and sexual HIV risk behaviors among individuals who reported nonmedical use of gabapentin and opioids (n = 62). Comparisons of people who injected stimulants to those who did not were conducted using chi-square and t-tests. Compared to those who did not, people who injected stimulants, were less likely to be African American/Black (p < 0.05) and more likely to report sex with another person who injects drugs (p < 0.01), recent injections of prescription and/or illicit opioids (p <.000), and hepatitis C infection (p < 0.01). Condomless intercourse during group sex was more prevalent among stimulant injectors, significant at the trend level (p < 0.1). Given the documented association between the use of opioids and nonmedical use of gabapentin and the growing trend of opioid-stimulant co-use, future research must examine whether nonmedical use of gabapentin is an indicator of substance use disorder severity and/or a risk factor for injection drug use. Education and intervention opportunities that address group sex and other sexual risk behaviors are warranted. [ABSTRACT FROM AUTHOR]

Adolescent substance use continues to be a global concern. Research has shown that two consistent predictors of this behavior are self-control and peer substance use. The objective of this study was to determine if these two variables interact to affect the frequency of substance use among young people. The analysis utilized three years of data from the Second International Self-Report Delinquency study (2005-2007) (ISRD-2), which gathered information from youth, ages 12-17, residing in 30 nations (n = 72,206). Illicit substance use included cannabis, ecstasy, stimulants, and other substances. A zero-inflated negative binomial model that adjusts for selection effects was estimated to predict the frequency of substance use. The results showed that adolescents with low self-control who associated with substance using peers tended to be the most frequent substance users. Yet, youth with higher levels of selfcontrol were likely to report no or low frequency use regardless of the number of their friends who used illicit substances. Self-control affects substance use among adolescents and can attenuate the influence of peer substance use. Research using longitudinal data is needed to disentangle changes in self-control, peer substance use, and one's own substance use. [ABSTRACT FROM AUTHOR]

BackgroundDrug-related emergency department (ED) visits are escalating, especially for stimulant use (i.e., cocaine and psychostimulants such as methamphetamine). We sought to characterize rates, presentation, and management of ED visits related to cocaine and psychostimulant use, compared to opioid use, in the United States (US).MethodsWe used 2008-2018 National Hospital Ambulatory Medical Care Survey data to identify a nationally representative sample of ED visits related to cocaine and psychostimulant use, with opioids as the comparator. To make visits mutually exclusive for analysis, we excluded visits related to 2 or more of the three possible drug categories. We estimated annual rate trends using unadjusted Poisson regression; described demographics, presenting concerns, and management; and determined associations between drug-type and presenting concerns (categorized as psychiatric, neurologic, cardiopulmonary, and drug toxicity/withdrawal) using logistic regression, adjusting for age, sex, race/ethnicity, and homelessness.ResultsCocaine-related ED visits did not significantly increase, while psychostimulant-related ED visits increased from 2008 to 2018 (2.2 visits per 10,000 population to 12.9 visits per 10,000 population; p

Recent reports indicate that stimulant-related deaths are increasing dramatically. People who die from acute stimulant toxicity have high rates of pre-existing cardiovascular disease (CVD), much of which is undiagnosed. Moreover, people who use stimulants with CVD often remain asymptomatic until presenting to an emergency department with an acute event. Prior research shows that symptoms of stimulant toxicity may occur on a regular basis, and that people who die from stimulant toxicity are older than those who die of opioid toxicity. Taken collectively, the existing evidence suggests that death from acute stimulant toxicity is often an outcome of long-term, cumulative exposure leading to cardiovascular dysfunction rather than acute intoxication. Strategies tailored to the distinct etiology of stimulant overdose are needed. We propose a three-part approach including (1) implementing stimulant use interventions that promote not only abstinence, but also use reduction, (2) treating ongoing stimulant use as a chronic cardiovascular condition, and (3) making stimulant toxicity interventions relevant to the populations most affected, which includes people outside of the traditional health-care system. In short, to reduce stimulant-related fatality, we need to transform our approach in ways that are tailored to address its natural history.

Fatigue jeopardises soldiers' lives, and despite caffeine being the approved wakefulness aid in the Australian Defence Force (ADF), its efficacy equals a placebo with unwanted side effects. The US Military uses modafinil as an alternative, but no ADF studies on modafinil exist. This article argues for exploring alternatives, ensuring consent and conducting willingness-to-participate studies before conducting ADF modafinil trials. [ABSTRACT FROM AUTHOR]

Common drugs of misuse, including cannabis, opioids, stimulants, alcohol, and anabolic steroids, have strikingly disparate acute and chronic vascular effects, leading to a wide range of clinical cardiovascular presentations. Acute cannabis smoking has been associated with increased risk for myocardial infarction and ischemic stroke in otherwise healthy young people. However, it remains uncertain if people who exclusively smoke cannabis have increased risk for accelerated atherosclerosis similar to that found in people who exclusively smoke tobacco cigarettes. Cocaine and methamphetamines, both stimulants, increase risk for stroke, myocardial infarction, aortic dissection, and accelerated atherosclerosis, but only methamphetamine use is strongly linked to pulmonary hypertension. Chronic alcohol use is strongly associated with chronic hypertension and hemorrhagic stroke, but perhaps confers a lower risk for myocardial infarction. Finally, anabolic steroid use, presumably through adverse effects on circulating lipids and the hematopoietic system, is associated with increased risk for accelerated atherosclerosis and myocardial infarction. Physicians, especially cardiologists, emergency medicine, and internal medicine physicians, should be familiar with the short- and long-term vascular consequences of use of these substances, thereby ensuring appropriate, specific, and informed counselling and treatment.

IntroductionInitiation of tobacco products typically occurs in adolescence. Adolescence is a critical period in development where the maturation of brain neurocircuitry is vulnerable to nicotine. Nicotine-containing products and psychostimulants, such as methamphetamine (METH), are often coabused. Rodent studies have shown that nicotine exposure in early adolescence increases subsequent drug intake and reward. Given the exponential increase in e-cigarette use among adolescents, there is a pressing need to understand whether adolescent nicotine exposure impacts concurrent increased METH use. The objective of this study is to evaluate age, sex, and longitudinal effects of nicotine pretreatment on METH reinforcement.Aims and methodsMale and female Sprague-Dawley rats were pretreated with a subchronic, low-dose nicotine (2×, 30 µg/kg/0.1 mL, intravenous) or saline during early adolescence (postnatal days [PN] 28-31) or adulthood (PN 86-89). Following nicotine pretreatment, on PN 32 or PN 90, animals underwent operant intravenous self-administration for METH (20 µg/kg/inf) over a 2-hour period for five consecutive days.ResultsEarly adolescent nicotine exposure enhances intravenous METH self-administration in male, but not female adolescents. Male adult rats self-administer METH over the 5-day testing period, independent of nicotine exposure. In contrast, nicotine exposure increases METH self-administration in female adults during the later sessions of the 5-day testing period.ConclusionsTaken together, our data highlight age- and sex-dependent effects of low dose, subchronic nicotine pretreatment on subsequent intravenous METH self-administration.ImplicationsA majority of polysubstance users begin smoking before the age of 18. Mounting evidence highlights adolescent susceptibility to nicotine exposure on brain and behavior. With the escalation in nicotine-containing products and stimulant use among adolescents, it is important to identify the consequences from adolescent nicotine use, including polysubstance use. Our study provides evidence that adolescent nicotine exposure enhances subsequent METH use, with important sex- and age-dependent effects.

Background: Prescription and illicit drugs are important social environmental variables in many suicides regardless of their role as an immediate cause of death. Objectives: To investigate the presence of prescription and illicit drugs, either through mention in the death record or toxicology reports, among suicides attributed to nonpoisonous causes to identify patterns of risk. Methods: Using the 2003-2017 National Violent Death Reporting System (NVDRS), we examined the presence of prescription and illicit drugs among 143,175 suicides (119,563 males 23,612 females) due to firearms and suffocation/hanging. The presence of drugs (opioids, stimulants, benzodiazepines, muscle relaxants, and cannabis) was determined from toxicology reports and text searches of coroner/medical examiner and law enforcement summaries. We fit multivariable logistic regression models to estimate associations between drug class and suicide method adjusting for decedent characteristics. Results: Overall prescription and illicit drugs were present in 22% of firearm deaths and 28% of suffocation deaths. Among victims with toxicology reports, over 20% tested positive for benzodiazepines. Benzodiazepines were mentioned in 4% of firearm and 5% of suffocation suicides without toxicology testing. Stimulants were more likely to occur in suffocation than firearm deaths among victims with toxicology testing (aOR = 1.44, 95% CI: 1.33-1.56) and without toxicology testing (aOR = 1.61, 95% CI: 1.31-1.98). Conclusions: Benzodiazepines were most frequently identified in both toxicology reports and narratives of suicides by firearms or suffocation. Better distinction of the presence of prescription and illicit drugs in the environment versus apparent ingestion among non-poisoning suicides are needed to inform prevention approaches.

As overdose rates increase for multiple substances, policymakers need to identify geographic patterns of substance-specific deaths. In this study, we describe county-level opioid and psychostimulant overdose patterns and how they correlate with county-level social vulnerability measures. A cross-sectional observational study, we used nationwide 2016-2018 restricted access Centers for Disease Prevention and Control county-level mortality files for 1,024 counties. We estimated quartiles of opioid and psychostimulant overdose mortality and provided estimates of their association with county-level Social Vulnerability Index (SVI) percentile. There was high opioid and psychostimulant overdose mortality in the Middle Atlantic, South Atlantic, East North Central, and Mountain regions. The Central US had the lowest opioid and psychostimulant overdose mortality rates. Counties with higher SVI scores (i.e. higher social vulnerability) were significantly more likely to experience high opioid and high psychostimulant overdose (high-high) mortality. A 10-percentile increase in SVI score was associated with a 3.1 percentage point increase in the likelihood of being a high-high county (p < 0.001) in unadjusted models and a 1.5 percentage point increase (p < 0.05) in models adjusting for region. Our results illustrated the heterogenous geographic distribution of the growing concurrent opioid and psychostimulant overdose crisis. The substantial regional variation we identified highlights the need for local data to guide policymaking and treatment planning. The association of opioid-psychostimulant overdose mortality with social vulnerability demonstrates the critical need in impacted counties for tailored treatment that addresses the complex medical and social needs of people who use both opioids and psychostimulants. [ABSTRACT FROM AUTHOR]

Context: Feedlot entry can be a period of stress for cattle due to transportation, altered diets and other influences. Stress can suppress host defence mechanisms. Innate immune stimulants, such as mycobacterial cell-wall fractions, attract attention for the primary objective of enhancing non-specific immune resistance of cattle against microbial diseases during periods of stress-induced susceptibility. These stimulants are also recognised for their capacity to modify responses of the adaptive immune system to vaccines. Aims: This study aims to evaluate the potential for mycobacterial cell-wall fractions in Amplimune® to modify adaptive immune responses to the commercial vaccines Rhinogard® (modified live bovine alphaherpesvirus-1 (BoHV-1)) and Bovilis MH + IBR® (inactivated Mannheimia haemolytica and BoHV-1) in yearling cattle during simulated feedlot induction. Methods: Fifty-four mixed-sex Angus yearling cattle were transported for 6 h on Day −1 and on Day 0. The cattle were assigned to the following six treatment groups (n = 9/group): Rhinogard plus 2 mL Amplimune, Rhinogard plus 5 mL Amplimune, Bovilis MH + IBR plus 2 mL Amplimune, Bovilis MH + IBR plus 5 mL Amplimune, Rhinogard plus 5 mL saline, and Bovilis MH + IBR plus 5 mL saline. Blood and nasal secretions were sampled at various time points following treatment and antigen-specific antibody (immunoglobulin G) responses to components of the vaccines were assessed. Interferon-γ production by peripheral blood mononuclear cells in response to BoHV-1, Concanavalin A or media only were assessed. Key results: No adverse clinical reactions were observed to administration of Amplimune and vaccines. A systemic antibody response to vaccination was observed for the Bovilis MH + IBR vaccine. Vaccine-specific antibody and cytokine responses were not modified by Amplimune. Conclusions: Amplimune can be administered at the same time as Rhinogard or Bovilis MH + IBR vaccines, without undesirable effects on specific immune responses to vaccination. Implications: The primary interest in using Amplimune is to potentiate non-specific immune defences as an alternative to antibiotics for the prevention and/or treatment of microbial diseases such as bovine respiratory disease in production animals. In view of its adjuvant-like activities, administration of Amplimune might also confer beneficial or detrimental effects on antigen-specific responses of the adaptive immune system to contemporaneous vaccination. Most vaccines do not confer immediate protection in the host; however, concurrent administration of immune stimulants may enhance or impair immune responses to those vaccines. Bovine respiratory disease (BRD) is costly for Australian cattle and, in this trial, concurrent vaccination against BRD with the stimulant Amplimune was investigated and found to have no detrimental effect on immune responses. These findings warrant further examination of the effect of Amplimune on morbidities and mortalities in feedlots. [ABSTRACT FROM AUTHOR]

Research has been inconclusive as to whether stimulant treatment causes or exacerbates sleep problems in adolescents with ADHD. This study examined sleep differences in adolescents with ADHD as a function of stimulant use. Participants were adolescents with ADHD (N = 159, ages 12–14). Parents reported on receipt of stimulant treatment (n = 92, 57.86%; n = 47 amphetamines, n = 45 methylphenidate). Adolescents wore actigraphs and completed daily diaries assessing sleep and daily use of stimulants for 2 weeks. Sleep parameters included daily-reported bedtime, sleep onset latency (SOL), sleep duration, daytime sleepiness, and difficulty waking the following morning; and actigraphy-measured sleep onset time, total time in bed, and sleep efficiency. We estimated between- and within-individual associations between stimulant medication use and sleep indices with all stimulants, after removing adolescents using sleep aids and weekend days, and as a function of stimulant type. Adolescent sleep did not differ between those receiving and not receiving stimulant treatment. Within individuals using stimulants, we largely observed no significant differences between medicated and unmedicated days, though findings were most often significant for school days only. Small effects were found indicating longer SOL, later sleep onset time, and more daytime sleepiness related to medication use. In contrast, there were slight improvements to sleep duration and sleep efficiency related to methylphenidate use, though methylphenidate was also associated with later sleep onset time and more daytime sleepiness. Given the inconsistent and small effects, findings suggest that stimulant medication may impact sleep, but does not appear to be a primary contributor to sleep problems in adolescents with ADHD. [ABSTRACT FROM AUTHOR]

Background: Polydrug use has been implicated in driving a "fourth wave" of the overdose crisis in North America, specifically through concurrent use of stimulants and opioids, especially fentanyl. In France, however, heroin has historically been and remains the easiest-to-access opioid, accounting for most drug treatment demand. Whether similar polydrug use is increasing in Western Europe remains understudied, despite severe health implications and potential inadequate public health responses. Methods: We take advantage of a nation-wide dataset containing information on all patients serviced in treatment centers in France from 2010 to 2020. We conduct Poisson regression to determine the main predictors of stimulant use among people who use heroin (PWUH) and opioids (PWUO) generally. Results: Heroin remains the primary opioid within drug treatment in France. A decreasing number of out-patients seeking treatment for heroin use has been accompanied by an increasing trend of stimulant use over time, most commonly with powder cocaine. Our results suggest a significant increase of crack cocaine use among the most vulnerable PWUH. Concurrent use of stimulants among PWUH was positively associated with use of alcohol, cannabis, unprescribed psychotropics and hallucinogens, and negatively with tobacco. Similar results were found for all in-treatment PWUO. Conclusions: Our results uncover heterogeneity in the profiles of PWUH that should be fully acknowledged to ensure better efficiency in substance use clinical practices and policy, while simultaneously drawing attention to trends in concurrent opioid-stimulant use outside North America. We advocate for an extension of the generalized risk framework and its implementation in prevention programs. [ABSTRACT FROM AUTHOR]

Many heterocyclic triazole rings and compounds containing triazole rings exhibit diverse biological activities. Heterocyclic derivatives of this class possess significant value for the discovery and development of new anticonvulsant medications as a result of successful synthesis of various triazole derivatives that hit the market for pharmaceuticals as CNS stimulants. The two isomers of triazole containing derivatives are 1,2,3-trizoles and 1,2,4-triazoles. From these two, 1, 2,4-triazole containing drugs exhibit a variety of pharmacological effects, including antimycobacterial, antitubercular, anticancer, anticonvulsant and herbicidal properties. Consequently, triazole-containing molecules function as potentially effective drug and may be useful for the design and development of new triazole derivatives that could be more efficacious and less toxic. This review summarizes data on various triazole derivatives and their significance. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) may increase the risk of suicide among children and youth, although the association between suicide risk and the combination of SSRIs with other medication such as stimulants in this population remains unclear. This study explored whether the combination of SSRIs with stimulants influenced suicide risk. Methods: A retrospective cohort study was conducted at a single children's hospital campus-based ambulatory psychiatric clinic between September 1, 2017, and September 30, 2020. Subjects were 6–21 years of age and prescribed either stimulants or stimulants and SSRIs only. The primary outcome was suicidal thoughts and behaviors (STB), defined by documented suicidal thoughts, plans, or behaviors. Firth logistic regression evaluated associations between medication class and STB. Results: Among 349 patients, the prevalence of STB was 5.7% (n = 20). In unadjusted model, patients prescribed SSRIs and stimulants had a 2.9-fold increase of STB compared to patients prescribed stimulants only, along with increasing age, male sex, and the diagnoses of anxiety and/or depression. In the final model adjusted for each of these factors, the observed association of medication regiment with STB was attenuated (odds ratio [OR]: 1.3, confidence interval [CI]: 0.3–4.9, p = 0.7). The magnitude of the adjusted association between depressive diagnosis and STB was notable (OR: 3.6, CI: 1.0–12.6, p = 0.049). Conclusions: Among patients followed in a children's hospital-based ambulatory psychiatric clinic, a combination medication regimen of SSRIs and stimulants after adjusting for genetic sex, age, anxiety diagnosis, and depression diagnosis, the observed association between STB and combination stimulant and SSRI treatment was attenuated. This finding suggests that other factors, including depression, may have contributed to the association between SSRI treatment and STB. Larger, prospective studies of the relationship between combination pharmacotherapy and suicide risk are warranted to guide clinical/pharmacological decision making and to better clarify these relationships. [ABSTRACT FROM AUTHOR]

Attention‐deficit hyperactivity disorder (ADHD) is characterized by persistent symptoms of inattention, hyperactivity, and impulsivity. Both, stimulant and nonstimulant medications have been approved for the treatment of this disorder. Several Western guidelines recommend the use of prescribed Food and Drug Administration (FDA)‐approved medications for ADHD along with parental training in behavior management and behavioral classroom intervention. In 2022, new Japanese guidelines for ADHD were issued, which recommended school environment management and psychosocial treatment as the first‐line treatment, with pharmacological treatment added as the second‐line treatment. Although Japanese guidelines, including pharmacological treatments, have been established, the guidelines and utilization of ADHD medications across Asian regions are unclear. Therefore, to appropriately evaluate the strategy of pharmacological treatments for ADHD, we investigated Asian regional guidelines for ADHD medication in children. We also reviewed the guidelines in Malaysia, Singapore, India, and the Republic of Korea and found that these guidelines differ from Western guidelines. [ABSTRACT FROM AUTHOR]

Introduction. Attention deficit and hyperactivity disorder (ADHD) is a common neurodevelopmental disorder affecting about 7% of those aged up to 12 years, 5% of teenagers and 3% of adults. It is associated with poor academic performance, substance abuse, criminality, poor social functioning and other negative outcomes. Psychotherapeutic treatment is moderately successful, whereas pharmacotherapy with stimulant medication is more efficacious and is recommended in many international guidelines. Anecdotal evidence suggests underuse of these medications in Aotearoa, New Zealand. Aim. To estimate how many patients with ADHD are prescribed psychostimulants in Aotearoa, New Zealand. Methods. National prescribing data for dexamphetamine and methylphenidate in 2022 were obtained and matched against estimated prevalence of ADHD by age. Results. There is a significant treatment gap for which inability to access firstline medication is likely to be the predominant explanation. Discussion. The data suggest failure of our health system to provide reasonable health care for a significant number of people with ADHD, and results in inequity in outcomes. New approaches are needed that will increase access to first-line medication, yet maintain appropriateness of diagnosis and limit risk of medication diversion. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect and dose‐response of methylphenidate (MP) use on the restorative treatment needs in young adults with attention deficit hyperactivity disorder. Participants and methods: This retrospective study comprises a cohort of military recruits aged 18–25 who served for 12 to 48 months between 2005 and 2017. The medical records of 213 604 participants were assessed of which: 6875 participants with ADHD who received treatment with MP, 6729 participants with ADHD who had no prescriptions for MP, and 200 000 healthy participants. The outcome was restorative treatment needs, which served as an indicator of caries: having at least one prescription for restorative treatment during the study period. Results: Frequency of prescription for restorative treatment among the treated, the untreated and the control groups was 24%, 22%, and 17%, respectively (p <.0001). On multivariate analysis, the dose‐response association between MP use and the odds of having at least one restorative treatment was confirmed (OR = 1.006 for each additional 1 gr of MP; 95% CI [1.004:1.009]) Conclusions: Participants with ADHD who receive chronic treatment with MP have higher restorative treatment needs than participants with untreated ADHD and healthy participants. Our results show that chronic MP medication among young adults leads to an elevated need for restorative treatment and implies a significant impact on oral health (OH). [ABSTRACT FROM AUTHOR]

A genetic predisposition to central nervous system (CNS) toxicity induced by antimicrobial drugs (antibiotics, antivirals, antifungals, and antiparasitic drugs) has been suspected. Whole genome sequencing of 66 cases and 833 controls was performed to investigate whether antimicrobial drug-induced CNS toxicity was associated with genetic variation. The primary objective was to test whether antimicrobial-induced CNS toxicity was associated with seventeen efflux transporters at the blood-brain barrier. In this study, variants or structural elements in efflux transporters were not significantly associated with CNS toxicity. Secondary objectives were to test whether antimicrobial-induced CNS toxicity was associated with genes over the whole genome, with HLA, or with structural genetic variation. Uncommon variants in and close to three genes were significantly associated with CNS toxicity according to a sequence kernel association test combined with an optimal unified test (SKAT-O). These genes were LCP1 (q = 0.013), RETSAT (q = 0.013) and SFMBT2 (q = 0.035). Two variants were driving the LCP1 association: rs6561297 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51–8.46]) and the regulatory variant rs10492451 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51–8.46]). No common genetic variant, HLA-type or structural variation was associated with CNS toxicity. In conclusion, CNS toxicity due to antimicrobial drugs was associated with uncommon variants in LCP1, RETSAT and SFMBT2. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17 years) ever diagnosed based on data from 2016-2019. ADHD is characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. Specific criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision assist with the diagnosis with multiple guidelines available providing non-pharmacologic and pharmacologic recommendations for the treatment of ADHD in the pediatric population. While all guidelines similarly recommend behavioral and/or stimulant therapy as first-line therapy based on age, not all stimulant products are equal. Their differing pharmacokinetic profiles and formulations are essential to understand in order to optimize efficacy and safety for patients. Additionally, new stimulant products and non-stimulant medications continue to be approved for use of ADHD in the pediatric population and it is important to know their differences in formulation, efficacy, and safety to other products currently available. Lastly, due to drug shortages, it is important to understand product similarities and differences to select alternative therapy for patients. [ABSTRACT FROM AUTHOR]

Background and Aims: There is currently no standard of care for pharmacological treatment of amphetamine‐type stimulant (ATS) use disorder (ATSUD). This systematic review with meta‐analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo‐controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD. Methods: Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random‐effect meta‐analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random‐effect meta‐analysis of continuous variables. Results: Ten RCTs (n = 561 participants) were included in the meta‐analysis. Trials studied methylphenidate (n = 7), with daily doses of 54–180 mg, and dextroamphetamine (n = 3), with daily doses of 60–110 mg, for 2–24 weeks. PPs significantly decreased end‐point craving [SMD −0.29; 95% confidence interval (CI) = −0.55, −0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85–1.01). No effect was observed for self‐reported ATS use, retention in treatment, dropout following adverse events, early‐stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79–0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention. Conclusions: Among individuals with amphetamine‐type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications. [ABSTRACT FROM AUTHOR]