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The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4′-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4′-DMAR are becoming increasingly available, yet the long-term effects are still almost unknown. In particular, no data on genotoxicity are available. Therefore, the aim of the present study was to evaluate its genotoxic potential using the "In Vitro Mammalian Cell Micronucleus Test" (MNvit) on (±)cis-4,4′-DMAR and (±)trans-4,4′-DMAR and their associations. The analyses were conducted in vitro on human TK6 cells. To select suitable concentrations for MNvit, we preliminarily evaluated cytotoxicity and apoptosis. All endpoints were analysed by flow cytometry. The results reveal the two racemates' opposite behaviours: (±)cis-4,4′-DMAR shows a statistically significant increase in micronuclei (MNi) frequency that (±)trans-4,4′-DMAR is completely incapable of. This contrast confirms the well-known possibility of observing opposite biological effects of the cis- and trans- isomers of a compound, and it highlights the importance of testing single NPSs that show even small differences in structure or conformation. The genotoxic capacity demonstrated stresses an additional alarming toxicological concern related to this NPS. Moreover, the co-treatments indicate that consuming both racemates will magnify the genotoxic effect, an aspect to consider given the unpredictability of illicit drug composition. [ABSTRACT FROM AUTHOR]

Emergent harms presented by the co-use of opioids and methamphetamine highlight the broader public health challenge of preventing and treating opioid and stimulant co-use. Development of effective therapeutics requires an understanding of the physiological mechanisms that may be driving co-use patterns, specifically the underlying neurobiology of co-use and how they may facilitate (or be leveraged to prevent) continued use patterns. This narrative review summarizes largely preclinical data that demonstrate clinically-meaningful relationships between the dopamine and opioid systems with direct implications for opioid and stimulant co-use. Synthesized conclusions of this body of research include evidence that changes in the dopamine system occur only once physical dependence to opioids develops, that the chronicity of opioid exposure is associated with the severity of changes, and that withdrawal leaves the organism in a state of substantive dopamine deficit that persists long after the somatic or observed signs of opioid withdrawal appear to have resolved. Evidence also suggests that dopamine supersensitivity develops soon after opioid abstinence and results in increased response to dopamine agonists that increases in magnitude as the abstinence period continues and is evident several weeks into protracted withdrawal. Mechanistically, this supersensitivity appears to be mediated by changes in the sensitivity, not quantity, of dopamine D2 receptors. Here we propose a neural circuit mechanism unique to withdrawal from opioid use with implications for increased stimulant sensitivity in previously stimulant-naïve or inexperienced populations. These hypothesized effects collectively delineate a mechanism by which stimulants would be uniquely reinforcing to persons with opioid physical dependence, would contribute to the acute opioid withdrawal syndrome, and could manifest subjectively as craving and/or motivation to use that could prompt opioid relapse during acute and protracted withdrawal. Preclinical research is needed to directly test these hypothesized mechanisms. Human laboratory and clinical trial research is needed to explore these clinical predictions and to advance the goal of developing treatments for opioid-stimulant co-use and/or opioid relapse prevention and withdrawal remediation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate possible trends and risk factors for overlapping stimulant and opioid prescriptions in Rhode Island (RI). METHODS: All RI residents with a stimulant prescription dispensed between April 1, 2016 and March 31, 2020 were obtained from the RI Prescription Drug Monitoring Program (PDMP). Individuals were stratified by overlapping stimulant/opioid exposure and compared by demographic and prescription characteristics. RESULTS: While stimulant prescribing remained relatively constant, the percent of individuals with an overlapping opioid prescription declined. Individuals prescribed overlapping stimulant/opioid prescriptions differed significantly as a function of age, sex, payment method, type of stimulant prescribed, and prescriber type. CONCLUSIONS: Among residents who were dispensed at least one stimulant prescription, individuals who were older, female, and on Medicare insurance were more likely to have an overlapping stimulant/opioid prescription. The RI PDMP can be used to identify trends and risk factors regarding prescribing patterns, which can inform future health policy and practice. [ABSTRACT FROM AUTHOR]

Caffeine is a psycho-active stimulant that can improve physical and cognitive performance. We systematically reviewed the evidence on the effects of acute caffeine ingestion on physiological parameters, physical and technical-skill performance during high-performance team-sport match-play. Following PRISMA guidelines, studies were identified using scientific databases (PubMed, Web-of-Science, Scopus, and SPORTDiscus) in February 2021. Of 281 results, 13 studies met inclusion, totalling 213 participants. Included studies adopted the randomised double-blinded cross-over design, involving caffeine and control conditions. In studies reporting physiological variables, responses to caffeine included higher peak (n=6/ 8 [n/ total studies measuring the variable]) and mean (n=7/ 9) heart rates, increased blood glucose (n=2/ 2) and lactate (n=2/ 2) concentrations. Improvements in physical performance were widely documented with caffeine, including greater distance coverage (n=7/ 7), high-speed distance coverage (n=5/ 7) and impact frequencies (n=6/ 8). From three studies that assessed technical-skills, it appears caffeine may benefit gross-skill performance, but have no effect, or negatively confound finer technical-skill outcomes. There is compelling evidence that ingesting moderate caffeine doses (~3 to 6 mg·kg−1) ~60 minutes before exercise may improve physical performance in team-sports, whereas evidence is presently too scarce to draw confident conclusions regarding sport-specific skill performance. [ABSTRACT FROM AUTHOR]

Objectives: Angelman syndrome is a neurogenetic disorder resulting from the loss of expression of the ubiquitin-protein ligase E3A gene on chromosome 15. Problematic behaviors including attention-deficit/hyperactivity disorder (ADHD) symptoms of hyperactivity, impulsivity and inattention are highly prevalent in Angelman syndrome. The efficacy, safety and tolerability of stimulant medications in children with Angelman syndrome for the treatment of ADHD symptoms have not been previously reported. Methods: We describe three boys with Angelman syndrome who were treated with open-label stimulant medications for ADHD symptoms. Results: Stimulant medications were highly intolerable, and treatment had to be discontinued after limited dosing in all three cases due to marked increases in hyperactivity and impulsivity along with worsened distractibility. Conclusion: The findings of this study suggest that stimulant medications may be ineffective and poorly tolerated in children with Angelman syndrome. [ABSTRACT FROM AUTHOR]

This paper analyses the effect of dosage (0.25 dm3 ha-1 or 0.50 dm3 ha-1) and time (the leaf development stage - BBCH 14-16, tuber initiation stage - BBCH 40-41, at both the leaf development stage and tuber initiation stage) of silicon-based stimulant Optysil application (200 g SiO2 and 24 g Fe in 1 dm3) on early potato yield and yield components. Optysil resulted in an increase in tuber number and tuber weight per plant. As a result, under periodic water deficits during tuber bulking, Optysil increased marketable tuber (with a diameter above 30 mm) yield by an average of 6.90 t ha-1 (50%) and under drought conditions during the potato growth period by 0.70 t ha-1 (8.6%). Under periodic water deficits during tuber bulking, the marketable tuber number per plant and marketable yield were greatest after applying 0.50 dm3 ha-1 of Optysil in the tuber initiation stage (BBCH 40-41). Under drought conditions, the most practical were two Optysil applications at 0.25 dm3 ha-1. The Optysil application improved the market value of the early potato yield by increasing the share of medium-sized tubers (with a diameter of 41-50 mm). [ABSTRACT FROM AUTHOR]

GYKI-13380 (4-[3-(cyclopentyloxy)-4-methoxybenzyl]-2-imidazolidinone) was synthesized with the idea to incorporate a phenethylamine-like structure into a hydantoin-like (or imidazolidinone) ring to create a novel appetite suppressant. In this study, GYKI-13380 was tested in rats trained to discriminate injections of either S(+)amphetamine (0.75 mg/kg, IP) or fenfluramine (1.5 mg/kg, IP) from saline in a two-lever drug discrimination task. After stable discrimination performances were attained in each group, stimulus generalization (substitution) tests were conducted with GYKI-13380 and currently marketed CNS stimulant/anorectic drugs (phentermine, (−)ephedrine, diethylpropion and phendimetrazine). The fenfluramine stimulus generalized completely to GYKI-13380, but not to S(+)amphetamine nor to the stimulant/anorectic agents. In contrast, S(+)amphetamine-stimulus generalization did not occur to fenfluramine nor GYKI-13380, but did occur to the stimulant/anorectics. Taken together, it was concluded that GYKI-13380 could be a "masked fenfluramine-like agent" that would likely be perceived by humans in drug discrimination studies as being similar to fenfluramine, but would be viewed quite differently from S(+)amphetamine or other central nervous system stimulant/anorectic drugs. [ABSTRACT FROM AUTHOR]

High-affinity monoamine transporters are targets for prescribed medications and stimulant drugs of abuse. Therefore, assessing monoamine transporter activity for candidate medications and newly-emerging drugs of abuse provides essential information for industry, academia, and public health. Radiotracer binding and uptake inhibition are the gold standard assays for determining drug–transporter interaction profiles. The combined results from such assays yield a unique biochemical fingerprint for each compound. Over time, different assay methods have been developed to assess transporter activity, and the comparability of data across various assay platforms remains largely unclear. Here, we compare the effects of six well-established stimulants in two different cell-based uptake inhibition assays, one method using adherent cells and the other using suspended cells. Furthermore, we compare the data from transfected cell lines derived from different laboratories and data reported from rat synaptosomes. For transporter inhibitors, IC50 values obtained by the two experimental methods were comparable, but using different transfected cell lines yielded disparate results. For transporter substrates, differences between the two cell lines were less pronounced but the drugs displayed different inhibition potencies when evaluated by the two methods. Our study illustrates the inherent limitations when comparing transporter inhibition data from different laboratories and stresses the importance of including appropriate control experiments with reference compounds when investigating new drugs of interest. [ABSTRACT FROM AUTHOR]

Evidence for acute amphetamine effects on behavioural impulsivity in healthy populations remains elusive and, at times, mixed. This review collates and reviews the clinical literature on the acute effects of amphetamines on measures of behavioural impulsivity in healthy adults. Randomised and placebo-controlled clinical trials that assessed behavioural impulsivity following the administration of an acute dose of amphetamine or a related psychostimulant (including amphetamine analogues and methylphenidate) were eligible for inclusion. The EBSCOHost, SCOPUS, PsychNet, Web of Science and ProQuest databases were searched from inception to 26 April 2021. Study selection, data extraction and the Cochrane risk of bias assessments were conducted by two independent reviewers. Reporting follows PRISMA guidelines, and the review was registered a priori on the PROSPERO database (Registration No: CRD42021249861). A total of 20 studies were included, comprising a total of 737 participants. Overall, results indicate that low-moderate doses of amphetamine and related psychostimulants may improve (i.e., reduce) impulsive responding without compromising performance, reflecting enhanced inhibitory control of behaviour. These effects are mild and appear most pronounced in individuals with high baseline impulsivity. This review highlights the need for greater consistency in behavioural task selection and future high-quality and well-designed studies to address current concerns around growing prescription psychostimulant use and misuse. [ABSTRACT FROM AUTHOR]

Background: Compared to heterosexual adults, lesbian, gay, and bisexual (LGB) adults have higher rates of any illicit drug use and any prescription drug misuse, yet disparities regarding specific drugs remain poorly characterized. Methods: We examined disparities by sexual identity and sex for 8 illicit and prescription drugs using 2015-2019 National Survey on Drug Use and Health data. Outcomes included past-year use/misuse of cocaine/crack, hallucinogens, inhalants, methamphetamine, heroin, prescription opioids, prescription stimulants, prescription tranquilizers/sedatives, and level of polydrug use/misuse (2 substances; 3+ substances). For each outcome, odds ratios relative to heterosexual adults of same sex were estimated using logistic regression controlling for demographics; significant estimates were interpreted as a disparity. Results: Among gay men, significant disparities were present for all drugs except prescription stimulants and heroin; inhalant use was particularly elevated. Bisexual women exhibited significant disparities for every drug examined, as did bisexual men (except heroin). Among lesbian/gay women, disparities were only present for prescription opioids and stimulants. Relative to heterosexual peers, use of 3+ substances was 3 times higher among gay men and bisexual women and 2 times higher among bisexual men. Conclusions: Consistent with minority stress theory, prevalences of illicit and prescription drug use/misuse were 2-3 times higher among LGB adults than heterosexual adults. Illicit drug use should not be perceived as only impacting gay/bisexual men – bisexual women had similar – or higher – prevalences of hallucinogen, cocaine, methamphetamine, and heroin use. Yet, in contrast to bisexual women, lesbian/gay women did not exhibit disparities for any illicit drugs. [ABSTRACT FROM AUTHOR]

Rationale: ±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg). Since this review comprised mostly of single-dose studies and an assortment of methodologies, an empirical dose-ranging study on this topic is warranted. Objectives: The current study aims to evaluate the conclusion from our systematic review that 3 mg/kg may be the threshold for MDMA-induced amnesia, and to further understand the dose-effect relationship of MDMA on behavioral assays of memory, addiction, and depression. Methods: We systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear conditioning; behavioral sensitization, conditioned place preference, and conditioned responding; and the Porsolt forced swim test in mice. Results: High doses of MDMA (≥ 3 mg/kg) produced amnesia of fear conditioning memory, some evidence of an addictive potential, and antidepressant effects, while low doses of MDMA (≤ 1 mg/kg) had no effect on these behaviors. Conclusions: The present dose-ranging study provides further evidence that 3 mg/kg is the threshold for MDMA-induced amnesia. These findings, in addition to our systematic review, demonstrate that careful selection of MDMA dose is critical. High doses (≥ 3 mg/kg) should likely be avoided due to evidence that they can produce amnesia and addiction. Conversely, there is little evidence to suggest that low doses, which are usually administered in clinical studies (approximately 1–2 mg/kg), will lead to these same adverse effects. Ultra-low doses (< 1 mg/kg) are likely even safer and should be investigated for therapeutic effects in future studies. [ABSTRACT FROM AUTHOR]

Emergent harms presented by the co-use of opioids and methamphetamine highlight the broader public health challenge of preventing and treating opioid and stimulant co-use. Development of effective therapeutics requires an understanding of the physiological mechanisms that may be driving co-use patterns, specifically the underlying neurobiology of co-use and how they may facilitate (or be leveraged to prevent) continued use patterns. This narrative review summarizes largely preclinical data that demonstrate clinically-meaningful relationships between the dopamine and opioid systems with direct implications for opioid and stimulant co-use. Synthesized conclusions of this body of research include evidence that changes in the dopamine system occur only once physical dependence to opioids develops, that the chronicity of opioid exposure is associated with the severity of changes, and that withdrawal leaves the organism in a state of substantive dopamine deficit that persists long after the somatic or observed signs of opioid withdrawal appear to have resolved. Evidence also suggests that dopamine supersensitivity develops soon after opioid abstinence and results in increased response to dopamine agonists that increases in magnitude as the abstinence period continues and is evident several weeks into protracted withdrawal. Mechanistically, this supersensitivity appears to be mediated by changes in the sensitivity, not quantity, of dopamine D2 receptors. Here we propose a neural circuit mechanism unique to withdrawal from opioid use with implications for increased stimulant sensitivity in previously stimulant-naïve or inexperienced populations. These hypothesized effects collectively delineate a mechanism by which stimulants would be uniquely reinforcing to persons with opioid physical dependence, would contribute to the acute opioid withdrawal syndrome, and could manifest subjectively as craving and/or motivation to use that could prompt opioid relapse during acute and protracted withdrawal. Preclinical research is needed to directly test these hypothesized mechanisms. Human laboratory and clinical trial research is needed to explore these clinical predictions and to advance the goal of developing treatments for opioid-stimulant co-use and/or opioid relapse prevention and withdrawal remediation.

Attention-Deficit Hyperactive Disorder (ADHD) is a neurobehavioral syndrome affecting children aged 6-17 with symptoms manifesting before age 12. ADHD presents heterogeneously and is associated with various psychiatric disorders. The cause remains elusive, but genetic and environmental factors, brain region maturation delays, and neurotransmitter dysregulation are implicated. Effective treatment requires a multi-disciplinary approach, primarily involving pharmacological and behavioral intervention. Stimulants like methylphenidate and amphetamines are first-line medications, but non-stimulants may be considered for some patients. However, stimulants face challenges related to misuse, dependence, and long-term tolerability issues. The etiology of ADHD involved genetic predisposition, environmental influences, and prenatal, perinatal, and postnatal factors. Prenatal causes encompass maternal diet, alcohol consumption, viral infections, and stress. Postnatal factors include head trauma, meningitis, toxin, nutritional deficiencies, as well as iodine deficiency and hypothyroidism. The gut microbiome's role in ADHD is emerging, influencing neurodevelopment through microbiota-gut-brain axis. Understanding these diverse etiological factors is essential for comprehensive ADHD management., (© 2024 Wiley Periodicals LLC.)

BackgroundImpulsivity has been proposed as an important factor in the initiation and maintenance of addiction. Indirect evidence suggests that some methamphetamine users report less impulsivity when they are using methamphetamine compared to when abstaining from drug use, but this hypothesis has not been directly tested.Objectives/methodsIn this study, self-reports of impulsivity were obtained from 32 methamphetamine-dependent (DSM-IV) research participants and 41 healthy control subjects, using the Barratt Impulsiveness Scale-11. The methamphetamine users were assessed during an active period of methamphetamine use, as determined through urinalysis, and again after approximately 1 week of confirmed abstinence. Control subjects likewise completed two assessments. A subset of participants also completed serial assessments of the Beck Depression Inventory (Methamphetamine Group, N = 17, Control Group, N = 38) and the Methamphetamine Withdrawal Questionnaire (Methamphetamine Group, N = 12).ResultsThere was a significant interaction of group with time on impulsivity (p = 0.044), reflecting a significant increase from the first to the second assessment in the methamphetamine users (p = 0.013), but no change among healthy control subjects. In contrast, depressive and withdrawal symptoms significantly decreased between the first and second assessments in the methamphetamine users (ps ≤0.01). Change in impulsivity in methamphetamine users was not significantly correlated with change in withdrawal or depression (ps >0.05).ConclusionsThese findings suggest that methamphetamine users report more impulsivity when abstaining from drug use, an effect that is not significantly related to methamphetamine withdrawal. Attenuation of impulsivity may reinforce continued methamphetamine use in these individuals.

ObjectivePsychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD.MethodChildren with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables.ResultsThe ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group.ConclusionCombined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD.Clinical trial registration informationSingle Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.

BackgroundCharacterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV.ObjectivesStudy aims were to investigate whether (i) methamphetamine use differs by age and HIV serostatus, and (ii) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV.MethodsThis study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment.ResultsMultivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (β = -0.16, p = 0.01) and a fewer number of days (β = -0.18, p = 0.004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e. grams per day used) was greater among the younger, relative to the older, HIV+ group (p = 0.02), and increased for both age groups following seroconversion (p < 0.001).ConclusionThese analyses indicate that although HIV serostatus may attenuate methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum.

The nonmedical use of amphetamine-type stimulants is a worldwide problem, with substantial medical and social consequences. Nonetheless, the identification of a pharmacological treatment for amphetamine use disorder remains elusive. Stimulant users exhibit neurochemical evidence of dopamine-system dysfunction as well as impulsive behaviors that may interfere with the success of treatments for their addiction. This review focuses on the potential role of dopaminergic neurotransmission in impulsivity, both in healthy individuals and chronic stimulant users who meet criteria for methamphetamine dependence. Presented are findings related to the potential contributions of signaling through dopamine D1- and D2-type receptors to self-control impulsivity in methamphetamine- dependent users. The information available points to signaling through striatal D2-type dopamine receptors as a potential therapeutic target for stimulant use disorders, but medications that target D2-type dopamine receptors have not been successful in treating stimulant-use disorders, possibly because D2-type receptors are downregulated. Other means to augment D2-type receptor signaling are therefore under consideration, and one promising approach is the addition of exercise training as an adjunct to behavioral treatment for addiction.

The nonmedical use of amphetamine-type stimulants is a worldwide problem, with substantial medical and social consequences. Nonetheless, the identification of a pharmacological treatment for amphetamine use disorder remains elusive. Stimulant users exhibit neurochemical evidence of dopamine-system dysfunction as well as impulsive behaviors that may interfere with the success of treatments for their addiction. This review focuses on the potential role of dopaminergic neurotransmission in impulsivity, both in healthy individuals and chronic stimulant users who meet criteria for methamphetamine dependence. Presented are findings related to the potential contributions of signaling through dopamine D1- and D2-type receptors to self-control impulsivity in methamphetamine- dependent users. The information available points to signaling through striatal D2-type dopamine receptors as a potential therapeutic target for stimulant use disorders, but medications that target D2-type dopamine receptors have not been successful in treating stimulant-use disorders, possibly because D2-type receptors are downregulated. Other means to augment D2-type receptor signaling are therefore under consideration, and one promising approach is the addition of exercise training as an adjunct to behavioral treatment for addiction.

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The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care. [ABSTRACT FROM AUTHOR]

Copyright of Avances is the property of Instituto de Informacion Cientifica y Tecnologica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents a multidimensional comparative analysis of apartment prices in seventeen cities in Poland from the first quarter of 2017 to the first quarter of 2021 in terms of the maintenance of economic security. Prices were analyzed in two aspects: value and dynamics of changes, referring to the first period under consideration in spatial terms (in each of the seventeen cities). The research used multidimensional comparative analyzes, such as: Chernoff faces and normalization with the use of stimulants. This, in turn, made it possible to examine the similarities and differences in the prices of 1 m2 of residential real estate in respective cities in Poland in a dynamic approach. [ABSTRACT FROM AUTHOR]

Economic security of any state is multifaceted. Affordability of basics, required for living serves are precondition for economic security of any state. The study presents a multidimensional comparative analysis of apartment sales in respective voivodships in Poland. The following dependent variables concerning apartments in sixteen voivodships were analyzed: price per m2, number of sales and its value. The dynamics indices on a constant basis and the normalization for stimulants were used for the analyzes. The results of the research were compiled on categorized bar charts, conducting the ranking, as well as indicating and outlining the level of deviation of the analyzed data adopted by the author. The conducted research clearly showed how much of an impact on the state's economy, with particular emphasis on the subject of research presented in the article, which is the apartment trade market, has a random incident, such as a pandemic, and how difficult it is to return to the conditions before Covid-19. [ABSTRACT FROM AUTHOR]

Purpose: Previous investigations have found positive effects of acute ingestion of capsules containing 4-to-9 mg of caffeine per kg of body mass on several aspects of judo performance. However, no previous investigation has tested the effectiveness of caffeinated chewing gum as the form of caffeine administration for judoists. The main goal of this study was to assess the effect of acute ingestion of a caffeinated chewing gum on the results of the special judo fitness test (SJFT). Methods: Nine male elite judo athletes of the Polish national team (23.7 ± 4.4 years, body mass: 73.5 ± 7.4 kg) participated in a randomized, crossover, placebo-controlled and double-blind experiment. Participants were moderate caffeine consumers (3.1 mg/kg/day). Each athlete performed three identical experimental sessions after: (a) ingestion of two non-caffeinated chewing gums (P + P); (b) a caffeinated chewing gum and a placebo chewing gum (C + P; ~2.7 mg/kg); (c) two caffeinated chewing gums (C + C; ~5.4 mg/kg). Each gum was ingested 15 min before performing two Special Judo Fitness Test (SJFT) which were separated by 4 min of combat activity. Results: The total number of throws was not different between P + P, C + P, and C + C (59.66 ± 4.15, 62.22 ± 4.32, 60.22 ± 4.08 throws, respectively; p = 0.41). A two-way repeated measures ANOVA indicated no significant substance × time interaction effect as well as no main effect of caffeine for SJFT performance, SJFT index, blood lactate concentration, heart rate or rating of perceived exertion. Conclusions: The results of the current study indicate that the use of caffeinated chewing gum in a dose up to 5.4 mg/kg of caffeine did not increase performance during repeated SJFTs. [ABSTRACT FROM AUTHOR]

Abstract Kratom, or Mitragyna, is a tropical plant indigenous to Southeast Asia, with unique pharmacological properties. It is commonly consumed by preparing the leaves into decoction or tea, or by grinding them into a powder. Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria, as well as stimulant properties, which together raise potential concern for dependence and addiction. Moreover, growing evidence suggests that the prevalence of kratom use is increasing in many parts of the world, raising important considerations for healthcare providers. This manuscript will discuss the most current epidemiology, pharmacology, toxicity, and management related to kratom, while seeking to provide a contemporary perspective on the issue and its role in the greater context of the opioid epidemic.

The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.

Background: Substance use disorder is characterized by long-lasting changes in reward-related brain regions, such as the nucleus accumbens. Previous work has shown that cocaine exposure induces plasticity in broad, genetically defined cell types in the nucleus accumbens; however, in response to a stimulus, only a small percentage of neurons are transcriptionally active-termed an ensemble. Here, we identify an Arc-expressing neuronal ensemble that has a unique trajectory of recruitment and causally controls drug self-administration after repeated, but not acute, cocaine exposure., Methods: Using Arc-CreER T2 transgenic mice, we expressed transgenes in Arc+ ensembles activated by cocaine exposure (either acute [1 × 10 mg/kg intraperitoneally] or repeated [10 × 10 mg/kg intraperitoneally]). Using genetic, optical, and physiological recording and manipulation strategies, we assessed the contribution of these ensembles to behaviors associated with substance use disorder., Results: Repeated cocaine exposure reduced the size of the ensemble while simultaneously increasing its control over behavior. Neurons within the repeated cocaine ensemble were hyperexcitable, and their optogenetic excitation was sufficient for reinforcement. Finally, lesioning the repeated cocaine, but not the acute cocaine, ensemble blunted cocaine self-administration. Thus, repeated cocaine exposure reduced the size of the ensemble while simultaneously increasing its contributions to drug reinforcement., Conclusions: We showed that repeated, but not acute, cocaine exposure induced a physiologically distinct ensemble characterized by the expression of the immediate early gene Arc, which was uniquely capable of modulating reinforcement behavior., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Adherence to treatment, i.e. the extent to which a patient's therapeutic engagement coincides with the prescribed treatment, is among the most important problems in mental health care. The current study investigated the influence of pairing an acute positive reinforcing dopaminergic/noradrenergic effect (methylphenidate, MPH) with a standard antidepressant on the rates of adherence to medication treatment. The primary objective of this study was to determine whether MPH + escitalopram resulted in higher rates of medication adherence relative to placebo + escitalopram. Methods: Twenty participants with moderate to severe depression were 1–1 randomized to either (1) 5 mg MPH + 10 mg escitalopram or (2) placebo + 10 mg escitalopram with the possibility for a dose increase at 4 weeks. A Bayesian analysis was conducted to evaluate the outcomes. Results: First, neither percent Pill count nor Medication Electronic Monitoring System adherence showed that MPH was superior to placebo. In fact, placebo showed slightly higher adherence rates on the primary (7.82% better than MPH) and secondary (7.07% better than MPH) outcomes. There was a less than 25% chance of MPH augmentation showing at least as good or better adherence than placebo. Second, both groups showed a significant effect of treatment on the QIDS-SR with a median effect of an 8.6-point score reduction. Third, neither subjective measures of adherence attitudes nor socio-demographic covariates had a significant influence on the primary or secondary outcome variables. Conclusions: These data do not support the use of MPH to increase adherence to antidepressant medication in individuals with moderate to severe depression. ClinicalTrials.gov identifier NCT03388164, registered on 01/02/2018. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) has a worldwide prevalence of 5.29% and stimulant medications are considered first-line treatment. Common adverse events with these medications include decreased appetite, increased sleep latency, tics, abdominal pain, and weight loss. Lisdexamfetamine dimesylate (LDX) is a stimulant used for treating ADHD and may lead to gastrointestinal, among other adverse effects. In this report, we present a case of constipation and retention of LDX capsules in the gastrointestinal tract. An 11-year-old male with a diagnosis of ADHD was being treated with once daily LDX 30 mg in our clinic. After about ten weeks of treatment, he was brought to an emergency department due to epigastric pain and constipation. An abdominal X-ray was significant for the presence of approximately 20 capsules in the large intestine. He was admitted to the pediatric gastroenterology service. Following management with two saline enemas, fewer capsules were seen on repeat X-ray. The patient was observed overnight, advised to discontinue LDX and discharged home in a stable condition. LDX may be associated with constipation and retention of intact capsules in the gastrointestinal tract. Further research is warranted to exclude the risk of sympathomimetic toxidrome if intact LDX capsules simultaneously disintegrate in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Objectives: To study the safety and efficacy of the long-acting methylphenidate formulation PRC-063 in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Adolescents 12 to ≤17 years who met Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for ADHD and had a baseline ADHD Rating Scale DSM-5 (ADHD-5-RS) score ≥24 participated in a randomized, double-blind, placebo-controlled, fixed-dose, parallel-group study. Participants were randomized 1:1:1:1:1 to receive placebo or one of four doses of PRC-063 once daily for 4 weeks. The primary endpoint was change from baseline in least-squares mean clinician-rated ADHD-5-RS total score for PRC-063 (all doses combined) versus placebo. Other efficacy assessments included Conners third Edition: Self-Report (C3SR) and Clinical Global Impression-Improvement (CGI-I). A subset of double-blind study participants entered a subsequent open-label, dose-optimized study. Safety outcomes in both studies included treatment-emergent adverse events (TEAEs). Results: Three hundred fifty-four participants were included in the primary analysis. The least-squares mean change from baseline in ADHD-5-RS total score was -15.17 for PRC-063 versus -10.98 for placebo (least-squares mean difference -4.2, p = 0.0067). For individual PRC-063 doses, improvements in ADHD-5-RS total score versus placebo were significant for 45 mg (p = 0.0155) and 70 mg (p = 0.0401), but not for 25 or 85 mg. A significant improvement for PRC-063 versus placebo was recorded for C3SR Inattention (p = 0.0168), but not for the other C3SR subscales. About 52.7% of participants randomized to PRC-063 were responders based on CGI-I versus 32.4% of those randomized to placebo (p = 0.0004). Further improvements in ADHD symptoms based on ADHD-5-RS were observed from 1 month through 6 months of open-label treatment (p < 0.0001). There were two serious adverse events (both during the open-label study), one of which (aggressive behavior) was assessed as related to study drug. The only TEAEs that occurred in >10% of participants during double-blind treatment were decreased appetite (20.1%) and headache (15.0%). Most TEAEs were of mild or moderate severity. Conclusion: PRC-063 significantly improved ADHD symptomatology in adolescents. It was generally well tolerated, with an AE profile consistent with other long-acting stimulants. NCT02139111 and NCT02168127. [ABSTRACT FROM AUTHOR]

Objective: To examine prevalence of past‐month prescription drug misuse (PDM) and alcohol co‐ingestion and its correlates in adults age 50 or older. Methods: Data were from the 2015–2018 US National Survey on Drug Use and Health (n = 35,190). PDM‐alcohol co‐ingestion was defined as prescription opioid, tranquilizer/sedative, or stimulant misuse while "drinking alcohol or within a couple of hours of drinking." Co‐ingestion prevalence was estimated, and logistic and negative binomial regressions examined the sociodemographic, physical health, mental health, substance use, and substance use disorder (SUD) correlates of co‐ingestion. Results: Over 344,000 adults aged 50 years or older (0.3%) engaged in past‐month PDM‐alcohol co‐ingestion, or 27.4% of those with past‐month PDM. Past‐month co‐ingestion was linked to greater past‐month alcohol use frequency and elevated adjusted odds ratios (aORs) for all examined substance use outcomes (e.g., non‐PDM SUD aOR = 21.8; 49.7% prevalence rate). The aOR for suicidal ideation was 506% higher in those with co‐ingestion than those without past‐year PDM. Conclusions: US adults aged 50 years or older with past‐month PDM‐alcohol co‐ingestion are at high risk for SUD and concerning mental health symptoms. Screening for mental health and substance use treatment is warranted among aging adults with signs of PDM, especially involving co‐ingestion. [ABSTRACT FROM AUTHOR]

Purpose: Emergency department syndromic surveillance and hospital discharge data have been used to detect and monitor nonfatal drug overdose, yet few studies have assessed the differences and similarities between these two data sources.Methods: The Centers for Disease Control and Prevention Drug Overdose Surveillance and Epidemiology system data from 14 states were used to compare these two sources at estimating monthly overdose burden and trends from January 2018 through December 2019 for nonfatal all drug, opioid-, heroin-, and stimulant-involved overdoses.Results: Compared to discharge data, syndromic data captured 13.3% more overall emergency department visits, 67.8% more all drug overdose visits, 15.6% more opioid-involved overdose visits, and 78.8% more stimulant-involved overdose visits. Discharge data captured 18.9% more heroin-involved overdoses. Significant trends were identified for all drug (Average Monthly Percentage Change [AMPC]=1.1, 95% CI=0.4,1.8) and stimulant-involved overdoses (AMPC=2.4, 95% CI=1.2,3.7) in syndromic data; opioid-involved overdoses increased in both discharge and syndromic data (AMPCDischarge=0.9, 95% CI=0.2,1.7; AMPCSyndromic=1.9, CI=1.1,2.8).Conclusions: Results demonstrate that discharge data may be better for reporting counts, yet syndromic data are preferable to detect changes quickly and to alert practitioners and public health officials to local overdose clusters. These data sources do serve complementary purposes when examining overdose trends. [ABSTRACT FROM AUTHOR]

Rationale: Misuse of dextroamphetamine occurs in work and recreational contexts. While acute drug effects broadly predict abuse liability, few studies have considered the relationship between acute effects and context. Objectives: This study examined how individual differences in acute effects of dextroamphetamine relate to desire to take dextroamphetamine again in different contexts. Methods: This secondary analysis used data from healthy adults with no history of moderate-to-severe substance use disorder, who received oral doses of placebo and dextroamphetamine (10 and 20 mg) over 3 sessions under double-blind, randomized conditions. Subjects rated subjective effects and completed reward-related behavioral tasks. Subjects rated their desire to take dextroamphetamine again in hypothetical work and recreational contexts. Multilevel models examined within-subjects change scores (10 mg-placebo; 20 mg-placebo) to determine how subjective effects and behavioral outcomes predicted desire to take dextroamphetamine again for work versus recreation. Results: Subjects reported more desire to take 20 mg dextroamphetamine again for work than for recreation. At 20 mg, there was an interaction between context and liking/wanting, such that liking/wanting predicted desire to use dextroamphetamine for work only. There was also an interaction at 20 mg between context and psychomotor speed, such that psychomotor speed predicted interest in using dextroamphetamine for recreation only. Conclusions: We found that positive subjective effects predicted desire to use dextroamphetamine again for work, while increased motor effects predicted desire to use dextroamphetamine recreationally. Hedonic effects may be perceived as advantageous when working, while increased physical energy may be preferred during recreation, suggesting that context of intended use is important when examining abuse liability. [ABSTRACT FROM AUTHOR]

Introduction: This paper aims to describe cocaine use, markets and harms in Australia from 2003 to 2019. Methods: Outcome indicators comprised prevalence of use from triennial household surveys; patterns of use from annual surveys of sentinel samples who use stimulants; and cocaine‐related seizures, arrests, hospitalisations, deaths and treatment episodes. Bayesian autoregressive time‐series analyses were conducted to estimate trend over time: Model 1, no change; Model 2, constant rate of change; and Model 3, change over time differing in rate after one change point. Results: Past‐year population prevalence of use increased over time. The percentage reporting recent use in sentinel samples increased by 6.1% (95% credible interval [CrI95%] 1.2%,16.9%; Model 3) per year from around 2017 (48%) until the end of the series (2019: 67%). There was a constant annual increase in number of seizures (count ratio: 1.1, CrI95% 1.1,1.2) and arrests (1.2, CrI95% 1.1,1.2), and percentage reporting cocaine as easy to obtain in the sentinel samples (percent increase 1.2%, CrI95% 0.5%,1.8%; Model 2). Cocaine‐related hospitalisation rate increased from 5.1 to 15.6 per 100 000 people from around 2011–2012 to 2017–2018: an annual increase of 1.3 per 100 000 people (CrI95% 0.8,1.8; Model 3). While the death rate was low (0.23 cocaine‐related deaths per 100 000 people in 2018; Model 2), treatment episodes increased from 3.2 to 5.9 per 100 000 people from around 2016–2017 to 2017–2018: an annual increase of 2.9 per 100 000 people (CrI95% 1.6,3.7; Model 3). Discussion and Conclusions: Cocaine use, availability and harm have increased, concentrated in recent years, and accompanied by increased treatment engagement. [ABSTRACT FROM AUTHOR]

Bayesian ideal observer models quantify individuals' context- and experience-dependent beliefs and expectations about their environment, which provides a powerful approach (i) to link basic behavioural mechanisms to neural processing; and (ii) to generate clinical predictors for patient populations. Here, we focus on (ii) and determine whether individual differences in the neural representation of the need to stop in an inhibitory task can predict the development of problem use (i.e. abuse or dependence) in individuals experimenting with stimulants. One hundred and fifty-seven non-dependent occasional stimulant users, aged 18-24, completed a stop-signal task while undergoing functional magnetic resonance imaging. These individuals were prospectively followed for 3 years and evaluated for stimulant use and abuse/dependence symptoms. At follow-up, 38 occasional stimulant users met criteria for a stimulant use disorder (problem stimulant users), while 50 had discontinued use (desisted stimulant users). We found that those individuals who showed greater neural responses associated with Bayesian prediction errors, i.e. the difference between actual and expected need to stop on a given trial, in right medial prefrontal cortex/anterior cingulate cortex, caudate, anterior insula, and thalamus were more likely to exhibit problem use 3 years later. Importantly, these computationally based neural predictors outperformed clinical measures and non-model based neural variables in predicting clinical status. In conclusion, young adults who show exaggerated brain processing underlying whether to 'stop' or to 'go' are more likely to develop stimulant abuse. Thus, Bayesian cognitive models provide both a computational explanation and potential predictive biomarkers of belief processing deficits in individuals at risk for stimulant addiction.

BackgroundOne of the most common causes of death among homeless and unstably housed women is acute intoxication where cocaine is present. While correlates of stimulant use have been determined in prior research, few studies have assessed risk factors of use specifically in this high-risk population.MethodsWe sampled biological women with a history of housing instability from community-based venues to participate in a cohort study. Baseline and 6-month follow-up data were used to determine the relative risk of stimulant use (crack cocaine, powder cocaine or methamphetamine) among individuals who did not use at baseline.ResultsAmong 260 study participants, the median age was 47 years, 70% were women of color; 47% reported having unmet subsistence needs and 53% reported abstinence from stimulants at baseline. In analyses adjusting for baseline sociodemographics and drug treatment, the risk of using stimulants within 6 months was significantly higher among women who reported recent sexual violence (Adjusted Relative Risk [ARR]=4.31; 95% CI:1.97-9.45), sleeping in a shelter or public place (ARR=2.75; 95% CI:1.15-6.57), and using unprescribed opioid analgesics (ARR=2.54; 95% CI:1.01-6.38).ConclusionWe found that almost half of homeless and unstably housed women used stimulants at baseline and 14% of those who did not use began within 6 months. Addressing homelessness and sexual violence is critical to reduce stimulant use among impoverished women.

ObjectiveTo describe the long-term psychopharmacological treatment of children first diagnosed with attention-deficit/hyperactivity disorder (ADHD) as preschoolers.MethodIn a systematic, prospective, naturalistic follow-up, 206 (68.0%) of the 303 children who participated in the Preschool ADHD Treatment Study (PATS) were reassessed 3 years (mean age 7.4 years) and 179 (59.1%) were reassessed 6 years (mean age 10.4 years) after completion of the controlled study. Pharmacotherapy and clinical data were obtained from the parents. Pharmacotherapy was defined as use of a specific class of medication for at least 50% of the days in the previous 6 months.ResultsAt year 3, a total of 34.0% of the participants were on no pharmacotherapy, 41.3% were on stimulant monotherapy, 9.2% were on atomoxetine alone or with a stimulant, 8.3% were on an antipsychotic usually together with a stimulant, and the remaining 7.2% were on other pharmacotherapy; overall, 65.0% were on an indicated ADHD medication. At year 6, a total of 26.8% of the participants were on no pharmacotherapy, 40.2% were on stimulant monotherapy, 4.5% were on atomoxetine alone or with a stimulant, 13.4% were on an antipsychotic, and 15.1% were on other pharmacotherapy; overall, 70.9% were on an indicated ADHD medication. Antipsychotic treatment was associated with more comorbidity, in particular disruptive behavior disorders and pervasive development disorders, and a lower level of functioning.ConclusionIn this study, the long-term pharmacotherapy of preschoolers with ADHD was heterogeneous. Although stimulant medication continued to be used by most children, about 1 child in 4 was off medication, and about 1 in 10 was on an antipsychotic.

BackgroundExercise influences drug craving and consumption in humans and drug self-administration in laboratory animals, but the effects can be variable. Improved understanding of how exercise affects drug intake or craving would enhance applications of exercise programs to human drug users attempting cessation.MethodsRats were trained in the intravenous self-administration (IVSA) of D-methamphetamine (METH; 0.05 mg/kg/inf), 3,4-methylenedioxymethamphetamine (MDMA; 0.5 mg/kg/inf) or methylone (0.5 mg/kg/inf). Once IVSA was established, the effect of ∼ 22 h of wheel access in the home cage on subsequent drug taking was assessed in a two cohort crossover design.ResultsProvision of home cage wheel access during the day prior to IVSA sessions significantly decreased the self-administration of METH, MDMA and methylone. At the individual level, there was no correlation between the amount a rat used the wheel and the size of the individual's decrease in drug intake.ConclusionsWheel access can reduce self-administration of a variety of psychomotor stimulants. It does so immediately, i.e., without a need for weeks of exercise prior to drug access. This study therefore indicates that future mechanistic investigations should focus on acute effects of exercise. In sum, the results predict that exercise programs can be used to decrease stimulant drug use in individuals even with no exercise history and an established drug taking pattern.

Purpose Previous investigations have found positive effects of acute ingestion of capsules containing 4-to-9 mg of caffeine per kg of body mass on several aspects of judo performance. However, no previous investigation has tested the effectiveness of caffeinated chewing gum as the form of caffeine administration for judoists. The main goal of this study was to assess the effect of acute ingestion of a caffeinated chewing gum on the results of the special judo fitness test (SJFT). Methods Nine male elite judo athletes of the Polish national team (23.7 ± 4.4 years, body mass: 73.5 ± 7.4 kg) participated in a randomized, crossover, placebo-controlled and double-blind experiment. Participants were moderate caffeine consumers (3.1 mg/kg/day). Each athlete performed three identical experimental sessions after: (a) ingestion of two non-caffeinated chewing gums (P + P); (b) a caffeinated chewing gum and a placebo chewing gum (C + P; ~2.7 mg/kg); (c) two caffeinated chewing gums (C + C; ~5.4 mg/kg). Each gum was ingested 15 min before performing two Special Judo Fitness Test (SJFT) which were separated by 4 min of combat activity. Results The total number of throws was not different between P + P, C + P, and C + C (59.66 ± 4.15, 62.22 ± 4.32, 60.22 ± 4.08 throws, respectively; p = 0.41). A two-way repeated measures ANOVA indicated no significant substance × time interaction effect as well as no main effect of caffeine for SJFT performance, SJFT index, blood lactate concentration, heart rate or rating of perceived exertion. Conclusions The results of the current study indicate that the use of caffeinated chewing gum in a dose up to 5.4 mg/kg of caffeine did not increase performance during repeated SJFTs.

To evaluate whether cognitive performance in adults with active methamphetamine use (MA-ACT) differs from cognitive performance in adults in remission from MA use disorder (MA-REM) and adults without a history of substance use disorder (CTLs). MA-ACT (n = 36), MA-REM (n = 48), and CTLs (n = 62) completed the Neuropsychological Assessment Battery (NAB). The MA-ACT group did not perform significantly worse than CTLs on any NAB Index. The MA-REM group performed significantly (p < 0.050) worse than CTLs on the NAB Memory Index. The MA-ACT group performed significantly better than CTLs and the MA-REM group on the Executive Functions Index. Some cognitive deficits are apparent during remission from MA use, but not during active use; this may result in clinical challenges for adults attempting to maintain recovery and continue with treatment. [ABSTRACT FROM AUTHOR]

Mixing alcohol (ethanol) with caffeinated beverages continues to be a common and risky practice. Energy drinks are one type of caffeinated beverage that may be especially problematic when used as mixers, due to their relatively high caffeine content in combination with their highly sweetened flavor profile. The present study used a mouse model of limited-access drinking and lickometer circuitry to examine the effects of an energy drink anid its caffeine content on ethanol consumption. Predictably, the highly sweetened energy drink significantly increased ethanol intake compared to a plain ethanol solution (6.34 ± 0.2 vs. 5.01 ± 0.3 g/kg; Cohen's d = 1.79). Interestingly, adulterating a plain ethanol solution with the same concentration of caffeine (without sweetener) found in the energy drink also increased ethanol intake (5.47 ± 0.3 vs. 4.11 ± 0.3 g/kg; Cohen's d = 1.4). A lower concentration of caffeine was without effect on ethanol drinking. Interestingly, plain caffeine solutions at both tested concentrations provoked high numbers of bottle contacts, indicating that the mice found the solution palatable. These findings suggest that altering the bitterness profile of an ethanol solution with the addition of caffeine can increase intake in a similar manner as sweetening the solution. Further, the findings underscore the importance of taste in motivating ethanol consumption and the potential role that caffeine can have in this process. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of a 16-hr multilayer-release methylphenidate (PRC-063) in a community-based adult ADHD population. Method: In a double-blind study, 375 participants were randomized to one of four fixed doses of PRC-063 or placebo. The primary outcome was the ADHD-Rating Scale-5 (RS). The first 50% of double-blind completers were invited to participate in a 6-month dose-optimized open-label study to assess response and safety. Results: In total, 333 participants completed the double-blind trial; 184 entered the open-label study. PRC-063 produced greater symptom reduction in ADHD-RS-5 total score from baseline compared with placebo in the double-blind study (least-square [LS] mean = −4.7 [−7.7, −1.6], p =.003). The most frequent adverse events were headache, insomnia, and decreased appetite. No significant sleep quality impact was observed (p =.123). Significant improvements in ADHD-RS-5 scores from baseline continued through the open-label study (p <.0001), coincident with dose optimization. Conclusion: PRC-063 was well tolerated and significantly improved ADHD symptomatology in adults. [ABSTRACT FROM AUTHOR]

Substance abuse is a major healthcare issue with effects on all aspects of patient care, including trauma. A large percentage of trauma patients have a positive drug screen, and acute and chronic abuse have impacts both on the acute and long-term management of these patients. This report is the first of a two-part series and focuses on stimulants and substances with sympathomimetic properties, with particular attention to the impact on the trauma patient. [ABSTRACT FROM AUTHOR]