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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]

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]

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]

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]

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]

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.

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]

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]

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]

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]

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]

This study examined the prevalence and correlates of intimate partner violence (IPV) among a cohort of racial/ethnically diverse men who have sex with men (MSM) in Los Angeles. An ongoing longitudinal cohort study of MSM in Los Angeles, constructed by design so half of the participants use substances (SU) and half are persons living with HIV, provided data. Data collection occured between 2014 and 2020. At semiannual study visits, participants completed a computer-assisted self-interview which included questions on substance use (past 6 months) and experiences of IPV (past 12 months). The criterion variable was reported physical and sexual IPV. Multivariable models generalized estimating equations (GEE) estimated associations between reported SU and physical and sexual IPV, adjusting for repeated measurement and confounders. In total, 557 persons (2,962 visits) contributed to the analysis; the median baseline age was 30 years (interquartile range: 28.0–39.0). The prevalence of IPV in the past 12 months was 22.3%, with 18.3% reporting physical and 10.2% reporting sexual IPV across study visits. Stimulant use prevalence was higher among those who reported IPV compared to those who did not (68% vs. 42.1%; p <.001); cannabis use prevalence was lower among those reporting IPV (42.3% vs. 49% respectively; p <.001). Adjusted analysis showed reported stimulant use associated with greater odds of physical IPV (adjusted odds ratio [aOR] = 2.0; 95% confidence interval [CI] [1.4, 2.8], p <.001) but not sexual IPV (aOR = 1.3; 95% CI [0.8, 2.0], p =.332). Models stratified by HIV status yielded similar results. Findings showed a high prevalence of past-year IPV experiences among MSM in Los Angeles. Findings highlight links between SU and IPV and underscore a significantly increased likelihood of IPV for MSM in Los Angeles who report current methamphetamine use. This study provides evidence to support universal IPV screening and to make available safety resources at all points where MSM seek healthcare. [ABSTRACT FROM AUTHOR]

Non-medical use (NMU) and diversion of prescription stimulants are prevalent on college campuses. Diversion represents a primary source of acquisition for NMU among young adults. This study examined relationships between stigmatizing beliefs related to NMU and diversion of stimulant medications and engagement in these behaviors, as well as how such perceptions are associated with indicators of psychological distress among those who engage in these behaviors. Young adults (N = 384) were recruited from a large US university to participate in this cross-sectional electronic survey-based study. Relationships between stigma variables and NMU and diversion were assessed. Among those who engage in NMU and diversion, we tested relationships between stigma variables and indicators of psychological distress, using validated instruments. Perceived social and personal stigmatic beliefs did not significantly predict NMU. However, perceived social and personal stigma of diversion significantly reduced diversion likelihood. For NMU, associations were found between stigma variables and indicators of psychological distress. Markedly, we found that as stigmatic perceptions of NMU increased, so did depressive, anxiolytic, and suicidal symptomatology among those who engage in NMU. Stigmatization does not deter NMU; however, stigmatization is positively associated with psychological harm among those who engage in NMU. Interventions should be developed to reduce stigmatization in order to improve psychological health among those who engage in NMU. Stigmatic perceptions of diversion were not predictive of psychological harm, though they are negatively associated with diversion behavior. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

Introduction: There is media concern over students using prescription stimulants as "cognitive enhancers" to try and improve their academic performance. However, there is limited evidence about the prevalence of this behaviour in the United Kingdom, or whether it has increased in recent years. Methods: We review survey studies on students' use of cognitive enhancers. Results: Overall reported use is low, with some inconclusive evidence that it is increasing. Use of modafinil appears to be higher than that of methylphenidate or dexamphetamine. Conclusion: There is a clear need for large‐scale research in this area, using representative sampling and survey methods that protect student anonymity. [ABSTRACT FROM AUTHOR]

The potential benefits of drug repurposing have gained attention as an alternative to developing de novo drugs. The potential of using central nervous system (CNS) drugs as anticancer drugs has been explored in several types of human cancers, such as breast and colon cancer, among others. Here, we examine the effect of the CNS drugs sertraline, paroxetine, and chlorpromazine on human squamous carcinoma cells of the bladder (UM-UC-5). After exposing UM-UC-5 cells to increased concentrations of each drug for 48 h, we assessed their metabolic activity using an MTT assay. Based on those results, we calculated cell viability and the half-maximal inhibitory concentration (IC50) values. The results suggest that the CNS drugs were effective against UM-UC-5 in the order of potency of sertraline > chlorpromazine > paroxetine. Interestingly, sertraline was more potent than 5-fluorouracil (5-FU), a widely used anticancer drug. This study demonstrated, for the first time, the promising anticancer activity of CNS drugs on human bladder cancer cells in vitro and supports the repurposing of CNS drugs to improve cancer treatment. Nevertheless, further studies are necessary to understand their mechanism of action and in vivo activity. [ABSTRACT FROM AUTHOR]

The efficacy and tolerability of psychotropic medications can vary significantly among children and adolescents, and some of this variability relates to pharmacogenetic factors. Pharmacogenetics (PGx) in child and adolescent psychiatry can potentially improve treatment outcomes and minimize adverse drug reactions. This article reviews key pharmacokinetic and pharmacodynamic genes and principles of pharmacogenetic testing and discusses the evidence base for clinical decision-making concerning PGx testing. This article reviews current guidelines from the United States Food and Drug Administration (FDA), the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Dutch Pharmacogenetics Working Group (DPWG) and explores potential future directions. This review discusses key clinical considerations for clinicians prescribing psychotropic medications in children and adolescents, focusing on antidepressants, antipsychotics, stimulants, norepinephrine reuptake inhibitors, and alpha-2 agonists. Finally, this review synthesizes the practical use of pharmacogenetic testing and clinical decision support systems. [ABSTRACT FROM AUTHOR]

The article focuses on treatments for unipolar major depressive disorder (MDD) and attention-deficit/hyperactivity disorder (ADHD). Topics discussed include the first step in the treatment of patients with depression and with partial or no response to current treatments, novel agents for the treatment of MDD, and disorders in clinical trials assessing the benefits of psilocybin.

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]

A systematic review and meta‐analysis of studies involving adults with attention‐deficit hyperactivity disorder (ADHD) has found small or no benefit from stimulant doses that exceed levels recommended in regulatory guidelines. Unlicensed doses of methylphenidate or amphetamines also were found to increase risk of treatment dropout due to adverse events. Results of the systematic review and meta‐analysis were published online Oct. 25, 2023, in JAMA Psychiatry.. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes. Methods: This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis). Discussion: We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release. Trial registration: ClinicalTrials.govNCT05842330. Registered on June 5, 2023. Kofam.ch SNCTP000005388. Registered on July 17, 2023. [ABSTRACT FROM AUTHOR]

We reviewed literature examining substance use among sexual and gender minorities (SGM) living in the former Soviet Union (USSR) nations Searches were conducted across five databases (PubMed, SocINDEX, CINAHL, PscyInfo, LGBTQ + Source) to identify peer-reviewed literature. Across 19 studies, high hazardous substance use prevalence was documented. Substance use was correlated with (a) sexual health and behaviors and (b) mental wellbeing and the use of other substances. We discuss minority stress implications and challenges presented by the paucity of evidence in the literature examining substance use among SGM women and SGM living in countries unrepresented in reviewed studies. [ABSTRACT FROM AUTHOR]

Background: The efficacy of structured physical exercise (SPE) has been examined in empirical studies to treat attention deficit hyperactivity disorder (ADHD). This review aimed (i) to systematically review and quantify the effects of SPE on ADHD symptomology and executive function (primary outcomes) and on physical health, physical fitness and mental health issues (secondary outcomes) in children/adolescents with ADHD; (ii) to evaluate the study quality and explore moderation of the effects of SPE; and (iii) to summarize the design of SPE interventions. Methods: An extensive literature search in the databases of PubMed, Web of Science and EBSCOhost was conducted to identify eligible intervention studies for meta‐analysis. A descriptive account of the features of the studies is provided, including assessment of risk/quality (ROB‐2/ROBINS‐I). Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated with random effects models to compare post‐intervention effects. Results: A total of 18 studies were included in the review. The majority of the studies examined the effects of SPE lasting for 3–12 weeks. Assessment of bias/quality indicated half of the included studies as high quality. The meta‐analysis (pooled n = 627) revealed that SPE had a positive effect on primary and secondary outcomes, that is, inattention (SMD = −1.79), executive function (SMD = 2.19), physical fitness (SMD = 1.39) and mental health issues (SMD = −0.89). Subgroup analysis showed that long‐term practice of SPE, featured/tailored SPE, non‐Chinese participants, taking methylphenidate and study with low quality had larger effects. Conclusions: There is emerging evidence that SPE is a promising option to enhance symptom management and physical/mental health in children/adolescents with ADHD. [ABSTRACT FROM AUTHOR]

Objective: Theory of mind (ToM) denotes the ability to understand the mental state of others and perceive their unique beliefs and emotions. In this study, we compared ToM between individuals with major depressive disorder (MDD) and stimulant-induced depressive disorder (SIDD). Method: This cross-sectional, causal-comparative study included patients with MDD or SIDD admitted to Ostad Moharary Neuropsychiatric Hospital between January and June 2022. Each diagnosis was confirmed through a semi-structured interview conducted by a single attending psychiatrist according to the DSM-5 criteria. After consecutive sampling of 110 individuals, 51 patients completed the study in each group. Demographic characteristics were recorded, and the Persian version of the revised Reading the Mind in the Eyes Test (RMET) was used to evaluate ToM. Statistical analysis was performed using SPSS v.25, employing the t-test, chi-squared test, linear regression, and analysis of covariance (ANCOVA). Results: Our analysis included 102 subjects (65.7% male) with a mean age of 35.17 ± 7.54 years. The two groups were similar in age, gender, marital status, working status, occupation, economic class, and ethnicity (P > 0.05). The RMET scores were 12.94 ± 4.03 and 11.86 ± 3.15 in the MDD and SIDD groups, respectively (P = 0.135). Almost all patients had low RMET scores (< 22); only two individuals in the MDD group achieved normal scores (22-30). ANCOVA revealed no significant confounding effects between the independent variables. Furthermore, regression analysis revealed that the level of education had a significant linear relationship (β= 0.249) with the RMET score (P = 0.021). Conclusion: Hospitalized patients with MDD and SIDD have similar ToM deficits, as measured by the RMET. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). Design: This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP‐NX) and extended‐release naltrexone (XR‐NTX). Setting: Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. Participants: A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non‐Hispanic White. Measurements The primary outcome was first self‐reported day of non‐prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time‐line follow‐back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self‐reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. Findings Forty‐seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80–12.50, P < 0.001] and over a 7‐day period (aHR = 1.27 for each additional day, CI = 1.18–1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05–5.39, P = 0.044). Conclusions: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non‐prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended‐release naltrexone. [ABSTRACT FROM AUTHOR]

In their recent examination of the Monitoring the Future (MTF) data, McCabe et al. (Journal of Child Psychology and Psychiatry, 2023) address the complex, longstanding, and clinically valuable questions of whether and how stimulant medication treatment for adolescents with ADHD relates to their risk for substance use. Here, we expand on the authors' interpretations of their nuanced findings of increased risk for illicit stimulant use and non‐prescribed stimulant medication use for youth with later age of medication treatment initiation and shorter treatment duration. We particularly focus on highlighting tangible clinical implications, and we recommend ways future research can build on the authors' findings to further clarify this important issue. [ABSTRACT FROM AUTHOR]

Background: To assess whether age of onset and duration of stimulant therapy for attention‐deficit/hyperactivity disorder (ADHD) are associated with cocaine, methamphetamine, and prescription stimulant misuse during adolescence. Methods: Nationally representative samples of US 10th and 12th grade students (N = 150,395) from the Monitoring the Future study were surveyed via self‐administered questionnaires from 16 annual surveys (2005–2020). Results: An estimated 8.2% of youth received stimulant therapy for ADHD during their lifetime (n = 10,937). More than one in 10 of all youth reported past‐year prescription stimulant misuse (10.4%)—past‐year cocaine (4.4%) and methamphetamine (2.0%) use were less prevalent. Youth who initiated early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years) did not have significantly increased adjusted odds of cocaine or methamphetamine use relative to population controls (ie, non‐ADHD and unmedicated ADHD youth). Youth who initiated late stimulant therapy for ADHD (≥10 years old) and for short duration (<1 year) had significantly higher odds of past‐year cocaine or prescription stimulant misuse in adolescence than those initiating early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years). Youth who initiated late stimulant therapy for ADHD (≥10 years) for short duration (<1 year) had significantly higher odds of past‐year cocaine, methamphetamine, and prescription stimulant misuse versus population controls during adolescence. No differences in past‐year cocaine, methamphetamine, and prescription stimulant misuse were found between individuals who only used non‐stimulant therapy for ADHD relative to youth who initiated early stimulant therapy (≤9 years old) and for long duration (≥6 years). Conclusions: An inverse relationship was found between years of stimulant therapy and illicit and prescription stimulant misuse. Adolescents with later initiation and/or shorter duration of stimulant treatment for ADHD should be monitored for potential illicit and prescription stimulant misuse. [ABSTRACT FROM AUTHOR]

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AbstractBackgroundObjectiveMethodsResultsConclusionsWhile FDA-approved treatments exist for opioid use disorder, none are available for stimulant use disorder. Kratom (Mitragyna speciosa), an unregulated plant-derived substance with known opioid- and stimulant-like effects, has been used to self-treat opioid use disorder; however, its use in relation to stimulant use disorder has not been described.To understand whether and how individuals use kratom to self-treat stimulant use disorder.Using a commercially available social listening platform, 3,820 publicly available social media posts published between January 1, 2020, and June 21, 2021, were reviewed for relevance to kratom and stimulant discontinuation. Manual qualitative thematic analysis was conducted on relevant data.Among the 398 relevant posts that discussed using kratom to discontinue stimulants, motivations and methods varied considerably. Posts predominantly identified benefits but also negative outcomes of kratom use. Some justified it as necessary despite consequences, while others reported a desire to quit.Although there is some awareness that kratom is used to self-treat opioid use disorder, its use to treat stimulant use disorder is more novel. In the absence of approved treatments, kratom was viewed as a natural and safe way to quit stimulants. Despite some reported success, this study shows self-treatment may pose significant risks, including kratom addiction and physical dependence. Healthcare practitioners, researchers, and public health professionals may benefit from understanding motivations for kratom use, associated benefits and risks, and the importance of discussing kratom use with patients/clients who have stimulant use disorder. [ABSTRACT FROM AUTHOR]

With rising therapeutic use worldwide, prescription stimulants are increasingly implicated in poisonings. Most of the limited research on stimulant poisoning focuses on illicit amphetamines. We aimed to investigate the clinical effects of intentional prescription stimulant poisoning. This is a retrospective review of hospitalised patients referred to a Poisons Information Centre and a toxicology unit following intentional exposures to prescription stimulants (dexamfetamine, lisdexamfetamine and methylphenidate) from 1 January 2018 through 31 December 2021. Patients were identified from both units' databases and data extracted from medical records. To facilitate comparison a dexamfetamine-equivalent dose was calculated. There were 186 intentional exposures in 178 patients (median age 17 years, males 54%) over the study period, consisting of 44 (24%) dexamfetamine, 50 (27%) lisdexamfetamine and 92 (49%) methylphenidate exposures. Stimulant exposures rose annually from 34 presentations in 2018 to 61 in 2021. Deliberate self-poisoning accounted for 139 (75%) presentations and the remaining 47 (25%) were recreational. Co-ingestions were taken in 101 (54%) presentations, leaving 85 (46%) single-agent exposures with a median dexamfetamine-equivalent dose ingested of 135 mg (range 15-4500 mg). Of the single-agent exposures tachycardia (69%), hypertension (47%) and agitation (58%) were the commonest clinical features. Most patients (58%) had mild-moderate symptoms, managed solely with supportive cares or oral sedation. Twenty-three (27%) patients had severe agitation receiving parenteral sedation. Rhabdomyolysis occurred in 3 single-agent exposures (4%) and 8 (9%) had an acute kidney injury. Severe cardiovascular toxicity was rare, with one patient developing hypertensive crisis and another having a supraventricular tachycardia. The median length of stay for single-agent exposures was 11 h (IQR 5-19 h). Prescription stimulant poisoning appears to be rising and commonly results in tachycardia, hypertension, and agitation. Severe cardiovascular toxicity was rare. [ABSTRACT FROM AUTHOR]

Research Question and Objective: While the number of pharmacoepidemiological studies on stimulant-based ADHD medications has expanded rapidly in recent years, likely due to the stimulant shortage, few studies have analyzed non-stimulant ADHD medications from a pharmacoepidemiological perspective. Such research is important because a significant number of individuals with ADHD have medical or psychiatric conditions that preclude stimulant use. Furthermore, no studies, to our knowledge, have analyzed atomoxetine exchanges on the black market. In this report, we seek to fill both these gaps in the research by analyzing black market diversions of atomoxetine, a non-stimulant medication for ADHD. As ADHD medication diversion is a growing issue, we also hypothesize the pharmacoepidemiologic contributors to and implications of such diversion. Method: This study analyzed black market atomoxetine purchases entered on the web-based platform StreetRx between January 2015 and July 2019. Data included the generic drug name, dosage, purchase price, date, and location in the United States. The mean price per milligram was determined and a heatmap was generated. Results: The average price per milligram of 113 diverted atomoxetine submissions was USD 1.35 (±USD 2.76 SD) (Median = USD 0.05, Min = USD 0.01, Max = USD 20.00). The states with the most submissions included Michigan (11), Pennsylvania (9), Indiana (8), and Ohio (8). Conclusion: The cost per milligram of atomoxetine on the black market is over 50 times the cost per milligram of the generic prescribed form. Future qualitative studies should investigate reasons why individuals are motivated to purchase atomoxetine, a non-stimulant medication, on the black market (recreational vs. nootropic vs. other clinical uses). [ABSTRACT FROM AUTHOR]

Aims: To characterize polysubstance death in the United States during the transition to the fourth wave of the drug overdose crisis. To characterize co‐involved substances in fatal overdose involving synthetic opioids (mainly illicitly manufactured fentanyl analogues) by year, state, and intersectional sociodemographic groups. Design: Population‐based study of national death records. Setting: United States. Participants/cases: All people who died from drug overdose in the United States between 2010 and 2021. Measurements Percentage of all fatal overdose involving fentanyls, stimulants, and other drugs. Most commonly co‐involved substances in fentanyl overdose by state and year. Percentage of fatal fentanyl overdose co‐involving stimulants by state and year. Percentage of fatal fentanyl overdose co‐involving stimulants by intersectional region, race/ethnicity, age, and sex. Findings The percent of US overdose deaths involving both fentanyl and stimulants increased from 0.6% (n = 235) in 2010 to 32.3% (34 429) in 2021, with the sharpest rise starting in 2015. In 2010, fentanyl was most commonly found alongside prescription opioids, benzodiazepines, and alcohol. In the Northeast this shifted to heroin‐fentanyl co‐involvement in the mid‐2010s, and nearly universally to cocaine‐fentanyl co‐involvement by 2021. Universally in the West, and in the majority of states in the South and Midwest, methamphetamine‐fentanyl co‐involvement predominated by 2021. The proportion of stimulant involvement in fentanyl‐involved overdose deaths rose in virtually every state 2015–2021. Intersectional group analysis reveals particularly high rates for older Black and African American individuals living in the West. Conclusions: By 2021 stimulants were the most common drug class found in fentanyl‐involved overdoses in every state in the US. The rise of deaths involving cocaine and methamphetamine must be understood in the context of a drug market dominated by illicit fentanyls, which have made polysubstance use more sought‐after and commonplace. The widespread concurrent use of fentanyl and stimulants, as well as other polysubstance formulations, presents novel health risks and public health challenges. [ABSTRACT FROM AUTHOR]

Background: The present study analysed data on children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who were referred to the ADHD reference centre of Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences in pharmacological treatment status (i.e., treatment continuation vs discontinuation) between patients. Methods: Seventy-seven children and adolescents (mean age at pharmacotherapy initiation = 9.5, standard deviation = 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used. Results: Pharmacological treatment status was examined for patients (n = 63) with at least 12 months of follow-up after the first pharmacological treatment for ADHD. After starting pharmacotherapy treatment, 77.8% (n = 49) patients were still on treatment whereas 22.2% (n = 14) discontinued it. No between group difference were observed in demographic and clinical data except for the intelligence quotient/intellectual disability and rule-breaking behavior (n = 40). Conclusions: This study stressed the need of periodical assessments, monitoring difficulties with treatment and/or reasons for poor treatment compliance to provide individualized care. [ABSTRACT FROM AUTHOR]

Objective: This study examined the relationship of students' academic beliefs to the theoretical predictors of prescription stimulant misuse outlined in the Theory of Planned Behavior. Participants: Participants included 147 college students (Mage = 19.65) from a mid-sized university in the Southwestern United States. Method: An online questionnaire distributed in the 10th week of the semester assessed students' academic locus of control, grade orientation, and academic entitlement in relation to their attitudes, subjective norms, perceived behavioral control, behavioral intention, and actual misuse behavior. Results: Partial correlations controlling for age, gender, and Greek life involvement indicated that academic locus of control is significantly related to all TPB variables aside from actual behavior, while grade orientation was related to perceived behavioral control and behavioral intention. Academic entitlement was not related to TPB variables in this study. Conclusions: The associations between academic beliefs and prescription stimulant misuse hold theoretical and practical implications. [ABSTRACT FROM AUTHOR]

This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations. [ABSTRACT FROM AUTHOR]

Objective: Stimulants are first-line pharmacotherapy for individuals with attention-deficit hyperactivity disorder. However, disparities in drug coverage may contribute to inequitable treatment access. In January 2018, the government of Ontario, Canada, implemented a publicly-funded program (OHIP+) providing universal access to medications at no cost to children and youth between the ages of 0 and 24. In April 2019, the program was amended to cover only children and youth without private insurance. We studied whether these policy changes were associated with changes in prescription stimulant dispensing to Ontario children and youth. Methods: We conducted a population-based observational natural experiment study of stimulant dispensing to children and youth in Ontario between January 2013 and March 2020. We used interventional autoregressive integrated moving average models to estimate the association between OHIP+ and its subsequent modification with stimulant dispensing trends. Results: The implementation of OHIP+ was associated with a significant immediate increase in the monthly rate of stimulant dispensing of 53.6 individuals per 100,000 population (95% confidence interval [CI], 36.8 to 70.5 per 100,000) and a 14.2% (95% CI, 12.8% to 15.6%) relative percent increase in stimulant dispensing rates between December 2017 and March 2019 (1198.6 vs. 1368.7 per 100,000 population). The April 2019 OHIP+ program amendment was associated with an increase in monthly stimulant dispensing trends of 10.2 individuals per 100,000 population (95% CI, 5.0 to 15.5), with rates increasing 7.5% (95% CI, 6.2% to 8.7%) between March 2019 and March 2020 (1368.7 vs. 1470.8 per 100,000 population). These associations were most pronounced among males, children and youth living in the highest income neighbourhoods and individuals aged 20 to 24. Conclusion: A publicly-funded pharmacare program was associated with more children and youth being dispensed stimulants. [ABSTRACT FROM AUTHOR]

Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the willingness to engage in cognitively or physically effortful behavior. However, the degree to which effort sensitivity is impaired in ADHD has rarely been tested, and the efficacy of stimulant medication in ameliorating any such impairments is unclear. Here, we tested 20 individuals with ADHD (11 males, 9 females) who were managed with amphetamine-based medication (dexamfetamine, lisdexamfetamine), and 24 controls (8 males, 16 females). Individuals with ADHD were tested over two counterbalanced sessions, ON and OFF their usual amphetamine-based medication. In each session, participants performed an effortbased decision-making task, in which they were required to choose how much cognitive or physical effort they were willing to engage in return for reward. Our results revealed three main findings. First, individuals with ADHD had lower motivation relative to controls to invest effort in both the cognitive and physical domains. Second, amphetamine increased motivation uniformly across both domains. Finally, the net effect of amphetamine treatment was to mostly restore motivation across both domains of effort relative to healthy controls. These data provide clear evidence for a heightened sensitivity to both cognitive and physical effort in ADHD, and reveal the efficacy of amphetamine-based drugs in restoring effort sensitivity to levels similar to controls. These findings confirm the existence of reduced motivational drive in ADHD, and more broadly provide direct causal evidence for a domain-general role of catecholamines in motivating effortful behavior. [ABSTRACT FROM AUTHOR]

Females who use drugs (FWUDs) are at risk of continuing illicit substance use during pregnancy and breastfeeding. We investigated the prevalence rates and factors associated with these practices in a sample of 200 FWUDs recruited from a publicly-run drug rehabilitation center. A semi-structured questionnaire was used to collect the data. The majority (86%) was Malay (n = 171/200), currently single (71%, n = 141/200), and 51% had nine years of education. The mean age of respondents was 32.2 years (SD = 8.61). Thirty-eight percent (n = 75/200) reported ever using illicit substances during pregnancy, while 15% (n = 30/200) had used them during breastfeeding. Higher odds of using drugs during pregnancy were associated with having an intimate male drug-using partner and with persons who reported abandoning an infant in the past. Lower odds were linked with women who used heroin with ATS (relative to those who used only ATS), and shorter-term ATS (≤3 years) relative to long term ATS users. At a lower level of significance (p = 0.054), being married also lowered the odds. Higher odds of drug use during breastfeeding were associated with having an intimate male drug-using partner, and previous methadone use history, while lower odds were associated with short-term ATS use and being employed. The findings highlight the need for timely and targeted interventions to inform, engage and promote the participation of FWUDs in pre- and post-natal care services. [ABSTRACT FROM AUTHOR]

Background: While prescription psychotherapeutic drug use (PPDU) and nicotine use pose substantial problems in isolation, they pose an increased risk in combination. This study aimed to estimate the prevalence of PPDU for young people, stratified by nicotine use status. A trend analysis was used to examine changes in PPDU and nicotine use over time. Methods: We used a cross-sectional population-based sample of young people aged 16–25 years (n = 10,454) from the National Health and Nutrition Examination Survey (NHANES, 2003–2018). For each data cycle, the prevalence of self-reported PPDU and nicotine including pain relievers, sedatives, stimulants, and tranquilizers was estimated. Using Joinpoint regression, we tested for significant changes in trends using a log-linear model and permutation test approach and produced the average data cycle percentage change (ADCPC). Results: From 2003 to 2018, 6.7% of young people had PPDU and 27.3% used nicotine. The prevalence of cigarette smoking decreased while other nicotine product use increased (p's < 0.001). Those who used nicotine were more likely to have PPDU (8.2%; 95% CI = 6.5%, 9.8%) vs. non-nicotine use (6.1%; 95% CI = 5.1%, 7.0%; p = 0.01). Results indicated a decreasing trend for nicotine use (ADCPC = −3.8, 95% CI = −7.2, −0.3; p = 0.04), but not for PPDU (ADCPC = 1.3; 95% CI = −4.7, 7.8; p = 0.61). On further examination, opioid use decreased, sedative use remained stable, and stimulant and tranquilizer use increased over time. Conclusions: From 2003 to 2018, young people who used nicotine had a higher prevalence of PPDU than those who did not. Clinicians should communicate the association between nicotine use and prescription drugs when prescribing or managing young patients' medications. [ABSTRACT FROM AUTHOR]

In recent years, mitragynine has been consistently detected in driving under the influence of drug (DUID) cases. In this paper, we evaluate 3 years (2017–2019) worth of DUID data from arrested drivers in Orange County, CA, USA. From the 25,398 DUID cases received in those 3 years, there were 60 (0.24%) cases with detectable concentrations, >10 ng/mL, of mitragynine. The majority of drivers were male (90%) and were stopped during the week (81%), considered Monday 0000 to Friday 1159. The concentration range for all mitragynine cases was 10.5–960 ng/mL, with a mean of 109 ng/mL and a median of 58 ng/mL. Forty four of the 60 cases were also screened for 7-hydroxymitragynine, and 27 (63%) were positive. The police reports and drug recognition expert evaluations were collected and evaluated. No case contained solely mitragynine, and the most common drugs detected in combination were central nervous system depressants (ethanol, followed by benzodiazepines), stimulants (methamphetamine and cocaine) and opioids (fentanyl and indication of heroin). Two cases containing only one other psychoactive substance are discussed more thoroughly to attempt to identify the contributions of mitragynine to driving impairment. Collected demographic, toxicological and field observations are presented for all cases. [ABSTRACT FROM AUTHOR]

The vast majority of research on cognitive enhancement has focused on pharmacological cognitive enhancement (PCE), with relatively little exploration of public attitudes towards non-pharmacological cognitive enhancing substances. Limited research has investigated how the lay public ethically evaluates nootropic supplements (i.e. legal and purportedly natural over-the-counter products), or how such attitudes may differ from attitudes towards other cognitive enhancers. This experimental between-subjects study used a contrastive vignette technique to explore Irish students' attitudes towards caffeine tablets, nootropic supplements and PCE. One-hundred-and-thirteen Irish university students participated in the study (46 male, 64 female), ranging from 18 to 25 years of age (M = 21.9). Quantitative analyses examined differences in mean attitudes between cognitive enhancement conditions and genders. Results suggest that the three forms of cognitive enhancement provoked similar moderate responses in relation to safety and authenticity, however, students were more concerned about implicit coercion in relation to PCE and reported heightened fairness concerns in relation to nootropic supplements. Nootropic supplements may have distinct ethical implications which are not simply equivalent to those that accompany PCE or caffeine tablets, raising questions surrounding the effects of novel cognitive enhancing products; financial barriers to legal non-pharmacological cognitive enhancement; and the permissibility of cognitive enhancement advertising. [ABSTRACT FROM AUTHOR]

The global rise in methamphetamine use and its negative effects warrants the need for research exploring harm reduction and treatment interventions for individuals with methamphetamine use disorder. Agonist medications have been utilized for years for the treatment of heroin and opioid addiction, but have yet to be incorporated into mainstream Canadian practice for methamphetamine dependence. This review aims to provide an overview of the current trends of prescription psychostimulant usage for individuals with methamphetamine use disorder from a Canadian perspective, identifies the barriers to accessing prescription psychostimulants for methamphetamine use disorder and highlights the nursing clinical practice implications in caring for individuals with the disorder. Discourse on the sustained abstinence and harm reduction debate is presented from the perspective of methamphetamine abuse is provided along with the neuropsychiatric complications of chronic methamphetamine use. The impacts of specific prescription psychostimulants on cognition are discussed as is the use of neuroimaging techniques to assess neuronal damage in methamphetamine users. Sign of toxicity, overdose and the contraindications for use of these prescription psychostimulants is also presented. The implications to nursing clinical practice in caring for this population is provided, touching on the clinical presentation of methamphetamine use, completing thorough assessment and screening and patient education. The findings of this review indicate the need for further research in this area exploring the benefits of prescription psychostimulants as a harm reduction and treatment intervention for the global problem of methamphetamine dependence. [ABSTRACT FROM AUTHOR]