Patient visits and prescriptions for attention-deficit/hyperactivity disorder from 2017-2021: Impacts of COVID-19 pandemic in primary care.

OBJECTIVE: To determine whether more patients presented with Attention-deficit/hyperactivity disorder (ADHD)-related visits and/or sought care from family physicians more frequently during the COVID-19 pandemic. METHODS: Electronic medical records from the University of Toronto Practice-Based Research Network were used to characterize changes in family physician visits and prescriptions for ADHD medications. Annual patient prevalence and visit rates pre-pandemic (2017-2019) were used to calculate the expected rates in 2020 and 2021. The expected and observed rates were compared to identify any pandemic-related changes. RESULTS: The number of patients presenting for ADHD-related visits during the pandemic was consistent with pre-pandemic trends. However, observed ADHD-related visits in 2021 were 1.32 times higher than expected (95% CI: 1.05-1.75), suggesting that patients visited family physicians more frequently than before the pandemic. CONCLUSION: Demand for primary care services related to ADHD has continued to increase during the pandemic, with increased health service use among those accessing care.

Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis.

Background: Non-stimulant guanfacine is a common second-line medication for attention-deficit hyperactivity disorder (ADHD). Numerous randomized controlled trials (RCTs) have explored the efficacy of guanfacine in ADHD treatment. This meta-analysis combined data from selected RCTs to analyze the efficacy and safety of guanfacine in treating ADHD. Methods: RCTs were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase (up to February 2022), defining the Clinical Global Impression of Improvement (CGI-I) treatment response score of ≤2 as the primary outcome. Subgroup analysis was performed with a bound treatment duration of 10 weeks. Safety was defined by treatment-emergent adverse events (TEAEs). Results: Twelve out of 332 studies with 2653 participants were included. All studies compared guanfacine with placebos. Guanfacine was significantly more effective in treating ADHD (Risk Ratio [RR] 1.78, 95% CI: 1.59-2.01). In the <10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 58.5% versus 29.4%, respectively (RR 1.97, 95% CI: 1.71-2.26). In the >10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 63.6% versus 39.7%, respectively (RR 1.57, 95% CI: 1.37-1.79). Both subgroups lacked heterogeneity (I2 = 0), and a funnel plot showed a low publication bias risk. Around 80% of participants in the guanfacine group experienced at least one TEAE, compared with 66.5% in the placebo group (RR 1.23, 95% CI: 1.14-1.32), with low heterogeneity (I2 = 46, p = 0.05). The most common TEAEs in the guanfacine group were somnolence (38.6%), headaches (20.5%), and fatigue (15.2%). Conclusions: Guanfacine is safe and effective for treating ADHD, with no serious adverse events. Guanfacine should be considered as an effective treatment option where effectiveness or tolerability of the central nervous system stimulant is of concern. There is stronger evidence of efficacy for children; more clinical studies are needed for adults.

Pharmacotherapy May Attenuate the Risk of Child Abuse in Attention-Deficit/Hyperactivity Disorder from the Real-World Evidence.

Objective: Psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), may serve as a risk factor for child abuse. Methods: This study aimed to evaluate the association between children and adolescents with ADHD diagnosis and the risk of child abuse. The effectiveness of a pharmacological intervention on reducing the risk of child abuse was also assessed. A nationwide, population-based, retrospective with a matched-cohort study design was used. Data were from the National Health Insurance Research Database of Taiwan over a 15-year period (2000-2015). Results: Increased risk of child abuse in the ADHD group was noticed and the adjusted hazard ratio (HR) was 1.797 (95% confidence interval [CI] = 1.245-2.388, p < 0.001). The Kaplan-Meier analysis showed a significantly higher cumulative incidence in the ADHD group over the 15-year period (Log-rank test p < 0.001). ADHD patients with other psychiatric comorbidities had a higher risk of child abuse. Pharmacological treatment of either methylphenidate or atomoxetine was associated with a reduced risk of child abuse. The total adjusted HR was 1.466 (95% CI = 1.077-1.883, p < 0.001) in medicine group compared with the controls. Conclusions: ADHD was associated with a subsequent risk of child abuse in Taiwan. Pharmacological treatment could reduce the risk of child abuse in ADHD patients.

The Burden of Attention-Deficit/Hyperactivity Disorder in Adults: A Real-World Linked Data Study.

Objective: To assess the humanistic and economic burden of attention-deficit/hyperactivity disorder (ADHD) among adult patients treated with immediate-release (IR) only or extended-release (ER) only stimulants and those unmedicated versus treated with ER + IR stimulants.Methods: This study analyzed linked data from National Health and Wellness Survey and claims to assess the differences in patient characteristics and outcomes, including health-related quality of life (HRQoL), work productivity and activity impairment, and health care resource utilization (HRU) and associated costs by comparing ADHD patients treated with either IR or ER and those unmedicated for ADHD versus ER + IR.Results: The burden of ADHD was compared among adults on stimulant medications with different duration of effect (DoE) (ER + IR: n = 34, ER: n = 184, IR: n = 149) and the unmedicated group (n = 114). Bivariate analysis showed the IR (P = .047) and unmedicated groups (P = .01) had significantly lower Medical Outcomes Study 36-item Short Form physical component summary scores versus ER + IR. The unmedicated group had higher HRU and associated costs versus other groups. Multivariable analysis revealed that the unmedicated group had twice as many outpatient visits (P = .001) and higher total annual direct costs than those on ER + IR (risk ratio = 2.20, P = .016). Patients with mental health comorbidities had significantly poorer HRQoL mental component summary scores and higher activity impairment versus those without mental health comorbidities (P = .001 and P < .001, respectively).Conclusions: Patients with ADHD treated with longer DoE formulations had substantially better economic outcomes versus shorter DoE formulation or unmedicated groups, offering potential cost savings to the health care system and the patient. Furthermore, it is important to consider the effect of mental health comorbidities in the overall management of ADHD.

Caloric state modulates locomotion, heart rate and motor neuron responses to acute administration of d-amphetamine in zebrafish larvae.

Psychostimulant drugs increase behavioral, cardiac and brain responses in humans and other animals. Acute food deprivation or chronic food restriction potentiates the stimulatory effects of abused drugs and increases the propensity for relapse to drug seeking in drug-experienced animals. The mechanisms by which hunger affects cardiac and behavioral activities are only beginning to be elucidated. Moreover, changes in motor neuron activities at the single neuron level induced by psychostimulants, and their modulation by food restriction, remain unknown. Here we investigated how food deprivation affects responses to d-amphetamine by measuring locomotor activity, cardiac output, and individual motor neuron activity in zebrafish larvae. We used wild-type larval zebrafish to record behavioral and cardiac responses and the larvae of Tg(mnx1:GCaMP5) transgenic zebrafish to record motor neuron responses. Physiological state gated responses to d-amphetamine. That is, d-amphetamine evoked significant increases in motor behavior (swimming distances), heart rate and motor neuron firing frequency in food-deprived but not fed zebrafish larvae. The results extend the finding that signals arising from food deprivation are a key potentiator of the drug responses induced by d-amphetamine to the zebrafish model. The larval zebrafish is an ideal model to further elucidate this interaction and identify key neuronal substrates that may increase vulnerability to drug reinforcement, drug-seeking and relapse.

Cyanidin prevents MDPV withdrawal-induced anxiety-like effects and dysregulation of cytokine systems in rats.

Psychostimulant exposure and withdrawal cause neuroimmune dysregulation and anxiety that contributes to dependence and relapse. Here, we tested the hypothesis that withdrawal from the synthetic cathinone MDPV (methylenedioxypyrovalerone) produces anxiety-like effects and enhanced levels of mesocorticolimbic cytokines that are inhibited by cyanidin, an anti-inflammatory flavonoid and nonselective blocker of IL-17A signaling. For comparison, we tested effects on glutamate transporter systems that are also dysregulated during psychostimulant free period. Rats injected for 9 d with MDPV (1 mg/kg, IP) or saline were pretreated daily with cyanidin (0.5 mg/kg, IP) or saline, followed by behavioral testing on the elevated zero maze (EZM) 72 h after the last MDPV injection. MDPV withdrawal caused a reduction in time spent on the open arm of the EZM that was prevented by cyanidin. Cyanidin itself did not affect locomotor activity or time spent on the open arm, or cause aversive or rewarding effects in place preference experiments. MDPV withdrawal caused enhancement of cytokine levels (IL-17A, IL-1ß, IL-6, TNF=α, IL-10, and CCL2) in the ventral tegmental area, but not amygdala, nucleus accumbens, or prefrontal cortex, that was prevented by cyanidin. During MDPV withdrawal, mRNA levels of glutamate aspartate transporter (GLAST) and glutamate transporter subtype 1 (GLT-1) in the amygdala were also elevated but normalized by cyanidin treatment. These results show that MDPV withdrawal induced anxiety, and brain-region specific dysregulation of cytokine and glutamate systems, that are both prevented by cyanidin, thus identifying cyanidin for further investigation in the context of psychostimulant dependence and relapse.

ADHD-A Clinician's Bird's Eye View of Current Status and New Vistas!

Objectives: Literature on ADHD has taken long strides recently as heaps of new data are pouring in through countless papers. Here, authors try to outline changing paradigms in ADHD practice. DSM-5 changes regarding the typology and diagnostic criteria are highlighted. Overview of co-morbidities, associations, developmental trajectories, and syndromic continuity across lifespan is outlined. Recent insights into aetiology and diagnostic tools are briefly discussed. New medications in the pipeline are also described. Methods: EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant updates in ADHD literature as of June, 2022. Results: DSM-5 brought about changes to the diagnostic criteria of ADHD. These included replacing types with presentations, pushing age to 12, and, incorporating adult diagnostic criteria. In the same vein, DSM-5 allows now for diagnosing concurrent ADHD and ASD. Associations of ADHD to allergy, obesity, sleep disorders, and, epilepsy have been demonstrated in recent literature. Neurocircuity underlying ADHD has been extended beyond frontal-striatal to include CTC as well as DMN accounting for ADHD heterogeneity. NEBA was FDA-approved to differentiate ADHD from hyperkinetic ID. Atypical antipsychotics use to address behavioural facets in ADHD is on the rise with no solid evidence-base. α-2 agonists are FDA-approved as monotherapy or adjunctive to stimulants. Pharmacogenetic testing is readily available for ADHD. Different formulations of stimulants abound on the market widening clinicians' repertoire. Stimulant-related exacerbation of anxiety and tics were challenged in recent studies. Drugs for ADHD in the pipeline include-dasotraline, armodafinil, tipepidine, edivoxetine, metadoxine, and memantine. Conclusions: Literature on ADHD keeps expanding towards advancing our understanding of the complex and heterogeneous intricacies of this commonplace neurodevelopmental disorder and hence informing better decisions on how best to manage its diverse cognitive, behavioural, social and medical facets.

Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers.

Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are widely abused due to their psychostimulant effects. As they are chiral molecules, studies of their stereochemical stability (racemization can occur in certain temperatures and acidic/basic environments) and of their biological and/or toxicity effects (enantiomers might display different properties) are of great relevance. In this study, the liquid chromatography (LC) semi-preparative enantioresolution of MDPV was optimized to collect both enantiomers with high recovery rates and enantiomeric ratio (e.r.) values. The absolute configuration of the MDPV enantiomers was determined by electronic circular dichroism (ECD) with the aid of theoretical calculations. The first eluted enantiomer was identified as S-(-)-MDPV and the second eluted enantiomer was identified as R-(+)-MDPV. A racemization study was performed by LC-UV, showing enantiomers' stability up to 48 h at room temperature and 24 h at 37 °C. Racemization was only affected by higher temperatures. The potential enantioselectivity of MDPV in cytotoxicity and in the expression of neuroplasticity-involved proteins-brain-derived neurotrophic factor (BDNF) and cyclin-dependent kinase 5 (Cdk5)-was also evaluated using SH-SY5Y neuroblastoma cells. No enantioselectivity was observed.

Perspectives of French adolescents with ADHD and child and adolescent psychiatrists regarding methylphenidate use.

Many studies have demonstrated the short-term efficacy and tolerability of methylphenidate treatment adolescents with attention deficit hyperactivity disorder (ADHD). Qualitative literature on this matter focused on school outcomes, long-term side effects, family conflicts, personality changes and stigmatization. Yet, no qualitative study has crossed the perspectives of child and adolescent psychiatrists (CAPs) prescribing methylphenidate and adolescents with ADHD. This French qualitative study followed the five stages IPSE-Inductive Process to analyze the Structure of lived Experience-approach. Fifteen adolescents with ADHD and 11 CAPs were interviewed. Data collection by purposive sampling continued until data saturation was reached. Data analysis, based on a descriptive and structuring procedure to determine the structure of lived experience characterized by the central axes of experience, produced two axes: (1) The process of methylphenidate prescription, highlighting how this prescription was motivated from the exterior, experienced as passive by the adolescents and required commitment from the CAPs; and (2) the perceived effects of methylphenidate treatment, in three domains: at school, in relationships and in the sense of self. Findings raised both the issues of the epistemic position and social representation of the adolescents about ADHD and methylphenidate within this specific French context, and the self-awareness and perception of the adolescents with ADHD. We conclude that these two issues need to be regularly addressed by the CAPs prescribing methylphenidate to avoid epistemic injustice and prevent the harmful effects of stigmatization.

Crash-involved THC-positive drivers in Norway have a high frequency of polysubstance use.

BACKGROUND: Tetrahydrocannabinol (THC) is the most frequently detected drug in blood samples from apprehended drug driving suspects in Norway. This investigation aimed to study the extent of polysubstance use among apprehended crash-involved drivers with THC concentrations above the legal limit and explore the importance of THC in polysubstance cases. METHODS: We selected all drug driving cases where blood samples had been submitted for forensic toxicology testing after involvement in road traffic crashes during 2013-2020, except drivers who were fatally injured. RESULTS: Twenty percent (n = 2133) of the 10,520 apprehended crash-involved drivers had concentrations of THC in their blood above the legal limit of 1.3 ng/mL, and 84 % of those also had concentrations of alcohol or other drugs above the legal limits; 61 % for sedatives, 38 % for stimulants, 33 % for alcohol, and 10 % for opioids. The most frequent substance combination was cannabis together with sedatives and stimulants (22.9 %; n = 488). Polysubstance use was least common among drivers under 24 years. The proportion of drivers with THC > 5 ng/mL was highest if the blood sample was collected within 90 min after the crash, and when only THC was detected. There was a statistically significant inverse association between THC > 5 ng/mL and concentrations of alcohol or amphetamines at the highest sanction level. CONCLUSIONS: Most apprehended crash-involved THC-positive drivers also tested positive for other psychoactive substances. Drivers with high blood THC concentrations had less often high concentrations of other substances; cannabis might then have been a more important contributor to impairment.

Lower-risk substance use guidelines accessible by youth.

BACKGROUND: Lower-risk substance use guidelines (LRSUGs) are an evidence-based harm reduction strategy used to provide information to people who use drugs so they can reduce harms associated with substance use. OBJECTIVES: This study aimed to identify LRSUGs accessible to youth and to characterize the recommendations within these guidelines. The overall goal is to identify gaps in current LRSUGs and to inform researchers and policymakers of the kinds of health information youth can access. METHODS: We conducted a digital assessment using the Google search engine to identify LRSUGs that could be identified by youth when searching for official sources of information related to commonly used substances, including cannabis, caffeine, alcohol, hallucinogens, prescription opioids, nicotine, and/or prescription stimulants. LRSUGs were coded and data were extracted from them to identify gaps. RESULTS: One hundred thirty LRSUGs were identified; most focused on alcohol (n = 40, 31%), cannabis (n = 30, 23%), and caffeine (n = 21, 16%). LRSUGs provided recommendations about dosing (n = 108, 83%), frequency of use (n = 72, 55%), and when to use (n = 86, 66%). Most LRSUGs were published by health (n = 51, 39%) and third-sector organizations (n = 41, 32%), followed by provincial/state (n = 18, 14%), government (n = 14, 11%), municipal (n = 4, 3%), and academic (n = 2, 2%) sources. Only 16% (n = 21) of LRSUGs were youth-specific and one-quarter (n = 32, 25%) of LRSUGs provided gender-specific recommendations. Most guidelines featured information on short (n = 76, 58%) and long-term (n = 69, 53%) negative effectives and positive effects of substances (n = 56, 43%). Less than half (n = 50, 38%) of LRSUGs cited evidence in support of the information they provided. CONCLUSIONS: We identified several areas in the current LRSUGs for youth that need to be addressed. Among the gaps are a lack of LRSUGs developed specifically for youth, a lack of youth engagement in developing harm reduction strategies centered around them, and a lack of evidence-based LRSUGs. Youth-oriented, evidence-based LRSUGs are needed to better support youth who use substances and help them manage the negative effects of substance use.

Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study.

Objective: Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A pivotal double-blind (DB) study of children aged 6-12 years with ADHD demonstrated efficacy for ADHD with good tolerability. In this study, we assessed the safety and tolerability of daily oral SDX/d-MPH for up to 1 year in children with ADHD. Methods: This was a dose-optimized, open-label safety study with SDX/d-MPH in children aged 6-12 years with ADHD that included subjects who successfully completed the DB study (rollover) and new subjects. The study consisted of a 30-day screening phase, a dose optimization phase for new subjects only, a 360-day treatment phase, and follow-up. Adverse events (AEs) were assessed from the first day of SDX/d-MPH administration to the end of the study. During the treatment phase, ADHD Rating Scale-5 (ADHD-RS-5) and Clinical Global Impressions-Severity (CGI-S) scale assessments were used to evaluate ADHD severity. Results: Of the 282 subjects enrolled (70 rollover; 212 new), 28 discontinued treatment in the dose optimization phase and 254 entered the treatment phase. By study completion, 127 had discontinued and 155 had completed the study. The treatment-phase safety population included all enrolled subjects who received ≥1 dose of study drug and had ≥1 postdose safety assessment. Of 238 subjects assessed in the treatment-phase safety population, 143 (60.1%) had ≥1 treatment-emergent adverse events (TEAEs), and 36 (15.1%), 95 (39.9%), and 12 (5.0%) had mild, moderate, or severe TEAEs, respectively. The most common TEAEs were decreased appetite (18.5%), upper respiratory tract infection (9.7%), nasopharyngitis (8.0%), decreased weight (7.6%), and irritability (6.7%). There were no clinically meaningful trends in electrocardiograms, cardiac events, or blood pressure events, and none led to discontinuation. Two subjects had eight serious AEs that were unrelated to treatment. There were overall reductions in ADHD symptoms and severity as assessed by ADHD-RS-5 and CGI-S during the treatment phase. Conclusions: In this 1-year study, SDX/d-MPH was found to be safe and well tolerated and comparable with other methylphenidate products, with no unexpected safety findings. SDX/d-MPH also showed sustained efficacy during the 1-year treatment period. ClinicalTrials.gov identifier: NCT03460652.

A wide range of Deep Brain Stimulation of the nucleus accumbens shell time independently reduces the extinction period and prevents the reinstatement of methamphetamine-seeking behavior in rats.

Methamphetamine (METH) addiction is a significant public health issue, and standard medical therapies are often not curative. Deep Brain Stimulation (DBS) has recently shown the potential to cure addiction by modulating neural activity in specific brain circuits. Recent studies have revealed that the nucleus accumbens shell (NAcSh) could serve as a promising target in treating addiction. Therefore, the present study aimed to investigate the therapeutic effects of NAcSh high- or low-frequency stimulation (HFS or LFS) in the different time points of application on the extinction and reinstatement of the METH-conditioned place preference (CPP). LFS or HFS (10 or 130 Hz, 150-200 µA, 100 µs) was delivered to the NAcSh for 30 min non-simultaneous (in a distinct non-drug environment) or simultaneous (in a drug-paired context) of the drug-free extinction sessions. The obtained results showed that both non-simultaneous and simultaneous treatments by HFS and LFS notably reduced the extinction period of METH-induced CPP. Furthermore, the data indicated that both non-synchronous and synchronous HFS prevented METH-primed reinstatement, while only the LFS synchronized group could block the reinstatement of METH-seeking behavior. The results also demonstrated that HFS was more effective than LFS in attenuating METH-primed reinstatement, and applying HFS synchronous was significantly more effective than HFS non-synchronous in reducing the relapse of drug-seeking. In conclusion, the current study's results suggest that DBS of the NAcSh in a wide range of frequencies (LFS and HFS) could affect addiction-related behaviors. However, it should be considered that the frequency and timing of DBS administration are among the critical determining factors.

Growth Trajectories in Stimulant-Treated Children Ages 6 to 12: An Electronic Medical Record Analysis.

OBJECTIVE: The aim of this study was to evaluate growth trajectories in stimulant-exposed and stimulant-unexposed children using electronic medical record data from a large health care organization attending to moderating effects of the magnitude of exposure to stimulants, sex, and race. METHODS: Weight, height, body mass index (BMI), prescription, and sociodemographic information were extracted from the electronic medical records of a large health care organization. Included were children who were 6 to 12 years at the time they were receiving stimulants with a concurrent growth assessment (index assessment) plus 1 to 4 years of additional growth assessments thereafter. Non-attention-deficit/hyperactivity disorder (ADHD) children who were unexposed to stimulants were age and sex matched to those exposed. Stimulant exposure was examined as the total number of months with stimulant prescriptions, percentage of follow-up time exposed to stimulants, and cumulative stimulant dose. RESULTS: Our sample consisted of 323 children exposed to stimulants with available growth data and 1615 unexposed children. Small but significant decreases in height trajectories were found over time in exposed children compared with those unexposed. Weight and BMI trajectories decreased in the first year of follow-up with stabilization and increased thereafter. Growth trajectory effects were largest in girls (height, weight, and BMI), White children (weight), and children with more total stimulant exposure (weight). CONCLUSION: This comprehensive analysis of an ecologically informative sample attending to key covariates of the magnitude of exposure to stimulants, sex, and race extends previous findings, showing that effects on growth trajectories are small and do not appear to pose a significant clinical concern for most children with ADHD treated with stimulants from childhood onto adolescent years.

Behavioral and Pharmacokinetics Studies of N-Methyl-2-Aminoindane (NM2AI) in Mice: An Aminoindane Briefly Used in the Illicit Drug Market.

Drug forums are considered as the main platform sources that have contributed to the increase in NPS popularity, especially for those not yet known to law enforcement and therefore not yet illegal. An example is the new synthetic stimulant NM2AI, which has a very short history of human use and abuse. Little is known regarding this compound, but some information from internet forums and the scientific literature indicates NM2AI as a structural derivate of MDAI, which is known for its entactogenic activity. Indeed, the purpose of this study is to evaluate, for the first time, the in vivo acute effect induced by the intraperitoneal injection of NM2AI (1-10-30-100 mg/kg) in mice. We demonstrate the sensory (by visual placing and object tests) and physiological (core temperature measurement) function variations, nociceptor (by tail pinch test) and strength (grip test) alterations, and sensorimotor (time on rod and mobility) decrease. Moreover, we verify the mild hallucinogenic effect of NM2AI (by startle/prepulse inhibition test). Lastly, we perform a pharmacokinetic study on mice blood samples, highlighting that the main active metabolite of NM2AI is 2-aminoindane (2AI). Taken together, our data confirm the suspected entactogenic activity of NM2AI; however, these in vivo effects appear atypical and less intense with respect to those induced by the classic stimulants, in surprising analogy with what is reported by networked users.

An overview of New Psychoactive Substances (NPS) in northeast Brazil: NMR-based identification and analysis of ecstasy tablets by GC-MS.

The actual illicit market for synthetic drugs is characterized by a wide variety of psychoactive substances of different chemical and pharmacological classes, such as amphetamine-type stimulants and new psychoactive substances. The knowledge about its chemical composition, as well as the nature and quantity of the active substances present, is important for emergency care in intoxication cases by these substances and to establish adequate chemical and toxicological analysis procedures in forensic laboratories. The aim of this work was to study the prevalence of amphetamine-type stimulants and new psychoactive substances in the states of Bahia and Sergipe, in the northeast region of Brazil, involving samples of drugs seized by the local police forces from 2014 to 2019. In a total of 121 seized and analyzed samples, in which ecstasy tablets predominated (n = 101), nineteen substances were identified using GC-MS and 1D NMR techniques, comprising classical synthetic drugs and new psychoactive substances (NPS). In order to determine the composition of ecstasy tablets, an analytical method based on GC-MS was applied after validation. Analyzes of 101 ecstasy tablets showed that MDMA was the main substance, being found in 57% of the samples, in amounts between 27.3 and 187.1 mg per tablet. In addition, mixtures of MDMA, MDA, synthetic cathinones and caffeine were observed in 34 samples. These results demonstrate that the variety of substances found and the composition of seized materials in northeast Brazil is similar to other studies carried out previously in other Brazilian regions.

The rising threat of illicit amphetamine-type stimulant use among methadone maintenance treatment patients in East Coast Malaysia: a retrospective observational study.

Background: In recent years, amphetamine-type-stimulants (ATS) have been extensively misused in South-East Asia, inducing major problems among methadone-maintenance-treatment (MMT) patients.Objective: We examine ATS-misuse prevalence and its determinants among MMT patients in East-Coast-Malaysia.Methods: A retrospective-observational study was conducted on government-subsidized medication for opioid-use-disorder (MOUD) treatment clinics involving 292 MMT-patients (98% males) who were selected using a multilevel-proportional-stratified random sampling technique. Information obtained during the mandatory monitoring procedure from January 1 to December 31 2019, was utilized to determine ATS misuse prevalence from consecutive random urine drug screening. The determinants associated with its use, namely sociodemographics, social networks, comorbidities, and pharmacological assessments were analyzed via a logistic model.Results: Overall, 52.2% of the MMT-patients (95% CI: 0.42-0.54) had misused ATS at least once during their methadone treatment. These misusing patients were active smokers, hepatitis B and C seronegative, concurrently misused opioids, and had received suboptimum prescribed doses of methadone. Multiple logistic regression analysis demonstrated that the odds of misusing ATS during methadone treatment were 37 times higher among those who concurrently misused opioids (AOR: 37.60, 95% CI: 14.03-100.74) and 12 times higher among those who received suboptimal methadone doses (<60 mg/day) (AOR: 12.24, 95% CI: 5.58-25.43).Conclusion: This study demonstrated the significant prevalence of ATS misuse among MMT-patients in East-Coast-Malaysia, especially among patients who were prescribed suboptimal doses of methadone and/or demonstrated concomitant opioid-misuse. Stringent urine-monitoring is crucial to prevent diversion to ATS misuse. Nonetheless, to avoid negligence and improve physician engagement, the relevant authorities should immediately plan a comprehensive national-standard training module comprising support activities for professional methadone-prescribers.

Methylphenidate Promotes Premature Growth Plate Closure: In Vitro Evidence.

It is well known that patients with attention deficit hyperactivity disorder treated with stimulants, such as methylphenidate hydrochloride (MPH), have reduced height and weight. Even though MPH has an anorexigenic effect, an additional impact of this drug on the growth plate cannot be discarded. In this study, we aimed to determine the cellular effect of MPH on an in vitro growth plate model. We tested the effects of MPH on the viability and proliferation of a prechondrogenic cell line via an MTT assay. In vitro differentiation of this cell line was performed, and cell differentiation was evaluated through the expression of cartilage- and bone-related genes as measured via RT-PCR. MPH did not alter the viability or proliferation of prechondrogenic cells. However, it reduced the expression of cartilage extracellular matrix-related genes (type II collagen and aggrecan) and increased the expression of genes involved in growth plate calcification (Runx2, type I collagen, and osteocalcin) at different phases of their differentiation process. Our results evidence that MPH upregulates genes associated with growth plate hypertrophic differentiation. This may induce premature closure of the growth plate, which would contribute to the growth retardation that has been described to be induced by this drug.