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Novel psychoactive substances (NPS) are a very diverse group of recreational drugs that mimic effects of classic drugs of abuse and, at least at the beginning, are not usually prohibited. Representative of this group is mephedrone – a cathinone derivative. It is widely used as a recreational drug, particularly among club guests. Mephedrone`s effects are compared to effects of cocaine and MDMA but are more short-lived and include: psychostimulation, enhanced empathy, reduced feeling of tiredness, euphoria, hallucinations. This drug also exerts adverse effects, such as: anxiety, delusions, paranoia, psychosis, increased body temperature, elevated blood pressure, sleep disturbances. According to surveys performed on mephedrone users, it may be addictive. Those findings confirms a growing number of behavioural and molecular studies on animals. Mephedrone acts mainly via increasing monoamine transmission through increasing release of dopamine, serotonin and noradrenaline into synaptic cleft, inhibiting their re-uptake and reducing their metabolism. However, participation of other transmitters, modulators and pathways are investigated, including glutamate and nitric oxide. Favorable routes of administering mephedrone is intranasal and per os. Moreover, most often drug users use it in a binge way, e.g. taking repeated doses of a drug in a short period of time. According to animal studies, this pattern of mephedrone use leaves more neural injuries than taking it regularly, but in smaller doses. Our aim was to present a short, but essential, overview of the current knowledge on mephedrone, focusing on its effects, mechanism of action, animal studies evaluating its influence on the brain structures, toxicity and pharmacokinetics.

Introduction: This study aimed to compare the rates of agitation-related interventions associated with initial holding versus continuation of home stimulant(s) in a child and adolescent population at the time of admission to an inpatient psychiatric facility. Methods: This retrospective chart review included patients less than 18 years of age who were admitted to an academic medical center between July 1, 2017, and July 1, 2018. Patients were divided into 2 groups: those continued on their home stimulant(s) and those who had them held. We compared both groups on agitation-related outcomes by examining the difference in the number of level I or II events or as-needed medication administrations. Mechanical restraints and closed-door seclusions were grouped as level I events, and level II events consisted of nonmechanical restraint. Results: The analysis included 169 patients. In total, 126 (75%) patients were continued on their home stimulant, and 43 (25%) had them held. The occurrence of the composite endpoint of level I or II events or as-needed intramuscular medication administration was numerically higher in the group that had their home stimulant held (27.9% vs 23%; P =.52). Level I events were also numerically higher but not statistically significant in the group that had their home stimulant held (16.3% vs 11.9%; P = .46). Discussion: The composite outcome of as-needed intramuscular medication administration and level I or II events was numerically higher in the group that had their home stimulant held. Use of a larger sample size and adjusted analyses may help elucidate covariates that impact agitation-related outcomes.

Objective: Psychostimulant use induces oxidative stress and alters redox imbalance, influencing epigenetic signatures in the central nervous system (CNS). Among the various epigenetic changes, DNA methylation is directly linked to oxidative stress metabolism via critical redox intermediates such as NAD+, S-adenosylmethionine (SAM), and 2-oxoglutarate. Fluctuations in these intermediates directly influence epigenetic signatures, which leads to detectable alterations in gene expression and protein modification. This review focuses on recent advances in the impact of psychostimulant use on redox-imbalance-induced DNA methylation to develop novel epigenetics-based early interventions. Methods: This review is based on collective research data obtained from the PubMed, Science Direct, and Medline databases. The keywords used in the electronic search in these databases were redox, substance use disorder, psychostimulants, DNA methylation, and neurological diseases. Results: Instability in DNA methylation levels and redox expression effects are reported in various behavioral models stimulated by psychostimulants and opioids, indicating the widespread involvement of epigenetic changes in DNA methylation signatures in neurological disorders. Discussion: This review summarizes the need for more studies and experimental evaluations of DNA-methylation-based strategies that may help to understand the association between psychostimulant use and oxidative stress or redox-linked metabolic recalibration influencing neuronal impairments.

The last two decades have seen an exponential growth in the consumption and prescription of psychostimulants for the treatment of attention deficit hyperactivity disorder (ADHD) worldwide. While much has been said in the literature about the medicalization and globalization of ADHD, comparatively less is known about how these processes play out on the ground and outside English-speaking countries, where psychostimulants have become the first-line treatment for ADHD. By combining historical and clinical ethnographic research, this article charts the transnational histories and everyday lives of psychostimulants in Portugal at the nexus between what I term processes of medical globalization and social localization. It explores how international medical standards and pharmaceutical regulations converged with local prescribing trends and sociomaterial contingencies that placed this small Southern European country among the top 20 world consumers of methylphenidate. Following a methylphenidate shortage and the social explanations of clinicians, this exploration also shows how the dissemination of pharmaceutical sales and prescribing data by the media triggered a public––and increasingly politicized––debate on psychostimulant drug treatments. More broadly, this article illuminates how psychopharmaceuticals are circulated, contextualized, marketed, and modulated in their journey and it advances a relational and processual understanding of their shifting, multiscalar configurations. [ABSTRACT FROM AUTHOR]

Background: The underground market is constantly flooded with newer synthetic as alternatives to the older cathinones. Drug Enforcement Administration (DEA) has identified four cathinone compounds of particular concern: 3,4-methylenedioxy-alpha-pyrrolidinohexanophenone (3,4-MD-α-PHP), 4-chloro-α-pyrrolidinopropiophenone (4-Cl-α-PPP), alpha-pyrrolidinoisohexiophenone (α-PiHP) and 4-chloro-pentedrone (4-Cl-pentedrone). Aims: The current study aimed to evaluate the behavioral pharmacology of four synthetic cathinones Methods: 3,4-MD-α-PHP, 4-Cl-α-PPP, α-PiHP, and 4-CPD were tested for locomotor activity in mice and in a drug discrimination assay with rats trained to discriminate either methamphetamine or cocaine. Results: Locomotor stimulant effects of 3,4-MD-α-PHP ((effective dose) ED50 = 1.98 mg/kg), α-PiHP (ED50 = 2.46 mg/kg), and 4-Cl-α-PPP (ED50 = 7.18 mg/kg) were observed within 10 min following injection and lasted from 2 to 3.5 h. The stimulant action of 4-CPD (ED50 = 17.24 mg/kg) was delayed, occurring 40–70 min following injection. The maximal motor stimulant actions of 3,4-MD-α-PHP and α-PiHP 1 were equivalent to that of cocaine and methamphetamine, whereas 4-CPD (50% of cocaine) and 4-Cl-α-PPP (73% of cocaine) were less efficacious. All of the test compounds fully substituted for the discriminative stimulus effects of cocaine, 3,4-MD-α-PHP (ED50 = 2.28 mg/kg), α-PiHP (ED50 = 3.84 mg/kg), and 4-Cl-α-PPP (ED50 = 15.56 mg/kg). Only 3,4-MD-α-PHP (ED50 = 1.65 mg/kg), α-PiHP (ED50 = 1.87 mg/kg), and 4-Cl-α-PPP (ED50 = 9.79 mg/kg) fully substituted for the discriminative stimulus effects of methamphetamine. 4-Cl-pentedrone caused 55–70% methamphetamine-appropriate responding at doses that also suppressed responding and produced convulsions. Conclusions: These data indicate that 3,4-MD-α-PHP, α-PiHP, and 4-Cl-α-PPP have a potential for abuse similar to that of methamphetamine and cocaine. In contrast, 4-Cl-pentedrone may not be popular for recreational use due to its convulsant effects. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated a close link between the inflammatory response, exacerbated by circadian disruption and psychostimulants such as cocaine and methamphetamine (METH). Indicators of this inflammation include cortisol and acute-phase proteins (APPs) like C-reactive protein (CRP), complement C3 (C3), and serum amyloid A (SAA). The connection between these inflammation markers and circulating mitochondrial DNA (mtDNA) has been gaining attention. However, the specific influence of cocaine and METH on APP, cortisol, and mtDNA levels in mice with disturbed circadian rhythm has yet to be explored, which is the main aim of this research. Methods: In our study, we employed 10–12-week-old male C57BL/6J mice, which underwent an imposed 6-h phase advance every six days for a total of eight cycles. This process led to the formation of mice with disrupted circadian rhythm and sleep disorders (CRSD). We administered 11 dosages of cocaine and METH 15 mg/kg and 20 mg/kg, respectively to these CRSD mice over the course of 22 days. Quantitative assessments of CRP, C3, SAA, cortisol, and cell-free circulating mtDNA were conducted using enzyme-linked immunosorbent assay (ELISA), Western Blot, and quantitative real-time polymerase chain reaction (qRT-PCR) techniques. Results: The experiment revealed that disruption in circadian rhythm alone or cocaine or METH on their own increased CRP, C3, SAA, and cortisol levels in comparison with the control group. CRSD mice, exposed to cocaine and METH, showed a significant rise in CRP, C3, and SAA, while those without exposure remained stable. We also found a reduction in circulating cell-free mtDNA in all CRSD mice, regardless of cocaine and METH exposure. Conclusions: The findings of our study affirm that the levels of CRP, C3, SAA, and cortisol, which reflect inflammation, are enhanced by circadian disruption, cocaine, and METH, and these levels show a strong correlation with the content of circulating cell-free mtDNA. Furthermore, it also shows the potential link between the disruption of the circadian clock and the inflammatory response triggered by cocaine and METH.

Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, we showed that mice (both females and males) with a heterozygous mutation in the first coding exon of Hnrnph1 (H1+/-) showed reduced methamphetamine reinforcement and intake and dose-dependent changes in methamphetamine reward as measured via conditioned place preference. Furthermore, H1+/- mice showed a robust decrease in methamphetamine-induced dopamine release in the NAc with no change in baseline extracellular dopamine, striatal whole-tissue dopamine, dopamine transporter protein, dopamine uptake, or striatal methamphetamine and amphetamine metabolite levels. Immunohistochemical and immunoblot staining of midbrain dopaminergic neurons and their forebrain projections for TH did not reveal any major changes in staining intensity, cell number, or forebrain puncta counts. Surprisingly, there was a twofold increase in hnRNP H protein in the striatal synaptosome of H1+/- mice with no change in whole-tissue levels. To gain insight into the mechanisms linking increased synaptic hnRNP H with decreased methamphetamine-induced dopamine release and behaviors, synaptosomal proteomic analysis identified an increased baseline abundance of several mitochondrial complex I and V proteins that rapidly decreased at 30 min after methamphetamine administration in H1+/- mice. In contrast, the much lower level of basal synaptosomal mitochondrial proteins in WT mice showed a rapid increase. We conclude that H1+/- decreases methamphetamine-induced dopamine release, reward, and reinforcement and induces dynamic changes in basal and methamphetamine-induced synaptic mitochondrial function.SIGNIFICANCE STATEMENT Methamphetamine dependence is a significant public health concern with no FDA-approved treatment. We discovered a role for the RNA binding protein hnRNP H in methamphetamine reward and reinforcement. Hnrnph1 mutation also blunted methamphetamine-induced dopamine release in the NAc, a key neurochemical event contributing to methamphetamine addiction liability. Finally, Hnrnph1 mutants showed a marked increase in basal level of synaptosomal hnRNP H and mitochondrial proteins that decreased in response to methamphetamine, whereas WT mice showed a methamphetamine-induced increase in synaptosomal mitochondrial proteins. Thus, we identified a potential role for hnRNP H in basal and dynamic mitochondrial function that informs methamphetamine-induced cellular adaptations associated with reduced addiction liability.

The transition from recreational drug use to addiction involves pathological learning processes that support a persistent shift from flexible, goal-directed to habit behavioral control. Here, we examined the molecular mechanisms supporting altered function in hippocampal (HPC) and dorsolateral striatum (DLS) memory systems following abstinence from repeated cocaine. After 3 weeks of cocaine abstinence (experimenter- or self-administered), we tested new behavioral learning in male rats using a dual-solution maze task, which provides an unbiased approach to assess HPC- versus DLS-dependent learning strategies. Dorsal hippocampus (dHPC) and DLS brain tissues were collected after memory testing to identify transcriptional adaptations associated with cocaine-induced shifts in behavioral learning. Our results demonstrate that following prolonged cocaine abstinence rats show a bias toward the use of an inflexible, habit memory system (DLS) in lieu of a more flexible, easily updated memory system involving the HPC. This memory system bias was associated with upregulation and downregulation of brain-derived neurotrophic factor (BDNF) gene expression and transcriptionally permissive histone acetylation (acetylated histone H3, AcH3) in the DLS and dHPC, respectively. Using viral-mediated gene transfer, we overexpressed BDNF in the dHPC during cocaine abstinence and new maze learning. This manipulation restored HPC-dependent behavioral control. These findings provide a system-level understanding of altered plasticity and behavioral learning following cocaine abstinence and inform mechanisms mediating the organization of learning and memory more broadly.

Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive-like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll-like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia-neural communication, and the profound effects that glial-derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region-specific functions, and glia in different brain regions have distinct contributions to drug-associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug-induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction.

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS.MethodsMedications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks.ResultsUse of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02).ConclusionsConcomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome.

Objective: The lack of a screening tool for substance use disorders is a significant problem for health care workers for patient care and referral. This study aimed to develop a Substance Use Disorder Screening Test (SUDST) to enable accurate classification of the severity of substance use disorders based on the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), that can be used by health professionals in all settings for basic screening for individuals at risk of substance use disorder. Material and Methods: Following close study of the DSM-5, 11 questions were developed, which were then tested on 207 participants who were receiving treatment for the use of methamphetamines. The participants were interviewed with the SUDST, the Ministry of Public Health Version 2 (normally ‘V.2’) screening test for risk of substance use, and were clinically diagnosed by their attending psychiatrist. Results: The Cronbach’s alpha coefficient for SUDST was 0.79. The scores obtained from the SUDST were in high agreement with the V.2 and clinical diagnosis (p-value

Drug self-administration and intracranial self-stimulation (ICSS) are two preclinical behavioral procedures used to predict abuse potential of drugs, and abuse-related drug effects in both procedures are thought to depend on increased mesolimbic dopamine (DA) signaling. Drug self-administration and ICSS yield concordant metrics of abuse potential across a diverse range of drug mechanisms of action. The "rate of onset," defined as the velocity with which a drug produces its effect once administered, has also been implicated as a determinant of abuse-related drug effects in self-administration procedures, but this variable has not been systematically examined in ICSS. Accordingly, this study compared ICSS effects produced in rats by three DA transporter inhibitors that have different rates of onset (fastest to slowest: cocaine, WIN-35428, RTI-31) and that produced progressively weaker metrics of abuse potential in a drug self-administration procedure in rhesus monkeys. Additionally, in vivo photometry using the fluorescent DA sensor dLight1.1 targeted to the nucleus accumbens (NAc) was used to assess the time course of extracellular DA levels as a neurochemical correlate of behavioral effects. All three compounds produced ICSS facilitation and increased DA levels assessed by dLight. In both procedures, the rank order of onset rate was cocaine > WIN-35428 > RTI-31; however, in contrast to monkey drug self-administration results, maximum effects did not differ across compounds. These results provide additional evidence that drug-induced increases in DA drive ICSS facilitation in rats and illustrate the utility of both ICSS and photometry to evaluate the time course and magnitude of abuse-related drug effects in rats. [ABSTRACT FROM AUTHOR]

Antisocial personality disorder (AsPD) is a pervasive pattern of violation of others' rights, related to the concept of psychopathy. AsPD is stable over time from adolescence, with evidence of conduct disorder (CD) before 15 years. DSM-5 included a specifier 'with limited prosocial emotions' (LPE), which characterizes adolescents with higher developmental vulnerability to develop AsPD. Despite being relatively frequent with considerable societal impact, AsPD is a difficult-to-treat condition with high comorbidity rates and poor evidence for effective pharmacological interventions. We conducted a narrative review and searched PubMed up to September 2022. We included RCTs and naturalistic studies evaluating pharmacological interventions on AsPD in adults, including those with comorbid substance use disorder or psychopathic traits. Evidence in youths with CD, callous-unemotional (CU) traits and aggression were also reviewed, exploring the role of CU traits as moderators of response. Psychosocial interventions are the first option, with possible improvement of CU traits, beyond behavioral and affective symptoms, particularly if implemented early during development. Limited information, based on low-quality studies, supports the pharmacological options. Second-generation antipsychotics, lithium, anti-epileptic drugs, and stimulants are first-line medications, according to different target symptoms. Developmental pathways including ADHD suggest a specific role of psychostimulants. [ABSTRACT FROM AUTHOR]

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota–gut–brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels. [ABSTRACT FROM AUTHOR]

Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a β-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone remains scarcely explored in humans. Herein, we aimed to evaluate the acute pharmacological effects of methylone and its abuse potential in humans when compared with that of MDMA following oral administration under controlled conditions. Seventeen participants of both sexes (14 males, 3 females) with a previous history of psychostimulant use completed a randomized, double-blind, placebo-controlled, crossover clinical trial. Participants received a single oral dose of 200 mg of methylone, 100 mg of MDMA, and a placebo. The variables included physiological effects (blood pressure, heart rate, oral temperature, pupil diameter), subjective effects using visual analog scales (VAS), the short form of the Addiction Research Center Inventory (ARCI), the Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire (VESSPA-SSE), and the Sensitivity to Drug Reinforcement Questionnaire (SDRQ), and psychomotor performance (Maddox wing, psychomotor vigilance task). We observed that methylone could significantly increase blood pressure and heart rate and induce pleasurable effects, such as stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone exhibited an effect profile similar to MDMA, with a faster overall onset and earlier disappearance of subjective effects. These results suggest that abuse potential of methylone is comparable to that of MDMA in humans. [ABSTRACT FROM AUTHOR]

Psychostimulants interacting with the dopamine transporter (DAT) can be used illicitly or for the treatment of specific neuropsychiatric disorders. However, they can also produce severe and persistent adverse events. Often, their pharmacological properties in vitro do not fully correlate to their pharmacological profile in vivo. Here, we investigated the pharmacological effects of enantiomers of pyrovalerone, α-pyrrolidinovalerophenone, and 3,4-methylenedioxypyrovalerone as compared to the traditional psychostimulants cocaine and methylphenidate, using a variety of in vitro, computational, and in vivo approaches. We found that in vitro drug-binding kinetics at DAT correlate with the time-course of in vivo psychostimulant action in mice. In particular, a slow dissociation (i.e., slow koff) of S-enantiomers of pyrovalerone analogs from DAT predicts their more persistent in vivo effects when compared to cocaine and methylphenidate. Overall, our findings highlight the critical importance of drug-binding kinetics at DAT for determining the in vivo profile of effects produced by psychostimulant drugs. [ABSTRACT FROM AUTHOR]

• D-amphetamine induces pS32-cFos in lumbar spinal cord. • Increased pS32-cFos occurs in both inhibitory and excitatory neurons in the lumbar spinal cord. • Blockade of dopamine transporter induces pS32-cFos in lumbar spinal cord. • Increased pS32-cFos by psychostimulants is independent of locomotion. Psychostimulant drugs, such as cocaine, d-amphetamine and methylphenidate, alter a wide range of behaviors including locomotor activity and somatosensory perception. These altered behaviors are accompanied by the activation of specific neuronal populations within reward-, emotion- and locomotion-related circuits. However, whether such regulation occurs at the level of the spinal cord, a key node for neural circuits integrating and coordinating sensory and motor functions has never been addressed. By evaluating the temporal and spatial expression pattern of the phosphorylated form of the immediate early gene cFos at Ser32 (pS32-cFos), used as a proxy of neuronal activation, we demonstrate that, in adult male mice, d-amphetamine increases pS32-cFos expression in both inhibitory and excitatory neurons in dorsal and ventral horns at the lumbar spinal cord level. Interestingly, a fraction of neurons activated by a first exposure to d-amphetamine can be re-activated following d-amphetamine re-exposure. Similar expression patterns were observed in response to cocaine and methylphenidate, but not following morphine and dozilcipine administration. Finally, the blockade of dopamine reuptake was sufficient to recapitulate the increase in pS32-cFos expression induced by psychostimulant drugs. Our work provides evidence that cFos expression can be activated in lumbar spinal cord in response to acute psychostimulants administration. [ABSTRACT FROM AUTHOR]

Background Conflicting evidence suggests a possible association between use of prescribed psychostimulants during pregnancy and adverse perinatal outcomes. Methods We conducted population-based cohort studies including pregnancies conceived between April 2002 and March 2017 (Ontario, Canada; N = 554 272) and January 2003 to April 2011 [New South Wales (NSW), Australia; N  = 139 229]. We evaluated the association between exposure to prescription amphetamine, methylphenidate, dextroamphetamine or lisdexamfetamine during pregnancy and pre-eclampsia, placental abruption, preterm birth, low birthweight, small for gestational age and neonatal intensive care unit admission. We used inverse probability of treatment weighting based on propensity scores to balance measured confounders between exposed and unexposed pregnancies. Additionally, we restricted the Ontario cohort to social security beneficiaries where supplementary confounder information was available. Results In Ontario and NSW respectively, 1360 (0.25%) and 146 (0.10%) pregnancies were exposed to psychostimulants. Crude analyses indicated associations between exposure and nearly all outcomes [OR range 1.15–2.16 (Ontario); 0.97–2.20 (NSW)]. Nearly all associations were attenuated after weighting. Pre-eclampsia was the exception: odds remained elevated in the weighted analysis of the Ontario cohort (OR 2.02, 95% CI 1.42–2.88), although some attenuation occurred in NSW (weighted OR 1.50, 95% CI 0.77–2.94) and upon restriction to social security beneficiaries (weighted OR 1.24, 95% CI 0.64–2.40), and confidence intervals were wide. Conclusions We observed higher rates of outcomes among exposed pregnancies, but the attenuation of associations after adjustment and likelihood of residual confounding suggests psychostimulant exposure is not a major causal factor for most measured outcomes. Our findings for pre-eclampsia were inconclusive; exposed pregnancies may benefit from closer monitoring. [ABSTRACT FROM AUTHOR]

Investigate the treatment patterns and prescribers of stimulants for attention deficit hyperactivity disorder (ADHD) in young people in New South Wales (NSW).Longitudinal cohort study of persons born after 1983 and prescribed stimulants for ADHD as per the NSW Ministry of Health Controlled Drugs Data Collection. Results were analyzed descriptively: a) treatment prevalence by year; age; sex; b) speciality of prescribers over time; c) rate of transition from paediatrics to adult psychiatry. The main analysis covered 2003–2015, with data on general practitioner prescribing to 2023.Treatment prevalence rates were highest at age 10 (22.8 per 1000 person years), declining among teenagers and stabilizing in adulthood at 2.5 per 1000. The childhood male treatment predominance (4:1) resolved to 1.6:1 in adulthood. Paediatricians were the main prescribers until age 20. The average annual percent increase in prescribers was: adult psychiatry – 13%, general practice – 20%, paediatrics – 2.6%. Only 6.3% of treated children had transitioned to adult psychiatrists by age 25; 50% starting treatment with adult psychiatrists had no previous treatment records.The proportion on treatment and the male predominance declined substantially with age. Future studies may determine whether increased prescribing by general practitioners and psychiatrists reduces treatment attrition during adolescence. [ABSTRACT FROM AUTHOR]

Background: Despite the positive dynamics in this scientific area, the prevalence of drug pathology in Russia and other countries of the world remains unfavorable. Determination of laboratory markers of pathobiochemical processes which are characteristic to the patients with substance use disorder is promising from the standpoint of monitoring the course of the disease and evaluating the effectiveness of therapy.Objective: To determine the characteristic changes in oxidative homeostasis of patients with addiction to psychostimulants and opioids at the rehabilitation and anti‑relapse stage.Material and methods: The study was performed with the participation of 20 relatively healthy male volunteers and 18 male patients with addiction to opioids or psychostimulants who then became participants of the rehabilitation and anti‑relapse course of treatment. Changes in oxidative stress markers during rehabilitation and anti‑relapse treatment were studied.Results: In comparison to the control values at the initial stage of the study, patients of the main group demonstrated decreased values of the iron‑reducing ability of blood plasma – by 25%, as well as those of the sorption radical ability of blood plasma – by 30%; the content of thiol groups of blood plasma proteins decreased by 24% while the concentration of glutathione in erythrocyte suspension lowered by 26%. The level of TBA‑reactive products in erythrocyte suspension corresponded to the control level. The performed rehabilitation manipulations contributed to the partial normalization of oxidative homeostasis, which was confirmed by a statistically significant increase in the ability of radical sorption of blood plasma by 20% and the concentration of reduced glutathione in erythrocyte suspension by 28% in comparison to the initial values of the corresponding parameters in patients of the 2nd group. The TBA‑reactive products remained within the control values.Conclusion: The studied markers are suitable for monitoring the state of oxidative homeostasis in patients with opioid or psychostimulant addiction, the imbalance of which at the end of the rehabilitation and anti‑relapse stage also indicates the prospects for strengthening the antioxidant component as part of drug or nutritional correction.

Sport nutrition used to reduce weight or improve performance may contain psychostimulant aliphatic amines. The most common of them are DMAA, octodrine and AMP citrate. There are no toxicometric data for above compounds, which prevents their preclinical and clinical study and the formation of optimal dosing regimens or algorithms for overdose therapy. We determined that all of the above drugs have a low degree of cumulation of

RationaleThe synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone.ObjectivesThe binge-like acquisition pattern is novel for rat IVSA; thus, the present study sought to determine if this effect generalizes to IVSA of α-PVP in female rats.MethodsFemale Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers containing an activity wheel. Groups were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move.ResultsApproximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution.ConclusionThis confirms the high reinforcer effectiveness of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.

Objectives: Increased drug overdose mortality among non-Hispanic Black people in the United States in the past 5 years highlights the need for better tailored programs and services. We evaluated (1) changes in drug overdose mortality for various racial and ethnic groups and (2) drug involvement to inform drug overdose prevention efforts in Kentucky. Methods: We used Kentucky death certificates and postmortem toxicology reports from 2016-2020 (provisional data) to estimate changes in age-adjusted drug overdose death rates per 100 000 standard population. Results: The age-adjusted drug overdose death rate per 100 000 standard population among non-Hispanic Black residents doubled from 2016 (21.2) to 2020 (46.0), reaching the rate among non-Hispanic White residents in 2020 (48.7; P =.48). From 2016 to 2020, about 80% of these drug overdose deaths involved opioids; heroin involvement declined about 20 percentage points; fentanyl involvement increased about 30 percentage points. The number of psychostimulant-involved drug overdose deaths increased 513% among non-Hispanic Black residents and 191% among non-Hispanic White residents. Cocaine-involved drug overdose deaths increased among non-Hispanic Black residents but declined among non-Hispanic White residents. Drug overdose death rates were significantly lower among Hispanic residents than among non-Hispanic White residents. Conclusions: Increased opioid-involved overdose deaths among non-Hispanic Black residents in Kentucky in combination with rapidly expanding concomitant psychostimulant involvement require increased understanding of the social, cultural, and illicit market circumstances driving these rapid trend changes. Our findings underscore the urgent need to expand treatment and harm reduction services to non-Hispanic Black residents with substance use disorder. [ABSTRACT FROM AUTHOR]

Background. There was no previous meta-analysis investigating the efficacy/tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder (ADHD) in preschool children. Methods. Databases including PubMed, the Cochrane Library, EMBASE, ScienceDirect, and ClinicalTrials.gov were searched from inception to March 2022 for randomized controlled trials (RCTs) on therapeutic efficacy of psychostimulants against ADHD symptoms in preschool children (age ≤6 years) compared with placebos. Primary outcomes were (a) changes in ADHD symptoms evaluated by validated rating scales from parents’/teacher’s observation, or (b) postintervention improvements in neuropsychological performance. Secondary outcomes were risks of adverse events. Results. Meta-analysis of nine eligible trials including 544 preschool children (mean age=4.86 years, female=11.98%, median treatment duration=4.33 weeks) supported the efficacy of psychostimulants against global symptoms from observations of parents (Hedges’ g=0.6152, p<0.0001) and teachers (Hedges’ g=0.6563, p=0.0039). Efficacy of psychostimulants was also noted against symptoms of inattention and hyperactivity/impulsivity, especially the latter (i.e., main symptoms in preschool children). Moreover, male gender, older age, and longer treatment duration were associated with better efficacy. Regarding adverse events, only the risk of poor appetite was higher in the psychostimulant group (odds ratio [OR]=2.39). However, the qualities of evidence were low to very low, indicating potential discrepancy between the true and estimated effect. Conclusions. Our results showed that psychostimulants might be beneficial for preschool children with ADHD, especially hyperactivity/impulsivity from teachers’ observation, with tolerable side effects. Nevertheless, the true magnitude of the effect needs to be confirmed with more research due to low to very low certainty of the evidence. [ABSTRACT FROM AUTHOR]

Until recently, most modern neuroscience research on addiction using animal models did not incorporate manipulations of social factors. Social factors play a critical role in human addiction: social isolation and exclusion can promote drug use and relapse, while social connections and inclusion tend to be protective. Here, we discuss the state of the literature on social factors in animal models of opioid and psychostimulant preference, self-administration, and relapse. We first summarize results from rodent studies on behavioral, pharmacological, and circuit mechanisms of the protective effect of traditional experimenter-controlled social interaction procedures on opioid and psychostimulant conditioned place preference, self-administration, and relapse. Next, we summarize behavioral and brain-mechanism results from studies using newer operant social-interaction procedures that inhibit opioid and psychostimulant self-administration and relapse. We conclude by discussing how the reviewed studies point to future directions for the addiction field and other neuroscience and psychiatric fields, and their implications for mechanistic understanding of addiction and development of new treatments. [ABSTRACT FROM AUTHOR]

Objective: Psychostimulant use induces oxidative stress and alters redox imbalance, influencing epigenetic signatures in the central nervous system (CNS). Among the various epigenetic changes, DNA methylation is directly linked to oxidative stress metabolism via critical redox intermediates such as NAD+, S-adenosylmethionine (SAM), and 2-oxoglutarate. Fluctuations in these intermediates directly influence epigenetic signatures, which leads to detectable alterations in gene expression and protein modification. This review focuses on recent advances in the impact of psychostimulant use on redox-imbalance-induced DNA methylation to develop novel epigenetics-based early interventions. Methods: This review is based on collective research data obtained from the PubMed, Science Direct, and Medline databases. The keywords used in the electronic search in these databases were redox, substance use disorder, psychostimulants, DNA methylation, and neurological diseases. Results: Instability in DNA methylation levels and redox expression effects are reported in various behavioral models stimulated by psychostimulants and opioids, indicating the widespread involvement of epigenetic changes in DNA methylation signatures in neurological disorders. Discussion: This review summarizes the need for more studies and experimental evaluations of DNA-methylation-based strategies that may help to understand the association between psychostimulant use and oxidative stress or redox-linked metabolic recalibration influencing neuronal impairments. [ABSTRACT FROM AUTHOR]

L'objectif de ce travail est de déterminer la fréquence des symptômes psychotiques induits par les psychostimulants, dont les nouveaux produits de synthèse (NPS), leurs caractéristiques cliniques, leur évolution et leurs traitements. Une revue de documents sélectionnés est effectuée suivant les principes de recherche systématique dans le Medline. La recherche retrouve 41 articles portant sur les psychostimulants hors NPS et 9 articles portant sur les NPS. Les symptômes psychotiques induits par les psychostimulants, y compris NPS, sont fréquents, présentent des caractéristiques typiques avec d'importants signes positifs malgré un insight en partie conservé, une possible évolution sur un mode chronique et répondent à des traitements comme les benzodiazépines et les antipsychotiques. Un récapitulatif des implications pratiques est proposé. Les symptômes psychotiques induits par les psychostimulants pourraient constituer un trouble à part ou une vulnérabilité qui devraient faire l'objet d'une prise en charge intégrée portant à la fois sur les consommations et la symptomatologie psychiatrique. Psychostimulants such as cocaine, amphetamines and their derivatives, methamphetamine or novel synthetic drugs such as cathinones are known to cause psychotic symptoms. The objective of this study is to determine the frequency of psychotic symptoms induced by psychostimulants, including novel psychoactive substances (NPS), their clinical characteristics, their evolution, and their treatments. A review of selected documents was carried out following the principles of systematic research in Medline from 02/12/2017 to 02/12/2022. We included articles in French or English dealing with psychotic symptoms, episodes and disorders induced by psychostimulants in humans, and excluded articles dealing with animal models, those not distinguishing between substances other than psychostimulants, and NPS and non-NPS psychostimulants, and articles focusing exclusively on individuals with previously diagnosed schizophrenia. The data was input in a table for non-NPS psychostimulants and another table for NPS psychostimulants. The search found 41 articles on non-NPS psychostimulants and 9 articles on NPS. Psychotic symptoms induced by psychostimulants, including NPS, are frequent in a population of medicalized consumers: 18 to 80% according to studies. Psychotic symptoms show typical features with prominent positive symptoms, especially persecutory delirium, auditory, visual and tactile hallucinations, less negative, and cognitive symptoms. We noted more agitation, even auto-aggressiveness or hetero-aggressiveness. The clinical presentation is frequently accompanied by signs of toxic impregnation, in particular tachycardia, palpitations, hypertension, sweating or mydriasis. The data suggest a possible evolution in a chronic presentation. Psychostimulant-induced psychotic symptoms appear to be improved by treatments such as benzodiazepines for agitation and antipsychotics. The data was less rich regarding NPS but broadly consistent with the findings presented above. A summary of practical implications is provided. The psychotic symptoms induced by psychostimulants present specific, although not exclusive, characteristics. They should be the subject of particular attention, in especially looking for urinary toxins, although certain substances such as cathinones are not detected by current laboratory practices. They may be subject to a specific treatment depending on their severity and duration. In some cases, they could evolve into a chronic presentation and constitute a separate disorder or a vulnerability that should be the subject of integrated care covering both consumptions and psychiatric symptoms. [ABSTRACT FROM AUTHOR]

Amphetamine (AMPH) abuse represents a major global public health issue, highlighting the urgent need for effective therapeutic interventions to manage addiction caused by this psychostimulant. This study aimed to assess the potential of m-trifluoromethyl-diphenyldiselenide [(m-CF 3 -PhSe) 2 ] in preventing the addictive effects induced by AMPH through targeting dopamine metabolism proteins. (m-CF 3 -PhSe) 2 is of interest due to its demonstrated efficacy in mitigating opioid abuse, establishing it as a promising candidate for addiction treatment research. Initially, in silico studies examined the affinity of AMPH and (m-CF 3 -PhSe) 2 for dopamine 1, 2, and 3 receptors (D1R, D2R, D3R), and dopamine transporter (DAT). In our experimental design, male Wistar rats were divided into four groups: I) Control; II) (m-CF 3 -PhSe) 2 ; III) AMPH; IV) (m-CF 3 -PhSe) 2  + AMPH. Animals were administered (m-CF 3 -PhSe) 2 (0.1 mg/kg, by gavage) or canola oil (vehicle) 30 min before AMPH (4.0 mg/kg, i.p.) administration. Drug administration occurred for 8 days in the conditioned place preference (CPP) paradigm. Twenty-four hours after the last CPP conditioning section, preference for the drug-compartment was assessed, with anxiety-related effects and working memory were evaluated using the Y-maze test. Finally, animals were euthanized for striatal dissection to quantify D1R, D2R, D3R, and DAT levels in western blot. In silico findings suggest that (m-CF 3 -PhSe) 2 may prevent AMPH activation in DAT, interacting with Asp46 and Phe319, preventing possible addictive effects of AMPH in DAT. In vivo results showed that (m-CF 3 -PhSe) 2 attenuated AMPH effects, reducing preference for the drug-compartment in CPP test. Furthermore, (m-CF 3 -PhSe) 2 prevented AMPH-induced anxiogenic effects in the elevated plus maze (EPM) test, similarly to light/dark test. No differences in locomotion or working memory were observed among the experimental groups in the Y-maze test. Ex vivo western blot analyses of the entire striatum indicates that (m-CF 3 -PhSe) 2 prevented the AMPH-induced increase in D1R levels and decrease in D2R and DAT levels, with no changes in D3R levels. Overall, our study suggests that (m-CF 3 -PhSe) 2 may interact with DAT sites similarly to AMPH, reducing drug-compartment preference and anxiogenic behaviors while maintaining dopaminergic metabolism proteins in the striatum, a key region involved in the onset and perpetuation of addiction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing for financial interests or personal relationships., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Many patients are taking psychotropic medications concomitantly with repetitive transcranial magnetic stimulation (rTMS), the latter of which is indicated for the treatment of moderate and severe depressive episodes that have not responded to first-line pharmacotherapy. While preclinical evidence suggests that psychotropic drugs can generally affect rTMS, the specific effect on the clinical response of rTMS for depression is not fully clear. A systematic search of all papers published prior to January 2023 in PubMed, APA, PsycInfo, and Scopus was conducted to identify clinical studies that examine the effects of different psychotropic medications on clinical outcomes in patients undergoing rTMS for depression. A total of 10 articles were identified and extracted for inclusion. This review outlines the results from 10 clinical studies and summarizes the current state of the literature describing rTMS outcomes with concomitant use of several groups of psychotropic agents, including antipsychotics, mood stabilizers, psychostimulants, and benzodiazepines. Antidepressants were excluded from this review due to the evidence base that already exists describing their efficacy with and without rTMS., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Funding support for the publication of this review was provided by Hackensack Meridian Health. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Intrator et al.)

ABSTRACT BACKGROUND: Attention deficit hyperactivity disorder (ADHD) has a prevalence of 5.3% among children and adolescents. It is characterized by attention deficit, hyperactivity, and impulsivity. OBJECTIVE: We aimed to conduct a survey involving pediatric neurologists in the management of ADHD and compare the results with the current literature and guidelines. DESIGN AND SETTING: Descriptive analytical study of a virtual environment, was used Test of equality of proportions for comparison between two groups of pediatric neurologists (working as specialists for > 6 versus ≤ 6 years), with a significance level of P = 0.05. METHODS: This cross-sectional study used a virtual questionnaire covering the steps in the diagnosis and treatment of children with ADHD. The inclusion criteria were professionals who had completed their residency/specialization in pediatric neurology and clinical neurologists working in pediatric neurology. RESULTS: Among the 548 electronic invitations sent, 128 were considered valid. For all participants, the diagnosis was clinically based on the disease classification manuals. Combination treatment promotes improvement of symptoms (96.9%). Among psychostimulants, short-acting methylphenidate was the most commonly prescribed medication (85.2%). Headache was the most common side effect (77.3%). Altogether, 73.4% of the participants requested laboratory tests, 71.1% requested an electrocardiogram, and 42.2% requested an electroencephalogram. Pediatric neurologists working as specialists for ≤ 6 years had more frequent referrals to psycho-pedagogists for diagnosis (P = 0.03). CONCLUSIONS: The participants complied with clinical guidelines, emphasizing the relevance of diagnostic manuals and treatment guidelines for an eminently clinical situation and enabling uniformity in quality treatment.

This narrative review examines two of the common comorbidities of attention-deficit/hyperactivity disorder, bipolar disorder (BD), and borderline personality disorder (BPD), which each share several common features with ADHD that can make assessment and diagnosis challenging. The review highlights some of the key symptomatic differences between adult ADHD and these disorders, allowing for more careful consideration before establishing a formal diagnosis. When the disorders are found to be comorbid, further complications may arise; thus, the review will also help to provide evidence-based treatment recommendations as well as suggestions on how to minimize adverse events. Incorporating evidence from systematic reviews, journal articles, randomized controlled trials, and case reports, this review highlights that the diagnosis of ADHD and some of its common comorbidities is challenging and requires full, in-depth assessment and management. The management strategies of these comorbidities will also be addressed, with emphasis on achieving mood stabilization for BD prior to initiating appropriate ADHD pharmacotherapy. Medications, specifically mood stabilizers, antipsychotics, and antidepressants, are fundamental in treating symptoms seen in BD and some cases of BPD, alongside psychotherapy and lifestyle modifications when appropriate. The review highlights the effectiveness of specific medications, including psychostimulants, atomoxetine, and bupropion, as add-on therapies to mood-stabilizing treatments for addressing ADHD symptoms in patients with these comorbidities. Despite limited research, the review will address various pharmacological and psychotherapeutic approaches for managing comorbid ADHD and BPD, emphasizing the need for further investigations to better understand the unique needs of this patient population.

Crystal methamphetamine, a potent psychostimulant, presents a complex clinical landscape. However, insights into the predisposing factors for suicidal tendencies among Iraqi users remain limited. Our study delves into these risks among 165 patients. Rigorous multivariable analysis was conducted, employing binary logistic regression, drawing from patients from Baghdad Medical City and Ibn-Rushd Teaching Hospital. Most participants were in their third decade (26.62 ± 0.53 years). Regarding suicidal ideation, our model demonstrated robust accuracy, supported by the Hosmer–Lemeshow goodness-of-fit test (NagelKerke’s R2 = 0.49, accuracy = 79.4%, p = 0.885). Notably, chronic methamphetamine use exceeding a year (OR = 6.15, p = 0.001), absence of psychological trauma (OR = 4.58, p = 0.006), and incidence of visual hallucinations (OR = 4.52, p = 0.001) rendered users more susceptible to suicidal ideation. Furthermore, our investigation unveiled risk factors tied to psychotic features and withdrawal manifestations. The study underscores pivotal predictors of suicidal ideation, warranting interdisciplinary vigilance from psychiatrists, clinical psychologists, and social workers. By monitoring at-risk individuals, progression toward the intricate spectrum of suicide can be potentially averted. These findings illuminate the urgency of tailored interventions for crystal methamphetamine users, contributing to enhanced holistic care.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. It was once thought to be a disorder affecting only children, but in those undiagnosed in childhood, symptoms do not disappear with age. There is now a growing recognition of the late diagnosis and treatment of adults with ADHD. The first-line drug in pharmacotherapy is methylphenidate, and information about its adverse effects, when used by adults, has not been as extensively described as in children. The aim of this article was to review the literature describing the risks of methylphenidate therapy for adults with ADHD. A total of 19 articles—15 clinical trials and 4 case reports presenting rare side effects resulting from methylphenidate therapy, such as reversible ischemic stroke, myocardial infarction, and psychotic episodes, were analyzed. The analysis from clinical trials included 3458 adult patients with ADHD and described the most common side effects, psychiatric adverse events, effects of methylphenidate treatment on sleep, laboratory results, body mass, and cardiovascular symptoms. Methylphenidate treatment is well tolerated, with side effects described, according to severity, as mild to moderate. We conclude that pharmacotherapy is not risk-free and methylphenidate, due to its side effects, may not be the first drug of choice for every patient.

While effectively the 'first antidepressants', the psychostimulants are rarely prescribed as antidepressant drugs seemingly in light of their judged low effectiveness, side effects, tolerance as well as concerns about dependency and abuse. Recent meta-analyses do find some support for them as being effective antidepressants for those with major depression, but they have not been closely evaluated in terms of their specific nuanced role for treating treatment-resistant (unipolar and bipolar) melancholic depression. The author has so prescribed them for over a decade and offers a case for their benefits for a distinct percentage of those with such conditions and notes their relatively few side effects. [ABSTRACT FROM AUTHOR]

Glucose is the brain's primary energetic resource. The brain's use of glucose is dynamic, balancing delivery from the neurovasculature with local metabolism. Although glucose metabolism is known to differ in humans with and without methamphetamine use disorder (MUD), it is unknown how central glucose regulation changes with acute methamphetamine experience. Here, we determined how intravenous methamphetamine regulates extracellular glucose levels in a brain region implicated in MUDlike behavior, the lateral hypothalamus (LH). We measured extracellular LH glucose in awake adult male and female drug-naive Wistar rats using enzyme-linked amperometric glucose biosensors. Changes in LH glucose were monitored during a single session after: 1) natural nondrug stimuli (novel object presentation and a tail-touch), 2) increasing cumulative doses of intravenous methamphetamine (0.025, 0.05, 0.1, and 0.2 mg/kg), and 3) an injection of 60 mg of glucose. We found second-scale fluctuations in LH glucose in response to natural stimuli that differed by both stimulus type and sex. Although rapid, second-scale changes in LH glucose during methamphetamine injections were variable, slow, minute-scale changes following most injections were robust and resulted in a reduction in LH glucose levels. Dose and sex differences at this timescale indicated that female rats may be more sensitive to the impact of methamphetamine on central glucose regulation. These findings suggest that the effects of MUD on healthy brain function may be linked to how methamphetamine alters extracellular glucose regulation in the LH and point to possible mechanisms by which methamphetamine influences central glucose metabolism more broadly. [ABSTRACT FROM AUTHOR]

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For decades, psychostimulants have been the gold standard pharmaceutical treatment for attention-deficit/hyperactivity disorder (ADHD). In the United States, an astounding 9% of all boys and 4% of girls will be prescribed stimulant drugs at some point during their childhood. Recent meta-analyses have revealed that individuals with ADHD have reduced brain volume loss later in life (>60 y.o.) compared to the normal aging brain, which suggests that either ADHD or its treatment may be neuroprotective. Crucially, these neuroprotective effects were significant in brain regions (e.g., hippocampus, amygdala) where severe volume loss is linked to cognitive impairment and Alzheimer’s disease. Historically, the ADHD diagnosis and its pharmacotherapy came about nearly simultaneously, making it difficult to evaluate their effects in isolation. Certain evidence suggests that psychostimulants may normalize structural brain changes typically observed in the ADHD brain. If ADHD itself is neuroprotective, perhaps exercising the brain, then psychostimulants may not be recommended across the lifespan. Alternatively, if stimulant drugs are neuroprotective, then this class of medications may warrant further investigation for their therapeutic effects. Here, we take a bottom-up holistic approach to review the psychopharmacology of ADHD in the context of recent models of attention. We suggest that future studies are greatly needed to better appreciate the interactions amongst an ADHD diagnosis, stimulant treatment across the lifespan, and structure-function alterations in the aging brain. [ABSTRACT FROM AUTHOR]