Central Stimulation Research Articles

Providing Patients Caffeinated Coffee in PICUS

Caffeine is a legally available, widely consumed psychoactive substance with mild central nervous system stimulant properties. There is sufficient caffeine in a cup of coffee to have a stimulant effect. Caffeine can adversely affect some mental health symptoms, notably sleep and anxiety. Effects would be worse if consumed excessively. This survey aimed to describe the pattern of provision of caffeinated coffee to patients admitted to UK adult psychiatric intensive care units (PICUs) in order to inform local practice. All NHS adult PICUs across the UK were contacted to establish what type of coffee they routinely provided to their patients. Two thirds of PICUs provided only decaffeinated instant coffee to their patients. However, a minority provided caffeinated coffee in an unregulated manner, including three units which did not routinely offer decaffeinated coffee. National guidance to inform and direct the practice of providing or restricting the consumption of drinks containing psychoactive substances on a PICU may be beneficial.

The jugular venous-to-arterial difference during rebreathing and end-tidal forcing: Relationship with cerebral perfusion.

We examined two assumptions of the modified rebreathing technique for the assessment of the ventilatory central chemoreflex (CCR) and cerebrovascular CO2 reactivity (CVR), hypothesizing: (1) that rebreathing abolishes the gradient between the partial pressures of arterial and brain tissue CO2 [measured via the surrogate jugular venous and arterial difference (Pjv-a CO2 )] and (2) rebreathing eliminates the capacity of CVR to influence the Pjv-a CO2 difference, and thus affect CCR sensitivity. We also evaluated these variables during two separate dynamic end-tidal forcing (ETF) protocols (termed: ETF-1 and ETF-2), another method of assessing CCR sensitivity and CVR. Healthy participants were included in the rebreathing (n=9), ETF-1 (n=11) and ETF-2 (n=10) protocols and underwent radial artery and internal jugular vein (advanced to jugular bulb) catheterization to collect blood samples. Transcranial Doppler ultrasound was used to measure middle cerebral artery blood velocity (MCAv). The Pjv-a CO2 difference was not abolished during rebreathing (6.2± 2.6mmHg; P<0.001), ETF-1 (9.3± 1.5mmHg; P<0.001) or ETF-2 (8.6±1.4mmHg; P<0.001). The Pjv-a CO2 difference did not change during the rebreathing protocol (-0.1±1.2mmHg; P=0.83), but was reduced during the ETF-1 (-3.9±1.1mmHg; P<0.001) and ETF-2 (-3.4±1.2mmHg; P=0.001) protocols. Overall, increases in MCAv were associated with reductions in the Pjv-a CO2 difference during ETF (-0.095±0.089mmHgcm-1 s-1 ; P=0.001) but not during rebreathing (-0.028±0.045mmHg·cm-1 ·s-1 ; P=0.067). These findings suggest that, although the Pjv-a CO2 is not abolished during any chemoreflex assessment technique, hyperoxic hypercapnic rebreathing is probably more appropriate to assess CCR sensitivity independent of cerebrovascular reactivity to CO2 . KEY POINTS: Modified rebreathing is a technique used to assess the ventilatory central chemoreflex and is based on the premise that the rebreathing method eliminates the difference between arterial and brain tissue . Therefore, rebreathing is assumed to isolate the ventilatory response to central chemoreflex stimulation from the influence of cerebral blood flow. We assessed these assumptions by measuring arterial and jugular venous bulb and middle cerebral artery blood velocity during modified rebreathing and compared these data against data from another test of the ventilatory central chemoreflex using hypercapnic dynamic end-tidal forcing. The difference between arterial and jugular venous bulb remained present during both rebreathing and end-tidal forcing tests, whereas middle cerebral artery blood velocity was associated with the difference during end-tidal forcing but not rebreathing. These findings offer substantiating evidence that clarifies and refines the assumptions of modified rebreathing tests, enhancing interpretation of future findings.

Quantitative Analysis of Caffeine in different commercial kinds of coffee in Iraq

Caffeine is a widely consumed pharmacologically active substance around the world, Caffeine is a purine alkaloid derived from methylxanthine that is readily permeable through the blood-brain barrier and stimulates the adenosine receptors in the brain leading to its central nervous system stimulant activity. Most people regulate their caffeine consumption in accordance with the objective and subjective effects produced from the methylxanthine, However, individual response to caffeine varies greatly from person to person due to the variation in metabolism, age, sex, hormones, clearance, weight, genes, medicine intake and smoking behavior, therefore the amount of caffeine required to achieve the desired effect also varies greatlyand Since that the coffee beans are the world's primary sources of dietary caffeine this study was designed to determine the percent of the caffeine in different commercial coffee brands, the isolated caffeine was identified by different qualitative methods like TLC, and FTIR.

Assessment of efficacy of drug evaluation and classification program in Florida

Objective The present study aims to assess the effectiveness of the Drug Evaluation and Classification (DEC) program in Florida. Methods Data from 236 completed DEC evaluations of central nervous system (CNS) depressants, CNS stimulants, narcotic analgesics, and cannabis were analyzed using a classification process comprising toxicology findings and corresponding Drug Recognition Expert (DRE) opinions. A series of standard measures (sensitivity, specificity, false-alarm rate, miss rate, corroboration, and accuracy) were calculated to assess the effectiveness of the DEC program. Results DREs provided 172 correct opinions and 23 missed opinions, resulting in an accuracy rate of 88%, sensitivity rate of 97%, specificity rate of 23%, false alarm rate of 77%, miss rate of 3%, and corroboration rate of 91%. The 12-step DRE protocol of the DEC program therefore has the desired effect of DREs formulating correct opinions. The specificity and false alarm rate were influenced by the restricted testing procedures in the state of Florida. In general, law enforcement officers certified in the DEC program with specialized training can identify drugged drivers and the correct drug category of the drug causing impairment at the time of operating a vehicle. The DEC program goals are met through rigorous training and a curriculum establishing the 12-step DRE protocol. Conclusions DRE drug classification opinions identify drugged drivers. The limitations of Florida’s biological sample testing procedures have an impact on the specificity of DRE opinions. Addressing these limitations could increase the confirmation rates of the presence of drugs in the individual’s biological samples, which would directly impact the conviction rates in DUI-related criminal cases. Further Florida’s testing procedures need to be further studied and updated to improve the DEC program in Florida.

Cocaine use is associated with cerebral white matter hyperintensities in HIV disease.

White matter hyperintensities (WMH), a marker of cerebral small vessel disease and predictor of cognitive decline, are observed at higher rates in persons with HIV (PWH). The use of cocaine, a potent central nervous system stimulant, is disproportionately common in PWH and may contribute to WMH. The sample included of 110 PWH on antiretroviral therapy. Fluid-attenuated inversion recovery (FLAIR) and T1-weighted anatomical MRI scans were collected, along with neuropsychological testing. FLAIR images were processed using the Lesion Segmentation Toolbox. A hierarchical regression model was run to investigate predictors of WMH burden [block 1: demographics; block 2: cerebrovascular disease (CVD) risk; block 3: lesion burden]. The sample was 20% female and 79% African American with a mean age of 45.37. All participants had persistent HIV viral suppression, and the median CD4+ T-cell count was 750. Nearly a third (29%) currently used cocaine regularly, with an average of 23.75 (SD = 20.95) days in the past 90. In the hierarchical linear regression model, cocaine use was a significant predictor of WMH burden (β = .28). WMH burden was significantly correlated with poorer cognitive function (r = -0.27). Finally, higher WMH burden was significantly associated with increased serum concentrations of interferon-γ-inducible protein 10 (IP-10) but lower concentrations of myeloperoxidase (MPO); however, these markers did not differ by COC status. WMH burden is associated with poorer cognitive performance in PWH. Cocaine use and CVD risk independently contribute to WMH, and addressing these conditions as part of HIV care may mitigate brain injury underlying neurocognitive impairment.

Structure-Activity Relationships for a Recently Controlled Synthetic Cathinone Dopamine Transporter Reuptake Inhibitor: α-Pyrrolidinohexiophenone (α-PHP).

α-Pyrrolidinohexiophenone (α-PHP) is the one-carbon unit α-extended homolog of the better-known and widely abused synthetic cathinone central stimulant α-PVP ("flakka"); both are now U.S. Schedule I controlled substances. Structurally, α-PVP and α-PHP possess a common terminal N-pyrrolidine moiety and differ only with respect to the length of their α-alkyl chain. Using a synaptosomal assay, we previously reported that α-PHP is at least as potent as α-PVP as a dopamine transporter (DAT) reuptake inhibitor. A systematic structure-activity study of synthetic cathinones (e.g., α-PHP) as DAT reuptake inhibitors (i.e., transport blockers), a mechanism thought responsible for their abuse liability, has yet to be conducted. Here, we examined a series of 4-substituted α-PHP analogues and found that, with one exception, all behaved as relatively (28- to >300-fold) selective DAT versus serotonin transporter (SERT) reuptake inhibitors with DAT inhibition potencies of most falling within a very narrow (i.e., <3-fold) range. The 4-CF3 analogue of α-PHP was a confirmed "outlier" in that it was at least 80-fold less potent than the other analogues and displayed reduced (i.e., no) DAT vs SERT selectivity. Consideration of various physicochemical properties of the CF3 group, relative to that of the other substituents involved here, provided relatively little insight. Unlike with DAT-releasing agents, as previously reported by us, a QSAR study was precluded because of the limited range of empirical results (with the exception of the 4-CF3 analogue) for DAT reuptake inhibition.

Role of Brain Endothelin Receptor Type B (ETB) in the Regulation of Tyrosine Hydroxylase in the Olfactory Bulb of DOCA-Salt Hypertensive Rats.

We previously reported that endothelins (ETs) regulate tyrosine hydroxylase (TH) activity and expression in the olfactory bulb (OB) of normotensive and hypertensive animals. Applying an ET receptor type A (ETA) antagonist to the brain suggested that endogenous ETs bind to ET receptor type B (ETB) to elicit effects. The aim of the present work was to evaluate the role of central ETB stimulation on the regulation of blood pressure (BP) and the catecholaminergic system in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt hypertensive rats were infused for 7 days with cerebrospinal fluid or IRL-1620 (ETB receptor agonist) through a cannula placed in the lateral brain ventricle. Systolic BP (SBP) and heart rate were recorded by plethysmography. The expression of TH and its phosphorylated forms in the OB were determined by immunoblotting, TH activity by a radioenzymatic assay, and TH mRNA by quantitative real-time polymerase chain reaction. Chronic administration of IRL-1620 decreased SBP in hypertensive rats but not in normotensive animals. Furthermore, the blockade of ETB receptors also decreased TH-mRNA in DOCA-salt rats, but it did not modify TH activity or protein expression. These findings suggest that brain ETs through the activation of ETB receptors contribute to SBP regulation in DOCA-salt hypertension. However, the catecholaminergic system in the OB does not appear to be conclusively involved although mRNA TH was reduced. Present and previous findings suggest that in this salt-sensitive animal model of hypertension, the OB contributes to chronic BP elevation.

Behavioral, electrocorticographic and electrocardiologic changes in Colossoma macropomum (Tambaqui) in the effect of cunaniol.

The Clibadium spp. is a shrub of occurrence in the Amazon, popularly known as Cunambi. The compounds in the leaves demonstrate ichthyotoxic properties, and its major substance, cunaniol, is a powerful central nervous system stimulant with proconvulsant activity. Few current studies relate behavioral changes to the electrophysiological profile of fish poisoning. This study aimed to describe the behavioral, electromyographic, electroencephalographic, electrocardiographic, and seizure control characteristics of anticonvulsant drugs in Colossoma macropomum submitted to cunaniol intoxication during bathing containing 0.3 μg/L cunaniol. The behavioral test showed rapid evolution presenting excitability and spasms, which were confirmed by the analysis of Electroencephalogram (EEG), Electromyogram (EMG), and changes in cardiac function detected in the ECG. Cunaniol-induced excitability control was evaluated using three anticonvulsant agents: Phenytoin, Phenobarbital, and Diazepam. While phenytoin was not effective in seizure control, diazepam proved to be the most efficient. These results demonstrate the susceptibility of Colossoma macropomum to cunaniol poisoning, given that the central nervous system and electrocardiographic changes were considered severe.

Methamphetamine increases force of contraction in isolated human atrial preparations through the release of noradrenaline

We measured the cardiac contractile effects of the sympathomimetic amphetamine-like drug methamphetamine alone and in the presence of cocaine or propranolol in human atrial preparations. For a more comprehensive analysis, we also examined the effects of methamphetamine in preparations from the left and right atria of mice and, for comparison, analyzed the cardiac effects of amphetamine itself. In human atrial preparations, methamphetamine and amphetamine increased the contractile force, the relaxation rate, and the rate of tension development, and shortened the time to maximum tension and the time to relaxation. Likewise, in mice preparations, methamphetamine and amphetamine increased the contractile force in the left atrium and increased the beating rate in the right atrium. The effect in human atrial preparations started at 1 µM, therefore methamphetamine was less effective and potent than isoproterenol in increasing contractile force. These positive inotropic effects of methamphetamine were greatly attenuated by 10 µM cocaine and abolished by 10 µM propranolol. The inotropic effects of methamphetamine in human atrial preparations were associated with, and are believed to be mediated at least in part by, an increase in the phosphorylation state of the inhibitory subunit of troponin. In conclusion, the sympathomimetic central stimulant drug methamphetamine (as well as amphetamine) increased contractile force and protein phosphorylation, presumably through a release of noradrenaline in isolated human atrial preparations. Thus, methamphetamine acts as an indirect sympathomimetic in the human atrium.

Clinical study of melodic intonation therapy combined with transcranial direct current stimulation for post-stroke aphasia: a single-blind, randomized controlled trial.

Globally, more than 10 million new stroke cases occur annually, of which aphasia accounts for about one-third. Aphasia has become an independent predictor of functional dependence and death for the stroke population. The closed-loop rehabilitation of combining behavioral therapy with central nerve stimulation seems to be the research trend of post-stroke aphasia (PSA) due to its advantages in improving linguistic deficits. To verify the clinical efficacy of a closed-loop rehabilitation program combining melodic intonation therapy (MIT) with transcranial direct current stimulation (tDCS) for PSA. This was a single-center, assessor-blinded, randomized controlled clinical trial, which screened 179 patients and included 39 PSA subjects, with the registration number ChiCTR2200056393 in China. Demographic and clinical data were documented. The primary outcome was the Western Aphasia Battery (WAB) used to assess language function, and the secondary outcomes included Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment (FMA), and Barthel Index (BI) for evaluating cognition, motor, and activities of daily living, respectively. With the computer-generated randomization sequence, subjects were randomly divided into the conventional group (CG), MIT combined with sham stimulation group (SG), and MIT combined with tDCS group (TG). After the three-week intervention, the functional changes in each group were analyzed by the paired sample T-test, and the functional difference between the three groups was analyzed by ANOVA. There was no statistical difference on the baseline. After the intervention, the WAB's aphasia quotient (WAB-AQ), MoCA, FMA, and BI were statistically different in SG and TG, including all the sub-items in WAB and FMA, while only listening comprehension, FMA, and BI were statistically different in CG. The differences of WAB-AQ, MoCA, and FMA were statistically different among the three groups, but BI was not. The post hoc test results revealed that the changes of WAB-AQ and MoCA in TG were more significant than the others. MIT combined with tDCS can augment the positive effect on language and cognitive recovery in PSA.

Pharmacology of R-(-)-Methamphetamine in Humans: A Systematic Review of the Literature.

Methamphetamine exists as two stereoisomers: S-(+)-methamphetamine ((+)-MAMP) and R-(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central nervous system stimulant, available as a pharmaceutical and clandestine drug of abuse. However, the (-)-MAMP stereoisomer is less well understood despite commercial availability for over 30 years as an over-the-counter (OTC) nasal decongestant in the Vicks Vapor Inhaler (a product of Procter & Gamble). Recently, several generic versions have become available, decreasing the cost and increasing the availability of (-)-MAMP-containing nasal sprays to consumers. Despite widespread commercial availability and use in the United States, a paucity of literature exists on the pharmacology of (-)-MAMP in humans. This knowledge gap is problematic, given the difficulty in separating (-)-MAMP and (+)-MAMP isomers in laboratory assays for workplace drug testing, suspected impaired drivers, post-mortem investigations, and assessment of drug involvement in crimes. In response, this systematic review of the literature coalesces and summarizes available knowledge of (-)-MAMP pharmacology in humans. It was found that available knowledge relies heavily on urine drug and metabolite concentrations, systematic pharmacokinetics studies are lacking, and existing knowledge has been derived from a total of 99 unique participants. The impacts of highlighted gaps in the literature are discussed, focusing on forensic toxicology and law enforcement, and future research directions are suggested.

EPH68 Impact of Treatment with Central Nervous System Stimulant and Risk of Substance Use Disorder in Adults with Attention-Deficit/Hyperactivity Disorder in West Virginia

Our objectives were to examine the relative risk of substance use disorder (SUD) and impact of SUD on healthcare resource utilization (HRU) among adults with Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) who were prescribed with stimulant compared who were not.

Salience and hedonic experience as predictors of central stimulant treatment response in ADHD – A resting state fMRI study

BackgroundRoughly 20–30% of patients with Attention-deficit/hyperactivity disorder (ADHD) fail to respond to central stimulant (CS) medication. Genetic, neuroimaging, biochemical and behavioral biomarkers for CS response have been investigated, but currently there are no biomarkers available for clinical use that help identify CS responders and non-responders. MethodsIn the present paper, we studied if incentive salience and hedonic experience evaluated after a single-dose CS medication could predict response and non-response to CS medication. We used a bipolar visual analogue ‘wanting’ and ‘liking’ scale to gauge incentive salience and hedonic experience in 25 healthy controls (HC) and 29 ADHD patients. HC received 30 mg methylphenidate (MPH) and ADHD patients received either MPH or lisdexamphetamine (LDX) as selected by their clinician, with dosage individually determined for optimal effect. Clinician-evaluated global impression – severity (CGI-S) and improvement (CGI-I) and patient-evaluated improvement (PGI-I) were used to assess response to CS medication. Resting state functional magnetic resonance imaging (fMRI) was conducted before and after single-dose CS to correlate wanting and liking scores to changes in functional connectivity. ResultsRoughly 20% of the ADHD patients were CS non-responders (5 of 29). CS responders had significantly higher incentive salience and hedonic experience scores compared to healthy controls and CS non-responders. Resting state fMRI showed that wanting scores were significantly associated to changes in functional connectivity in ventral striatum including nucleus accumbens. ConclusionIncentive salience and hedonic experience evaluated after a single-dose CS medication segregate CS responders and non-responders, with corresponding neuroimaging biomarkers in the brain reward system.

Heavy Metals and Cardiovascular Disease on Wetlands

Heavy metals are metal elements with a relatively high density compared to water. One area that is vulnerable to heavy metal pollution is the wetland environment. In South Kalimantan, an alkaline land area, pollution is mainly caused by mining activities, especially coal mining and oil palm plantation activities. The presence of heavy metals in the sediments of the Martapura River in South Kalimantan, which have passed the threshold for sediment contamination, includes Mn, Fe and Hg. The potential link between chronic heavy metal exposure and cardiovascular disease (CVD) has several implications. Although the cardiovascular system is not usually viewed as the main target of heavy metal toxicity, imbalances in antioxidant protection mechanisms lead to oxidative stress in cells as a major effect of heavy metal exposure. Heavy metals can cause oxidative stress by producing reactive oxygen species (ROS). Heavy metals are associated with an increase in systemic inflammation. They can lead to impaired immune function and accumulation of immune complexes, causing CVD, including the uncontrolled release of inflammatory cytokines, kidney damage, and central nervous system stimulation. However, some research results are contradictory and say no relationship exists between heavy metals, such as mercury, and cardiovascular disease. The presence of heavy metals is still a health risk in wetlands. Metal content that crosses this threshold can be a cause or a risk factor for cardiovascular disease. The effects of heavy metal content, such as mercury, on health, especially cardiovascular disease, are still not fully understood, requiring further investigation and research.

Feasibility and tolerability of moderate intensity regular physical exercise as treatment for core symptoms of attention deficit hyperactivity disorder: a randomized pilot study.

Attention deficit hyperactivity disorder (ADHD) is associated with sedentary lifestyle, low quality of life and low physical fitness. Studies in children with ADHD have shown that regular physical exercise can help reduce core ADHD symptoms, but evidence for this is lacking in adults. Although guidelines recommend multi-modal treatment, central stimulants (CS) remain the mainstay of treatment. CS are effective in the short-term, but their long-term efficacy remains to be established. There is thus huge unmet need for developing non-pharmacological treatment options, and for well-designed randomized controlled trials (RCTs). The study aimed to test the feasibility and tolerability of structured moderate-intensity 12-week physical exercise program for adults with ADHD, as a prelude to an adequately powered RCT which includes long-term follow-up. Fourteen adults with ADHD were recruited, 9 randomized to an intervention group and 5 to a control group. The intervention group received physiotherapist-led 50-minute mixed exercise program, three times a week for 12 weeks, and the control group treatment as usual. Participants were assessed at baseline and after 6 and 12 weeks using clinical and physical evaluations, self-rating questionnaires, and functional magnetic resonance imaging (fMRI) together with paradigms that tested attention, impulsivity and emotion regulation. Three participants (21%) dropped out shortly after inclusion before receiving any intervention, while roughly 80% completed the intervention according to protocol. One participant from the intervention group participated in less than 60% of treatment sessions, and one who had done baseline fMRI was unwilling to do post-intervention imaging. Four participants in the intervention group (67%) reported increased stress in prioritizing the intervention due to time-management difficulties. Overall, consistent trends were observed that indicated the feasibility and potential benefits of the intervention on core ADHD symptoms, quality of life, body awareness, sleep and cognitive functioning. Physiotherapist-led twelve-week regular physical exercise is a feasible and potentially beneficial intervention for adults with ADHD. There was a 20% drop-out initially and 67% of those who completed the intervention reported stress with time management difficulties due to participation. A third arm was thus added to the planned RCT where cognitive intervention administered by an occupational therapist will be given together with physical exercise.Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT05049239.

Regulation of arousal and performance of a healthy non-human primate using closed-loop central thalamic deep brain stimulation.

Application of closed-loop approaches in systems neuroscience and brain-computer interfaces holds great promise for revolutionizing our understanding of the brain and for developing novel neuromodulation strategies to restore lost function. The anterior forebrain mesocircuit (AFM) of the mammalian brain is hypothesized to underlie arousal regulation of the cortex and striatum, and support cognitive functions during wakefulness. Dysfunction of arousal regulation is hypothesized to contribute to cognitive dysfunctions in various neurological disorders, and most prominently in patients following traumatic brain injury (TBI). Several clinical studies have explored the use of daily central thalamic deep brain stimulation (CT-DBS) within the AFM to restore consciousness and executive attention in TBI patients. In this study, we explored the use of closed-loop CT-DBS in order to episodically regulate arousal of the AFM of a healthy non-human primate (NHP) with the goal of restoring behavioral performance. We used pupillometry and near real-time analysis of ECoG signals to episodically initiate closed-loop CT-DBS and here we report on our ability to enhance arousal and restore the animal's performance. The initial computer based approach was then experimentally validated using a customized clinical-grade DBS device, the DyNeuMo-X, a bi-directional research platform used for rapidly testing closed-loop DBS. The successful implementation of the DyNeuMo-X in a healthy NHP supports ongoing clinical trials employing the internal DyNeuMo system (NCT05437393, NCT05197816) and our goal of developing and accelerating the deployment of novel neuromodulation approaches to treat cognitive dysfunction in patients with structural brain injuries and other etiologies.

CNTN1 in the Nucleus Accumbens is Involved in Methamphetamine-Induced Conditioned Place Preference in Mice.

Methamphetamine (Meth), a commonly used central nervous system stimulant, is highly addictive. Currently, there is no effective treatment for Meth dependence and abuse, although cell adhesion molecules (CAMs) have been shown to play an important role in the formation and remodeling of synapses in the nervous system while also being involved in addictive behavior. Contactin 1 (CNTN1) is a CAM that is widely expressed in the brain; nevertheless, its role in Meth addiction remains unclear. Therefore, in the present study, we established mouse models of single and repeated Meth exposure and subsequently determined that CNTN1 expression in the nucleus accumbens (NAc) was upregulated in mice following single or repeated Meth exposure, whereas CNTN1 expression in the hippocampus was not significantly altered. Intraperitoneal injection of the dopamine receptor 2 antagonist haloperidol reversed Meth-induced hyperlocomotion and upregulation of CNTN1 expression in the NAc. Additionally, repeated Meth exposure also induced conditioned place preference (CPP) in mice and upregulated the expression levels of CNTN1, NR2A, NR2B, and PSD95 in the NAc. Using an AAV-shRNA-based approach to specifically silence CNTN1 expression in the NAc via brain stereotaxis reversed Meth-induced CPP and decreased the expression levels of NR2A, NR2B, and PSD95 in the NAc. These findings suggest that CNTN1 expression in the NAc plays an important role in Meth-induced addiction, and the underlying mechanism may be related to the expression of synapse-associated proteins in the NAc. The results of this study improved our understanding of the role of cell adhesion molecules in Meth addiction.

Managing Growth Deceleration Associated With Attention-Deficit/Hyperactivity Disorder and Stimulant-Induced Appetite Suppression

Central nervous system stimulants are prescribed to children and adolescents with increasing frequency for treatment of attention-deficit/hyperactivity disorder (ADHD).1 Due to their well-established safety profile and high efficacy, stimulants are used first line to support learning and interpersonal functioning in children with ADHD. Caution must still be used when prescribing stimulants, which are associated with appetite suppression and weight loss in children. Since the benefits of stimulants were first established, concern has grown for stimulant-associated growth deceleration and persisting limits on adult height.

Stimulant Use for ADHD in a Cardiac Transplant Recipient: A Case Report

AbstractIntroductionMethylphenidate is a central nervous system stimulant used as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). CNS stimulant use is associated with increased risk of cardiovascular events such as increased resting heart rate and blood pressure, sudden cardiac death, arrhythmia, and stroke. Its safety profile in recipients of cardiovascular transplants is unknown, and more research is warranted to determine the risk of adverse cardiac events due to stimulant medication in this population.MethodsClinical case report, n=1Results/Clinical CaseA 19-year-old female with a history of restrictive cardiomyopathy, cardiac arrest, and orthotopic cardiac transplant has been treated with methylphenidate for ADHD for approximately 2 years without incident. The patient was diagnosed with ADHD between the ages of 8 and 10 and historically was treated with stimulant medication. At age 13, she experienced a cardiac arrest after a volleyball game with 4–6 minutes of pulselessness. She was successfully resuscitated and underwent defibrillator placement. It was concluded that the patient had restrictive cardiomyopathy undetected at birth, leading to the need for orthotopic cardiac transplantation at age 16. After her cardiac arrest, the patient’s memory and cognition worsened, and approximately 1 year after her transplant, she was prescribed amantadine. The patient remained untreated for her ADHD until approximately 1.5 years after her cardiac transplant, at which time she underwent neuropsychological testing that showed findings consistent with attention deficit disorder, and was restarted on stimulant medication. Her transplant cardiologist and psychiatrist have collaborated in her ongoing treatment with methylphenidate 40 mg daily and monitoring symptom response and cardiac stability. Because the patient had previously been stable on stimulant medication for many years, it is reasonable to conclude that stimulant medication did not lead to her cardiac arrest. The patient reports that methylphenidate has been helpful in improving her functioning as a college student, through reduction of her ADHD symptoms. The patient’s blood pressure and heart rate remain within an acceptable range and she has not experienced any adverse cardiac events to date while taking methylphenidate.ConclusionThis case sheds light on the potential to treat cardiac transplant recipients with stimulant medication for ADHD. Although a careful evaluation of risk factors must be undertaken in cooperation with cardiology and other specialists, a role exists for the safe use of stimulant medications in the cardiac transplant population.FundingNo Funding

Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis

ObjectiveExamine patterns of adult medical use of amphetamine and methylphenidate stimulant drugs, classified in the USA as Schedule II controlled substances with a high potential for psychological or physical dependence.DesignCross-sectional...