Central Stimulation Research Articles

Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. Patients aged 55-80years with symptoms of heart failure, body mass index ≤ 35kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

Beyond the buzz: the fatal consequences of caffeine overconsumption.

Caffeine is a naturally occurring stimulant present in dozens of plant species including Coffea arabica and Camellia sinensis, from which we obtain coffee and tea, respectively. It is one of the world's most widely consumed psychoactive substances frequently used to increase alertness, elevate mood, and ward off fatigue. In traditional preparations, caffeine is generally well-tolerated by the consumer. However, complications can arise with the addition of caffeine to products like energy drinks, medications, and supplements. Furthermore, with pure caffeine accessible online, a consumer may unknowingly or inadvertently consume caffeine in dangerous amounts. Symptoms of caffeine toxicity include classic central nervous system stimulation side effects, such as agitation, insomnia, gastrointestinal distress, tachycardia, seizures, and death in extreme cases. To evaluate concentrations of toxicological significance, caffeine cases were assessed at a large reference laboratory (NMS Labs). From 2019 to 2023, 406 blood cases underwent confirmation testing via LC-MS-MS; the mean and median caffeine concentrations were 35 and 4.8 µg/mL, respectively. While most caffeine-containing cases indicate traditional use in the general population with concentrations <25 µg/mL (62%, N = 254), 10% (N = 42) of the cases were >100 µg/mL, indicating levels which may contribute to a fatal outcome. To gain insight into the significance of caffeine in determining the cause and manner of death, cases with various manners of death are presented. Despite being one of the most common toxicological findings in medicolegal death investigations, caffeine is often overlooked. Screening results should undergo scrutiny, and confirmation testing should be considered in cases where caffeine intoxication is prominently featured in the case history or scene investigation.

Effects of central intermittent theta-burst stimulation combined with repetitive peripheral magnetic stimulation on upper limb function in stroke patients.

Intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation can improve motor function in poststroke patients, but the therapeutic effect of this combination remains unclear. To determine the effects of central intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation on upper limb function. Fifty-six subacute stroke patients were randomly assigned to three groups: the CMS (n = 18), peripheral magnetic stimulation (PMS) (n = 19) and CPS (n = 19) groups. The CMS group received intermittent theta-burst stimulation and peripheral false stimulation, while the PMS group received repetitive peripheral magnetic stimulation and central false stimulation once a day for five days a week over four weeks. The CPS group received intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation simultaneously once daily for four weeks. The Fugl-Meyer Assessment, Action Research Arm Test, Modified Barthel Index and Modified Ashworth Scale evaluated outcomes before and after four weeks of treatment. The motor function scores of all groups were significantly increased after treatment compared with before treatment, while the Modified Ashworth Scale score showed no significant change. There was a significant difference in the motor function score of the CPS group compared with that of the CMS and PMS groups, but there was no significant improvement in the Modified Ashworth Scale score. Combining the two treatment methods can improve patients' motor function and daily living abilities but cannot improve muscle tone.

Review Paper on Models for CNS Stimulant Drug Screening

Drugs called central nervous system (CNS) stimulants hasten both mental and physical functions. Narcolepsy and new born apnea are two disorders characterised by a lack of adrenergic stimulation that are treated with central nervous system stimulants. Moreover, the paradoxical effects of dextroamphetamine sulphate (Dexedrine) and methylphenidate (Ritalin) on attention-deficit hyperactivity disorder are invoked to justify their use (ADHD). The majority of CNS stimulants mimic the classic "fight or flight" condition linked to sympathetic nervous system activation and are chemically comparable to the neurohormone norepinephrine. The xanthines, including theophylline, and caffeine are more intimately connected to one another. A few more CNS stimulant class members do not belong to any particular chemical classes. A detailed analysis of CNS stimulant medications, their mechanisms of action, and in vivo CNS stimulant models is provided in the review on central nervous system stimulants.

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

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

Effect of acute intranasal insulin administration on muscle sympathetic nerve activity in healthy young adults.

Systemic insulin increases muscle sympathetic nerve activity (MSNA) via both central actions within the brainstem and peripheral activation of the arterial baroreflex. Augmented MSNA during hyperinsulinemia likely restrains peripheral vasodilation and contributes to the maintenance of blood pressure (BP). However, in the absence of insulin action within the peripheral vasculature, whether central insulin stimulation increases MSNA and influences peripheral hemodynamics in humans remains unknown. Herein, we hypothesized intranasal insulin administration would increase MSNA and BP in healthy young adults. Participants were assigned to time control [TC, n = 13 (5 females/8 males), 28 ± 1 yr] or 160 IU of intranasal insulin administered over 5 min [n = 15 (5 females/10 males), 26 ± 2 yr]; five (1 female/4 males) participants completed both conditions. MSNA (fibular microneurography), BP (finger photoplethysmography), and leg blood flow (LBF, femoral Doppler ultrasound) were assessed at baseline, and 15 and 30 min following insulin administration. Leg vascular conductance [LVC = (LBF ÷ mean BP) × 100] was calculated. Venous insulin and glucose concentrations remained unchanged throughout (P > 0.05). Following intranasal insulin administration, MSNA (burst frequency; baseline = 100%; minute 15, 121 ± 8%; minute 30, 118 ± 6%; P = 0.009, n = 7) and mean BP (baseline = 100%; minute 15, 103 ± 1%; minute 30, 102 ± 1%; P = 0.003) increased, whereas LVC decreased (baseline = 100%; minute 15, 93 ± 3%; minute 30, 99 ± 3%; P = 0.03). In contrast, MSNA, mean BP, and LVC were unchanged in TC participants (P > 0.05). We provide the first evidence that intranasal insulin administration in healthy young adults acutely increases MSNA and BP and decreases LVC. These results enhance mechanistic understanding of the sympathetic and peripheral hemodynamic response to insulin.NEW & NOTEWORTHY Systemic insulin increases muscle sympathetic nerve activity (MSNA) via central actions within the brainstem and peripheral activation of the arterial baroreflex. In the absence of peripheral insulin action, whether central insulin stimulation increases MSNA and influences peripheral hemodynamics in humans was unknown. We provide the first evidence that intranasal insulin administration increases MSNA and blood pressure and reduces leg vascular conductance. These results enhance mechanistic understanding of the sympathetic and hemodynamic response to insulin.

Advancements in liquid chromatography‐mass spectrometry for amphetamine analysis in unconventional biological matrices: Focus on oral fluid and hair samples

AbstractAmphetamines (AMPHs) and their derivatives are potent central nervous system stimulants, in 2020 an astonishing 34 million regular users were reported worldwide. Consequently, there has been a critical need for the development of methods capable of detecting these compounds in alternative biological matrices. The review article discusses the analysis of amphetamines and their derivatives in alternative biological matrices, such as hair and oral fluid (OF), using liquid chromatography‐mass spectrometry. Compiles data from 28 articles published between 2012 and 2022, focusing on 13 articles on OFs and 15 on hair analysis. The article highlights the advantages of using these alternative matrices, including less invasive collection methods, greater sample stability, and simplified extraction processes. Additionally, prevalent analytical practices such as the use of C18 columns and the incorporation of formic acid and methanol into mobile phases are discussed. Furthermore, it demonstrates that the most used method for collecting OF is the Quantisal device, as well as solid phase extraction is also the most used for the same matrix. The review serves as a guide for researchers interested in analytical methods for identifying AMPHs, offering insights into advances, challenges, and the most used in the area.

A review of methamphetamine use and stroke in the young.

Methamphetamine (meth) is a potent and addictive central nervous system stimulant with increasing use. Stroke is one severe possible complication of meth use. Due to high levels of manufacturing in Mexico, the western United States has experienced greater consequences of meth use. The literature reviewed herein is comprised of case studies and series, and it suggests that hemorrhagic stroke (including hypertensive-like intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage), as opposed to ischemic stroke, is the more common type of neurovascular complication of meth use. Meth-related strokes are a particular concern for younger patients with stroke and may be a partial explanation for increasing stroke rates in this age group. We describe two cases (one intraparenchymal hemorrhage and one ischemic stroke) in young patients (<50 years old) with recent meth use to illustrate clinical characteristics and therapeutic considerations. There are several proposed pathophysiological explanations for meth-associated hemorrhagic stroke including an induced hypertensive surge, vasospasm, blood brain barrier breakdown, chronic hypertension, aneurysm development and rupture, and very rarely associated vasculitis. The increased risk of ischemic stroke related to meth use is less well supported in the literature, but this may, in part, be related to a lack of appropriately designed and powered research studies. Proposed mechanisms for ischemic stroke complications of meth use include those affecting blood vessels such as accelerated atherosclerosis, chronic hypertension, vasospasm, and vasculitis, plus mechanisms that affect the heart including cardiomyopathy, arrhythmias, and infective endocarditis (especially with injection drug use). Standard therapeutic interventions for acute stroke and approaches to secondary stroke prevention seem appropriate for meth-associated strokes, with the addition of abstinence from continued meth use. There is no evidence for any meth-specific stroke treatments. Finally, the prolonged duration of meth withdrawal is described. Larger, prospective studies of meth-related strokes are needed to allow for a better understanding and improved care for this often-devastating consequence of an increasingly prevalent cause of strokes in young patients.

Harm caused by the use of lisdexamfetamine to increase the academic performance of medical students: integrative review

Lisdexamfetamine (LIS) is a central nervous system stimulant used to treat Attention-deficit/hyperactivity disorder (ADHD), improving attention, concentration and reducing hyperactivity. However, it is important to highlight that the National Health Surveillance Agency (ANVISA), the regulatory body for medicines in Brazil, does not recognize the efficacy and safety of LIS outside of its indications contained in the medicine leaflet and, in addition, the inappropriate use of this substance becomes a risk factor for the occurrence of anxiety, cardiac arrhythmias and glaucoma. This is an integrative literature review carried out in PubMed, LILACS and SciELO databases searching the descriptors “Lisdexamfetamine”, “ADHD”, and “Students”. Around 23.3% of medical students use these substances to overcome fatigue and improve performance, with Ritalin and Venvanse being the most common. However, 57.1% use these medications without a prescription or diagnosis of ADHD, obtaining them illegally. In general, all medications should only be used after medical evaluation and verification of real need, however, in the case of psychostimulants, caution must be even greater. Therefore, it is crucial to raise awareness among patients who are not diagnosed with ADHD about the long and short-term implications of self-medication with LIS, seeking to combat this public health problem.

A two-year review of cocaine findings in impaired driving investigations in Ontario, Canada.

Drug-impaired driving is an increasing public safety concern across Canada, particularly due to the demonstrated increase in use of recreational drugs such as cocaine. Cocaine is a central nervous system stimulant drug; however, it can impair an individual's driving ability in both the stimulant and crash phases. Despite the scientific consensus regarding cocaine's potential for driving impairment, there is relatively little information available regarding blood concentrations and associated observations of impairment in suspected impaired drivers. Retrospective data analysis was performed to evaluate suspected impaired driving cases in which cocaine and/or benzoylecgonine were detected alone, or in combination with other drugs, in blood and urine samples submitted to the Toxicology Section of the Centre of Forensic Sciences with incident dates between 2021 and 2022. Cocaine and/or benzoylecgonine were detected in 46% (blood) and 66% (urine) of the total impaired driving samples submitted. In 41 cases where cocaine and/or benzoylecgonine were the only drug finding in blood, concentrations of cocaine and benzoylecgonine ranged from 0.0073 to 0.26 mg/L (mean 0.096 mg/L) and 0.13 to 5.3 mg/L (mean 2.1 mg/L), respectively. Driving observations reported by the arresting officer in cases where cocaine and/or benzoylecgonine were the only drug finding in blood and urine included the driver being involved in a collision, the vehicle leaving the roadway, erratic driving and the driver being asleep at the wheel; observations of drug impairment reported by the drug recognition expert at the time of driver evaluation included abnormal speech patterns, poor balance/incoordination, abnormal body movements and the individual falling asleep. The results provide concentrations of cocaine and benzoylecgonine observed in suspected impaired drivers, insight into observations that may be associated with prior cocaine use and additional information to inform on the effects of cocaine on driving.

Synergistic efficacy of repetitive peripheral magnetic stimulation on central intermittent theta burst stimulation for upper limb function in patients with stroke: a double-blinded, randomized controlled trial

BackgroundNon-invasive techniques such as central intermittent theta burst stimulation (iTBS) and repetitive peripheral magnetic stimulation (rPMS) have shown promise in improving motor function for patients with stroke. However, the combined efficacy of rPMS and central iTBS has not been extensively studied. This randomized controlled trial aimed to investigate the synergistic effects of rPMS and central iTBS in patients with stroke.MethodIn this study, 28 stroke patients were randomly allocated to receive either 1200 pulses of real or sham rPMS on the radial nerve of the affected limb, followed by 1200 pulses of central iTBS on the ipsilesional hemisphere. The patients received the intervention for 10 sessions over two weeks. The primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT). Secondary outcomes for activities and participation included the Functional Independence Measure-Selfcare (FIM-Selfcare) and the Stroke Impact Scale (SIS). The outcome measures were assessed before and after the intervention.ResultsBoth groups showed significant improvement in FMA-UE and FIM-Selfcare after the intervention (p < 0.05). Only the rPMS + iTBS group had significant improvement in ARAT-Grasp and SIS-Strength and activity of daily living (p < 0.05). However, the change scores in all outcome measures did not differ between two groups.ConclusionsOverall, the study’s findings suggest that rPMS may have a synergistic effect on central iTBS to improve grasp function and participation. In conclusion, these findings highlight the potential of rPMS as an adjuvant therapy for central iTBS in stroke rehabilitation. Further large-scale studies are needed to fully explore the synergistic effects of rPMS on central iTBS.Trial registrationThis trial was registered under ClinicalTrials.gov ID No.NCT04265365, retrospectively registered, on February 11, 2020.

Frequently asked questions about adverse drug reactions of methylphenidate

Summary This article addresses frequently asked questions about the adverse drug reactions associated with methylphenidate treatment. Methylphenidate is a central nervous system stimulant used primarily for the treatment of attention-deficit/hyperactivity disorder. It utilizes insights from the combined knowledge of pharmacists and physicians who advise healthcare professionals in the Capital Region of Denmark on patient-specific medication queries. The article provides an overview of the clinical challenges and safety considerations associated with methylphenidate use, integrating empirical data and clinical expertise to facilitate informed decision-making by practitioners.

Hormonal Dysfunction in Paediatric Patients Admitted to Rehabilitation for Severe Traumatic Brain Injury: Analysis of the Associations with Rehabilitation Outcomes.

Traumatic brain injury is often accompanied by defects in hormone levels, caused by either peripheral gland dysfunctions or by an insufficient central stimulation of hormone production. The epidemiology of endocrinological defects after traumatic brain injury is quite well described, but the consequences of hormone defects are largely unknown, especially in paediatric patients undergoing neurological rehabilitation. Only one previous study reported on a cohort of 20 children with traumatic brain injury and found a low incidence of hormone defects and a correlation between some hormone levels and neurological recovery. In this study, we performed a retrospective chart review on patients affected by severe subacute traumatic brain injury. Their levels of cortisol, ACTH, IGF-1, TSH, free T4, free T3, and prolactin were collected and compared with reference ranges; we then used regression models to highlight any correlation among them and with clinical variables; last, we probed with regression models whether hormone levels could have any correlation with clinical and rehabilitation outcomes. We found eligible data from the records of 52 paediatric patients with markedly severe traumatic brain injury, as shown by an average GCS of 4.7; their age was 10.3 years, on average. The key results of our study are that 32% patients had low IGF-1 levels and in multiple regression models, IGF-1 levels were correlated with neurological recovery, indicating a possible role as a biomarker. Moreover, 69% of patients had high prolactin levels, possibly due to physical pain and high stress levels. This study is limited by the variable timing of the IGF-1 sampling, between 1 and 2 months after injury. Further studies are required to confirm our exploratory findings.

Perceived advantages and disadvantages of substance use in a dual diagnosis population with severe mental disorders and severe substance use disorder. Considering the self-medication hypothesis

Aim Based on a large cohort of dual diagnosis patients, the aim of this study was to quantify the patient-perceived problems and advantages of their substance use and relate the quantity of problems to the substance type and psychiatric diagnosis. Material Data comes from a naturalistic cohort admitted to an in-patient facility in Denmark specialized in integrated dual diagnosis treatment. We included 1076 patients at their first admission to the facility from 2010 to 2017. Participants completed 607 DrugCheck and 130 DUDIT-E questionnaires. Method we analyzed the questionnaires and included admission diagnosis by use of t-test and ANOVA to depict the patterns in substance use in relation to psychiatric diagnosis. Results The three most common substance related problems according to the DrugCheck questionnaire were: feeling depressed, financial problems, and losing interest in daily activities. From DUDIT-E, the highest-ranking negative substance related effects were financial ruin, deterioration of health, and problems at work. Effects on social life relationships were also evident with more than 40% of participants. The top three positive substance related effects reported were relaxation, improved sleep, and control over negative emotions. The number of problems listed varied significantly with the type of preferred substance. Patients using pain medication, sedatives, central stimulants, and alcohol reported most problems. Diagnosis did not differentiate the problems experienced. Results partially support the broad self-medication hypothesis for patients with severe mental illness, but also points out that patients are well aware of negative effects.

The Possibility of Improvement in Balance and Function Following Conjunct Effects of Transcranial Direct Current Stimulation and Whole-Body Vibration Therapy in Spastic Cerebral Palsy Patients: A Hypothesis Study

Cerebral palsy (CP) results from developmental brain injury, affecting posture and muscular coordination. Traditional treatments offer varying effectiveness, among them the most recent therapies are whole-body vibration therapy (WBVT) and transcranial direct current stimulation (tDCS). WBV enhances proprioceptive function, muscle mass, bone density, and joint stability by stimulating muscle spindle fibers and activating dormant motor units. It also modulates spastic reflexes through mechanoreceptors, proving more effective than traditional physiotherapy. tDCS, a non-invasive neuromodulation, reshapes cortical excitability and modulates synaptic plasticity by altering neuronal activity. It affects long-term potentiation and depression, crucial in learning and adaptive functions. tDCS's interaction with neurotransmitters, especially dopamine and GABA, and its effect on NMDA and dopaminergic receptors make it promising for CP rehabilitation. Both therapies offer novel insights into CP rehabilitation through their influence on central and peripheral neural system. This hypothesis study tends to explore the conjunct effects of transcranial direct current stimulation (tDCS) and whole-body vibration therapy (WBVT) on improving balance and function in children with spastic cerebral palsy. The hypothesis suggests that WBVT's vibratory input, alongside tDCS's central stimulation, enhances function by modulating neuronal excitability and sensory information. The tonic vibration reflex (TVR) from WBV is believed to amplify muscle strength and modulate spinal excitability. When integrated with tDCS, it might accelerate excitability in the motor cortex, essential for brain-injured patient rehabilitation. Despite evidence of individual benefits from both therapies, conjunct effects remain under-researched. Preliminary results show improvements in balance, gait velocity, and motor functions. Validating this combined approach could revolutionize treatment for children with spastic cerebral palsy.

Adrenal insufficiency in liver diseases - pathophysiology and underlying mechanisms.

Relative adrenal insufficiency (RAI) is common in critically ill patients with cirrhosis, but it has been also documented in non-critically ill patients. Its pathophysiology is complex and not well understood yet. In this review, we aimed to present potential mechanisms and causal pathways implicated in the pathogenesis of RAI in cirrhosis. There is accumulating evidence supporting a suboptimal baseline adrenal function in cirrhosis mainly due to decreased cortisol synthesis and metabolism rates from the adrenal gland. Apart from this peripheral impairment, more recent studies suggest that there is a greater defect in the central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis (hypothalamus/pituitary gland). Pro-inflammatory mediators, which are elevated in cirrhosis, have been also implicated through suppression of the HPA axis, decrease in cortisol synthesis and tissue glucocorticoid resistance. All abovementioned support the hepatoadrenal syndrome hypothesis that during episodes of acute decompensation there is suboptimal adrenocortical response that leads to worse outcomes. In conclusion, the complex pathophysiology of adrenal dysfunction in cirrhosis has not been fully elucidated yet and further research is needed in order to better understand this rather common entity in cirrhosis.

Visual Neuroprosthesis - Stimulation of Visual Cortical Centers in The Brain. Design of Non-Invasive Transcranial Stimulation of Functional Neurons.

The purpose of the article is to present the history and current status of visual cortical neuroprostheses, and to present a new method ofstimulating intact visual cortex cells. This paper contains an overview of the history and current status of visual cortex stimulation in severe visual impairment, but also highlights its shortcomings. These include mainly the stimulation of currently damaged cortical cells over a small area and, from a morphological point of view, possible damage to the stimulated neurons by the electrodes and their encapsulation by gliotic tissue. The paper also presents a proposal for a new technology of image processing and its transformation into a form of non-invasive transcranial stimulation of undamaged parts of the brain, which is protected by a national and international patent. The paper presents a comprehensive review of the current options for compensating for lost vision at the level of the cerebral cortex and a proposal for a new non-invasive method of stimulating the functional neurons of the visual cortex.

Luteolin amends neural neurotransmitters, antioxidants, and inflammatory markers in the cerebral cortex of Adderall exposed rats

BackgroundAdderall is a central nervous system stimulant while luteolin has neuroprotective activity. This study aimed to determine whether luteolin can amend neural neurotransmitters, antioxidants, and inflammatory markers in the cerebral cortex of Adderall exposed rats. MethodsThirty-six male albino rats were divided into 6 equal groups, Control, Luteolin (1 g/kg)-treated, and Luteolin (2 g/kg)-treated groups: normal rats were orally administrated once a day with 2 ml distilled water, luteolin (1 g/kg), and luteolin (2 g/kg), respectively for 4 weeks. Adderall rats, Adderall rats + luteolin (1 g/kg)-treated, and Adderall rats + luteolin (2 g/kg)-treated groups: normal rats were orally administrated once a day with 10 mg/kg of Adderall, 3 days/week for 4 weeks, then these rats orally administrated daily once a day with 2 ml of distilled water, luteolin (1 g/kg), and luteolin (2 g/kg), respectively for another 4 weeks. Results and conclusionAdderall decreased superoxide dismutase, glutathione peroxidase, catalase, NADPH oxidase, interleukin-10, serotonin, dopamine, norepinephrine, γ-aminobutyric acid, and acetylcoline estrase but increased malondialdehyde, conjugated dienes, oxidative index, tumour necrosis factor-α, interleukin-1β, and interleukin-6 levels in the cerebral cortex. Adderall increased the expression of glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and anti-calbindin in the cerebral cortex of Adderall-treated rats. In Adderall-treated rats, daily oral administration of luteolin for 4 weeks brought all these parameters back to values that were close to control where higher dose was more effective than lower dose. The importance of this research is to provide natural compound that amends Adderall-related neural disturbances and this natural compound is cheap, avaliable without any side effect and it does not interfer with Adderall efficiency.

Clinical manifestations and analytical reports for MDPHP acute intoxication cases

MDPHP is a synthetic cathinone (SC) belonging to α-pyrrolidinophenone derivatives. It is a central nervous system stimulant and may induce hallucinations, paranoia, tachycardia, hypertension, chest pain, and rhabdomyolysis. In literature, a few cases of intoxication have been reported. In the present study, 17 cases of MDPHP intake were described including the analytical findings and clinical manifestations. MDPHP was quantified by liquid chromatography–tandem mass spectrometry in blood (range 1.26–73.30 ng/mL) and urine (range 19.31–8769.64 ng/mL) samples. In three cases the presence of α-PHP was observed. In one case, MDPHP was the only detected substance. Concomitant use of MDPHP with other substances, particularly psychostimulants, was common and it was difficult to describe the peculiar clinical characteristics of this SC. Most of the symptoms overlapped those expected, some of them were unusual and all of them particularly severe thus inducing the research of NPS in laboratory tests. We demonstrated the presence of psychiatric, neurological, and respiratory symptoms, as well as the possible presence of rhabdomyolysis and cardiotoxicity associated with the use of MDPHP. ED admissions were also more frequent in patients with addiction problems. In some cases, MDPHP intake required intensive supportive care. A multidisciplinary approach, including specialist consultation, is recommended for patients showing challenging features. Moreover, we demonstrated that the adoption of advanced analytical techniques, i.e., liquid chromatography–tandem mass spectrometry, is necessary to detect these molecules. Further studies are needed to understand MDPHP intake patterns and associated symptoms. It is essential to raise awareness in addiction treatment centers and among potential users, especially young people, and chemsex addicted.

Modafinil, an atypical CNS stimulant?

Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.