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International Journal of Molecular... Jun 2022The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However,...
The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D) expression and behavior (non-selective attention "NSA") in the mesocorticolimbic system of young healthy Sprague-Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.
Topics: Adolescent; Animals; Attention; Central Nervous System Stimulants; Glutamic Acid; Humans; Male; Modafinil; Nucleus Accumbens; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Ventral Tegmental Area; gamma-Aminobutyric Acid
PubMed: 35743046
DOI: 10.3390/ijms23126602 -
ARYA Atherosclerosis Nov 2021Pulmonary complications following cardiopulmonary bypass (CPB) pump during coronary artery bypass grafting (CABG) are relatively common and the incidence of cognitive...
BACKGROUND
Pulmonary complications following cardiopulmonary bypass (CPB) pump during coronary artery bypass grafting (CABG) are relatively common and the incidence of cognitive dysfunction is reported as ranging in rate from 30% to 80% in the early postoperative period. The purpose of this study was to assess the effect of modafinil administration on the prevention of pulmonary and cerebral complications and shortening the hospital stay after CABG surgery.
METHODS
This randomized double-blind intervention-controlled clinical trial was performed on 74 patients (37 in the intervention group and 37 in the control group) undertaking CABG surgery. The intervention group was orally treated with doses of 200 mg of modafinil on the day of surgery, and on the morning of the day after surgery, the second dose of modafinil 200 mg was given to patients. The control group underwent a placebo with the same intervals.
RESULTS
Administration of modafinil in intervention group significantly decreased the time to reach consciousness (P = 0.001), ventilator time in intensive care unit (ICU) (P < 0.001), length of stay in ICU (P = 0.009), duration of hospitalization (P = 0.008), and arterial blood carbon dioxide pressure (PaCO2) (P = 0.047). In the intervention group, no patients with delirium, agitation, respiratory depression, non-invasive respiratory ventilation, and endotracheal re-intubation were observed.
CONCLUSION
Modafinil tablet as a respiratory and brain stimulant through the central nervous system (CNS) can improve the quality of breathing and arterial blood gases (ABGs) and also can increase the level of consciousness and shorten the recovery time.
PubMed: 35685446
DOI: 10.22122/arya.v17i0.2371 -
Nicotine & Tobacco Research : Official... Jan 2023Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA...
Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA terminology), with the vast majority failing to show efficacy. Even small randomized clinical trials (RCTs), the most common early Phase 2 tests, are costly undertakings, made more unappealing by their high likelihood of failure. At the same time, another early Phase 2 approach, acute tests of drug effects on surrogate endpoints such as withdrawal or craving severity, are more practical but have little predictive clinical validity. Described here is an innovative procedure that optimally combines the validity of clinical trials with the practical advantages of surrogate endpoint studies to more efficiently determine whether or not a novel drug warrants continued clinical development. This CrEATE procedure, or Crossover Evaluation of Addiction Treatment Efficacy, does so by assessing short-term quit success in smokers highly motivated to quit when briefly treated with active drug versus placebo in a crossover design, so that quit efficacy from both conditions is compared within participants. The program to develop and evaluate CrEATE demonstrates its sensitivity to efficacy from all three FDA-approved first-line cessation medications (NRT, varenicline, bupropion), tested here as model drugs, as well as specificity in identifying lack of efficacy with a drug known to be ineffective for cessation (modafinil). CrEATE has subsequently been used to evaluate a few novel interventions, concluding they lack efficacy in increasing quit success. Future directions for the potential utility of CrEATE are provided. Implications: The ability of CrEATE to reach a Go/No Go decision more quickly and with far less cost lowers the risk of failure, meaning widespread use of the procedure should encourage the evaluation of more novel candidate drugs. With its greater efficiency, failed tests, unfortunately the most likely outcome in early Phase 2 studies, will cause less waste of resources. At the same time, CrEATE tests that indicate a novel treatment has efficacy will justify the substantial time and expense of moving forward to evaluate the drug in late Phase 2 RCTs.
Topics: Humans; Nicotinic Agonists; Cross-Over Studies; Benzazepines; Smoking; Varenicline; Bupropion; Treatment Outcome
PubMed: 35671343
DOI: 10.1093/ntr/ntac139 -
Human Brain Mapping Oct 2022Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional... (Randomized Controlled Trial)
Randomized Controlled Trial
Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant-induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large-scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism.
Topics: Adult; Brain; Brain Mapping; Caffeine; Central Nervous System Stimulants; Cognition; Double-Blind Method; Humans; Magnetic Resonance Imaging; Male; Methylphenidate; Modafinil; Neural Pathways
PubMed: 35670369
DOI: 10.1002/hbm.25949 -
American Journal of Neurodegenerative... 2022Examining the differences in the Functional Connectivity (FC) network while using Functional Magnetic Resonance Imaging (fMRI) between two groups can expand the...
BACKGROUND
Examining the differences in the Functional Connectivity (FC) network while using Functional Magnetic Resonance Imaging (fMRI) between two groups can expand the understanding of neural processes and help diagnose and prevent neurological progression disorders. The present study evaluated the Modafinil effect on the FC of brain Regions of Interest (ROI) among healthy young individuals between the Modafinil and placebo groups.
METHOD
The data used in this study were downloaded from the open fMRI site and analyzed after preprocessing. Data included brain scan images of 26 healthy young men with no history of neurological disorders. These people are divided into two groups of drugs and a placebo. The drug group was given 100 mg of Modafinil, and the placebo group was assigned the same dose. Data were analyzed using a longitudinal variance component model.
RESULT
After taking the drug and placebo by the two groups, the study of the difference between FC in the drug and placebo group and the baseline effect showed a statistically significant difference in one pair of ROIs. Also, in examining the difference between FC in the drug and placebo groups of the longitudinal trend, there was a statistically significant difference between 5 pairs of ROIs.
CONCLUSION
After taking Modafinil and placebo, it was observed that FC in most areas in the drug group increased compared to the placebo group, indicating Modafinil has cognitive enhancement properties and has a role in visual, auditory, memory learning, and self-awareness functions and enhances these functions.
PubMed: 35600512
DOI: No ID Found -
Saudi Pharmaceutical Journal : SPJ :... Mar 2022Armodafinil inclusion complex (AIC) hydrogel was prepared and evaluated for its therapeutic effect on Post-traumatic Stress Disorder (PTSD). After computer simulation...
Armodafinil inclusion complex (AIC) hydrogel was prepared and evaluated for its therapeutic effect on Post-traumatic Stress Disorder (PTSD). After computer simulation and physicochemical property investigation, the AIC was formed by lyophilization of armodafinil with ethanol as solvent and hydroxypropyl-beta-cyclodextrin (HP-β-CD) aqueous solution, in which the molar ratio of armodafinil and HP-β-CD was 1-1. The AIC encapsulation efficiency (EE) was (90.98 ± 3.72)% and loading efficiency (LE) was (13.95 ± 0.47)% and it increased the solubility of armodafinil in aqueous solution to 21 times. AIC hydrogel was prepared by adding AIC to methylcellulose (MC) hydrogels (3.33% w/v), and its higher drug release amount and slower release rate were testified by the in-vitro release assay and the rheological test. The mucosa irritation of AIC hydrogel was also evaluated. Healthy group, Model group, Sertraline group with 30 mg/kg sertraline gavage, AIC Hydrogel group with 20 mg/kg AIC hydrogel intranasal administration and AIC Aqueous Solution group with 20 mg/kg AIC aqueous solution gavage were set up for the treatment of mice with PTSD generated from foot shock method. Based on freezing response test in fear-conditioning box and open field test, compared with other groups, PTSD mice in AIC Hydrogel group showed significant improvement in behavioral parameters after 11 days of continuous drug administration and 5 days of drug withdrawal. After sacrifice, the plasma CORT level of PTSD mice in AIC Hydrogel group was elevated compared to Model group. Besides, the western blot (WB) of hippocampal brain-derived neurotrophic factor (BDNF) and amygdala dopamine transporter (DAT) immunohistochemistry sections indicated that AIC hydrogel had a protective effect on the brain tissue of PTSD mice. The brain targeting of intranasal administration was evaluated by fluorescence imaging characteristics of Cy7 hydrogel in the nasal route of drug administration, pharmacokinetics and distribution of armodafinil. In short, AIC hydrogel is a promising formulation for the treatment of PTSD based on its high brain delivery and anti-PTSD effect.
PubMed: 35498223
DOI: 10.1016/j.jsps.2022.01.009 -
Psychopharmacology Aug 2022Modafinil has been proposed as a potentially effective clinical treatment for neuropsychiatric disorders characterized by cognitive control deficits. However, the...
RATIONALE
Modafinil has been proposed as a potentially effective clinical treatment for neuropsychiatric disorders characterized by cognitive control deficits. However, the precise effects of modafinil, particularly on brain network functions, are not completely understood.
OBJECTIVES
To address this gap, we examined the effects of modafinil on resting-state brain activity in 30 healthy adults using microstate analysis. Electroencephalographic (EEG) microstates are discrete voltage topographies generated from resting-state network activity.
METHODS
Using a placebo-controlled, within-subjects design, we examined changes to microstate parameters following placebo (0 mg), low (100 mg), and high (200 mg) modafinil doses. We also examined the functional significance of these microstates via associations between microstate parameters and event-related potential indexes of conflict monitoring and automatic error processing (N2 and error-related negativity) and behavioral responses (accuracy and RT) from a subsequent flanker interference task.
RESULTS
Five microstates emerged following each treatment condition, including four canonical microstates (A-D). Modafinil increased microstate C proportion and occurrence regardless of dose, relative to placebo. Modafinil also decreased microstate A proportion and microstate B proportion and occurrence relative to placebo. These modafinil-related changes in microstate parameters were not associated with similar changes in flanker ERPs or behavior. Finally, modafinil made transitions between microstates A and B less likely and transitions from A and B to C more likely.
CONCLUSIONS
Previous fMRI work has correlated microstates A and B with auditory and visual networks and microstate C with a salience network. Thus, our results suggest modafinil may deactivate large-scale sensory networks in favor of a higher order functional network during resting-state in healthy adults.
Topics: Adult; Brain; Cognition Disorders; Cognitive Dysfunction; Electroencephalography; Humans; Modafinil
PubMed: 35471613
DOI: 10.1007/s00213-022-06149-x -
Biomolecules Mar 2022Previous studies have shown that atypical dopamine-transporter-inhibitors such as modafinil and its analogues modify behavioral and cognitive functions in rodents. Here,...
Previous studies have shown that atypical dopamine-transporter-inhibitors such as modafinil and its analogues modify behavioral and cognitive functions in rodents. Here, we tested potential promnestic effects of the novel, more dopamine-transporter selective modafinil analogue CE-158 in the social discrimination memory task in male mice. Systemic administration of CE-158 1 h before the social learning event prevented the impairment of social-recognition memory following retroactive interference 3 h after the learning session of a juvenile conspecific. This effect was dose-dependent, as mice treated with 10 mg/kg, but not with 1 mg/kg CE-158, were able to discriminate between the novel and familiar conspecific despite the presentation of an interference stimulus, both 3 h and 6 h post learning. However, when 10 mg/kg of the drug was administered after learning, CE-158 failed to prevent social memory from interference. Paralleling these behavioral effects, the systemic administration of 10 mg/kg CE-158 caused a rapid and sustained elevation of extracellular dopamine in the nucleus accumbens, a brain area where dopaminergic signaling plays a key role in learning and memory function, of freely moving mice, while 1 mg/kg was not sufficient for altering dopamine levels. Taken together, our findings suggest promnestic effects of the novel dopamine-transporter-inhibitor CE-158 in a social recognition memory test that may be in part mediated via increased dopamine-neurotransmission in the nucleus accumbens. Thus, selective-dopamine-transporter-inhibitors such as CE-158 may represent interesting drug candidates for the treatment of memory complaints observed in humans with cognitive impairments and dementia.
Topics: Animals; Dopamine; Learning; Male; Mice; Modafinil; Nucleus Accumbens; Recognition, Psychology
PubMed: 35454095
DOI: 10.3390/biom12040506 -
Journal of Clinical Medicine Apr 2022Prader-Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered... (Review)
Review
Prader-Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients' caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects.
PubMed: 35407596
DOI: 10.3390/jcm11071986 -
Revista Espanola de Salud Publica Mar 2022Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder characterised primarily by three core symptoms: inattention,...
OBJECTIVE
Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder characterised primarily by three core symptoms: inattention, hyperactivity and impulsivity. It is one of the most commonly diagnosed childhood psychiatric disorders, with a worldwide prevalence of between 3% and 5%, and between 6% and 7% in the Spanish population. The aim of the study is to analyse the trend in the consumption of drugs used for the treatment of ADHD between 2010-2019 in Castilla y León.
METHODS
Epidemiological registry study of all dispensing in pharmacies in Castilla y León between 2010 and 2019 to patients under 19 years of age, of active substance N06BA04 (methylphenidate), N06BA09 (atomoxetine), N06BA12 (lisdexamfetamine), N06BA07 (modafinil) and C02AC02 (guanfacine). Data on drug use were obtained from the information system for the pharmaceutical provision of Castilla y León, CONCYLIA. Frequencies in absolute values and the corresponding percentages were calculated. Student's t-test was used to estimate differences between continuous variables and Pearson's Chi-square test for categorical variables, while the trend in consumption was analysed using the Cochran-Armitage test.
RESULTS
ADHD medication was dispensed annually to 1.77% of the population, with consumption being more than three times higher in boys than in girls (2.69% vs 0.81%; p=0.001). The age group with the highest peak use was 10-14 years with 3.42%. Methylphenidate was the drug used by the highest percentage of the population (2.44%) followed by lisdexamfetamine (0.37%).
CONCLUSIONS
Approximately 2 out of every 100 people aged 0-19 years were treated with some ADHD medication, mainly methylphenidate, in Castilla y León between 2010 and 2019.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Methylphenidate; Spain; Substance-Related Disorders; Young Adult
PubMed: 35318300
DOI: No ID Found