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1.
Nutrients ; 16(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38732503

ABSTRACT

(1) Background: This study investigated the effects of caffeinated chewing gum on the basketball-specific performance of trained basketball players. A double-blind, randomized crossover design was employed. (2) Methods: Fifteen participants (age: 20.9 ± 1.0 years; height: 180.9 ± 5.4 cm; mass: 77.2 ± 7.5 kg; training age: 8.2 ± 0.3 years) were recruited and divided into a caffeine trial (CAF) and placebo trial (PL). The participants in the CAF trial chewed gum containing 3 mg/kg of caffeine for 10 min, while those in the PL trial chewed a placebo gum without caffeine. Following a 15 min rest, all the participants completed basketball-specific performance tests. (3) Results: The free throw accuracy for the CAF trial was significantly higher than that for the PL trial (CAF: 79.0 ± 4.31%; PL: 73.0 ± 9.16%; p = 0.012; Cohen's d = 0.94). Additionally, the CAF trial demonstrated significantly better performance in the 20 m segmented dash (CAF: 2.94 ± 1.12 s; PL: 3.13 ± 0.10 s; p < 0.001; Cohen's d =1.8) and squats (p < 0.05), and exhibited lower fatigue indexes (CAF: 3.6 ± 1.6%; PL: 5.2 ± 1.6%; p = 0.009; Cohen's d =1.0). (4) Conclusions: These findings suggest that chewing gum containing 3 mg/kg of caffeine offers moderate-to-large improvements in key performance aspects relevant to professionally trained basketball players.


Subject(s)
Athletic Performance , Basketball , Caffeine , Chewing Gum , Cross-Over Studies , Humans , Basketball/physiology , Double-Blind Method , Caffeine/administration & dosage , Athletic Performance/physiology , Young Adult , Male , Adult , Athletes , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/pharmacology
2.
J Head Trauma Rehabil ; 39(3): E122-E131, 2024.
Article in English | MEDLINE | ID: mdl-38709832

ABSTRACT

OBJECTIVE: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. SETTING: Inpatient pediatric rehabilitation. PARTICIPANTS: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. DESIGN: Multicenter, retrospective medical record review. MAIN MEASURES: Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). RESULTS: Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. CONCLUSION: This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.


Subject(s)
Brain Injuries, Traumatic , Central Nervous System Stimulants , Methylphenidate , Practice Patterns, Physicians' , Humans , Methylphenidate/therapeutic use , Methylphenidate/administration & dosage , Child , Female , Brain Injuries, Traumatic/rehabilitation , Male , Adolescent , Child, Preschool , Retrospective Studies , Central Nervous System Stimulants/therapeutic use , Central Nervous System Stimulants/administration & dosage , Infant , Practice Patterns, Physicians'/statistics & numerical data , Young Adult , Inpatients , Length of Stay , Rehabilitation Centers
3.
J Atten Disord ; 28(8): 1186-1197, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38600754

ABSTRACT

OBJECTIVE: DR/ER-MPH (formerly HLD200) is an evening-dosed delayed-release and extended-release methylphenidate approved for the treatment of ADHD in patients ≥6 years. Post hoc analyses of two pivotal Phase 3 trials: HLD200-107 (NCT02493777) and HLD200-108 (NCT02520388) evaluated emotional lability (EL) with DR/ER-MPH treatment. METHODS: Differences in Conners Global Index-Parent (CGI-P) EL subscale scores and age- and gender-adjusted T-scores over an open-label titration phase (HLD200-107) and between treatment and placebo groups at endpoint (HLD200-108) were evaluated. RESULTS: In HLD200-107 (N = 117) mean CGI-P EL subscale scores improved from 5.3 to 1.3 (p < .0001) after 6 weeks; in HLD200-108 significant improvements were observed in the treatment group (n = 81) versus placebo (n = 80; 3.11 vs. 4.08; p = .0053). T-scores showed an improvement with DR/ER-MPH treatment in both trials. Few emotional adverse events (AEs) were reported. CONCLUSION: DR/ER-MPH treatment resulted in statistically significant improvements in EL to the level of non-ADHD peers as contextualized by T-scores.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Delayed-Action Preparations , Methylphenidate , Humans , Methylphenidate/administration & dosage , Methylphenidate/pharmacology , Child , Male , Female , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/pharmacology , Attention Deficit Disorder with Hyperactivity/drug therapy , Double-Blind Method , Treatment Outcome , Affective Symptoms/drug therapy
4.
Biol Pharm Bull ; 47(4): 861-867, 2024.
Article in English | MEDLINE | ID: mdl-38644196

ABSTRACT

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.


Subject(s)
Caffeine , Gestational Age , Infant, Premature , Models, Biological , Humans , Caffeine/blood , Caffeine/pharmacokinetics , Caffeine/administration & dosage , Female , Infant, Newborn , Infant, Premature/growth & development , Infant, Premature/blood , Male , Pregnancy , Central Nervous System Stimulants/blood , Central Nervous System Stimulants/pharmacokinetics , Central Nervous System Stimulants/administration & dosage
5.
J Integr Neurosci ; 23(4): 83, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38682231

ABSTRACT

BACKGROUND: Much of the existing animal literature on the devaluation task suggests that prior repeated exposure to drugs of abuse during adulthood can impair goal-directed action, but the literature on human drug users is mixed. Also, the initiation of drug use often occurs during adolescence, but examinations of the effects of drug exposure during adolescence on behavior in the devaluation task are lacking. METHODS: We examined whether repeated exposure during adolescence to amphetamine (3 mg/kg injections every-other day from post-natal day 27-45) or ketamine (twice daily 30 mg/kg injections from post-natal day 35-44) would impair behavior in a devaluation test when tested drug-free in adulthood. Rats were trained to press a left lever with a steady cue-light above it for one reinforcer and a right lever with a flashing cue-light above it for a different reinforcer. We tested whether any impairments in goal-directed action could be overcome by compensation between strategies by giving rats information based on lever-location and cue-lights during the test that was either congruent (allowing compensation) or incongruent (preventing compensation between strategies) with the configurations during training. RESULTS: Our results provided no evidence for impairment of goal-directed action during adulthood after adolescent amphetamine or ketamine exposure. CONCLUSIONS: We discuss possible reasons for this discrepancy with the prior literature, including (1) the age of exposure and (2) the pattern in the previous literature that most previous demonstrations of drug exposure impairing devaluation in laboratory animals may be attributed to either drug-associated cues present in the testing environment and/or accelerated habit learning in tasks that predispose laboratory animals towards habit formation with extended training (with training procedures that should resist the formation of habits in the current experiment). However, additional research is needed to examine the effects of these factors, as well a potential role for the particular doses and washout periods to determine the cause of our finding of no devaluation impairment after drug exposure.


Subject(s)
Amphetamine , Ketamine , Animals , Ketamine/pharmacology , Ketamine/administration & dosage , Amphetamine/pharmacology , Amphetamine/administration & dosage , Male , Rats , Conditioning, Operant/drug effects , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/administration & dosage , Rats, Long-Evans , Behavior, Animal/drug effects , Age Factors , Cues
6.
Int J Dev Neurosci ; 84(3): 251-261, 2024 May.
Article in English | MEDLINE | ID: mdl-38469915

ABSTRACT

OBJECTIVE: The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high-dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus. MATERIALS AND METHODS: A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9-20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10 mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti-GFAP, and antisynaptophysin staining methods. RESULTS: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group. CONCLUSION: It is concluded that high-dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.


Subject(s)
Caffeine , Hippocampus , Melatonin , Neuroprotective Agents , Rats, Wistar , Animals , Female , Melatonin/pharmacology , Melatonin/administration & dosage , Hippocampus/drug effects , Pregnancy , Caffeine/administration & dosage , Caffeine/pharmacology , Rats , Neuroprotective Agents/pharmacology , Neuroprotective Agents/administration & dosage , Central Nervous System Stimulants/toxicity , Central Nervous System Stimulants/administration & dosage , Dose-Response Relationship, Drug
7.
Pharmacol Biochem Behav ; 239: 173751, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38548247

ABSTRACT

Risky choice is associated with maladaptive behaviors, particularly substance use disorders. Current animal models of risky choice are often confounded by other constructs like behavioral flexibility and suboptimal choice. The purpose of the current experiment was to determine if the psychostimulant methamphetamine, a drug whose popularity has increased in recent years, increases risky choice in an equivalent expected value (EEV) task. In the EEV task, rats are given a choice between two reinforcer alternatives that differ in magnitude and probability of delivery, but have equivalent expected value. Forty-eight Sprague Dawley rats were tested in three versions of the EEV task. In the first version of the EEV task, both reinforcer magnitude and probability were adjusted across blocks of trials for both alternatives. In the second and the third versions of the EEV task, reinforcer magnitude was held constant across each block of trials (either 1 vs. 2 pellets or 4 vs. 5 pellets). We found that male rats preferred the "riskier" option, except when reinforcer magnitudes were held constant at 4 and 5 pellets across each block of trials. Methamphetamine (0.5 mg/kg) increased preference for the risky option in both males and females, but only when both reinforcer magnitude and probability were manipulated across blocks of trials for each alternative. The current results demonstrate that both magnitude of reinforcement and probability of reinforcement interact to influence risky choice. Overall, this study provides additional support for using reinforcers with expected value to measure risky choice.


Subject(s)
Central Nervous System Stimulants , Choice Behavior , Methamphetamine , Rats, Sprague-Dawley , Reinforcement, Psychology , Risk-Taking , Animals , Methamphetamine/pharmacology , Methamphetamine/administration & dosage , Male , Rats , Choice Behavior/drug effects , Female , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/administration & dosage , Conditioning, Operant/drug effects , Probability
8.
Int J Drug Policy ; 126: 104364, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38408416

ABSTRACT

BACKGROUND: Overdoses involving opioids and stimulants are on the rise, yet few studies have examined longitudinal trends in use of both substances. We sought to describe use and co-use of opioids and stimulants, 2005-2019, in the AIDS Linked to the Intravenous Experience (ALIVE) cohort - a community-based cohort of people with a history of injection drug use living in or near Baltimore, MD. METHODS: We included 2083 ALIVE participants, who had at least two visits during the study period. Our outcome was based on self-reported use of opioids and stimulants in the prior 6 months. We estimated prevalence of 4 categories of use (neither stimulants nor opioids, only stimulants, only opioids, stimulants and opioids), using a non-parametric multi-state model, accounting for the competing event of death and weighting for informative loss to follow-up. All analyses were stratified by enrollment cohort, with the main analysis including participants who enrolled prior to 2015 and a sub-analysis including participants who enrolled 2015-2018. RESULTS: In the main analysis, prevalence of using stimulants and opioids decreased from 38 % in 2005 to 12 % 2013 but stabilized from 2014 onwards (13-19 %). The prevalence of using only stimulants (7-11 %) and only opioids (5-10 %) was stable across time. Participants who reported using both were more likely to report homelessness, depression, and other substance use (e.g., marijuana and heavy alcohol use) than participants in the other use categories. On average, 65 % of visits with use of both were followed by a subsequent visit with use of both; of participants transitioning out of using both, 13% transitioned to using neither. CONCLUSIONS: While use of stimulants and opioids declined in the cohort through 2013, a meaningful proportion of participants persistently used both. More research is needed to understand and develop strategies to mitigate harms associated with persistent use of both stimulants and opioids.


Subject(s)
Analgesics, Opioid , Central Nervous System Stimulants , Substance Abuse, Intravenous , Humans , Male , Female , Adult , Analgesics, Opioid/administration & dosage , Substance Abuse, Intravenous/epidemiology , Longitudinal Studies , Baltimore/epidemiology , Prevalence , Central Nervous System Stimulants/administration & dosage , Middle Aged , Opioid-Related Disorders/epidemiology , Cohort Studies , Drug Overdose/epidemiology , Acquired Immunodeficiency Syndrome/epidemiology , HIV Infections/epidemiology
9.
Neuropsychopharmacology ; 49(6): 924-932, 2024 May.
Article in English | MEDLINE | ID: mdl-38326458

ABSTRACT

The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced dopamine increases impacts brain network communication remains unresolved. We manipulated route of MP administration to generate fast versus slow dopamine increases. We hypothesized that fast versus slow dopamine increases would result in a differential pattern of global brain connectivity (GBC) in association with regional levels of dopamine D1 receptors, which are critical for drug reward. Twenty healthy adults received MP intravenously (0.5 mg/kg; fast dopamine increases) and orally (60 mg; slow dopamine increases) during simultaneous [11C]raclopride PET-fMRI scans (double-blind, placebo-controlled). We tested how GBC was temporally associated with slow and fast dopamine increases on a minute-to-minute basis. Connectivity patterns were strikingly different for slow versus fast dopamine increases, and whole-brain spatial patterns were negatively correlated with one another (rho = -0.54, pspin < 0.001). GBC showed "fast>slow" associations in dorsal prefrontal cortex, insula, posterior thalamus and brainstem, caudate and precuneus; and "slow>fast" associations in ventral striatum, orbitofrontal cortex, and frontopolar cortex (pFDR < 0.05). "Fast>slow" GBC patterns showed significant spatial correspondence with D1 receptor availability (estimated via normative maps of [11C]SCH23390 binding; rho = 0.22, pspin < 0.05). Further, hippocampal GBC to fast dopamine increases was significantly negatively correlated with self-reported 'high' ratings to intravenous MP across individuals (r(19) = -0.68, pbonferroni = 0.015). Different routes of MP administration produce divergent patterns of brain connectivity. Fast dopamine increases are uniquely associated with connectivity patterns that have relevance for the subjective experience of drug reward.


Subject(s)
Brain , Dopamine , Magnetic Resonance Imaging , Methylphenidate , Positron-Emission Tomography , Raclopride , Humans , Male , Adult , Female , Brain/drug effects , Brain/diagnostic imaging , Brain/metabolism , Dopamine/metabolism , Methylphenidate/pharmacology , Methylphenidate/administration & dosage , Double-Blind Method , Young Adult , Raclopride/pharmacology , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/administration & dosage , Receptors, Dopamine D1/metabolism , Neural Pathways/drug effects , Neural Pathways/diagnostic imaging , Dopamine Antagonists/pharmacology , Dopamine Antagonists/administration & dosage , Brain Mapping
10.
Hum Psychopharmacol ; 39(3): e2896, 2024 May.
Article in English | MEDLINE | ID: mdl-38353526

ABSTRACT

OBJECTIVE: Stimuli received beyond a very short timeframe, known as temporal binding windows (TBWs), are perceived as separate events. In previous audio-visual multisensory integration (McGurk effect) studies, widening of TBWs has been observed in people with schizophrenia. The present study aimed to determine if dexamphetamine could increase TBWs in unimodal auditory and unimodal visual illusions that may have some validity as experimental models for auditory and visual hallucinations in psychotic disorders. METHODS: A double-blind, placebo-controlled, counter-balanced crossover design with permuted block randomisation for drug order was followed. Dexamphetamine (0.45 mg/kg, PO, q.d.) was administered to healthy participants. Phantom word illusion (speech illusion) and visual-induced flash illusion/VIFI (visual illusion) tests were measured to determine if TBWs were altered as a function of delay between stimuli presentations. Word emotional content for phantom word illusions was also analysed. RESULTS: Dexamphetamine significantly increased the total number of phantom words/speech illusions (p < 0.01) for pooled 220-1100 ms ISIs in kernel density estimation and the number of positive valence words heard (beta = 2.20, 95% CI [1.86, 2.55], t = 12.46, p < 0.001) with a large effect size (std. beta = 1.05, 95% CI [0.89, 1.22]) relative to placebo without affecting the TBWs. For the VIFI test, kernel density estimation for pooled 0-801 ms ISIs showed a significant difference (p < 0.01) in the data distributions of number of target flash (es) perceived by participants after receiving dexamphetamine as compared with placebo. CONCLUSIONS: Overall, healthy participants who were administered dexamphetamine (0.45 mg/kg, PO, q.d.) experienced increases in auditory and visual illusions in both phantom word illusion and VIFI tests without affecting their TBWs.


Subject(s)
Cross-Over Studies , Dextroamphetamine , Illusions , Visual Perception , Humans , Double-Blind Method , Male , Adult , Female , Illusions/drug effects , Illusions/physiology , Young Adult , Dextroamphetamine/pharmacology , Dextroamphetamine/administration & dosage , Visual Perception/drug effects , Visual Perception/physiology , Hallucinations/chemically induced , Time Factors , Photic Stimulation/methods , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/administration & dosage , Acoustic Stimulation , Speech Perception/drug effects , Auditory Perception/drug effects , Auditory Perception/physiology , Adolescent
11.
Cogn Affect Behav Neurosci ; 24(2): 351-367, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38253774

ABSTRACT

The rapid serial visual presentation (RSVP) task and continuous performance tasks (CPT) are used to assess attentional impairments in patients with psychiatric and neurological conditions. This study developed a novel touchscreen task for rats based on the structure of a human RSVP task and used pharmacological manipulations to investigate their effects on different performance measures. Normal animals were trained to respond to a target image and withhold responding to distractor images presented within a continuous sequence. In a second version of the task, a false-alarm image was included, so performance could be assessed relative to two types of nontarget distractors. The effects of acute administration of stimulant and nonstimulant treatments for ADHD (amphetamine and atomoxetine) were tested in both tasks. Methylphenidate, ketamine, and nicotine were tested in the first task only. Amphetamine made animals more impulsive and decreased overall accuracy but increased accuracy when the target was presented early in the image sequence. Atomoxetine improved accuracy overall with a specific reduction in false-alarm responses and a shift in the attentional curve reflecting improved accuracy for targets later in the image sequence. However, atomoxetine also slowed responding and increased omissions. Ketamine, nicotine, and methylphenidate had no specific effects at the doses tested. These results suggest that stimulant versus nonstimulant treatments have different effects on attention and impulsive behaviour in this rat version of an RSVP task. These results also suggest that RSVP-like tasks have the potential to be used to study attention in rodents.


Subject(s)
Amphetamine , Atomoxetine Hydrochloride , Attention , Central Nervous System Stimulants , Ketamine , Methylphenidate , Nicotine , Animals , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/administration & dosage , Atomoxetine Hydrochloride/pharmacology , Atomoxetine Hydrochloride/administration & dosage , Attention/drug effects , Attention/physiology , Male , Rats , Methylphenidate/pharmacology , Methylphenidate/administration & dosage , Nicotine/pharmacology , Nicotine/administration & dosage , Amphetamine/pharmacology , Amphetamine/administration & dosage , Ketamine/pharmacology , Ketamine/administration & dosage , Photic Stimulation/methods , Adrenergic Uptake Inhibitors/pharmacology , Adrenergic Uptake Inhibitors/administration & dosage , Serial Learning/drug effects , Serial Learning/physiology , Reaction Time/drug effects , Reaction Time/physiology , Visual Perception/drug effects , Visual Perception/physiology , Rats, Sprague-Dawley
12.
Retina ; 44(5): 820-830, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38194677

ABSTRACT

PURPOSE: To evaluate novice and senior vitreoretinal surgeons after various exposures. Multiple comparisons ranked the importance of these exposures for surgical dexterity based on experience. METHODS: This prospective cohort study included 15 novice and 11 senior vitreoretinal surgeons (<2 and >10 years' practice, respectively). Eyesi-simulator tasks were performed after each exposure. Day 1, placebo, 2.5 mg/kg caffeine, and 5.0 mg/kg caffeine; day 2, placebo, 0.2 mg/kg propranolol, and 0.6 mg/kg propranolol; day 3, baseline simulation, breathalyzer readings of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentrations; day 4, baseline simulation, push-up sets with 50% and 85% repetitions maximum; and day 5, 3-hour sleep deprivation. Eyesi-generated score (0-700, worst-best), out-of-tolerance tremor (0-100, best-worst), task completion time (minutes), and intraocular pathway (in millimeters) were measured. RESULTS: Novice surgeons performed worse after caffeine (-29.53, 95% confidence interval [CI]: -57.80 to -1.27, P = 0.041) and alcohol (-51.33, 95% CI: -80.49 to -22.16, P = 0.001) consumption. Alcohol caused longer intraocular instrument movement pathways (212.84 mm, 95% CI: 34.03-391.65 mm, P = 0.02) and greater tremor (7.72, 95% CI: 0.74-14.70, P = 0.003) among novices. Sleep deprivation negatively affected novice performance time (2.57 minutes, 95% CI: 1.09-4.05 minutes, P = 0.001) and tremor (8.62, 95% CI: 0.80-16.45, P = 0.03); however, their speed increased after propranolol (-1.43 minutes, 95% CI: -2.71 to -0.15 minutes, P = 0.029). Senior surgeons' scores deteriorated only following alcohol consumption (-47.36, 95% CI: -80.37 to -14.36, P = 0.005). CONCLUSION: Alcohol compromised all participants despite their expertise level. Experience negated the effects of caffeine, propranolol, exercise, and sleep deprivation on surgical skills.


Subject(s)
Clinical Competence , Vitreoretinal Surgery , Humans , Prospective Studies , Male , Female , Caffeine/administration & dosage , Adult , Simulation Training/methods , Propranolol/administration & dosage , Central Nervous System Stimulants/administration & dosage , Psychomotor Performance/drug effects , Psychomotor Performance/physiology , Internship and Residency
13.
Paediatr Drugs ; 26(3): 319-330, 2024 May.
Article in English | MEDLINE | ID: mdl-38280943

ABSTRACT

BACKGROUND AND OBJECTIVES: Concerns exist regarding the rising use of methylphenidate. A double-blind, placebo-controlled methylphenidate titration (PCT) for children with attention-deficit/hyperactivity disorder (ADHD) has shown potential to improve titration (i.e., detection of placebo responders and larger ADHD symptom improvement) in experimental settings. This study aims to determine if these advantages can be transferred to clinical settings. METHOD: Children (aged 5-13 years) with an ADHD diagnosis and an indication to start methylphenidate (MPH) treatment were recruited. Participants were randomized to PCT or care as usual (CAU) in a 1:1 ratio followed by a 7-week randomized controlled trial (T1) and 6-month, naturalistic, open-label follow-up (T2). Parents, teachers, and physicians rated ADHD symptoms, ADHD medication use, MPH dosing, and treatment satisfaction using questionnaires. RESULTS: A total of 100 children were enrolled and randomized to PCT (n = 49) or CAU (n = 51). In the PCT group, we found 8.2% placebo responders, 16.3% non-responders, and 65.3% responders to MPH. With PCT compared with CAU, a significantly larger number of children discontinued MPH (T1: 24.5 vs 5.9%, p = 0.009; T2: 41.7 vs 10.4%, p < 0.001) and refrained from using other pharmacological treatment (T1: 20.4 vs 3.9%, p = 0.013; T2: 20.83 vs 6.25%, p = 0.002). At both timepoints, there were no significant differences between the groups in the average dose of MPH, ADHD symptoms, or treatment satisfaction. CONCLUSIONS: PCT can be used to improve detection of children who do not benefit from MPH, and may therefore potentially reduce overtreatment of ADHD with MPH.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Methylphenidate , Humans , Attention Deficit Disorder with Hyperactivity/drug therapy , Methylphenidate/administration & dosage , Methylphenidate/therapeutic use , Child , Female , Male , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/therapeutic use , Double-Blind Method , Adolescent , Child, Preschool , Treatment Outcome
14.
Cogn Affect Behav Neurosci ; 24(2): 269-278, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38168850

ABSTRACT

Translation of drug targets from preclinical studies to clinical trials has been aided by cross-species behavioral tasks, but evidence for brain-based engagement during task performance is still required. Cross-species progressive ratio breakpoint tasks (PRBTs) measure motivation-related behavior and are pharmacologically and clinically sensitive. We recently advanced elevated parietal alpha power as a cross-species electroencephalographic (EEG) biomarker of PRBT engagement. Given that amphetamine increases breakpoint in mice, we tested its effects on breakpoint and parietal alpha power in both humans and mice. Twenty-three healthy participants performed the PRBT with EEG after amphetamine or placebo in a double-blind design. C57BL/6J mice were trained on PRBT with EEG (n = 24) and were treated with amphetamine or vehicle. A second cohort of mice was trained on PRBT without EEG (n = 40) and was treated with amphetamine or vehicle. In humans, amphetamine increased breakpoint. In mice, during concomitant EEG, 1 mg/kg of amphetamine significantly decreased breakpoint. In cohort 2, however, 0.3 mg/kg of amphetamine increased breakpoint consistent with human findings. Increased alpha power was observed in both species as they reached breakpoint, replicating previous findings. Amphetamine did not affect alpha power in either species. Amphetamine increased effort in humans and mice. Consistent with previous reports, elevated parietal alpha power was observed in humans and mice as they performed the PRBT. Amphetamine did not affect this EEG biomarker of effort. Hence, these findings support the pharmacological predictive validity of the PRBT to measure effort in humans and mice and suggest that this EEG biomarker is not directly reflective of amphetamine-induced changes in effort.


Subject(s)
Amphetamine , Central Nervous System Stimulants , Electroencephalography , Mice, Inbred C57BL , Motivation , Amphetamine/pharmacology , Humans , Animals , Male , Electroencephalography/drug effects , Adult , Young Adult , Double-Blind Method , Motivation/drug effects , Motivation/physiology , Female , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/administration & dosage , Mice , Alpha Rhythm/drug effects , Alpha Rhythm/physiology
15.
Neuropsychopharmacology ; 49(7): 1120-1128, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38287172

ABSTRACT

Neural complexity correlates with one's level of consciousness. During coma, anesthesia, and sleep, complexity is reduced. During altered states, including after lysergic acid diethylamide (LSD), complexity is increased. In the present analysis, we examined whether low doses of LSD (13 and 26 µg) were sufficient to increase neural complexity in the absence of altered states of consciousness. In addition, neural complexity was assessed after doses of two other drugs that significantly altered consciousness and mood: delta-9-tetrahydrocannabinol (THC; 7.5 and 15 mg) and methamphetamine (MA; 10 and 20 mg). In three separate studies (N = 73; 21, LSD; 23, THC; 29, MA), healthy volunteers received placebo or drug in a within-subjects design over three laboratory visits. During anticipated peak drug effects, resting state electroencephalography (EEG) recorded Limpel-Ziv complexity and spectral power. LSD, but not THC or MA, dose-dependently increased neural complexity. LSD also reduced delta and theta power. THC reduced, and MA increased, alpha power, primarily in frontal regions. Neural complexity was not associated with any subjective drug effect; however, LSD-induced reductions in delta and theta were associated with elation, and THC-induced reductions in alpha were associated with altered states. These data inform relationships between neural complexity, spectral power, and subjective states, demonstrating that increased neural complexity is not necessary or sufficient for altered states of consciousness. Future studies should address whether greater complexity after low doses of LSD is related to cognitive, behavioral, or therapeutic outcomes, and further examine the role of alpha desynchronization in mediating altered states of consciousness.


Subject(s)
Dose-Response Relationship, Drug , Dronabinol , Electroencephalography , Lysergic Acid Diethylamide , Methamphetamine , Humans , Methamphetamine/administration & dosage , Methamphetamine/pharmacology , Dronabinol/pharmacology , Dronabinol/administration & dosage , Male , Adult , Lysergic Acid Diethylamide/pharmacology , Lysergic Acid Diethylamide/administration & dosage , Female , Young Adult , Electroencephalography/drug effects , Hallucinogens/administration & dosage , Hallucinogens/pharmacology , Brain/drug effects , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/administration & dosage
16.
Rev. int. med. cienc. act. fis. deporte ; 23(92): 383-395, aug.-sept. 2023. ilus, tab, graf
Article in English | IBECS | ID: ibc-229411

ABSTRACT

Objective: This research aims to develop and validate a collaborative RP-HPLC method, with input from key industry players, for the simultaneous determination of modafinil and scopolamine hydrobromide in compound sublingual tablets. The focus is on ensuring the safety and efficacy of these substances for enhancing the physical and cognitive fitness of athletes and players. Method: Utilizing a C18 chromatographic column (200mm×4.6mm, 5μm), the method employs a mobile phase of acetonitrile-water (25:75) with 0.02mol/L ammonium acetate and 0.02% triethylamine, pH adjusted to 6.0. The flow rate was set at 1 mL/min, detection at 225 nm wavelength, and an injection volume of 20 μL.Results: Scopolamine hydrobromide showed a linear range of 1-50 μg/mL, with a standard curve equation of A=0.2187C+0.0708 (R²=0.9993), and modafinil exhibited a range of 10-500 μg/mL, with A=0.6702C-1.6855 (R²=0.9993). Both substances demonstrated average recoveries of over 99%, within acceptable variance limits, signifying reliable quantification for fitness-related applications. Conclusion: The developed method is sensitive, precise, accurate, and reproducible, conforming to the standards of the Chinese Pharmacopoeia (2020 edition). It is particularly valuable for monitoring the quality of substances used by athletes and players to ensure their safe application in enhancing fitness and performance. The method benefits significantly from the collaboration with industry experts, addressing the specific needs of fitness and sports professionals (AU)


Subject(s)
Humans , Central Nervous System Stimulants/administration & dosage , Modafinil/administration & dosage , Scopolamine/administration & dosage , Athletes , Physical Functional Performance , Chromatography, High Pressure Liquid , Administration, Sublingual
17.
Rev. chil. neuro-psiquiatr ; 60(4): 479-489, dic. 2022. tab
Article in Spanish | LILACS | ID: biblio-1423711

ABSTRACT

Introducción: el consumo de estimulantes de tipo anfetamínico (ETA) y sus derivados está cada vez más presente en los estudiantes universitarios y, en particular, en los programas de medicina. El objetivo principal de este estudio fue revisar la literatura sobre el uso de ETA y sus derivados en estudiantes de medicina latinoamericanos. Materiales y método: se realizó una revisión de la literatura disponible, utilizando las bases de datos PubMed, SciELO y LILACS. Se encontraron un total de 1.054 artículos, de los cuales 17 fueron seleccionados para esta revisión. Resultados: la revisión muestra, en general, una mayor frecuencia de uso de ETA en estudiantes de medicina de América Latina en comparación con la población general y estudiantes de otras carreras universitarias. También existe una tendencia a un mayor uso en hombres, de mayor nivel socioeconómico y en cursos posteriores del programa. La razón más informada para usar ETA fue aumentar el rendimiento académico. Como factor protector se destacaron los deportes, el tiempo en familia y la profesión de alguna creencia religiosa. De los artículos seleccionados, no se encontraron estudios sobre las consecuencias a largo plazo del uso de ETA en estudiantes de medicina. Discusión: en resumen, los estudiantes de medicina latinoamericanos tienen un alto consumo de ETA, por lo que es evidente la necesidad de nuevos estudios para mejorar la precisión estadística, determinar factores de riesgo específicos, estudiar las consecuencias a largo plazo y establecer políticas de prevención y tratamiento.


Introduction: the consumption of amphetamine-type stimulants (ATS) and their derivatives are increasingly present in university students and in particular in medical programs. The main objective of this study was to review the literature on the use of ATS and their derivatives in Latin American medical students. Materials and method: a review of the literature available was performed, using PubMed, SciELO, and LILACS databases. A total of 1054 articles were found, of which 17 were selected for this review. Results: the review generally shows a higher frequency of use of ATS in medical students of Latin America compared to the general population and students from other university degrees. There is also a tendency of a higher use in men, from higher socioeconomic status, and in later courses of the program. The most reported reason for using ATS was to increase the academic performance. As a protective factor, sports, family time and professing some religious belief stood out. Of the selected articles, no studies were found on the long-term consequences of the use of ATS in medical students. Discussion: in summary, Latin American medical students have a high consumption of ATS, and therefore there is an evident need for new studies to improve statistical precision, to determine specific risk factors, to study long-term consequences, and to stablish prevention policies and treatment.


Subject(s)
Humans , Students, Medical , Amphetamine-Related Disorders/epidemiology , Amphetamines/administration & dosage , Academic Performance , Central Nervous System Stimulants/administration & dosage , Latin America , Methylphenidate/administration & dosage
19.
Pak J Pharm Sci ; 35(1(Special)): 361-364, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35236648

ABSTRACT

To explore the application effect of aminophylline combined with caffeine citrate and GMs in the evaluation of neurodevelopmental treatment and follow-up in high-risk preterm infants. A retrospective analysis of 66 high-risk preterm infants admitted to Hengshui People's Hospital from January 2020 to June 2021 was conducted. The children who received only conventional treatment were set as the control group, while those who received aminophylline and caffeine citrate on the basis of conventional treatment were set as the experimental group, 33 cases each group; GMs were used to evaluate the neurodevelopmental function of the children, and the treatment effect was analyzed. The normal proportion of GMs assessment results in the twisting phase and restless movement phase of the experimental group was superior to the control group (P<0.05); The proportion of children with normal neurodevelopment in the experimental group was significantly higher than that in the control group (P<0.05). Aminophylline in combination with caffeine citrate can help promote the neurodevelopment of children and improve their physical health using GMs assessment in the treatment and follow-up of high-risk preterm infants.


Subject(s)
Aminophylline/therapeutic use , Caffeine/therapeutic use , Central Nervous System/drug effects , Central Nervous System/growth & development , Child Development/drug effects , Citrates/therapeutic use , Aminophylline/administration & dosage , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/therapeutic use , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/therapeutic use , Humans , Infant , Infant, Premature , Motor Activity
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