modafinil / Generic mfg. - LARVOL DELTA

The impact of modafinil on memory and brain oxidative stress: contrasting effects of acute and chronic administration in healthy rats. (PubMed, Metab Brain Dis) - "In addition, chronic administration of this drug increased oxidative lipid damage, evaluated through 8-ISO and 4-HNE. These findings suggest a potential link between chronic MD use, memory impairment, and oxidative stress in the brains of rats, emphasizing the importance of further research in this area."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • CAT

Assessing bias in AI-driven psychiatric recommendations: A comparative cross-sectional study of chatbot-classified and CANMAT 2023 guideline for adjunctive therapy in difficult-to-treat depression. (PubMed, Psychiatry Res) - "Notable discrepancies were observed in the overestimation of medications such as quetiapine and lithium and the underestimation of modafinil and ketamine. Additionally, a distinct bias pattern was observed in OpenAI's chatbots, which demonstrated a tendency to over-recommend lithium and bupropion. Our study highlights both the promise and the challenges of employing AI tools in psychiatric practice, and advocates for multi-model approaches to mitigate bias and improve clinical reliability."

Journal • Observational data • CNS Disorders • Depression • Mood Disorders • Psychiatry

RECOVER-SLEEP: Platform Protocol (clinicaltrials.gov) - P2 | N=1074 | Recruiting | Sponsor: Duke University | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Jul 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Sleep Disorder

Neurostimulant Use for Rehabilitation and Recovery After Stroke: A Narrative Literature Review. (PubMed, Stroke) - "The qualitative analysis included 34 trials testing the following neurostimulants: methylphenidate (n=6), amphetamines (n=8), memantine (n=2), modafinil (n=2), levodopa (n=14), amantadine (n=1), bromocriptine (n=3), and ropinirole (n=1). In conclusion, there are promising results of positive effects of neurostimulants with few side effects, though studies are limited by heterogeneous designs and small sample sizes. Neurostimulant efficacy must be assessed in conjunction with specific rehabilitation modalities as part of larger, well-designed studies to best understand their effects on impairment."

Journal • Cardiovascular • CNS Disorders • Cognitive Disorders • Depression • Fatigue • Psychiatry

Transition-metal free chemoselective C-H hydroxylation of bisarylmethanes enabled by a phosphite as a sacrificial reductant. (PubMed, Org Biomol Chem) - "This methodology has been employed to synthesize useful active pharmaceutical ingredients (APIs), modafinil and adrafinil. By using DMSO-d6 as the deuterium reagent, the hydroxylation-deuteration of 3-benzylpyridines and diphenylmethanes proceeded well, with excellent deuterium ratios. Preliminary kinetic experiments and 1H NMR studies provided significant insight into the reaction mechanism."

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Modafinil Ameliorated Fibromyalgia Syndrome in Rats by Modulating Mast Cells and Microglia Activation Through Dopamine/Substance P/MRGPRX/Histamine and PI3K/p-Akt/NF-κB Signaling Pathways. (PubMed, J Neuroimmune Pharmacol) - "In groups 3 and 4, modafinil (100 mg/kg/day; p.o) was administered either alone or in conjunction with haloperidol (1 mg/kg/day; ip), respectively, for the following 21 days. Ultimately, modafinil alleviated FMS behavioral, histopathological, and biochemical abnormalities and suppressed mast cell-microglial neuroinflammation in the thalamus of rats exposed to reserpine. This study highlights the potential of repurposing modafinil to improve FMS symptoms."

Journal • Preclinical • CNS Disorders • Depression • Fibromyalgia • Inflammation • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology • IL17A • IL6 • TNFA

Comparative cardiovascular safety of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. (PubMed, Lancet Psychiatry) - "Practitioners should monitor blood pressure and pulse in patients with ADHD treated with any pharmacological intervention, and not stimulants only. Given the short duration of available randomised controlled trials, new research providing insights on the causal effects of ADHD medications on cardiovascular parameters in the longer term should be funded."

Journal • Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiovascular • CNS Disorders • Psychiatry

Beware of misattributing 'modafinil' in diphenhydramine-positive cases. (PubMed, Forensic Toxicol) - "In the analysis of benzhydryl compounds, particular caution should be exercised, with each case verified by comparison with a certified analytical standard, and, where possible, by detecting the metabolites of these compounds."

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Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics. (PubMed, ADMET DMPK) - "The study demonstrates that microwave energy effectively alters the crystalline structure of modafinil in the presence of Gelucire® 48/16, enhancing its amorphousness, compressibility, and compatibility. These findings highlight the potential of microwave-assisted complexation as a novel approach to improve the pharmaceutical performance of BCS Class II drugs like modafinil."

Journal • Excessive Daytime Sleepiness • Fatigue • Narcolepsy • Sleep Disorder

Development of Modafinil Dependence Following Self-medication for Sexual Dysfunction: A Case Series. (PubMed, Indian J Psychol Med) - No abstract available

Journal • Sexual Disorders

POP: Psilocybin Therapy for Chronic Low Back Pain (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Joshua Woolley, MD, PhD | Trial completion date: Dec 2024 ➔ Apr 2026 | Trial primary completion date: Dec 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Making modafinil: Classification and serendipity in drug development. (PubMed, Soc Stud Sci) - "We highlight these contingencies to show the considerable efforts that go into finding, and creating, markets for drug development. Taking these efforts for granted may confuse invention with innovation and is likely to lead to understatement of the costs and choices involved in drug development, particularly where mental health categories are concerned."

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Long-term quality of life and hypothalamic dysfunction after craniopharyngioma. (PubMed, J Neurooncol) - "Hypothalamus-sparing treatment strategies and further research on novel therapeutic agents for hypothalamic syndrome are warranted."

HEOR • Journal • Review • Brain Cancer • Cardiovascular • CNS Disorders • CNS Tumor • Fatigue • Genetic Disorders • Hypothalamic Injury-associated Obesity • Metabolic Disorders • Obesity • Psychiatry

Amantadine and Modafinil use in critically ill patients without acute brain injury (IARS-SOCCA 2025) - "Our initial analyses suggest that there are no differences in mental status in patients who received either amantadine or modafinil during their admission to ICU. The limitations of this study include small sample size and the multiple etiologies of altered mental status in our studied population. The confounding factors such as sedation, infectious state and metabolic derangements may have contributed to a lack of positive effect on mental status with the use of amantadine and modafinil."

Clinical • Anesthesia • Cardiovascular • CNS Disorders • Hematological Disorders • Metabolic Disorders • Vascular Neurology

Effects of Dimenhydrinate on Motor Behavior and Vascular Function: Possible Implications for the Field of Sports. (PubMed, Drug Test Anal) - "Four study groups were formed: (1) vehicle (Veh), (2) modafinil (MOD), (3) DMH at 50 mg/kg (DMH-50), and (4) DMH at 200 mg/kg (DMH-200)...In this case, the study groups were (1) Veh, (2) MOD, (3) DMH, (4) diphenhydramine (DPH), (5) 8-chlorotheophylline (8-Cl-T), and (6) theophylline (TEO)...Regarding cardiovascular effects, DMH decreased vascular reactivity to phenylephrine and acetylcholine. Finally, in the DMH formulation, 8-Cl-T was identified as the compound responsible for increasing blood pressure and heart rate."

Journal • Cardiovascular

Efficacy of pharmacologic treatments for fatigue in multiple sclerosis: A systematic review and meta-analysis. (PubMed, Mult Scler Relat Disord) - "The studied medications have minimal to no efficacy and an uncertain clinical significance in reducing fatigue in PwMS."

Clinical • Journal • Retrospective data • CNS Disorders • Fatigue • Multiple Sclerosis

Protective effect of modafinil in bisphenol A-induced lung injury in rats: roles of SIRT1-dependent signaling pathways. (PubMed, Immunopharmacol Immunotoxicol) - "MOD showed a significant improvement in all parameters. MOD possesses potent ameliorative effects against lung injury caused by BPA via reducing oxidative stress, inflammatory process, and apoptosis through regulation of SIRT1/Nrf2 and SIRT1/FOXO1 signaling pathways."

IO biomarker • Journal • Preclinical • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Respiratory Diseases • BAX • BCL2 • CASP3 • HMOX1 • IL1B • IL6 • KEAP1 • TNFA

Determinants of substance use patterns in patients with narcolepsy type 1: A multi-center comparative cross-sectional study. (PubMed, Sleep Med) - "Patients with NT1 do not seem less vulnerable to psychoactive substance use/misuse. Consumptions patterns are associated with multiple dimensions of the disease including sleep-related symptoms, comorbidities, treatments, and psycho-behavioral factors."

Journal • Observational data • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Genetic Disorders • Narcolepsy • Obesity • Psychiatry • Sleep Disorder

SAFETY OF NEUROSTIMULANT USE IN THE INTENSIVE CARE UNIT AFTER NEUROLOGIC EMERGENCIES (SCCM 2025) - "Adult ICU patients admitted from 2015-2023 that received scheduled amantadine (AMT), modafinil (MOD), and/or methylphenidate (MPH) while in the ICU to promote wakefulness were included. NS were initiated 8 days after injury. There was not a statistically significant difference in the cardiovascular and neurologic events between groups, but a trend towards fewer events in the AMT group. Due to a small sample size and confounding variables, safety differences between each NS when started early remains uncertain."

Clinical • Cardiovascular • CNS Disorders • Critical care • Epilepsy • Hypertension • Vascular Neurology

MODAFINIL THERAPY IN BILATERAL THALAMIC STROKE SECONDARY TO OCCLUSION OF THE ARTERY OF PERCHERON (SCCM 2025) - "The patient received supportive care with Aspirin, Plavix, and Atorvastatin and was extubated; however, she continued to remain hypersomnolent and exhibited bradylalia and hypophonia. A trial of caffeine and methylphenidate aroused the patient excessively, and therefore, non-amphetamine modafinil was given, which showed significant improvement in the patient's hypersomnolence without hyperactivity... Largely unrecognized on imaging due to its small diameter, AOP occlusions account for thalamic strokes that cause decreased responsiveness. The mechanism of action of modafinil to imitate wakefulness remains largely to be studied; however, its use in our patient showed rapid improvement in hypersomnolence, given its predicted role in increasing extracellular dopamine."

Atrial Fibrillation • Cardiovascular • CNS Disorders • Coronary Artery Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Epilepsy • Hypertension • Ischemic stroke • Metabolic Disorders • Sleep Disorder • Type 2 Diabetes Mellitus

Healthcare Burden and Productivity Loss Due to Narcolepsy in Sweden. (PubMed, Clocks Sleep) - "This study provides evidence of the magnitude of the substantial societal economic burden due to narcolepsy in Sweden, evidenced by higher healthcare resource utilization and indirect costs."

Journal • Reimbursement • US reimbursement • Narcolepsy • Sleep Disorder

The observation of seasonal variation of fatigue in multiple sclerosis depends on the measurement instrument. (PubMed, Mult Scler Relat Disord) - "We analyzed the effect of the season on the baseline fatigue levels in our randomized, placebo-controlled, crossover, double-blind trial, Treatment of Fatigue with Methylphenidate, Modafinil, and Amantadine in MS (TRIUMPHANT-MS) conducted in two sites with very different climates. MFIS scores varied with season and study site, while Neuro-QoL fatigue scores did not. The impact of temperature on multiple sclerosis fatigue depends on the specific patient-reported outcome measure employed."

Clinical • Journal • CNS Disorders • Fatigue • Multiple Sclerosis

Fatigue in multiple sclerosis: A scoping review of pharmacological and nonpharmacological interventions. (PubMed, Mult Scler J Exp Transl Clin) - "We found that pharmacological interventions are few and have included the use of Amantadine, Ondansetron, Methylphenidate, and Modafinil, with little effects on fatigue. Lack of knowledge of the pathophysiology of fatigue limits its prevention, control, and management recommendations. A comprehensive and interdisciplinary approach is required to manage this symptom in patients with MS."

Journal • Review • CNS Disorders • Fatigue • Multiple Sclerosis

Contrasting the reinforcing effects of the novel dopamine transport inhibitors JJC8-088 and JJC8-091 in monkeys: Potential translation to medication assisted treatment. (PubMed, J Pharmacol Exp Ther) - "The dopamine transport inhibitor and releaser d-amphetamine has been shown to decrease cocaine self-administration (SA), although it has abuse liability. Recently, several modafinil analogs reduced cocaine SA in rats and monkeys, including JJC8-088, characterized as "cocaine-like" in rats, and JJC8-091, characterized as "atypical" and not SA by rats...This study found that both compounds maintained SA in monkeys responding under several conditions. However, when given access to an alternative reinforcer during the SA session, JJC8-091 was not reinforcing, suggesting that JJC8-091 may have lower abuse liability than cocaine and may be a viable candidate for cocaine use disorder because, in the human population, alternatives to drug use are often available."

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Assessing acute effects of methylphenidate and modafinil on inhibitory capacity, time estimation, attentional lapses, and compulsive-like behavior in rats. (PubMed, Behav Pharmacol) - "However, an exploratory analysis of changes in behavioral performance within sessions suggested that methylphenidate fostered favorable, yet short-lived, effects. We discuss our results in terms of the risks and cost-benefits of doses above or below the effective dose of cognitive enhancement drugs."

Journal • Preclinical