modafinil / Generic mfg. - LARVOL DELTA

Multi-Trajectory Analysis of Craving and Drug Use in the Course of Medication Treatment Trials of Cocaine Use Disorder (CPDD 2025) - "Compared to the placebo arm participants, those on modafinil 200 mg daily were more likely to be in the Decreasing craving/Decreasing use group (Relative Risk Ratio [RRR]=4.84, 95% CI=1.38-17.00, p=0.014) or Decreasing craving/High use group (RRR=5.55, 2.04-14.08, p=0.001) than in the High craving/High use group. There is considerable variation in trajectories of craving and drug use in the course of clinical trials for cocaine use disorder. Participants experiencing the greatest reduction in cocaine craving and use in the course of treatment also experience the greatest improvement on other measures of drug use and psycho-social functioning."

Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Co-Use of Alcohol and Nicotine with Cocaine Reduces the Efficacy of Behavioral and Pharmacological Interventions in Nonhuman Primates (CPDD 2025) - "Together, these data suggest that cocaine users who engage in polysubstance use should be viewed as a distinct and more prevalent population that requires differential behavioral and pharmacological approaches to reduce cocaine use."

Clinical

Effective Interventions for Reducing the Negative Effects of Night Shifts on Doctors' and Nurses' Health and Well-Being: A Systematic Review. (PubMed, Cureus) - "Across 74 studies, we explored interventions including bright light exposure, melatonin, dietary changes, scheduled naps, medications like modafinil and caffeine, and complementary approaches such as aromatherapy, exercise, and acupuncture...These findings suggest that no single solution fits everyone, and that a personalized, flexible approach combining different strategies may work best. There's a clear need for more long-term, real-world studies to help healthcare professionals stay well while caring for others overnight."

Journal • Review • CNS Disorders • Sleep Disorder

Valacyclovir Toxicity in ESRD Unmasked by Thorough History in Intubated Patient (ATS 2025) - "An EEG confirmed epileptiform activity, and she was treated with Keppra and Vimpat...Her ICU stay was prolonged by failed spontaneous breathing trials (SBTs), and she showed minimal response to modafinil on Day 14...Neurotoxicity arises from the accumulation of acyclovir's active metabolite, which, without adequate renal clearance, crosses the blood-brain barrier and leads to encephalopathic symptoms, as seen in this patient... The patient's condition improved following discontinuation of valacyclovir and ongoing dialysis. This case emphasized the critical role of careful medication management in ESRD patients, particularly for drugs like valacyclovir that have neurotoxic potential."

Clinical • Anesthesia • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Epilepsy • Heart Failure • Herpes Zoster • Infectious Disease • Movement Disorders • Nephrology • Psychiatry • Renal Disease • Varicella Zoster

Spotlight on Seniors with Narcolepsy: Comorbidities and Management. (PubMed, J Clin Med) - "Fewer patients were currently on wake-promoting agents (85.7%), with over half on modafinil (55.6%)...It is important to consider cardiometabolic comorbidities in the management of narcolepsy in this population. Geriatricians should be educated on narcolepsy with specific programs for these seniors."

Journal • Cardiovascular • Cataplexy • CNS Disorders • Depression • Excessive Daytime Sleepiness • Hypertension • Migraine • Narcolepsy • Pain • Psychiatry • Sleep Disorder

Repurposing of modafinil as an anti-inflammatory drug: a systematic review of experimental studies. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Recent studies attempted to provide evidence for repurposing modafinil for several diseases, including autoimmune encephalomyelitis, nonalcoholic liver disease, gastric mucosal injury, neuropathic pain, atherosclerosis, intestinal ischemia, pulmonary hypertension, pancreatitis, ischemic stroke, testicular torsion, and lithium-pilocarpine-induced status epilepticus. Current evidence supports that modafinil can modulate inflammation, suppress the immune response, and improve disease severity partly by inhibiting NF-κB, NOS, Kca3.1, Kca2.3, and COX-2. By reviewing recent findings from experimental studies, we discussed the beneficial effects of modafinil on several inflammatory diseases, with a particular focus on the underlying mechanisms."

Journal • Atherosclerosis • Cardiovascular • CNS Disorders • Epilepsy • Hepatology • Hypertension • Immunology • Inflammation • Ischemic stroke • Multiple Sclerosis • Neuralgia • Pain • Pancreatitis • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Fatigue and management of warfighter mental endurance. (PubMed, BMJ Mil Health) - "Countermeasures include engagement strategies, brain endurance training to extend physical endurance, and caffeine and modafinil to temporarily sustain performance. An infrastructure for physiological monitoring and integrated analyses will advance team performance enhancement, along with the use of explainable and interpretable artificial intelligence modelling, refined through iterative experimentation. More precise definitions that distinguish MF from other types of fatigue will help advance the development of monitoring technologies and countermeasures by targeting the right physiological and behavioural metrics."

Journal • Review • Fatigue

Treatment of idiopathic hypersomnia with modafinil in an individual at clinical high risk for psychosis: A case report. (PubMed, PCN Rep) - "However, whether modafinil use increases the risk of transition to psychosis remains unclear. Further research is required on modafinil as a treatment for hypersomnia in individuals with CHR-P."

Journal • CNS Disorders • Depression • Excessive Daytime Sleepiness • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Discovery of a New Class of Orexin 2 Receptor Agonists as a Potential Treatment for Narcolepsy. (PubMed, J Med Chem) - "For example, psychostimulants (e.g., modafinil) reduce excessive daytime sleepiness (EDS) and sodium oxybate (gammaaminobutyric acid receptor agonist) reduces both EDS and cataplexy...In healthy dogs, they increased time in wakefulness. These results highlight their potential as treatment for narcolepsy and other types of hypersomnolence."

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

Case Report: Narcolepsy patients masked behind obstructive sleep apnea syndrome (OSAS): report of 2 cases and literature review. (PubMed, Front Neurosci) - "Treatment with modafinil in conjunction with CPAP therapy led to significant improvement in symptoms and quality of life...Comprehensive evaluation, including detailed patient history and sleep studies, is crucial. Combined therapy targeting both conditions may be effective in managing symptoms and improving patient outcomes."

Journal • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • Sleep Wake Cycle Disorder

Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex. (PubMed, Neuroimage) - "The topography of these functional modifications mainly overlaps with the distribution of glutamatergic and serotonergic receptors. In summary, our findings highlight modafinil's influence on thalamocortical circuits, emphasizing the role of higher-order pulvinar nuclei and ventrolateral anterior complex."

Journal

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."

Journal

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."

Journal

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."

Journal

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