Modafinil

Authors:

Alexia Kesta, Philip M. Newton

Findings:

Most UK university students surveyed did not view non-prescribed modafinil use for cognitive enhancement as cheating, often comparing it to caffeine or believing it doesn't grant new knowledge. A minority held strong opposing views based on fairness and access. These perspectives remained largely stable even when presented with ethical moderators.

Participants:

UK University students

Study Quality Assessment:

Preprint, not peer-reviewed. Used a scenario-based approach. No competing interests declared. No specific funding received. Ethical guidelines followed, IRB approval obtained (Swansea University Medical School Research Ethics Committee), participant consent obtained. Reporting guidelines followed. Data available as supplementary material.

All Effects:

Authors:

Karl Greenblatt, Ninos Adams

Participants:

patients with fatigue or excessive daytime sleepiness (EDS) secondary to traumatic brain injury (TBI)

Study Quality Assessment:

Literature search of Medline and PubMed using EBSCOhost database. Included primary literature, observational studies, meta-analyses, case reports.

Findings:

The overall positive effect of single-dose modafinil over placebo across cognitive domains (attention, executive functioning, memory, processing speed) was small but significant (g = 0.10). No significant differences were found between cognitive domains, modafinil doses (100 mg vs 200 mg), or populations studied (psychiatric vs nonpsychiatric). The evidence indicates limited potential for modafinil as a cognitive enhancer in non-sleep-deprived populations.

Participants:

Non-sleep-deprived adults (including psychiatric vs nonpsychiatric populations).

Dosage:

Single-dose effects studied; doses compared were 100 mg vs 200 mg.

Study Quality Assessment:

Systematic Review and Meta-Analysis of 19 placebo-controlled trials; calculated 67 cognitive domain-specific effect sizes.

All Effects:

Authors:

Maddalena Mereu

Findings:

Modafinil (MOD) enhances cognitive functions like attention, learning, and memory, likely via dopamine transporter (DAT) inhibition and effects on other neurotransmitter systems (e.g., glutamate, GABA, histamine, orexin) and brain areas distinct from typical psychostimulants. Despite inconsistent results in clinical trials for substance use disorders, it shows potential for improving cognitive deficits in these populations and as an ADHD treatment, with relatively low abuse liability. Non-dopaminergic mechanisms may contribute significantly to its wake-promoting and cognitive effects.

Participants:

The review covers studies involving human participants (healthy volunteers, patients with mental disorders including schizophrenia, substance abusers [cocaine, methamphetamine, tobacco smokers], individuals with ADHD, military personnel/pilots) and animal models (rats, mice, monkeys, marmosets, guinea-pigs). Specific human clinical studies mentioned include sample sizes ranging from N=6 to N=210.

Dosage:

Human studies reviewed used various oral dosages, including single doses (e.g., 200-800mg), daily doses (e.g., 100mg, 200mg, 400mg, 800mg) for periods ranging from days to 12 weeks. Specific regimens mentioned include 100mg/day, 200mg/day, 400mg/day, 200-600mg, 200-800mg ranges, and high-dose military use (e.g., 3x100mg or 3x200mg per day). Animal studies used doses like 75 mg/kg and 300 mg/kg. The R-enantiomer (R-MOD/Armodafinil) is also mentioned.

Study Quality Assessment:

The review discusses studies using various methodologies including preclinical (in vitro, in vivo animal studies using techniques like microdialysis, c-Fos, PET, single unit recordings, behavioral tasks) and clinical studies (human PET, functional neuroimaging, clinical trials). Several clinical trials are described as double-blind, placebo-controlled, or open-label. Methods mentioned include subjective effects ratings, urine analysis for metabolites, cognitive/neuropsychological testing (e.g., working memory, attention tasks), assessment of safety/tolerability, and use of specific questionnaires. Some trials included cognitive behavioral therapy. Challenges like medication compliance in trials are noted.

All Effects:

Study Quality Assessment:

Cognitive testing started 2 hours after dosing, timed to coincide with peak plasma levels (2-4 hours post-dose). Dose selection based on previous studies reporting procognitive effects.