Eugeroics

Authors:

Andrew Jones, Carl A Roberts, Catharine Montgomery, Harry Sumnall, Suzanne H Gage

Findings:

Modafinil showed a small overall effect (SMD=0.12) and improved memory updating (SMD=0.28). Methylphenidate (MPH) demonstrated a small overall effect (SMD=0.21), driven by improvements in recall (SMD=0.43), sustained attention (SMD=0.42), and inhibitory control (SMD=0.27). D-amphetamine showed no overall effects. The study concludes that while MPH and modafinil exhibit enhancing effects in specific cognitive sub-domains, these effects are small, and current evidence does not support the user perception of these drugs as broadly effective cognitive enhancers.

Participants:

healthy non-sleep-deprived adults

Dosage:

acute administration

Study Quality Assessment:

Series of meta-analyses (3 meta-analyses, k=47 studies total: modafinil k=14 studies with 64 effect sizes, Methylphenidate k=24 studies with 47 effect sizes, d-amphetamine k=10 studies with 27 effect sizes) comparing drug effects to placebo. Adherence to PRISMA guidelines reported. Subgroup analysis by cognitive domain was performed. Acknowledged limitations include small effect sizes and that experiments do not accurately reflect actual use in the wider population. No funding sources were involved in the work. Authors declared no conflict of interest.

All Effects:

Authors:

Andrade C, Kisely S, Monteiro I, Rao S

Participants:

Patients with schizophrenia experiencing negative symptoms

Study Quality Assessment:

Systematic review and meta-analysis of randomized controlled trials

Authors:

A.-K. Brem, R.M. Battleday

Findings:

This systematic review found that modafinil intake enhances executive function in healthy non-sleep-deprived humans. While studies using basic testing paradigms showed variable improvements in attention and learning/memory (with a few reporting impairments in divergent creative thinking), studies using more complex assessments consistently showed enhancement of attention, executive functions, and learning. Importantly, no preponderances for side effects or mood changes were observed.

Participants:

Healthy non-sleep-deprived humans.

Study Quality Assessment:

Systematic review of 24 primary studies (both parallel and cross-over designs) published in English from January 1990 until December 2014. Inclusion criteria for reviewed studies: prospective, conducted on healthy humans that were not sleep-deprived, compared performance on modafinil to placebo, included randomisation protocols. Methodological discrepancies and reliance on psychometric tests designed for ill populations were noted as issues in the literature. The authors declare no conflict of interests and state the work was conducted without input from funding sources.

All Effects:

Authors:

Claus J Loland

Findings:

R-modafinil binds to the dopamine transporter (DAT) and inhibits dopamine uptake less potently than cocaine, with R-modafinil having approximately threefold higher affinity than its S-enantiomer. In microdialysis studies, R-modafinil increased extracellular dopamine concentrations in the mouse nucleus accumbens shell less efficaciously than cocaine but with a longer duration of action, and it fully substituted for cocaine in discrimination tests. R-modafinil displays an in vitro profile different from cocaine, warranting future trials as a substitute therapy with potential cognitive enhancement benefits for psychostimulant addiction.

Participants:

Animal model: mice (for microdialysis and cocaine discrimination studies); In vitro studies using human dopamine transporter (DAT) wild-type and mutants.

Study Quality Assessment:

Methods included synthesis of enantiomers, in vitro testing for inhibition of [(3)H] dopamine (DA) uptake and [(3)H]WIN 35428 binding in human DAT, molecular docking studies, microdialysis studies in mouse nucleus accumbens shell, and a cocaine discrimination procedure in mice. Data were compared with cocaine and JHW 007. All authors reported no biomedical financial interests or potential conflicts of interest.

All Effects:

Authors:

Cameron S Carter, Michael J Minzenberg

Findings:

Modafinil (MOD) enhances cognitive functions like attention, learning, and memory, with neurochemical actions and brain activation patterns distinct from typical psychostimulants, resulting in very low abuse liability. While clinical studies on MOD for treating drug abuse have shown inconsistent outcomes, positive trends suggest its potential as a cognitive enhancer may benefit certain patient populations, including those with substance use disorders or ADHD, and it can maintain alertness in sleep-deprived individuals.

Participants:

The review discusses studies involving various human populations including healthy individuals (adults, volunteers), patients with mental disorders (e.g., schizophrenia, ADHD), substance abusers (cocaine, methamphetamine users), tobacco smokers, individuals with sleep disorders (narcolepsy), experimentally sleep-deprived subjects, and military personnel/pilots. Animal models mentioned include rats, mice, monkeys, and marmosets. Specific sample sizes (N=X) are cited for individual studies within the text and a summary table of clinical trials.

Dosage:

The review covers studies using various oral dosages of Modafinil (MOD) in humans, generally ranging from 100mg to 800mg per day (e.g., 100mg/day, 200mg/day, 400mg/day, 200-600mg, 200-800mg, single or divided doses). Specific regimens for military personnel include 3x100mg or 3x200mg daily. Animal studies mentioned doses such as 75 mg/kg and 300 mg/kg of MOD.

Study Quality Assessment:

This review article was published in 'Psychopharmacology (Berl)' and is available via PMC (an official U.S. government NLM/NIH database), with a provided DOI (10.1007/s00213-013-3232-4), PMCID (PMC3800148), and PMID (23934211). The text includes a PMC Disclaimer and Copyright Notice. Funding is disclosed as 'NIDA Intramural Research Program, NIH/DHHS', and the authors declare 'no conflict of interest'. The review cites multiple studies, including those with designs such as 'human PET studies', 'double-blind', 'placebo-controlled', and 'randomized controlled trials'.

All Effects: