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Modafinil is an awakefulness enchancing drug that was created for treatment of daytime sleep related disorders such as Narcolepsy. It seems to have benefits for cognition via increasing levels of stimulatory neurotransmitters in the brain, and is used recreationally as a smart-drug.
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2-[(Diphenylmethyl) sulfinyl]acetamide, Provigil, Modalert, Modapro, Alertex
Standard dosages are 100-200mg, or perhaps 4mg/kg bodyweight, either taken in a sleep deprived state (if the user desires to not fall asleep) or taken first thing in the morning if the user does not wish to impair sleep.
The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Modafinil has in your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
|Level of Evidence ||Effect||Change||Magnitude of Effect Size ||Scientific Consensus||Comments|
Cognition is significantly improved in persons undergoing sleep deprivation or other conditions in which attention processing is highly impaired, while other conditions... show
There may be a slight increase in systolic blood pressure with acute usage of modafinil (when measured at its peak blood levels), although it does not appear to modify... show
Heart rate and pulse do not appear to be influenced from modafinil supplementation, despite a small increase in systolic blood pressure.
An improvement in working memory is noted in most persons tested, even otherwise healthy and nonfatigued controls.
An improvement in reaction time (decrease) is noted in both healthy and normal persons as well as those undergoing either drug addiction or sleep deprivation. This may... show
Fatigue is notably reduced with modafinil supplementation, particularly during instances of sleep deprivation or hypersomnia.
|C||ADHD in Children|
Modafinil appears to be able to reduce symptoms of ADHD in children when taken as a daily preventative at the lowest active dose
Modafinil appears to be able to reduce appetite, and 'loss of appetite' is a common side-effect of modafinil supplementation.
There is currently no evidence to suggest a significant reduction of weight associated with modafinil, although as a trend to reduce weight has been noted alongside appetite... show
There appears to be somewhat of an increase in subjective attention with modafinil secondary to its arousal promoting effects
Subjective well being and enjoyment during cognitive tasks appears to be significantly improved modafinil supplementation, and this is notable as it has been noted to occur... show
Modafinil (300mg) taken prior to sleep is as potent as 20mg D-amphetamine in reducing the need to sleep and improving cognitive performance during intentional sleep deprivation.... show
Alcohol dependence, particularly the impulsivity thereof, appears to be slightly reduced with modafinil administration
Modafinil can decrease impulsivity in studies assessing addiction, although it appears to only significantly affect those with higher baseline impulsivity (more impulsive... show
|C||Symptoms of Multiple Sclerosis|
Memory impairment in multiple sclerosis may be attenuated with supplementation of modafinil (250mg armodafinil), although other cognitive impairments associated with MS... show
There does not appear to be a significant influence on processing speed, with some evidence suggesting a possible reduction thereof.
Memory (usually studies investigate short term) appears to be beneficially influenced with modafinil supplementation, possible secondary to the improvements in working... show
Motivation to complete a cognitive task appears to be improved in persons supplementing modafinil.
There do not appear to be any significant influences on self-reported ratings of calmness with supplementation of modafinil.
There is a possible improvement in processing accuracy with supplementation of modafinil.
An increase in alertness has been reported in persons using modafinil supplementation.
Modafinil is a pharmaceutical designed for usage in sleep-related disorders, and is related to improved mental function in a sleep deprived state.
The term 'modafinil' refers to a racemic mixture of two isomers, R-modafinil and S-modafinil. The R-isomer by itself is referred to as armodafinil.
Modafinil is a racemic mixture of S-modafinil and R-modafinil, whereas Armodafinil is just the R-modafinil by itself
The half-life of modafinil appears to be 13-15 hours, and steady state concentrations in serum are reached 2 days following supplementation. Although the S-isomer by itself seems to have a short elimination half-life (4-5 hours) whereas the R-isomer is more prolonged (15 hours) ingesting armodafinil does not appear to significantly differ from modafinil.
An analysis of studies has noted, however, that armodafinil has an 18% higher Cmax value (5.44+/-1.64µg/mL relative to 4.61+/-0.73µg/mL) with a more rapid Tmax (1.8 hours relative to 2.5) and that the overall AUC of armodafinil appears to be 32-40% greater than modafinil.
Although the two variants of modafinil (modafinil and armodafinil) appear to have similar half-lives, armodafinil has a higher overall exposure to the body (assessed by AUC) as well as a higher and more rapid peak in the blood
According to c-Fos immunocytochemistry (c-Fos being a gene that rapidly activates in response to stimuli and can be detected following neuronal stimulation or sleep deprivation), modafinil administration to cats is associated with strong c-Fos activation in the anterior hypothalamic nucleus and surrounding areas with weaker activation in the dorsal portion of the suprachiasmatic nuclei (SCN) with minimal activation in other brain regions such as the cortex or striatum. This selective activation of the hypothalamus has been noted elsewhere, and the amygdala also implicated. Modafinil has been confirmed in humans to have a different profile than does amphetamine.
In contrast to amphetamine or methylphenidate induced wakefulness (characterized by widespread neuronal activation), modafinil appears to be somewhat selective for the hypothalamus and amygdala with some influence on the SCN
Modafinil seems to be able to increase extracellular levels of dopamine in the rat nucelar accumbens and prefrontal cortex and the dog caudate nucleus. It has been shown to occupy both the dopamine and noradrenaline receptors (in the striatum) and prevention of dopamine receptor occupancy abolishes the sleep-promoting effects in mice, suggesting this mechanism of action is crucial to the sleep-promoting effects.
The wakefulness effects of modafinil are significantly attenuated by antagonists of adrenergic receptors (both alpha and beta subunits) although inhibiting catecholamine synthesis via α-methylparatyrosine does not appear to impair these effects.
In those with faulty orexin levels (narcoleptics), modafinil shows benefit possibly by acting on orexic neurons directly. This effect is more potent in orexin-knockout mice than in normal mice, and the effects of modafinil on the orexin system of healthy persons is unknown.
Some studies assess the effects of modafinil on intentional sleep deprivation, and modafinil (300mg) appears to be effective in reducing the disturbed mood and cognition seen during sleep deprivation with a potency comparable to 20mg D-amphetamine. Elsewhere, it has been noted that the impairment of self-monitoring (ability to accurately assess oneself and their environment) is effectively reversed to a degree where an overconfidence effect (higher percieved assessment of skills relative to actual skills) is seen.
Modafinil intervention prior to sleep can highly disrupt the sleep cycle and accompanying sedation, and usage of modafinil in this manner can attenuate the side-effects of sleep deprivation (cognitive and mood impairment)
Rebound hypersomnia is the phenomena where an anti-sleep agent is successful in reducing sleep, but after the effects of the drug wear off the user is significantly sleepier than before. Unlike amphetamine based drugs, modafinil does not appear to be associated with rebound hypersomnia in the cat nor rats or mice. In humans who miss two nights sleep due to modafinil intervention (64 continuous hours awake), there does not appear to be any rebound hypersomnia like is seen with D-amphetamine.
Modafinil does not appear to be associated with rebound hypersomnia
The increase in alertness during sleep deprivation seen with 300mg modafinil appears to be comparable to 20mg D-amphetamine over the course of 10-12 hours following one-time administration.
The anti-sleep efficacy of modafinil (300mg) appears to be comparable to 20mg D-amphetamine
The sleep wake cycle of the brain is a balance of the 'ascending arousal system' consisting of arousing neurotransmitters (catecholamines, acetylcholine, orexin, etc.) and the neurotransmitters (GABA, Galanin) which act to suppress stimulation and promote sleep. Varying levels of arousing and depressing neurotransmitters form an 'on-off' switch for arousal and sleep.
Overall regulation of the wakefulness and rest cycle seems to be in part due to the circadian rhythm, mediated by the Suprachiasmatic Nuclei (SCN), and in part due to homeostatic needs for sleep that are gained during wakefulness.
Modafinil seems to be able to interact with a multitude of stimulatory systems including serotonergic, noradrenergic, dopaminergic, glutaminergic, histaminergic, and orexinergic pathways; and also influences GABAergic pathways.
Some studies that use modafinil for the treatment of some other states note that the side-effect of insomnia persists more than placebo and modafinil is able to prevent participants from voluntarily falling asleep when taken prior to sleep.
Supplementation of modafinil is able to preserve cognition in fatiged states.
In otherwise healthy persons, 100mg or 200mg of modafinil taken two hours prior to cognitive testing is able to improve working memory (digit span tests), visuospatial planning, and reaction time whereas elsewhere it was found to improve cognition (task enjoyment, planning, and working memory) in completely normal and non-sleep deprived persons at 200mg. Working memory and processing accuracy have been found to be improved with 200mg elsewhere.
Alongside the improvements in working memory are improvements in the actual performance of the task, most notably an increase in motivation and enjoyment for undergoing the task.
There is some cognitive enhancing properties of modafinil acute usage in otherwise healthy persons, and may increase motivation and enjoyment from doing a cognitive task
In methamphtamine dependent persons (known to have a degree of cognitive impairment), modafinil at 400mg for three days is able to improve working memory and trended to improve fatigue in those with worse baseline scores yet was unable to improve performance in those with higher baseline scores and 200mg for a single dose does not appear to be cognitive enhancing in this same population.
In persons with possible cognitive decline associated with methamphetamine usage, modafinil has the potential to improve cognition although acute usage doesn't appear to be effective and the overall cognitive enhancement is relatively minor
Studies that assess the effects of modafinil sometimes report a reduction in appetite as a side-effect, measured at 16% (164 persons)
Studies that note reductions in appetite sometimes note trends towards weight loss over a period of weeks, but usually do not reach statistical significance.
Supplementation of modafinil in the range of 170–425mg for six weeks (dose titrated up from 170mg to 425mg unless tolerance was compromised) was able to reduce symptoms of ADHD as assessed by both CGI-I and ADHD-RS-IV in youth.
It is thought that modafinil has a low potential for wide-spread drug abuse
Response inhibition (the ability to inhibit a prepotent response, and thought to be indicative of impulsivity in persons undergoing drug abuse) is improved in rats and humans (alcohol dependence, methamphetamine dependence, and gambling) with modafinil, but only in those with worse baseline scores rather than the whole group.
It is possible for modafinil to reduce impulsivity in persons addicted to drugs or some addictive behaviours, although this only appears to be significantly effective for persons with worse impuslivity prior to testing
Acute supplementation of armodafinil (250mg) in persons with multiple sclerosis has noted improvements in memory recall relative to placebo, although other measured parameters (fatigue, executive function, processing speed) were unaffected by supplementation. This inefficacy on fatigue and arousal has not been noted elsewhere, where modafinil is attributed to possessing an antifatigue effect in MS.
Adverse effects usually reported in trials are predominantly headache, dizziness, increased diuresis, palpitations and tachycardia, restlessness, nervousness, gastrointestinal complains such as nausea, dry mouth and abdominal pain. Despite these isolated adverse events, they usually do not differ significantly from placebo and thus modafinil is seen as well tolerated.
Reported side-effects that sometimes occur significantly more than placebo include insomnia and sleeplessness as well as appetite reduction.
General side-effects of modafinil include insomnia and/or sleeplessness as well as a reduction in appetite
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