Does Modafinil Make You More Cognitive and Wakefulness?

Modafinil has been shown to improve wakefulness and vigilance in large randomized double-blind placebo-controlled studies in patients with narcolepsy. A 3-day regimen of modafinil significantly improved performance on a digit symbol substitution test in sleep-deprived emergency medicine physicians (Walsh et al 2004).

These effects are largely due to its primary actions on catecholamine systems. Modafinil has also been reported to increase self-reported vigor and activity in obstructive sleep apnea patients.

Effects on Sleep

Buy Modafinil Online is a novel wake-promoting agent that has been shown to improve cognitive performance and reduce physiologic sleepiness in individuals with narcolepsy. It is also approved by the FDA to reduce daytime somnolence in individuals with shift work sleep disorder and obstructive sleep apnea/hypopnea syndrome.

Using the subjective ESS questionnaire, we examined the effects of modafinil on ratings of subjective sleepiness and objective measures of physiologic sleepiness after a period of overnight sleep deprivation in healthy individuals. A single dose of either 200 or 400 mg of modafinil significantly reduced ratings of sleepiness and improved objective measures of physiologic sleepiness (eg, sleep latency). The 400-mg dose was more effective in improving subjective ratings than the lower dosage, but both doses of modafinil significantly improved sleep quality, with the improvement occurring at a level comparable to that observed in the placebo group.

In addition, the 400-mg dose of modafinil was effective in preventing the reductions in cognitive performance that typically occur following a period of overnight sleep deprivation. These improvements were attributed to a significant interaction effect between the treatment group and abstinence week, with the improvements in cognitive performance being mediated by increased levels of slow-wave sleep during the treatment period. This is of particular importance because it is the only stage of a normal sleep cycle that does not tend to be reduced after extended periods of total sleep deprivation in humans, and is thought to play an important role in the restoration of normal cognition and physiology following prolonged sleep deprivation.

Effects on Memory

In healthy adults who are not sleep-deprived, modafinil has been found to improve performance on tasks requiring working memory and inhibition of pre-potent responding (such as the digit span test). Modafinil also appears to increase vigilance without adversely affecting other cognitive functions such as perceptual or arithmetic performance. In addition, the arousal and activity-promoting effects of modafinil are likely to be mediated by activation of catecholamine systems rather than glutamate or GABA. The adrenergic antagonist’s clonidine and propranolol inhibit the stimulant effects of modafinil, and the DA autoreceptor blockers terazosin and quinpirole reduce its arousal and activity-promoting actions.

Interestingly, Modvigil 200 Australia increases Fos-immunoreactivity in identified orexin cells within the perifornical cortex of both normal and orexin knockout mice. It also potently induces wakefulness in orexin-knockout narcoleptic dogs, and it enhances both extracellular striatal DA and the hypothalamic arousal regions evoked by oxytocin in orexin-deficient narcoleptic cats.

Furthermore, in a 4-week trial of flexible dosing (ranging from 400 to 600 mg/day) added to antidepressants, modafinil significantly improved error rates on the WCST and Hayling sentence completion task compared to placebo in patients with major depression. Similarly, modafinil significantly reduced errors on the WCST in narcoleptic patients with obstructive sleep apnea. This improvement may have been due to a reduction in the impact of daytime sleepiness on cognition mediated by a reduction in obstructive sleep apnea-related hypothalamic arousal deficits.

Effects on Alertness

Modafinil has been studied for its alertness-enhancing effects, particularly compared to placebo. It is less likely to generate excess locomotor activity, anxiety, or jitteriness or cause rebound hypersomnolence than other stimulants [2-6]. In addition, it has been found to improve cognitive performance without the deterioration of memory. It has been used to treat attention-deficit disorder, Alzheimer’s disease, depression, idiopathic hypersomnia, schizophrenia, myotonic dystrophy, post-anesthesia grogginess, and jet-lag [7-13].

Several studies have shown that modafinil can enhance vigilance, especially in patients with shift work sleep disorders and narcolepsy. Large, double-blind, placebo-controlled studies showed significant improvement in objective and subjective measures of wakefulness in narcolepsy patients after 4 weeks of modafinil 200 mg/day. In addition, a shorter auditory P300 latency in narcolepsy patients was associated with clinical response to modafinil (Sangal et al, 1999a).

One study of healthy adults exposed to 85 h of sleep deprivation found that a single dose of modafinil 400 mg significantly reduced errors on the Wisconsin Card Sort Test and interference on the Stroop task, comparable to 600 mg of caffeine and 20 mg of amphetamine. Similarly, another study of narcoleptic patients who experienced excessive daytime sleepiness showed that modafinil reduced their symptoms after four weeks at 200 or 400 mg/day.

The alertness-enhancing effect of modafinil is independent of DA neurotransmission. It is also not dependent on catecholamine reuptake inhibitors or adrenoceptor stimulation. It is also not inhibited by the NE neurotoxin DSP-4, nor is it blunted by the DA autoreceptor agonist terazosin or quinpirole.

Effects on Mood

Modafinil is most often prescribed for narcolepsy but is also used as an off-label drug to enhance cognitive functioning in the general population, particularly when people need to remain awake and alert for long periods. It is reported to increase performance on tests of memory, speed of response, and concentration in healthy individuals. However, there is less evidence of its effectiveness in people who are not sleep-deprived.

Research has shown that modafinil increases the release of monoamines in the brain, including serotonin. This may contribute to its effects on mood and alertness. For example, one study showed that modafinil enhances the increase in extracellular serotonin induced by the antidepressant drugs fluoxetine and imipramine via the DAT (see Ferraro et al, 2000).

Other studies have indicated that modafinil is associated with increased levels of corticotropin-releasing hormone (CRH) and decreases in plasma corticosterone in stressed subjects. It is also associated with reduced blood pressure and increased cardiovascular endurance in stressed patients. A single dose of modafinil can also improve performance in a test of working memory, as well as increase plasma histamine levels and modulate the activity of the central histaminergic system (see Passani et al, 2000; Blandina et al, 2001).

In one double-blind, placebo-controlled study in healthy adults under simulated night shift conditions, a four-day regimen of modafinil 200 mg per day significantly reduced errors on the Wisconsin Card Sorting Task and a version of the Hayling Sentence Completion Test. This improved performance was associated with activation of the dorsolateral prefrontal cortex and anterior cingulate cortex measured by fMRI.