What Are the Positive Effects of Modafinil?

Modafinil has been shown to improve cognitive performance in healthy people. It has also been used to treat various psychiatric disorders and conditions, such as schizophrenia, narcolepsy, and fatigue syndrome.

Increased Energy

Modafinil 200 Australia is a wakefulness agent and cognitive enhancer. It has been shown to improve cognition in patients with attention-deficit/hyperactivity disorder, myotonic dystrophy, narcolepsy and depression. In addition, it has been shown to reduce the effects of jet lag and everyday grogginess. It has been compared to stimulants but is less likely to cause side effects such as excess locomotor activity, anxiety and jitteriness.

Modafinil’s procognitive effects are thought to be related to its primary actions on catecholaminergic systems in the brain. Several studies have shown that modafinil increases gamma oscillations in the prefrontal cortex (LFPFC), and that these changes are associated with improved performance on a number of cognitive tasks, including memory-related tasks.

Moreover, using in vivo microdialysis and high-performance liquid chromatography, Ferraro et al showed that modafinil significantly increases extracellular glutamate in the medial preoptic and posterior regions of the hypothalamus. Local administration of the GABAA receptor antagonist bicuculline prevented modafinil’s increased glutamate release. The same results were obtained when the glutamate uptake inhibitor L-trans-PDC was administered. Modafinil’s increase in the availability of this amino acid in these areas suggests that it decreases the GABAergic tone in the area.

Increased Focus

Modafinil has been reported to increase dopamine levels in the brain by inhibiting the dopamine transporter. This is likely to increase LC phasic activity and may be involved in modulating cognitive task performance. Modafinil also enhances pupillary dilation and has been shown to interact with a2A receptors. These receptors mediate a number of behavioral effects including the euphoric “high” that is associated with other stimulants. Unlike amphetamine, modafinil does not produce significant tolerance or withdrawal symptoms, and it is less likely to be abused.

Many studies have shown that modafinil improves performance on a variety of tasks in healthy people and sleep-deprived populations. One study of adults with 85 hours of sleep deprivation found that a single dose of modafinil 400 mg significantly reduced errors on the Wisconsin Card Sorting Test and interference on the Stroop test, comparable to 600 mg of caffeine and 20 mg of amphetamine.

Modafinil (Modvigil 200 mg) can be used to improve focus and concentration in narcoleptic patients and has shown potential as an adjunct therapy for attention-deficit/hyperactivity disorder and schizophrenia. In addition, modafinil has been shown to be of interest to the US military for its ability to enhance alertness and reduce battle fatigue.

Increased Mood

Modafinil has been used for psychiatric disorders in addition to its use as an alertness-enhancing agent. It has been shown to improve parent, teacher and clinician ratings of ADHD in children in an open label study (Rugino and Copley, 2001) Modafinil has also been demonstrated to reduce symptoms of ADD/ADHD in a double-blind placebo controlled trial in adults (Turner et al, 2004b). In a schizophrenic population, modafinil has been reported to enhance performance on both digit span forwards and backwards tests, and trend toward improved performance in delayed visual recognition memory and the Tower of London task.

It is known that the arousal and activity-promoting effects of modafinil are mediated by activation of catecholamine systems, including a and b adrenergic receptors and 5HT and GABA receptors. Microdialysis studies have indicated that modafinil increases extracellular glutamate-glutamine, along with elevations in the synthesis of aspartate and creatine-phosphocreatine, but not N-acetyl aspartate or taurine.

A psychoneuroimmunological approach may help elucidate the immunomodulating effects of modafinil. Prolonged sleep deprivation can induce stress responses that impair immune function, and a large number of people who use Modafinil to wake up or enhance their cognition are already under great stress, for example cancer patients or soldiers in a battle field.

Increased Concentration

Modafinil increases extracellular NE in medial PFC pyramidal cells, an effect blocked by prazosin but not by yohimbine. It also potentiates NE-induced inhibition of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO) and reduces evoked activity in these cells in the absence of exogenous NE. Modafinil also increases glutamate release from these neurons, presumably through effects on the neurotransmitter NMDA receptors. It also elevates evoked phosphorylation of the non-NMDA receptor AMPAR in VLPO and decreases AMPAR phosphorylation in the nucleus accumbens, suggesting that this is another mechanism by which modafinil enhances cognitive function.

In one study, 3-week modafinil treatment of medication-free narcolepsy patients titrated to 400 mg/day remediated the decrement in a-2 and b-2 power on the Pauli test, as measured by LORETA (Saletu et al, 2004). These improvements were associated with a reduction of a-2 and b-2 power on resting EEG, localized to frontal and cingulate cortices.

Other studies in healthy participants undergoing prolonged sleep deprivation or simulated night shifts have also reported improvements in cognition with modafinil, although these effects were less pronounced than those seen in narcolepsy patients. In one of these studies, a single dose of modafinil reduced errors on the Wisconsin Card Sorting Task and Stroop interference in subjects exposed to 85 h of sleep deprivation. This improvement in arithmetic and RT performance was paralleled by decreased th and d power on the EEG.

Increased Memory

Modafinil is known to have several central neurochemical effects, but the data that are available are not clear about its influence on cognition. One study that tested healthy adults with 85 h of sleep deprivation found that single-dose modafinil 400 mg significantly reduced errors on the Wisconsin Card Sort Test and interference on the Stroop task, but had no effect on measures of RT or arithmetic performance (Wesensten et al, 2005).

Another group has studied university students who appear to have a high IQ, but have found only ceiling effects of modafinil on digit span and a sustained attention task. This group also has reported that daily administration of modafinil increases learning on a context-appropriate reversal memory task in rats. This learning is accompanied by c-Fos activation in the anterior cingulate cortex, but not in the mediodorsal nucleus of the thalamus.

Modafinil causes a dose-dependent decrease in GABA in the cortex, medial preoptic area and posterior hypothalamus, striatum and globus pallidus, and at higher doses, in the hippocampus, substantia nigra, and nucleus accumbens (Tanganelli et al, 1994). It has also been shown to increase histamine release in the anterior hypothalamus of monkeys.