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In clinical trials, modafinil is effective for shift work sleep disorder and has a low liability to abuse. It has no anti-cataplectic or hypertensive effects and does not increase adrenergic neurotransmission.
Boosts Memory
Research in animal models and human behavioral studies indicates that modafinil enhances cognition in a variety of cognitive domains, including working memory, episodic memory, and processes requiring cognitive control. These effects may be related to the drug’s ability to increase dopamine availability and/or its inhibition of NMDA receptor activity in certain brain regions.
The cognitive-enhancing properties of modafinil have also been observed in psychiatric populations, including patients with BD. A double-blind placebo-controlled study of emergency department physicians following a 64-h overnight work shift found that modafinil significantly improved performance on a series of logical reasoning, RT, and memory tasks compared to placebo (Gill et al, 2006).
Similarly, a randomized, double-blind trial investigating the effects of modafinil in people with BD showed that this medication significantly increased the speed of processing in the 2-back WM task and VAC task versus placebo.
Additionally, BOLD fMRI results indicated that modafinil (Modawake 200 mg) reduced the amplitude of the amygdala response to fearful stimuli and decreased prefrontal cortical activity during these tasks. Moreover, the clinical assessments found that modafinil produced a modest, yet significant, improvement in mood. Patients on the drug reported decreased anxiety levels, fewer feelings of fatigue-inertia and depression, and an overall feeling of activity and increased energy.
It is worth noting that the study used a very low dose of modafinil in a small group of carefully screened participants and therefore, these results are far from conclusive. A within-subject dose-response curve study in a larger sample of BD individuals is needed to further explore the cognitive-enhancing benefits of this medication.
Improves Concentration
Many studies have shown that modafinil helps improve concentration. In one 2003 trial, participants taking modafinil performed better on digit span and visual recognition tests. In addition, they improved in other cognitive tasks. However, the study was small and used a very complex design, making it difficult to determine whether the improvements were due to modafinil or other factors, such as sleep quality or mood stabilizers.
Another study used a more robust experimental approach to determine whether modafinil improves concentration and cognitive functioning in people with effectively stable bipolar disorder. Twelve individuals with BD were randomized to take either modafinil or placebo in addition to their standard BD treatments. They were seen weekly for in-person interviews and had their sleep, mood, and neurocognitive functions measured. In this study, both the placebo and modafinil groups showed improvements in cognitive functioning, but the differences were greater for the modafinil group.
The results of this study suggest that modafinil may help improve concentration in people with BD, particularly when it is used in conjunction with a mood stabilizer. These improvements are likely related to its effects on NMDA receptors and dopamine.
In addition, several other studies have found that modafinil enhances performance in tasks requiring sustained attention and inhibition of prepotent responses. For example, a 2007 study using oral doses of modafinil ranging from 8 to 64 mg/kg found that it improves the ability of rats to sustain visual discrimination learning and delay responding, whereas it did not affect omission errors or speed.
Reduces Stress
Research suggests that modafinil reduces agitation, depression, anxiety, and fatigue. It can also improve cognitive function and reduce the rate of automobile accidents during the post-work commute. Studies of shift work sleep disorder in both healthy individuals and those with obstructive sleep apnea have found that a 4-day regimen of modafinil 200 mg reduces errors on the WCST and a version of the Hayling sentence completion task, which requires cognitive control, compared to placebo (Hart et al, 2006).
A recent double-blind placebo-controlled study of healthy volunteers undergoing simulated night-shift work also reported improvements with modafinil on the HAM-A scale and the Profile of Mood States questionnaire, as well as decreased anxiety, fatigue-inertia, and anger-hostility. Brain imaging with BOLD fMRI showed that modafinil reduces amygdala reactivity to fearful stimuli and enhances prefrontal cortical activity during a WM task and a VAC task requiring cognitive control.
Modafinil’s effect on neurocognitive functioning is consistent with its effects on arousal, although the results are more mixed than for mood-enhancing drugs such as methylphenidate or dexamphetamine.
This is likely because the placebo-controlled design of the current study used a flexible dosing schedule, which may have introduced confounding variables and reduced the power to detect significant differences in outcome measures. It is also worth noting that the study included a fairly large percentage of participants who were taking other mood stabilizers at screening, which may have increased the variability and weakened the observed differences in cognitive outcomes.
Increases Energy
Modafinil is used to treat narcolepsy, as well as excessive daytime sleepiness associated with obstructive sleep apnea and shift work sleep disorder. It has also been used as a cognitive enhancer in healthy non-sleep-deprived people and has been shown to improve performance on several tasks, including decision-making, planning, and understanding different points of view. However, it has been found to negatively affect creativity, although the effect was mild and only occurred in a few studies.
Modafinil acts to increase energy by enhancing the neurotransmitter dopamine in the brain. Dopamine is a key neurochemical that modulates many important biological processes, including the reward and motivation circuitry. It is also involved in the inhibition of pre-potent responses. Modafinil increases extracellular dopamine and norepinephrine by directly binding to their transporters in vivo. It also decreases g-aminobutyric acid (GABA) levels and elevates levels of serotonin, dopamine, orexin, and glutamate.
In a series of functional magnetic resonance imaging (fMRI) experiments during executive cognition tasks, such as a working memory task and visual analysis of complex scenes task, modafinil significantly decreased amygdala reactivity to fearful stimuli compared with placebo conditions.
In addition, during the WM and VAC tasks, modafinil reduced the BOLD signal in the prefrontal cortex and anterior cingulate. This may reflect an improvement in the efficiency of information processing in these regions that are richly innervated by catecholaminergic neurons.