Introduction
Human Beings are complex creatures that rely on their physical and mental faculties to survive. While physical aspects comprise the skeletal and tissue framework, mental faculties are formed by the brain and cerebral cortex, which plays a vital role in memory, thinking, learning, reasoning, problem-solving, emotions, consciousness, and functions related to your senses.
The cerebral cortex consists of activation states that impact the ability to process information, referred to as arousal/ alertness/vigilance/ attention, and play an essential role in determining a person’s mental health. Several psychologists and cognitive neuroscientists consider vigilance to be an umbrella term encompassing the terms of attention, alertness, and arousal and use the term to describe the ability to sustain attention to a task for a particular period. In contrast, others use the term vigilance to describe the arousal level of the sleep-wake spectrum.
A word about Alertness and Arousal
Studies have defined arousal as a non-specific activation of the cerebral cortex in relation to sleep-wake states and described attention as a focussed activation of the cerebral cortex that enhances information processing along with dividing it into the categories of focussed attention, divided attention, shifting of attention and sustained attention that is nomenclature as alertness and that includes a combination of vigilance and sustained attention and the levels of which are decreased in catatonia, apathy, and attention deficit disorder.
A number of factors like sleep loss, high blood pressure, and motivational factors ( intrinsic and extrinsic ) impact the alertness level of an individual and affect their ability to perform day-to-day tasks with impacts on their motivation levels. These factors create disruptions in concentration and focus levels and result in increased accidents in the workplace.
Modafinil and Alertness
Initially designed for the treatment of narcolepsy, the psychostimulant effects of Modafinil came into the limelight after being used for improved cognitive efficiency by the US Military when it was observed that use of Modafinil maintained alertness, feelings of well-being, cognitive function, judgment, risk perception, and situation awareness of sleep-deprived aviators consistently better than placebo and without side effects of aeromedical concern.
Further helicopter studies conducted on six pilots exposed to two 40 hours periods of continuous wakefulness and administered Modafinil with placebo showed attenuated sleep deprivation effects on four of six flight maneuvers, reduced slow-wave EEG activity, and lessened self-reported problems with mood and alertness in comparison to placebo.
A quasi-experimental, single-blind, counterbalanced design tested the effects of Modafinil in 10 Air Force F-117 pilots in which its use maintained flight accuracy within approximately 15-30% of baseline levels, whereas performance under the placebo condition declined by as much as 60-100%. Modafinil further decreased self-ratings of depression and anger while improving alertness, confidence, and Vigur ratings.
Open-label studies on Modafinil have found it to be a well-tolerated and effective treatment in improving daytime weakness in narcolepsy patients previously treated with psychostimulants. Small short-term trials have shown Modafinil to reduce excessive sleepiness in myotonic dystrophy patients, while more extensive studies have proved its effectiveness in reducing attention deficit in ADHD patients. While showing effectiveness for bipolar disorder in patients without stimulant-induced mania, using Modafinil has proven to hasten recovery from general anesthesia after surgeries. Even physicians have observed effective results with its use in driving home after attending the night shift and attending day lectures.
Mechanism of action
To understand the mechanism of action of Modafinil for heightened alertness and focus, animal studies were conducted about the drug that revealed a modafinil-induced increase of histamine release in intact orexinergic neurons. Simply put, Modafinil activates the histaminergic system of the CNS, which plays a vital role in maintaining wakefulness, appetite, and the alertness/arousal levels of a person to exert its therapeutic effects. But it indirectly exerts its effect by attenuating the inhibitory GABAergic input to the histaminergic neurons.
The orexinergic neurons located in the lateral hypothalamic area that regulate sleep/wake states, energy levels, reward systems, and cognition with mood are impacted through the use of Modafinil, resulting in synaptic plasticity or an increase in the Modafinil-induced awareness of the person.
Oral administration of Modafinil in steadily increasing doses in Marmoset monkeys showed increased locomotor activity with increased anxiolytic effects without inducing hand-motor coordination impairment.
Modafinil Combinations – Full Guide 2022
Use of Modafinil in healthy subjects
Despite the cognitive benefits offered by Modafinil, there are comparatively fewer studies on the advantages provided by Modafinil in healthy non-sleep deprived persons. Within the few studies conducted, researchers have observed methodological discrepancies in detecting cognitive effects produced by the drug in people diagnosed with sleep disorders rather than healthy adults.
To provide an up-to-date schematic evaluation addressing these concerns, a scanning of medical websites containing trial papers on the use of Modafinil in non-sleep-deprived adults was conducted. Any studies matching the search conducted within the previous 5 years were taken into consideration and evaluated in a detailed manner.
The sum-total of the studies made researchers conclude that most studies show Modafinil intake enhances executive function. Half of the studies show an improvement in attention, learning, and memory caused by the drug. Very few studies have mentioned an improvement in creative thinking caused by its use in healthy adults. Modafinil can successfully work in attention, executive functions, and learning without significant side effects or mood changes.
Modafinil can enhance mood, motivation, wakefulness, attention, and vigilance while improving memory, learning, and overall capacity for executive functions.
But there is a catch in using Modafinil as a cognitive enhancer.
Previous studies have concluded that the abuse potential in Modafinil is much lower than that of other psychostimulants like Amphetamine and Methylphenidate. However, the memory improvement produced by Modafinil is lesser than other drugs. But there is still a risk factor involved in its use that makes it inadvisable to be used for longer.
Every substance affects the brain differently. Still, all addictive drugs, including alcohol, opioids, and cocaine, produce a pleasurable neurotransmitter dopamine surge, the increase of which has been reported during Modafinil usage in healthy adults. Modafinil is not directly involved in dopamine release in the brain’s nuclear accumbens, which plays a significant role in addiction behavior.
But it interacts with multiple molecular targets in the brain and is sensitive to dopamine signaling in an indirect manner. Animal studies have shown Modafinil regulates the Dopamine and Norepinephrine neuroreceptors in the brain and impacts alertness and wakefulness by interacting with the catecholamine transporters. Some studies even suggest it of interacting with dopamine and norepinephrine transporters in a living primate brain and using the dopamine pathway to inhibit dopamine reuptake.
The entire process increases extracellular levels of dopamine without wholly contributing to the wake-promoting effects for which it was initially taken. The increase in dopamine involves the nucleus accumbens and other brain parts. Medications that increase dopamine in the nucleus accumbens have the potential for abuse. Its uses, when conducted for a long term, can result in abuse and dependence, especially in vulnerable populations.
The above factors are mere conjecture, and the results obtained from trials are insufficient to reach a definitive conclusion about addiction. But the possibility of addiction remains to avoid which injudicious use of Modafinil should be avoided in people planning to use it for cognitive stimulation.
Conclusion
While using it can be a solution for long-lasting alertness,
prolonged sleeplessness induces stress responses and impairs immune function. While Modafinil has been FDA-approved for conditions like narcolepsy, SWSD, and sleep apnea, its use as a cognitive enhancer in healthy patients should be conducted under physician guidance.
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