Is Modafinil the Ultimate Smart Drug? A Critical Look at Its Effects and Risks

Introduction

In today’s increasingly pressure-driven competitive world, the stakes are high, and everyone needs an extra edge to survive. The urgency of being ahead of others has resulted in an increased demand for smart drugs to keep up with the challenges of academics and work pressure. A review of 25 smart drug surveys has shown that among the 79,640 respondents in 2015 and 29,758 in 2017, 14% reported using stimulants at least once in the preceding 12 months in 2017, up from 5 percent in 2015.

Among the various smart drugs claiming to be the best for cognitive stimulation, the name that stands out is the prescription stimulant Modafinil. Modafinil was developed in France by Lafon Laboratories and was among a series of compounds being tested for narcolepsy patients. Its role as a stimulant came into the limelight when soldiers in the French Army reported its use with a heightened sense of alertness and wakefulness. Ballon and Feifel, over time, demonstrated Modafinil’s novel mechanism and localized working on hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate receptors in the

Is Modafinil a smart drug

Modafinil was initially FDA-approved as a eugeroic drug designed to maintain or recover wakefulness, alertness, and cognitive performance in clinically sleep-deprived individuals. The context of the ‘Smart drug’ evolved much later when Harvard researchers evaluated 24 studies dealing with different benefits of Modafinil and found the performance-enhancing capacity of Modafinil to vary according to the task. What surprised them further was the longer and more complex the task tested, the more consistent were the results.

As Professor Guy Goodwin, President of the European College of Neuropsychopharmacology, Modafinil observed based on the available evidence; Modafinil could be regarded as a pharmaceutical nootropic or an example of a Smart drug, provided it obtained the license for such purpose.

To further investigate the role of Modafinil on cognitive performance, researchers examined four research questions based on knowledge of Modafinil in sleep-deprived individuals.

1) Is there a difference between Modafinil’s effects as a smart drug in repeated doses versus

single doses?

(2) Is Modafinil effect as an intelligent drug dose-dependent?

(3) Are there individual-related and task-related impact factors?

(4) What are Modafinil’s reported mental and somatic side effects as a smart drug?

And conducted systematic literature research in PubMed, Web of Science, and Scopus databases, using the search terms “Modafinil” and “Cognitive enhance*” in combination with specific terms related to the research questions.

No literature was found on the impact of repeated intake of Modafinil as a smart drug or any substantial research into the risk of overconfidence in healthy individuals after using it. Furthermore, its enhancing effects were beneficial only in persons with initially lower performance levels and performing more difficult tasks. Based on their evaluation, they concluded Modafinil was acceptable for sleep-deprived individuals but concluded against using it as a performance enhancer.

A comparison of Modafinil vs. other smart drugs

Researchers have previously regarded coffee as the most widely used nootropic, with caffeine-modulating noradrenaline, dopamine, serotonin, acetylcholine, glutamate, and GABA neurotransmitters to boost arousal, mood, concentration, and learning even when you are exhausted.

Other than its energizing effects, coffee has been shown to contain phytochemicals like

caffeine, trigonelline, chlorogenic acids, and mangiferin are useful in scavenging toxic radicals after oxidative stress by generating antioxidants

Despite its several nootropic advantages, a comparison of the effects of Modafinil and coffee has found it to be effective for a longer time than coffee without the feeling of shakiness, anxiety, or bladder risks resulting from coffee. Vigilance and fatigue parameters are two advantages offered by Modafinil that are crucial for people of all working professions and young minds to stay focused and ahead of others in their field.

In a clinical trial aimed at determining the effect of 200 mg modafinil on vigilance during a limited period of sleep deprivation compared to 300 mg caffeine and placebo, Thirty-two volunteers of the Royal Netherlands Air Force were double-blindly administered Modafinil, caffeine, and placebo on three non-consecutive trial days after being awake for median 17 h. Afterward, subjects completed six series of the Vigilance and Tracking test psychomotor vigilance task to evaluate the study results.

Image Credit – https://journals.sagepub.com/doi/10.1177/02698811221142568#:~:text=Modafinil%20was%20effective%20for%20longer,2%20h%20after%20drug%20administration.

Modafinil sustained flight performance and mood state during continuous wakefulness when tested during simulated or in-flight operations, while the results for caffeine were mixed and inconclusive in these studies. Modafinil and caffeine improved vigilance and performance based on the PVT and VigTrack and resulted in a lower level of reported sleepiness after a limited period of sleep deprivation. Modafinil was effective for longer than caffeine, which is consistent with its longer half-life.

Other comparative tests between Modafinil and Coffee concluded Modafinil maintained alertness and performance during the circadian trough or early morning hours when the effects of sleep loss were strongest.

Modafinil, Methylphenidate, and 3,4-methylenedioxymethamphetamine

In a double-masked, within-subject, placebo-controlled, cross-over design, Methylphenidate, Modafinil, and 3,4-methylenedioxymethamphetamine were administered to 21 healthy subjects; Methylphenidate significantly increased activation in the right middle frontal gyrus middle/superior temporal gyrus, inferior parietal lobule, pre-supplementary motor area, and anterior cingulate cortex compared with placebo.

Methylphenidate also induced significantly higher activation in the anterior cingulate cortex and pre-supplementary motor area – sensorimotor and cognitive processing.

Modafinil significantly increased activation in the right middle frontal gyrus and superior/inferior parietal lobule relative to placebo. – numeracy, perception of emotions in facial stimuli, and interpretation of sensory information

3,4-methylenedioxymethamphetamine significantly increased activation in the right middle/inferior frontal gyrus and superior parietal lobule.- numeracy

Image Credit- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581485/

Methylphenidate and Modafinil improved inhibitory performance in healthy people during the go/no-go task relative to placebo, supporting the view of the beneficial effect of Methylphenidate and Modafinil on cognitive performance in healthy people. MDMA administration has increased impulse control when serotonin levels are high, making Modafinil a more reliable and safe method.

Overall it was safe to surmise that Modafinil is the efficient, reliable, and safe option for improving cognitive quality in healthy individuals and could be regarded as the ultimate smart drug.

But it comes with risks.

Several studies have previously stated that Modafinil use, while improving cognitive quality, can result in oxidative damage to the proteins, lipids, and DNA and changes in the enzymes oxidants and mitochondrial respiratory chain complexes, initiating the pathophysiological changes to neuropsychiatric disorders.

In an animal study conducted to evaluate the effect of Modafinil on behavior and oxidative stress pattern in the hippocampus, prefrontal cortex, amygdala, and striatum of rats, 40 male Wistar Rats weighing 250-350g were administered with Modafinil single dose of 75 100 or 300 mg/kg body weight or a vehicle dose in the control group.

Trace of TBARS ( Thiobarbituric acid reactive substance ); lipid peroxidation products in cells, tissues, and body fluids were measured as an indicator of reactive oxygen species or oxidative damage.

The results were interpreted in the form of various parameters like

Locomotor Analysis

Biochemical Analysis

Proving that a single dose of Modafinil can result in hyperlocomotion in rats and increase the activity and smoothness of the locomotor paths. At the same time, The increase in extracellular dopamine concentration induced by Modafinil can cause overproduction of the toxic metabolite of dopamine oxidation leading to oxidative damage to proteins and lipids in the brain.

Conclusion

Modafinil use has accelerated in the last decade due to its cognitive advantages and safe pharmacodynamics with fewer addiction risks. Overusing it can result in oxidative damage and increase the risk of withdrawal effects after discontinuing it. Using it under the physician’s guidance is highly recommended to obtain its effects safely.