Modafinil

Modafinil is a stimulant that promotes ‘wakefulness’ and treats sleep disorders. It prevents daytime sleepiness and fatigue, with benefits such as enhancing mood, increasing mental alertness, increasing motivation, improving reaction time, reducing fatigue, and even enhancing memory.

Overview of Modafinil

In use by the French army, the American Air Force, the Indian Air Force, and Canadian astronauts….. (astronauts!) [R].

It is a powerful stimulant that promotes wakefulness and treating daytime sleep disorders such as narcolepsy – excessive, uncontrollable daytime sleepiness.

Besides tats, it offers nootropic benefits such as enhancing mood, increasing mental alertness, increasing motivation, improving reaction time, reducing fatigue, and even enhancing memory.

As a prescription medicine, it is available in the US, Canada, the UK, and almost every developed country today. It is also available in the UAE where I had it prescribed for a month.

Aside from the original name, it also sells under brand names Provigil, Modvigil, and Alertec. 

It’s a eugeroic (a class of medical drugs that promotes wakefulness and alertness) used to treat conditions such as narcolepsy, a disorder that decreases the ability to regulate sleep-wake cycles, as well as the effects of shift work and similar sleep disorders.

It’s used off-label by students, businesswomen, men, and shift-workers due to its nootropic effects.

Sold under the brand name Provigil among others, is a medication to treat sleepiness due to narcolepsy, shift work sleep disorder, or obstructive sleep apnea. In OSA continuous positive airway pressure is the preferred treatment. – Wikipedia

Modafinil Benefits

  1. Improves Alertness
  2. Reduces Fatigue
  3. Improves Cognition
  4. Reduces Daytime Sleepiness
  5. Enhances Learning Capacity
  6. Effective Neuroprotectant
  7. Reduces Anxiety and Anger Response
  8. Reduces ADHD and Multiple Sclerosis Symptoms

Supporting research:

Improves Alertness

Although its effects are comparable to amphetamines like Adderall, which produce a temporary increase in cognition, Modafinil reports providing smoother and jitter-free energy. It also has fewer side effects and better toleration. Furthermore, it has low abuse and addiction potential.

Reduces Fatigue

It increases resistance to fatigue more than amphetamines, along with improving mood, motivation, and reaction time. It is also effective at reducing “impulse response,” i.e., bad decisions. A study on forty-one military subjects receiving Modafinil shows better scores in not only fatigue but also reaction time. Additionally, measurable scores are showing in performance, mood, logical thinking, and even memory. [R]

Improves Cognition

It improves cognitive function by increasing wakefulness and enhancing mental performance during a sleep-deprivation state.

A by-product of the ground-breaking stimulant Adrafinil, Modafinil acted faster and was promoted as a different drug in the 1970’s. After extensive clinical trials, it got the FDA’s approval to use as hypersomnia treatment. [R]

Reduces Daytime Sleepiness

Modafinil is useful for shift workers. It is used to help pilots staying alert throughout operations by the American military.

According to the World Health Organization, off-label users take it as a nootropic.

Moreover, with that, reports showing they get the most cognitive boost as well as most of the compelling benefits when they are not sleep-deprived. It is useful for both, still. [R]

Enhances Learning Capacity

Modafinil is powerful strengthening the ability to learn and expanding the capacity to process information. Research confirms that it reinforces mental endurance and performance, especially in cases of drug dependence and ADHD individuals.

According to the clinical trials, it enhances mood, performance, response time and even memory in healthy individuals as well as those who are sleep-deprived.

Effective Neuroprotectant

Experiments further suggest it promotes brain health. In brain tissue, its inhibitors properties decrease the manifestation of damaging free radicals, thereby making it an effective neuroprotectant [R], [R], [R].

Reduces Anxiety and Anger Response

Although less of a featured trait, it seems to have the ability to reduce anxiety as well as decreasing anger. A result of the reduction it allows in the reactivity stimuli within the brain [R].

There is a paradoxical study [R] for the curious cats like myself.

The research shows that on the contrary, it increases aggression and anxiety in a subject taking a 100mg dose.

When the treatment is doubling to 200mg, the items display a reduction in anxiety. It’s a case where less is not more and more is more.

Reduces ADHD and Multiple Sclerosis Symptoms

Modafinil is one of the standard stimulants for the treatment of attention hyperactivity deficit disorder (ADHD). Furthermore, research suggests that it is an effective treatment for memory impairment in cases of multiple cases of sclerosis.

Current clinical trials measure modafinil as a treatment for conditions such as depression, psychosis, seasonal depression, and even drug addiction.

It confirms that it strengthens mental performance, thereby becoming beneficial in ADHD and drug dependence. [R] [R]

How Does Modafinil Work

The unique mechanisms of action differentiates its effect from the traditional stimulants though they are similar.

Modafinil activates neurons by focusing on the hypothalamus and amygdala, unlike amphetamine, methylphenidate, and other central nervous stimulants that only induce wakefulness by general widespread neuronal activation.

The precise mechanisms of action have not been identified regarding locating a single site of action, though it modulates the brain’s histamine, serotonin, norepinephrine, orexin, and dopamine systems.

However, it is evident that its effect on numerous essential neurotransmitters is at the heart of its potency, both as a eugeroic and nootropic.

Orexin Neuropeptide

Orexin neurons exist in the hypothalamus but project to many different parts of the brain including several areas that regulate wakefulness.

Leading cause of Narcolepsy is lack of orexin, which Modafinil addresses by acting on orexin neurons.

Activation of these neurons also increases production of histamines and other important neurotransmitters that are related to wakefulness and alertness.

On Histamine

Histamine is known to allergies and local immune responses, it also plays an essential part in regulating the sleep/wake cycle. Modafinil actions elevate hypothalamic histamine, a known wakefulness mechanism.

On Dopamine

Dopamine is an essential neurotransmitter associating with stimuli/reward response, and therefore can enhance mood as well as increase motivation and focus.

Modafinil works by blocking the receptors that remove dopamine from synapses, which raises levels of dopamine available for instant use in the brain.

Unlike amphetamines, which stimulate the release and increase of dopamine levels in a high but rapid amplified manner.

This indirect gradual action on the dopamine system is a primary feature of how it works in the brain. It decreases the “rush” type of euphoria that associates with addiction.

On Norepinephrine

It increases the availability of norepinephrine, a stimulant neurotransmitter that promotes wakefulness and increases alertness in the hypothalamus. How it does that, is unclear.

On Glutamate

Modafinil elevates levels of glutamate, the primary neurotransmitter in the brain which is responsible for excitement, by activating the extracellular release of glutamate in the hypothalamus.

Glutamate plays a crucial role in human’s psychological functions, playing a significant role in its enhancing effects.

Such effects include increased memory, focus, and even brain modification.

Pharmacokinetics

Absorption

It is well-absorbed with peak plasma concentration reached approximately two to four hours after administration. Food has no effect on overall modafinil bioavailability; however, absorption (tmax) may be delayed by approximately one hour if taken with food.

Distribution

It is moderately bound to plasma protein (approximately 60%), primarily to albumin, which indicates that there is a low risk of interaction with strongly bound drugs.

Biotransformation

It is metabolised by the liver. The chief metabolite (40 – 50% of the dose), modafinil acid, has no pharmacological activity.

Elimination

The excretion of modafinil and its metabolites is chiefly renal, with a small proportion being eliminated unchanged (< 10% of the dose).

Half-life

The effective elimination half-life of modafinil after multiple doses is about 15 hours.

For patients 6 to 7 years of age, the estimated half-life is approximately 7 hours and increases with increase in age until half-life values approach those in adults (approximately 15 hours).

This difference in clearance is partially offset by the younger patients’ smaller size and lower weight which results in comparable exposure following administration of comparable doses.

Higher concentrations of one of the circulating metabolites, modafinil sulfone, are present in children and adolescents as compared to adults. [R]

The electronic Medicines Compendium (eMC)

Modafinil vs Amphetamines

Modafinil vs Amphetamines: despite causing the lesser motor activity increase when comparing to methamphetamine, a 1997 study still reported that Modafinil is a better inhibitor of sleep drive and a producer of more periods of wakefulness. Although it is possible to get to addiction to Modafinil is also being proposed as a treatment for methamphetamine and cocaine addictions, restoring normal levels of learning ability and generally yielding more positive results than amphetamines. [R]

Effects on Exercise and Sports Performance

It enhances sports and exercise performance by the duration of time before exhaustion and reduces the feelings of fatigue. In 2004, it got banned by Anti-Doping Agencies. [R]

Effects on Cognitive Abilities

Several years of research explain that Modafinil improves a big range of psychological feature talents.

From memory and fluid intelligence to each abstract and personal memory, government performance, pattern recognition, and performance on tasks that requires a high level of thinking.

Further research also states that its effects may be most marked among low-performing subjects.

Though it might end up in anxiety, clinical trials have examined that it improves mood in healthy subjects. [R] [R]

Modafinil Dosage

It is safe for continuous use at moderate doses (100-200 mg).

Large-scale clinical trials show no significant indications of tolerance over periods of up to several months.

Modafinil Side Effects

Commonly reported side effect of modafinil (although minor) can include anxiety, insomnia, headache, nausea, digestion issues, dizziness, diarrhea, dry mouth, and inflammation. Many of these side effects are temporary. If they persist, its advisable to seek professional advice.

Conclusion

Everyone responds differently to nootropics, but decades of research have shown modafinil is safe, effective, and well-tolerated.

If you’re into maximizing cognitive abilities and minimizing fatigue, modafinil is a nootropic worth trying. My personal experience with it has been very interesting and positive. I mostly noticed the massive interest in learning as well as the capacity to process information.

Nevertheless, I still prefer Adrafinil over Modafinil, even though they are almost identical products.

Frequently Asked Questions

What is Modafinil?

It’s a medication that promotes wakefulness through a variety of mechanisms. Although Modafinil is structurally like central nervous system stimulants like amphetamines, its effects and mechanisms of action are notably different. Modafinil influences the activity of the neurotransmitters dopamine, norepinephrine, glutamate, GABA and serotonin. Dopamine is one of the neurotransmitters that seems to be most strongly affected. Modafinil inhibits the reuptake of dopamine through specific dopamine transporter channels but is very selective as to which ones it inhibits. Serotonin activity increases in both the amygdala and frontal cortex with Modafinil use.

How Long Does Modafinil Stay In Your System?

The half-life of it ranges from 12 to 15 hours, although the metabolism of Modafinil can be affected by several factors, including genetic predispositions, kidney and liver health. Allergy and hypersensitivity are the only contraindications to using Modafinil. Scientists are still trying to understand precisely how Modafinil achieves its effects. Modafinil targets several neurotransmitters, including dopamine and norepinephrine.

Further Readings

  1. Adrafinil
  2. Phenylpiracetam
  3. Agmatine Sulfate
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