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Modafinil Reviews?

“The focus I felt was amazing. I was able to read through code and tedious data diagrams not only with ease but with great interest. It seemed all so riveting all of the sudden. At meetings, I had the answers to questions in nanoseconds. I could sit at my desk, crank out code, documentation, PowerPoint presentations, and 15 emails without stopping for anything - and I enjoyed it!” - by Carl B. Sather, MBA from Stanford Graduate School of Business?

“Modafinil is the most unique stimulant I’ve ever taken. It’s not a CNS stimulant - it only seems to affect your mind. Modafinil has a very clean effect- it doesn’t induce euphoria or anxiety, nor does it seem to have any physical effects on the body. What it does is make you sharp, awake, and focused.” by Jacob S, 5+ years of researching and experimenting with Nootropics?

Modafinil Introduction?

Modafinil is a psychostimulant with a waking property. Psychoactive drugs [drugs that modify the functions of the nervous system] are generally classified into four groups: depressants, tranquilizers, stimulants and hallucinogens. However, the boundaries between these groups are not precisely delineated; rather, they have several effects that overlap or combine into a new, different one.?

Depressants and tranquilizers are used to treat anxiety, fear, and excessive tension, whereas stimulants treat fatigue, stress, and depression. Stimulants, in combination with depressants or tranquilizers, are commonly used to treat sleep disorders as shift work sleep disorder or to maintain alertness for an extended period of time. Amphetamine and caffeine are two examples of psychoactive drugs that have traditionally been used to improve alertness or combat fatigue.?

Amphetamine, which is a prescription drug of the phenylethylamine family, is a stimulant. Amphetamine maintains alertness by inhibiting norepinephrine and dopamine reuptake and stimulating the secretion of catecholamines stored in neuronal cell vesicles.??

The reward circuits of the brain, which are related to dopaminergic transmission, play a role in the pharmacological effects of amphetamine on the nervous system.?

Although amphetamine is used to treat traumatic brain injury, chronic fatigue syndrome, attention deficit hyperactivity disorder (ADHD), and hypnolesy in clinical settings, it has a negative rebound effect that causes depression or anxiety after the intended effects wear off.?

Caffeine, a methylxanthine derivative, has also long been used as a psychoactive drug. Caffeine works as an adenosine receptor antagonist to improve concentration and task performance in people who have accumulated fatigue from a lack of sleep.?

However, many psychoactive drugs cause tolerance or dependence; in other words, they cause addiction to variable extents. Thus, these psychoactive drugs may result in problems when medicated repeatedly or continuously unlike a novel class of psychostimulants called eugeroics.?

Eugeroics is a new class of psychostimulants and it includes multiple prescription drugs that treat sleep disorders as modafinil, adrafinil, and ampakine. Eugeroic means good arousal; that is, eugeroics show no sign of common adverse effects of other psychostimulants such as interference in recovery sleep, psychiatric problems, and addiction.?

Modafinil [2-diphenylmethyl sulfinyl acetamide] is a non-amphetamine central nervous system (CNS) stimulant that promotes wakefulness. Modafinil was first sold as a waking drug in 2003. It's used to treat conditions that cause excessive sleepiness, especially conditions with daytime sleepiness.??

Modafinil (brand name Provigil) is FDA-approved in the United States for the treatment of a variety of conditions, including narcolepsy, sleep work shift disorder, and obstructive sleep apnea.?

Many studies have shown that modafinil does not only have wake-promoting properties but also antioxidative and neuroprotective effects making it a valid doctor's prescription to treat many health conditions.??

These antioxidative and neuroprotective properties may play a role to some degree in its effects as a waking drug. Recent research suggests that free radicals are linked to both sleep induction and cellular damage, implying that a common target of action may mediate modafinil's ability to counteract both of these effects.?

The US military is interested in modafinil for improving alertness and reducing battle fatigue. Modafinil is also becoming more widely available as a lifestyle drug, specifically as a non-prescription medicine among healthy individuals. More university students and low-to-high level executives use it for late-night work as the half-life of modafinil is 12 to 15 hours.?

Indications?

Modafinil (Provigil) is a non-amphetamine prescription drug that works as a central nervous system (CNS) stimulant promoting wakefulness. It is a valid prescription to treat many conditions, including those that cause excessive daytime sleepiness.?

Modafinil's FDA-approved indications include:?

1. Narcolepsy: Modafinil is a prescription medication used to treat the daytime fatigue associated with narcolepsy, but it has not been shown to improve cataplexy symptoms.?

2. Shift work sleep Disorder: First-line prescription medication for Shift work sleep Disorder.?

3. Obstructive sleep apnea: Adjunctive to continuous positive airway pressure (CPAP).?

Off-labeled the indications are:?

1. Attention deficit hyperactivity disorder (ADHD): There is some evidence of efficacy in the pediatric population but great caution is required to avoid modafinil overdose. A recent study of adult ADHD patients found modafinil to be ineffective.?

2. Unipolar and bipolar depressive episodes that are acute.??

3. Cocaine dependence: The evidence for modafinil's efficacy in this regard is mixed.??

4. Cancer-related fatigue: The evidence for modafinil's efficacy in this setting is mixed.?

5. Fatigues caused by multiple sclerosis.?

6. As a cognitive enhancer: Although the use of modafinil as a "cognitive enhancer" in healthy subjects has been proposed in the literature, the precise benefits and risks associated with this use among different modafinil users are unknown.?

According to several scientific studies, modafinil improves productivity, memory, cognition, and lets you work long hours without feeling fatigue.??

Modafinil Mechanism of Action?

Modafinil has been shown in clinical trials to have neuroprotective and antioxidative properties in addition to its wake-promoting properties. Orexin, a peptide family that promotes wakefulness and inhibits sleep, is involved in the induction of narcolepsy.??

Orexin neurons can only be found in the lateral hypothalamus, and orexin neurons in the hypothalamic area project to the entire central nervous system. Modafinil may activate orexin neurons. Thus, modafinil's action in the anterior hypothalamus may cause wakefulness making it a valid prescription to treat sleep disorders.?

In a recent study, equal doses of amphetamine and methylphenidate increased c-fos gene expression throughout the brain, including the caudate (a subcortical structure deep within the brain), but modafinil induced c-fos expression selectively and prominently in the hypothalamus. Modafinil did not bind to most receptors related to sleep and wake cycle and did not inhibit monoamine oxidase or phosphodiesterase activities.?

However, experimentally, some other mechanisms of waking effects have been proposed. As an agonist, modafinil activates the central alpha 1-adrenergic receptor.??

Modafinil's current mechanism of action suggests that it induces alertness via the alpha-adrenergic receptor. However, alpha-adrenergic transmission cannot fully explain why alpha-adrenergic receptors are activated in only one part of the brain for enhancing or maintaining wakefulness.?

Modafinil inhibits noradrenaline reuptake in noradrenergic nerve endings. As a result, the noradrenaline signal is amplified between sleep-promoting neurons in the ventrolateral preoptic nucleus. Modafinil has a significant effect on excitatory glutamatergic signaling by decreasing local-amino butyric acid transmission.??

Modafinil also increases the release of cortical serotonin. The selective activation of certain electro neurosecretory pathways by modafinil is responsible for? serotonin release, whereas the reuptake process has no role in serotonin release.?

Modafinil significantly increases histamine release in the anterior hypothalamus. Modafinil, on the other hand, did not cause histamine release in orexin knockout mice. Modafinil's increase in histamine release necessitates orexinergic transmission.??

Modafinil inhibits dopamine transporter (DAT) and norepinephrine transporters in the brain of a living primate. It prevents dopamine reuptake via DAT. As a result, modafinil administration raises extracellular dopamine levels in the brain. Modafinil inhibits DAT and increases dopamine levels in the animal and human brain, including the nucleus accumbens, eliciting the same response as other waking drugs.?

Modafinil activates glutamatergic circuits while inhibiting gamma-aminobutyric acid production (GABA). Free radicals have been linked to both sleep stimulation and cellular destruction, implying that modafinil may have a common target of action to combat both of these outcomes.??

Modafinil has a low potential for abuse when compared to other stimulants because it lacks significant pleasurable or euphoric properties. A synergistic combination of mechanisms as shown above has been attributed to modafinil as a drug with neuroprotective, antioxidative, and most importantly wakefulness-promoting properties.?

Pharmacokinetics?

Modafinil is a racemic compound (substances that have dissymmetric molecular structures) containing l and d isomers. The enantiomers have different pharmacokinetic properties and do not interconvert.??

The half-life of the l-isomer in adult humans is approximately three times that of the d-isomer, so overall exposure to the l-isomer is nearly three times that of the d-isomer.?

Following a once-daily dose of modafinil, the l-isomer and the d-isomer account for 90% and 10% of the circulating drug concentration, respectively. The drug's efficient elimination half-life after multiple doses is approximately 15 hours.??

Peak plasma concentrations of the drug occur 2-4 hours after administration, indicating that modafinil absorption is rapid. Modafinil has nearly the same bioavailability as a liquid suspension.?

The total oral bioavailability of modafinil was not determined because of its water insolubility (<1 mg/mL), which prevented intravenous administration. Although food has no effect on overall modafinil bioavailability, it can delay absorption by nearly an hour if taken with food. With repeated dosing, steady-state plasma concentrations are achieved in 2 to 4 days.?

Modafinil is distributed properly in tissues by moderately binding to plasma proteins. The volume of distribution of modafinil (0.9 L/kg) is clearly greater than the volume of total body water (0.6 L/kg). Modafinil is shown to be moderately bound to plasma protein in vitro (60%, primarily to albumin).?

At serum concentrations of 500lM, modafinil shows no dislocation of protein binding of diazepam, warfarin, or propranolol. Modafinil acid reduces warfarin binding at concentrations greater than 500lM, but these concentrations are more than 35 times those obtained therapeutically.??

Elimination occurs primarily in the liver through amide hydrolysis, with a minor contribution from cytochrome P450-mediated oxidation. The metabolites are excreted in urine, with less than 10% of the oral dose excreted as unchanged drug. In the elderly or those with hepatic or renal impairment, elimination is slowed.?

Modafinil Dosage and Precautions?

Modafinil is only available in 100 mg and 200 mg oral tablets; the usual modafinil dosage is 200mg once daily. In the treatment of narcolepsy or obstructive sleep apnea, the recommended dose of modafinil tablets is 200 mg orally administered once a day in the morning.??

Modafinil 200 mg once a day is taken about one hour before the start of the work shift to treat shift work disorder. Modafinil and metabolite elimination may be reduced in elderly patients, so consider using lower doses and closely monitoring patients.?

In pregnancy, modafinil is classified as pregnancy category C medicine by FDA. Category C means there is no evidence to suggest or exclude harm to the human fetus associated with modafinil. In patients with severe hepatic impairment, the modafinil dose should be reduced by one-half of the usual recommended dosage. In patients with severe renal impairment, modafinil should be used with caution.??

However, there are no recommendations for renal dosing. Modafinil is not approved by the FDA for use in the pediatric population.?

Uses of Modafinil?

1. Anti-fatigue Agent for Cancer and Depression Patients?

Fatigue is a common symptom among cancer patients, lowering their quality of life. Depression in cancer patients may be accompanied by fatigue. When self-administered for four weeks, modafinil is well tolerated and effective against fatigue in cancer patients.??

Those patients' moods and quality of life improved. Modafinil has been shown to be effective in treating fatigue caused by depression, amyotrophic lateral sclerosis, and multiple sclerosis. Modafinil is effective in reducing fatigue in cancer and multiple sclerosis patients, but its positive effects on cognitive dysfunction associated with diseases are still debated.?

2. Military Use of Modafinil as a Countermeasure of Combat Fatigue?

Fatigue is a major issue in a combat environment. Combat fatigue is primarily caused by sleep deprivation as a result of extended duty periods, unpredictable work hours, circadian disruption, fear, anxiety, and other factors.??

Medication can help combat fatigue caused by chronic sleep deprivation or a sleep disorder. A pharmacological countermeasure is to use hypnotics for deep sleep and sleep control, as well as waking drugs to improve alertness and psychomotor activities.??

Modafinil, when combined with traditional psychostimulants like amphetamines and cocaine, improves alertness and reduces fatigue in a combat environment.?

Modafinil Alternatives?

• Armodafinil (chemical formula: C15H15NO2S) has better wakefulness effects and a longer half-life while side effects are similar to modafinil.?

Side Effects of Modafinil?

Modafinil is a stimulant that is generally well tolerated. Less than 10% of users have reported side effects. The most common modafinil side effects are nausea and headache. According to research studies and user reviews, headaches are the most common side effect that can occur in more than 35% of modafinil users.??

Mild side effects have included diarrhea, nose and throat congestion, back pain, dry mouth, anxiety, nervousness, insomnia, allergic reactions, dizziness, and mental side effects.?

Side effects may occur in some cases when taking modafinil for the first time. When an adjustment period is required, side effects usually subside after a few weeks as the body adjusts to the agent.??

The occurrence of side effects could simply be due to the dosage level. During 14 days of observation, no withdrawal symptoms were observed in patients who had stopped taking modafinil.?

Modafinil Interactions?

In the liver, 3 A isoform subfamily of hepatic cytochrome P450 (CYP3A4) metabolizes a large proportion of modafinil. However, modafinil is known to be a potent suppressor of CYP2C19 and CYP2C9, and an enhancer of CYP3A4, CYP1A2 and CYP2B69. The drug-metabolizing enzyme CYP2C19 is involved in the elimination of diazepam, phenytoin, and propranolol. As a result, co-administration of modafinil with the previously mentioned drugs may result in higher circulating levels of those compounds.?

According to reports, 7-10% of the Caucasian population (similar or lower in other populations) is deficient in the enzyme CYP2D6. Modafinil co-administration may increase the levels of CYP2D6 substrates (For example, selective serotonin reuptake inhibitors and tricyclic antidepressants) with supplementary elimination pathways via CYP2C19 in such individuals.??

According to, when co-administering modafinil with the previously mentioned therapeutics, the drug dosages must be adjusted to avoid severe drug interactions. Other central nervous system (CNS) active therapeutics, such as dextroamphetamine and methylphenidate, have no discernible effect on the pharmacokinetics of modafinil.?

Chronic administration of modafinil 400 mg has been shown to induce CYP3A4 and, as a result, reduce systemic exposure to CYP3A4 substrates such as ethinyl estradiol and triazolam. Chronic modafinil administration can increase the removal of CYP3A4 substrates. Individuals taking these and similar drugs may need to adjust their doses.?

Modafinil Tolerance?

Much of the research on modafinil has revealed that it is well tolerated and that modafinil overdose is rarely reported. For example, one study on depressed patients used modafinil to alleviate depression symptoms such as fatigue and sleepiness.??

During the two months of treatment, the patients showed no signs of mood swings, tolerance, or abuse of modafinil. Some studies were carried out to investigate the possibility of modafinil tolerance in pediatric patients who used the drug to treat narcolepsy.?

The findings revealed that no significant number of patients developed tolerance. However, there is some evidence that long-term use of modafinil can cause tolerance in some patients.??

As a result, the patient may require higher daily doses to achieve the same cognitive enhancement benefits or level of sleepiness relief. To avoid the risk of developing modafinil tolerance issues, skip a dose of the drug on one or even two days per week.?

Contraindications?

There are few, if any, absolute contraindications to modafinil use. However, there are a number of relative contraindications and special considerations including allergic reactions:?

1. Dermatological reaction: If a severe rash, including Stevens-Johnson syndrome, develops, stop taking modafinil immediately, unless the rash is clearly not drug-related.?

2. Angioedema and Anaphylaxis Reactions: If angioedema or anaphylaxis is suspected, discontinue modafinil.?

3. Multiorgan Hypersensitivity Reactions: Discontinue modafinil if this is suspected.?

4. Persistent Sleepiness: Check patients frequently for signs of sleepiness and, if necessary, advise them to avoid engaging in or driving in any potentially dangerous activity.?

5. Cardiovascular disease: Consider increased monitoring in patients with preexisting cardiovascular conditions. Modafinil should not be used in patients who have documented left-ventricular hypertrophy or a history of previous cardiotoxicity from psychostimulant use.?

A recent study found that modafinil has an addictive potential. There is substantial evidence that modafinil, like other addictive drugs, is dopamine signaling sensitive in the brain. Modafinil inhibits dopamine transporter (DAT) and norepinephrine transporters in the brain of a living primate.?

It prevents dopamine reuptake via DAT. As a result, modafinil administration raises extracellular dopamine levels in the brain, whereas DAT-knock-out mice lack wake-promoting effects. Modafinil inhibits DAT and increases dopamine levels in the animal and human brain, including the nucleus accumbens, eliciting the same response as other waking drugs.??

A rise in dopamine levels in the nucleus accumbens may be linked to drug abuse. The results of the above-mentioned experiment are insufficient for conclusive evidence of addiction because the main focus of those experiments was not addiction.?

Modafinil FAQ?

Is Modafinil Legal??

Yes, Modafinil is legal in the US. You can purchase it from local retail pharmacies. According to the ClinCalc database, 1 056 221 modafinil prescriptions were issued in 2020.??

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You cannot buy modafinil over the counter in the US. That is the reason why high-achieving individuals choose to buy modafinil online.??

Can I Drink Alcohol When On Modafinil??

Avoid taking modafinil when drinking alcohol as it can lead to blackouts and increased alcohol tolerance.??

Disclaimer: This article does not contain any legal advice and is meant for informational purposes only. Always consult with your doctor before taking modafinil.??

Disclaimer: The above is a sponsored post, the views expressed are those of the sponsor/author and do not represent the stand and views of Outlook Editorial.