How Long Does Modafinil Last in Your System? Uses, Efficacy, Duration of Action & More

Key Takeaways: 
Modafinil is an oral medication that promotes wakefulness, reduces fatigue and excessive sleepiness. It’s FDA-approved for the treatment of sleep-related medical conditions, e.g., narcolepsy, shift work sleep disorder, and obstructive sleep apnea. 
Its off-label use includes treatment of ADHD symptoms, bipolar disorder, and multiple sclerosis (MS).
Some people use it as a cognitive enhancer or “smart drug”. It is believed to improve memory and increase alertness and concentration. 
The drug typically dissolves and kicks in within 2 hours. It will help you stay alert and awake for 10-12 hours. But it stays in your system longer.
The time it remains in the body may vary according to various factors, e.g., age, gender, liver and kidney functions, metabolism, dosage, and overall health.

You’re not alone if you’re wondering how long modafinil will stay in your system. This question is asked by many people using this medication as a “smart drug” or for treating their medical condition, e.g., narcolepsy, shift work disorder, or apnea. Before knowing the exact amount of time modafinil (Modalert 200) lasts, it’s important to know how it works. In this article, we will explore vital information about its usage, efficacy, and dosage and how they vary from person to person.

How Does Modafinil Work on the Brain?

Modafinil’s chemical structure is 2-[(phenylmethyl)sulfinyl]acetamide. It’s a psychostimulant, which means it has mood-enhancing and fatigue-fighting properties. 

Modafinil stimulates the central nervous system (CNS). CNS, made up of your brain and spinal cord, is the whole body’s control center.

The drug may work on the brain’s norepinephrine, serotonin, and dopamine systems. These substances are released by neurons (nerve cells). They are our body’s chemical messengers. 

Research suggests that the drug might work on dopamine reuptake transporters, though we don’t know exactly how.

Source: “Modafinil Activates Phasic Dopamine Signaling in Dorsal and Ventral Striata”, The Journal of Pharmacology and Experimental Therapeutics

Blockaging the dopamine transporter (DAT) increases dopamine levels in the brain’s nucleus accumbens. Dopamine is important in controlling our wakefulness, attention, motivation, and other functions. By increasing its level, it may help in keeping you awake and alert. It also acts as a memory and cognitive enhancer.

Modafinil may affect other neurotransmitter systems, such as orexin (hypocretin), which also controls wakefulness and arousal. 

However, we haven’t fully understood its exact mechanism of action yet.

Modafinil Pharmacokinetics – How Long Does the Drug Take to Work?

This is what your body does to the drug: 

1. The pill is taken orally (swallowed as a whole by mouth). 
2. It’s absorbed into the blood through the walls of the digestive tract. 
3. It reaches peak concentration in plasma in about 2-4 hours. The onset of effect is 2 hours. That’s when it starts to work.
4. It’s metabolized in the liver mainly by CYP3A4 enzyme
5. “Elimination half-life” (explained below) of the modafinil dose is 12-15 hours
6. The duration of action is 11.5 hours. By this time, you should experience the positive therapeutic effects.
7. Less than 10% of the unchanged medication is flushed out of the body via urine.
8. It can still be traced in your urine for 48-72 days. 

Note that “half-life” and “duration of action” are different. Still, both affect how long the drug has effects on your body. Let’s find out how.

Half-Life of Modafinil: How Long Is It Good For?

The half-life refers to the time the body takes to reduce the amount of the drug in the blood or plasma to 50% of its original value. Let’s say a medication’s half-life is 6 hours, and you took a dose of 50 mg. This means that 25 mg will still remain in your body after 6 hours. On the other hand, the duration of action is how long the drug works. 

Knowing the half-life and duration of action is important. Because it will help determine how often you should take it. 

Medications that have a long half-life stay longer in your system. So they have a longer duration of action. 

A 2012 study in Clinical Pharmacokinetics confirms that modafinil has a half-life of 12-15 hours. This doesn’t mean the drug completely leaves your body in 15 hours. It means that 50% of the original amount has been removed, so its effects will wear off after this time. 

Source: “Armodafinil and Modafinil Have Substantially Different Pharmacokinetic Profiles Despite Having the Same Terminal Half-Lives”, Springer Link

When an oral drug has a half-life of 12-48 hours, it is usually taken no more than once a day. Hence, your doctor will likely prescribe a once-daily dosing schedule.

Your doctor will probably prescribe a dose in the morning to prevent daytime sleepiness. For shift work, you may need to take it one hour before the shift starts. 

So, for the usual recommended dose of 100-200 mg, modafinil remains effective for 12-15 hours in healthy subjects. After that, as plasma concentration in the blood is reduced to 50%, its effects are negligible. The dosage depends on your condition. Doses of up to 400 mg are given to patients who don’t respond to the 200mg dose.

How Long Exactly Will Modafinil Stay in My System?

The plasma concentrations (drug’s concentrations in the blood) and half-lives may vary.

• Dosage/Strength 

If you take higher doses or multiple doses, it will have a longer elimination half-life and may last longer. 

• Severe kidney problem

How the body processes modafinil isn’t any different in patients who have renal impairment (creatinine clearance ≤ 20mL/min). However, the inactive modafinil acid (a by-product of the process) increases in their body about nine times because the kidneys cannot properly excrete the drug into the urine. 

• Severe liver problem

In patients with hepatic impairment, the drug clears out from the system slower than usual. The liver is the organ that breaks down (metabolizes) the medication. Having a weak liver reduces oral clearance by 60%. This doubles the concentration of the medication in the body.

• Different sexes 

The length of time modafinil lasts in the system is similar for males and females.  However, due to differences in body composition, drugs may last longer in females.  

• Different ages 

As we age, kidney and liver functions get weaker. Due to normal aging processes, the half-life may be higher e.g., almost two times higher in elderly in their 80s than younger populations. So, its effects may last longer in their body. 

• Different metabolism

People metabolize drugs differently. Because of their genetic makeup, some users would process the tablet very fast. This may lead to its low concentration in the blood. So, the desired effects will wear off too quickly or will not be experienced at all. 

Those who process it slowly will experience a delay in time, which it takes to eliminate it from the body.

• Certain medications 

Some other drugs or substances you take might speed up or slow your metabolism. This affects how long modafinil can stay in your system. 

For example, Rifampicin (an antibiotic) is a strong CYP3A4 inducer. We have learned that CYP3A4 helps break down modafinil. So, taking them together can metabolize modafinil too quickly, flushing out of your body faster. 

Ketoconazole is a well-known inhibitor of CYP3A4. It slows down metabolism, prolonging the effects of modafinil. 

So, who are the people this medicine is intended for?

FDA-Approved Uses of Modafinil

The U.S. FDA has approved its use for the following conditions: 

Narcolepsy

Narcolepsy is a brain disorder. Those who have it suffer from excessive daytime sleepiness, which can seriously hamper their day-to-day life. A study in CNS Drugs journal suggests that modafinil is 64% effective in treating narcolepsy patients. 

Obstructive sleep apnea/hypopnea

Obstructive sleep apnea is a sleep disorder that causes partial or complete blockage of the upper airway during sleep. This can make breathing and sleeping difficult. 

A study in the Oxford Academic Sleep Journal shows that modafinil helps treat sleep apnea/hypopnea in 61%-68% of patients. It’s used along with other therapies, e.g., continuous positive airway pressure (CPAP).

Shift Work Sleep Disorder (SWSD)

Shift work sleep disorder affects people who work during nontraditional hours, e.g., night shifts or rotating shifts. These irregular work schedules can disrupt the natural sleep-wake cycle, resulting in excessive sleepiness and difficulty staying awake when needed. A review indicates that 71% of SWSD patients taking modafinil may see improvement in their condition.

Off-Label Uses of Modafinil

Physicians also prescribe this medicine off-label to help with other conditions, such as: 

• There’s evidence that it may improve attention-deficit hyperactivity disorder (ADHD) in children. 
• It can help treat depressive episodes in people with unipolar and bipolar disorders, lowering the risk of mania. 
• The medication has been proposed to treat jet lag to fix the sleep‐wake cycle.
• Modafinil could be used as a treatment for cocaine dependence. It may help cancer patients feel better. 
• The drug may relieve fatigue and sleepiness in multiple sclerosis patients. 

However, studies show mixed results regarding these uses.

Cognitive Enhancement as a “Smart Drug”

A growing number of people are using modafinil as a cognitive enhancer and “smart drug”, “study drug” or “smart pill”.  

The medical term is “nootropic drug” because of its ability to improve mental performance, e.g., thinking, learning, and memory. 

Modafinil for Students 

The medicine is believed to enhance cognitive abilities. It may improve focus, attention, and alertness during long study sessions. This may be a solution to handle exam stress and boost academic performance. 

Modafinil in Competitive Work Environments

High-pressure corporate jobs or careers, e.g., tech or finance, have high workloads and tight deadlines. The off-prescription use of the drug is common in these situations. It may relieve burnout, stress and improve productivity. 

Modafinil for Entrepreneurs and Other Professionals 

Entrepreneurs, founders, and business owners experience a lot of stress every day. People in certain professions, e.g., pilots, soldiers, surgeons, drivers, and performers, must be alert for long, irregular hours. 

This drug can help manage their “circadian rhythm,” i.e., the internal body clock that decides when to wake up, remain alert, and when to sleep. It may also improve executive functions, e.g., decision-making and problem-solving. 

The air forces in Singapore, France, the Netherlands, India, and the United States have approved use of modafinil to fight fatigue and avoid flight risks in certain missions. However, a meta analysis in The Journal of Clinical Pharmacology suggests that when it comes to acting as a “smart drug” or improving cognitive functions, this medicine has limited effectiveness.

Benefits & Advantages of Using Modafinil

• Research suggests that withdrawal symptoms are minimal or none. On the contrary, other stimulants, e.g., methamphetamine (MA) and cocaine, have a higher risk. 

And what’s more, this pill may reduce anxiety that might have been induced by other drugs/their withdrawal. 

• The effects of this narcolepsy drug last for about 12 hours, much longer than other stimulants, e.g., caffeine (3-4 hours), methylphenidate (1-4 hours), and amphetamines (6-8 hours). 
• It may have less side effects than other psychostimulants. For example, amphetamines may make you more jittery or anxious than modafinil.  
• Modafinil has a limited number of drug interactions as well. So this may be useful for elderly patients because older adults are more likely to take multiple medications at the same time.
• The wake-promoting agent may also improve mood. The mood-brightening effect can help patients whose minds can use a quick boost, and who need to feel good. 
• Modafinil may help manage long-term tiredness and fatigue caused by illnesses, e.g., chronic fatigue syndrome (ME/CFS) or neurological disorders. 
• It’s a class IV drug as classified by the U.S. Drug Enforcement Administration (DEA). This means it has a lower chance of dependence and addiction. 
• It’s not only an anti-fatigue but also an antipsychotic med. This means the possible applications may extend beyond sleep problems to mental and emotional health.
• It can prevent work-related mishaps and increase safety even on roads for certain individuals. For example, research shows that it can prevent accidents and near misses in patients with SWSD during their daily commute.

It’s usually safe and well-tolerated. However, no drugs can be effective for everyone and 100% free from potential adverse effects.

Possible Disadvantages

• Common side effects include headache, nausea, dizziness, dry mouth, stomach upset, etc. These are mild to moderate in severity and usually go away over time. 
• Although in rare cases, it can still have side effects, e.g., aggression, anxiety, depression, mania, hallucinations, thoughts of self-harm, or other mental health symptoms
• It’s a controlled substance (despite being a class IV drug). It’s not free from the risk of misuse or dependence.
• Despite being a medication used to treat sleep disorders, modafinil may cause sleep problems in some cases.  For example, it can impair your sleep if you try to sleep within its duration of action.

A study involving bipolar disorder patients shows that it has negative effects on their sleep quality and energy levels.

• Performing “cognitive enhancement” using drugs raises a lot of legal, social, and ethical concerns. For example, a student taking it may perform better in an exam, which could come across as an unfair advantage. It is against the idea of equal opportunity for everyone.  

Things to Consider 

• Although more studies are needed on humans, women trying to get pregnant should not use this drug.
• Women trying not to get pregnant using contraceptives should know that this drug can make your contraceptive less effective. For other potential drug interactions, speak to your doctor. 
• Modafinil is not known to harm the liver. Still, if you have a liver condition, discuss it with a healthcare professional. 
• Even healthy patients taking low doses should be under medical supervision to make sure they are not developing any mental health conditions (e.g., psychosis) or any kind of allergic or severe reactions. 
• Long-term usage of this medication can lead to tolerance in some users. Even so, dependence after prolonged use of the drug is very rare. 
• Modafinil might be safer than other wakefulness agents, e.g., amphetamine for the heart. It is found to cause no serious arrhythmic events, e.g., irregular heartbeat, shortness of breath, or chest pain. 

However, since it’s a stimulant, it still impacts heart rate and blood pressure. So, talk to your healthcare provider if you have an existing cardiac condition.

How to Get the Maximum Effect from Modafinil?

Regardless of how long it lasts, use these tips to make the pill work better for you: 

• Follow the right schedule and stick to your medication routine. This is a time-sensitive medicine, and taking it at the wrong time will result in unwanted effects. 
• The medicine can cause dry mouth as a side effect. Drink lots of water to relieve this symptom. 
• Eat small, frequent meals to sustain energy and prevent nausea or stomach upset. 
• Avoid using caffeine (coffee, tea) with this pill. Both are CNS stimulants. Coffee can intensify the drug’s effects on heart and blood pressure.  Also, do not drink alcohol while its effect lasts. 
• Don’t take more or less than the prescribed doses to minimize the risk of side effects or dependence.  
• Use stress management for side effects like anxiety or nervousness  
• Follow up with your doctor to check how well it’s working for you.

Conclusion 

Modafinil stays 12-15 hours in your system with a standard 100-200 mg dose. You will experience alertness and reduced sleepiness for 10-12 hours.

This means you have to time your doses correctly and ensure they don’t disrupt your sleep pattern. The pill will likely keep you awake for over 12 hours.  

However, it hasn’t consistently shown efficacy in research as a “study drug” or “smart pill”. So, we can’t tell if it will work for you for non-medical “cognitive enhancement” purposes. 

FAQ

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