Is Modafinil Safe Long Term? Modafinil’s Long Term Effects

Modafinil is becoming fairly well-known in academic circles and among business executives. This is especially true in places like silicon valley.

People are enticed by its effects on enhancing focus and memory and its ability to keep us awake and motivated for several hours at a time.

Supplement companies and nootropic blogs have been talking about the benefits of modafinil for years. We know that modafinil can be beneficial in the short term for studying or finishing tasks, but how does it affect us long-term?

Is it safe? Are there any lasting effects of modafinil?

There Are 3 Types of Modafinil Users:

In order to talk about the side effects, we need to discuss the different ways modafinil is used.

People that use modafinil more often are going to have a higher chance of side effects both long-term and short-term.

1. Daily Prescription Users

People suffering from conditions like narcolepsy or sleep apnoea fall into this category.

Other people that use modafinil in this way are people who have attention deficit disorder (ADD/ADHD) or chronic conditions like multiple sclerosis that often produce severe fatigue as a side effect.

Most people prescribed modafinil to treat a medical condition take the medication on a daily basis.

2. Occasional Users Looking to Boost Their Competitive Edge

These are the people using modafinil specifically on days they want a boost in their productive output.

People in this category may include:

• Students looking to boost their study efforts in preparation for an exam
• Business executives looking to get through a particularly tough or tedious project
• Interns looking to excel in performance to score a job opportunity once the internship is over
• CEOs and business executives with heavy workloads and a need to perform at the highest capacity possible
• Creatives looking for a boost in their creative process

These users may take modafinil anywhere from 1–4 times per week or less. Some only take it once or twice per month when they have a project or exam to finish.

3. Frequent Users Looking for Daily Cognitive Enhancement

Others will take the medication every day for general cognitive enhancement.

Usually, the people in this category are ultra-high achievers and are very productive people. They take modafinil every morning to enhance their workday performance.

In order to sustain this practice, people in this category usually have a good routine with their modafinil use. They often don’t drink, don’t smoke, eat healthily, and ensure they get enough sleep each night.

They then take modafinil to get as much as possible out of the working hours in their day.

How Does Modafinil Work?

Modafinil uses a few different mechanisms to produce its effects on the brain:

1. Modafinil Increases Dopamine Concentrations

Dopamine is an essential neurotransmitter in the brain. It’s involved in the process of learning, emotion, memory, and focus. It’s also an integral part of the reward system responsible for regulating our habits and routines.

Much of modafinil’s benefits relies on its ability to increase dopamine.

This neurotransmitter has been found to be in lower levels in people with attention issues like ADHD. In healthy people, modafinil increases dopamine levels outside of the normal range, helping us zone in on the task at hand.

It can significantly improve our attention spans and may help with the storage and retrieval of memories.

Long-Term Side Effects of Increased Dopamine:

• Higher potential for addiction
• Depression
• Hormonal imbalance

2. Modafinil Tells Our Brain To Wake Up

Modafinil is considered a eugeroic medication.

A eugeroic is a compound that puts the brain into a state of wakefulness. It essentially tells the brain to enter “wake” mode. It does this by interacting with some of the neurotransmitters used to regulate our sleep-wake cycle.

The Sleep-Wake Cycle

Everybody contains a special biological clock that regulates the release of stimulatory compounds, as well as sedative compounds.

We calibrate our internal clock with our daily routines and exposure to sunlight.

Many people can picture this when they think back to a time where they got a new job, forcing them to wake up earlier than usual. Most people experience difficulty getting out of bed for the first few weeks once the body clock has adapted to the new schedule, they often find themselves waking up naturally right before their alarm was scheduled to go off.

In the morning when we wake up, our biological clock turns on the waking portion of the sleep-wake cycle.

When the sun goes down, and we start to get closer to bedtime, the biological clock shifts to releasing sedative compounds instead.

Overriding The Internal Body Clock

Modafinil works by stimulating the waking side of the nervous system directly.

It causes a release of a neuropeptide known as orexin, which the brain uses to carry out the effects of the waking portion of the nervous system.

Modafinil’s ability to override the sleep-wake cycle makes it useful for treating conditions like narcolepsy or sleep apnea that involve dysfunctions of the sleep-wake cycle. It’s also useful for getting over the symptoms of jetlag, or for patients experiencing chronic disease like multiple sclerosis with accompanying daytime tiredness.

Long-Term Effects of Overriding the Sleep-Wake Cycle:

• Chronic insomnia
• Fatigue
• Poor concentration
• Anxiety

3. Modafinil Increases Norepinephrine Levels In The Brain

Norepinephrine is a neurotransmitter and hormone used to regulate the fight or flight system.

This system is activated under stressful conditions. It’s designed to help us get away from danger when we need to.

Norepinephrine increases our focus by stimulating the brain. It also increases available glucose in the blood to give our muscles additional energy to fight or run, and it turns down systems that aren’t immediately necessary. This includes immune function and digestion.

Long-Term Effects of Increased Norepinephrine:

• Poor stress resistance
• Weight gain
• Adrenal fatigue
• Insomnia OR excessive sleeping
• Low immunity
• Poor digestive function

Is Modafinil Safe Long-Term?

In general, modafinil is considered a safe medication.

It’s well-studied and has been used by millions of people over the last two decades.

Doctors and researchers have spent countless hours monitoring and recording the effects of modafinil both in the short-term and over several years of use.

Although the chances of long-term reactions are low, there are a few areas of concern. If some extra care is applied to these areas of weakness, we can reduce the chances of long-term adverse effects from happening.

Issues With Neurotransmitter Balance

Our brains are made up of complex interactions between neurotransmitters. They carry out the transfer of information from one area of the brain to another, sending signals out to the rest of the body,

This chemical reaction is kept at an equilibrium. Everything is connected, so if you increase or decrease one neurotransmitter, it will affect all the others as well.

Modafinil causes a shift in this neurotransmitter balance.

Once the modafinil is metabolized and cleared from the body, neurotransmitter levels will return to baseline.

If the drug is taken frequently, dopamine levels may be perceived by the brain to be higher than they really are. The body will adapt to this and may change the balance of these neurotransmitters.

This can cause long-term issues with drug tolerance and dependency.

The body will now depend on the medication to produce adequate dopamine levels.

If this happens, and a dose of modafinil is missed, it may cause the body to have low dopamine levels. This would come with effects like inability to concentrate, lowered libido, and emotional sensitivity.

The Importance Of Sleep

Many different issues can arise when you go without sleep for too long.

In 1965, a man named Randy Gardner achieved the world record of the longest a human has gone without sleep.

He made it a total of 11 days

After just two days without sleep, Randy lost the ability to focus on objects with his eyes. By day three he was unable to identify objects by touch and became uncoordinated in his movements.

By the eleventh day, Randy was expressionless, had slurred speech, was unable to concentrate on tasks. He had also been experiencing occasional hallucinations and appeared to be very unwell.

Although this is an extreme example, sleep deprivation is a common problem in the modern world.

As many as 90% of teenagers are sleep deprived according to one study [1].

Even minor sleep deprivation can have adverse effects on health. As we become fatigued, our brains turn up the stress response to give us the energy to keep going.

Long-term, this can cause changes in body weight, energy levels, and can make us less adaptable to stresses in our environment.

Why This Is Important

When we’re sleep deprived, our brain doesn’t work efficiently.

Reaction times slow, we develop issues with short and long-term memory, and our motor movement becomes clumsy.

Modafinil is an excellent tool for making us feel awake and alert, but it’s NOT an alternative for sleeping. Having at least 7 hours of sleep per night is important.

Immune Function

Modafinil stimulates the sympathetic nervous system (SNS).

This is the stimulating side of our nervous system, responsible for the fight or flight response.

The fight or flight response is designed to help us get away from danger. It increases energy levels, makes us feel alert and awake, increases heart rate, and turns down all systems that are not immediately necessary.

Let’s say you come face to face with a hungry bear. Your fight or flight system immediately recognizes the threat and kicks in.

You feel your senses heighten, your eyes sharpen, and your muscles have access to a rich source of fuel should you need to start running or climb a tree.

At the same time, this fight or flight response tells the immune system to shut down. It can be turned back on later once the danger has been dealt with.

In the short term, this is very useful. As humans evolved this feature, it was used in short durations.

The danger was either dealt with (fight), or avoided (flight). Then once the danger was gone, we could recover, and all body systems were restored to normal function.

In the modern world, it’s become common to be in a constant state of stress (fight or flight).

This means that our immune system is suppressed over extended periods of time which has a more significant impact over long-term immune health.

If the immune system is suppressed over long periods of time, it can lead to the development of hypersensitivities and allergies, inflammation, and frequent or more severe infections.

How to Avoid It

The best way to avoid the side effects of long-term use is to allow recovery from the SNS activation as often as possible.

This means not only taking periodic breaks, but finding time regularly to relax, and allow the PNS to turn immune function once the drug has worn off.

How to use Modafinil Safely Long-Term

Most of modafinil’s long-term side effects are the result of overstimulation in the central nervous system.

Whenever one side of the immune system is more active than the other for too long, problems can arise.

The best way to avoid this is to allow the nervous system to recover and normalize between doses.

This involves spending enough time sleeping and finding time to take breaks on Modafinil and relax.

References

1. Loessl, B., Valerius, G., Kopasz, M., Hornyak, M., Riemann, D., & Voderholzer, U. (2008). Are adolescents chronically sleep‐deprived? An investigation of sleep habits of adolescents in the Southwest of Germany. Child: care, health and development, 34(5), 549-556.
2. Volkow, N. D., Fowler, J. S., Logan, J., Alexoff, D., Zhu, W., Telang, F., … & Hubbard, B. (2009). Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. Jama, 301(11), 1148-1154.
3. Lin, J. S., Hou, Y., & Jouvet, M. (1996). Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proceedings of the National Academy of Sciences, 93(24), 14128-14133.
4. Qu, W. M., Huang, Z. L., Xu, X. H., Matsumoto, N., & Urade, Y. (2008). Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. Journal of Neuroscience, 28(34), 8462-8469.
5. Arrang, J. M., Devaux, B., Chodkiewicz, J. P., & Schwartz, J. C. (1988). H3‐receptors control histamine release in human brain. Journal of neurochemistry, 51(1), 105-108.
6. Nasr, S., Wendt, B., & Steiner, K. (2006). Absence of mood switch with and tolerance to modafinil: a replication study from a large private practice. Journal of affective disorders, 95(1), 111-114.