Modafinil Side Effects & How to Avoid Them

Modafinil is a powerful nootropic and eugeroic drug (a drug that promotes wakefulness).

It’s popular among university students and high-functioning executives for its ability to boost work output and efficiency.

As with any performance enhancement medication, some side effects can occur.

We investigate what the side effects of modafinil are, why they happen, how common they are, and what you can do to avoid them.

We also highlight what the more serious side effects look like and what to do if they happen to you.

What is Modafinil Used For?

Doctors prescribe modafinil for conditions involving the central nervous system. Conditions like ADD/ADHD and narcolepsy are the most common uses of the medication. However, there are also a lot of off-label uses for the drug.

1. Modafinil for ADHD

ADHD is a condition involving an imbalance in dopamine levels.

Dopamine is an important neurotransmitter in the brain. It’s an integral component of the “reward center,” as well as learning and memory.

Low dopamine levels make it harder to trigger the reward center, causing those affected to have to work extra hard to stimulate it. The results are excessive fidgeting and an inability to concentrate on one task at a time.

Modafinil helps by increasing dopamine levels within the brain by limiting the rate at which it’s reabsorbed into the neuron. The official term for this action is called a “dopamine reuptake inhibitor.”

2. Modafinil for Narcolepsy

Narcolepsy is a medical condition involving a dysfunctional orexin system.

Orexin is an important part of our central nervous system tasked with controlling the waking portion of the sleep-wake cycle. The sleep-wake cycle is essential for making us feel tired at night awake during the day.

People with a dysfunction in this system can become suddenly and severely tired at inappropriate times throughout the day. This is exactly the case with a condition called narcolepsy.

Narcolepsy is a debilitating condition that causes excessive sleepiness and at times— to suddenly fall into a deep sleep for several minutes.

Modafinil works by increasing orexin levels in the brain, causing us to feel awake and alert. In narcoleptics, this can dramatically reduce symptoms of the condition, and in healthy people, this forces a state of wakefulness.

3. Off-Label Use of Modafinil

Although modafinil is a prescription medication, it’s become popular outside of the prescribed uses. People are using it to take advantage of its ability to boost dopamine above normal levels, increasing attention and productivity along with it.

Modafinil is also used for its wakefulness-promoting (eugeroic) effects.

Students take it to allow them to stay up for many hours studying in preparation for a big exam or to finish a tough project.

Many people use modafinil for combating the adverse effects of jet lag as well. Instead of forcing themselves to fall asleep and feel groggy the next day, they take modafinil when they should feel awake. Usually, by the time the drug wears off at the end of the day, they’re tired and ready to go to bed.

How Modafinil Works

In order to summarise the side effects of modafinil and describe how to prevent them, it’s important to understand how modafinil works in the brain.

1. The Effects of Modafinil on Dopamine

As mentioned, dopamine is an important neurotransmitter. It has many roles in the human body, including the regulation of focus and concentration. Dopamine is also essential for regulating hormone balance in both men and women.

Modafinil works to increase dopamine in the brain by inhibiting its reuptake into the synapses.

The neurons release dopamine to transfer a message to other neurons. Once this message is sent, dopamine is reabsorbed and broken down. Modafinil blocks this process from happening by blocking the dopamine reuptake transporters located on the nerve cells.

2. The Effects of Modafinil on Norepinephrine

Norepinephrine is involved with the fight or flight response. Levels are lowest in our bodies while we’re asleep and heighten as we start to wake up. Norepinephrine levels surge when we are stressed or panicked.

Modafinil works similarly on norepinephrine as it does dopamine. Part of the reason for this is that dopamine is an essential precursor for norepinephrine, and therefore follows many of the same pathways. 

Norepinephrine works on a special set of receptors found throughout the body that controls the fight or flight stress response.

Norepinephrine’s Effects On The Body:

1. The airways widen to let in more oxygen
2. The heart beats faster to push blood around faster
3. The immune and digestive systems shut down to designate more energy to other organ systems such as the muscles and brain
4. Blood vessels tighten to raise blood pressure and force blood into the microcapillaries with more force

Many of the side effects of modafinil come from its effect on norepinephrine and its role on the stress response.

3. The Effects of Modafinil on Orexin

Orexin is a neurotransmitter released from the control center of the brain, the hypothalamus.

The hypothalamus controls many aspects of the body with the help of other hormones. It’s like the air traffic control system of the brain. It delegates work to other organs of the body to carry out its demands. By delegating these tasks, it can focus on looking at the big picture going on and take control of the body as a whole.

The hypothalamus uses orexin to carry out its demand for wakefulness and arousal.

Orexin travels to other areas of the brain to initiate “wake-up mode.” This results in a feeling of alertness and wakefulness. This system is naturally active in the morning and mid-afternoon.

Modafinil has been shown to increase the activation of the neurons responsible for releasing orexin in the brain [1]. This is the mechanism thought to be the most accountable for modafinil’s benefits in treating narcolepsy, which is known to be a condition involving poor orexin function [2].

4. The Effects of Modafinil on Histamine

Histamine is another multifunctional compound in the human body. Outside the brain, histamine is an important inflammatory molecule. It’s one of the leading causes of the symptoms we experience during an allergic reaction.

Histamine is also an important neurotransmitter in the brain but has a very different job here. It plays a major role in the waking process [3].

This is the same reason why antihistamines often used for allergies can also be used as sedatives. By blocking histamine, the brain is unable to stimulate itself, making us feel dizzy and tired.

Modafinil has been shown to increase histamine release in the brain by up to 150% [4].

Where to Buy Modafinil

Modafinil can be bought with a doctor’s prescription from a pharmacy, although this can be very expensive and nearly impossible to get if you can’t prove you have either ADHD or narcolepsy.

The best option is to buy modafinil online.

Most online vendors sell generic modafinil, which is virtually identical to brand name modafinil but costs only a fraction of the price. Additionally, few online vendors require a prescription for purchase.

Generic versions of modafinil and armodafinil such as Modvigil, Modalert, Artvigil, and Waklert can be bought for a fraction of the cost to brand-name versions — and are shipped straight to your door.

What are the Side Effects of Modafinil?

Now that we understand what modafinil is changing in the brain to produce its results, we can start to investigate the common side effects associated with it and find techniques we can use to avoid them.

The main side effects of modafinil include:

1. Insomnia

Insomnia is by far the most common side effect of taking modafinil.

This makes sense when you consider the fact that the majority of modafinil’s effects work to increase the feeling of wakefulness. If drug concentrations remain high when it’s time to go to bed, it will become very difficult to fall asleep.

This is a direct result of the increased concentration of orexin, histamine, and norepinephrine in the brain.

How to Avoid it:

A common reason why people experience insomnia after taking modafinil is that they took it too late in the day. Consider the fact that Modafinil remains active for around 10 and 15 hours.

This means that to reduce your chances of lying in bed wide awake at night; you need to take modafinil first thing in the morning or at least 10 hours before you plan on going to sleep.

It’s also important to avoid all other stimulants when taking modafinil to prevent their effects from stacking on top of each other.

2. Headaches

Another common side effect of modafinil is headaches.

This is a side effect that some users can’t seem to avoid, while others remain unaffected.

Although there are many possible causes, the most likely is an increase in a neurotransmitter known as glutamate. Its concentrations are increased as a byproduct of the stimulation of other neurotransmitters like dopamine and orexin.

Some users have high levels of glutamate in the brain already, especially those suffering conditions like anxiety or obsessive-compulsive disorder.

Taking modafinil can push these users over the edge, causing them to feel headaches, as well as other side effects like jitteriness and anxiety.

Another cause for headaches when taking modafinil is dehydration.Often, modafinil users become so focused on the tasks they are working on, that they forget to eat and drink, causing dehydration headaches later on.

How to Avoid it:

The best way to prevent headaches while taking modafinil is to make sure you’re drinking plenty of water throughout the day, and take measures before-hand to lower glutamate levels.

A great way to manage glutamate levels is to supplement daily with L-Theanine. This compound is one of the active components in green tea and has been shown to lower anxiety in humans [5].

3. Poor Appetite

Poor appetite isn’t as much of a problem for occasional modafinil users, but it can become a major problem in people that use modafinil every day.

The stimulating effects of modafinil on the central nervous system can kill our hunger cravings. Users often report that on the days they took modafinil, they didn’t even realize they’d gone all day without a proper meal.

Only later on in the evening when the drug’s effects have worn off do they realize how hungry they are.

Long term, low appetite can lead to significant health problems.

We need adequate nutrition to build neurotransmitters, blood cells, skin cells, and even to process modafinil and other compounds in our body through the liver. If we go too long without adequate nutrition, all of these systems can start to become dysfunctional and cause problems.

How to Avoid it:

This can be a challenging side effect to avoid. The most common method of ensuring we’re eating enough food while on modafinil is to set a timer for lunch and dinner reminding us to eat periodically.

Some people might think this sounds ridiculous, but it’s a lot easier to forget to eat when you have no hunger cravings whatsoever.

Another way to ensure we get enough nutrition while on modafinil is to pack nutrient-rich shakes or power bars with us. This makes it easier to get a large hit of nutrition even though we aren’t hungry enough to eat an entire meal.

4. Diarrhea

Diarrhea and mild gastrointestinal discomfort can be common. The issue involves a slow breakdown of Modafinil in the intestinal tract, causing it to irritate the intestinal tissue.

Additionally, in some people, activation of the fight or flight system with modafinil can cause a stimulating effect on the lower intestines— resulting in diarrhea.

How to Avoid it:

The best way to avoid gastrointestinal discomfort of any kind with Modafinil is to ensure it’s taken withfood, especially food containing fats like butter, olive oil, or animal fats.

This is because the same foods that allow fat to enter the bloodstream will act on modafinil. As a fat-soluble compound, modafinil takes the same path of absorption in the gastrointestinal tract as dietary fats.

5. Anxiety

Anxious people often have higher activity of neurostimulators in the brain. Neurotransmitters like norepinephrine are especially abundant in anxious individuals.

This makes it more common for anxious people taking modafinil to experience an increase in their anxiety symptoms.

A common way we measure brain activity is to measure weak electrical impulses in the brain. This is done using a specialized piece of medical equipment called an electroencephalogram (EEG).

We have theta, alpha-, and beta-waves. By measuring their activity using an EEG, we can determine what our general mental state is at the moment. This is often used in scientific research to see how various substances affect the brain.

Anxious states are often associated with low alpha-wave activity and high beta-wave activity as recorded by an EEG. This gives us an excellent way of measuring substances that both induce and alleviate anxiety.

How to Avoid it:

L-Theanine is one of the best ways to reduce the chances of developing anxiety while taking modafinil. Studies have shown that just a single dose of L-Theanine can significantly increase alpha-wave activity and reduce anxiety symptoms [6].

L-Theanine is used similarly for reducing the anxiety-inducing side effects of another common stimulant, caffeine.

Another way to avoid anxiety while taking modafinil is to practice breathing techniques whenever symptoms start to appear.

Breathing is considered by experts to be the most effective way of taking over our parasympathetic nervous system (PNS). This part of our nervous system directly opposes the sympathetic nervous system (SNS), which is responsible for symptoms of anxiety when it becomes to hyperactive.

With slowed, rhythmic breathing for even just a few seconds we can completely inhibit anxiety attacks and reach a much calmer state.

For more information on how this works, we suggest you take a look at this video of Dr. Gevirtz explaining this concept in greater detail.

6. Dry Mouth

Another frustrating side effect of modafinil is a dry mouth. It’s the result of overstimulation of our central nervous system by modafinil.

Receptors outside the brain known as muscarinic receptors are triggered by norepinephrine. They bring all digestive secretions to a halt so that the energy can be re-routed to more critical areas like the brain and muscles.

Our body does this during the fight or flight response to help us escape a hungry tiger or other dangerous situations.

Saliva is considered a digestive secretion, and once it stops flowing, can cause an excessively dry mouth. For short durations, this is nothing more than an annoyance, but if this happens for too long, we can begin to experience issues like mouth ulcers and symptoms of poor digestion like constipation or diarrhea later on.

How to Avoid it:

The fix for this is the same as many of the other side effects mentioned above. If we can keep ourselves in a state of relaxation, with supplements like L-Theanineor relaxation techniques like slow, rhythmic breathing exercises, we can prevent overactivation of our fight or flight response.

Some More Serious Side Effects to be Aware of:

Although far rarer, there are some serious side effects that can come from modafinil use. If any of these symptoms are experienced, it’s important to see a doctor as soon as possible.

More serious side effects of modafinil include:

1. Fever

This is an excessive activation of the sympathetic nervous system. The hypothalamus is essentially losing control of homeostasis. This will eventually lead to much more serious consequences like blood pH changes, enzyme breakdown, and eventually seizures if it’s not controlled effectively.

This is best avoided by drinking plenty of water and staying within the recommended doses for modafinil as set by the manufacturer.

2. Hallucinations

This is an indication of much deeper neurological dysfunction. 

Modafinil SHOULD NOT be causing hallucinations. Visit a doctor immediately if you are experiencing these side effects.

3. Severe Depression

Modafinil is actually used as a treatment for depression; however, in some cases, dopamine levels can drop as modafinil wears off.

This can be prevented by ensuring modafinil is not mixed with other medications or alcohol and ensuring that you are in good mental health before taking modafinil. If you suffer from depression, it’s important to talk to your doctor before taking modafinil.

4. Chest Pain

Although we haven’t found any reports of heart-attack induced by modafinil, any unexplained chest pain should be examined by a doctor. This is theoretically possible due to the central nervous system stimulating effects of modafinil— though very uncommon.

5. Severe Skin Reaction

This condition is rare, but there are some reports of severe skin reactions resulting from modafinil use in select individuals.

Some users have a severe allergy to modafinil and will break out in skin rashes after taking the drug. This is referred to as Steven Johnson Syndrome.

It’s imperative that anybody experiencing these symptoms visits a medical doctor immediately.

Conclusion

Modafinil is a popular medication for promoting wakefulness and improving productivity. Although rare, some side effects can occur from taking modafinil.

The most common side effects are insomnia and headaches. These side effects and most of the others are the results of overstimulation of the central nervous system and dehydration.

The best way to avoid side effects is to ensure you’re drinking plenty of water, and do things that make you feel calm while the medication is active. Things like L-Theanine supplementation, periodic breaks from work, and breathing exercisescan go a long way in keeping you calm, without negating any of the beneficial effects of the medication.

It’s also important to know what the more serious side effects are and when you should seek medical support.

References

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2. Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., … & Mignot, E. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell, 98(3), 365-376.
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4. Ishizuka, T., Sakamoto, Y., Sakurai, T., & Yamatodani, A. (2003). Modafinil increases histamine release in the anterior hypothalamus of rats. Neuroscience letters, 339(2), 143-146.
5. Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological psychology, 74(1), 39-45.
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