What Does Modafinil Tolerance Mean and How to Handle It

Modafinil Tolerance 101

Often, when we consume something regularly, our body gets used to it. For example, coffee or alcohol.

It takes you to drink a couple cups of coffee to finally start feeling more awake, or alcohol intoxication kicks in only after a few more shots.

This is what is called “tolerance”.

You develop tolerance towards substances you consume on a regular basis. Your body becomes less and less affected by them.

In the medical field, this phenomenon is not rare either. Patients often develop tolerance towards their medications, which can have many negative consequences.
The main danger of developing tolerance is that you have to increase the dose of your medication each time. When the dosage surpasses the advised level, it can be harmful to your physical and mental health. The liver is especially vulnerable in this scenario.

It is extremely important to find out how to handle the level of tolerance in order to keep the dosage within the safe range.

How do We Define Tolerance?

Drug tolerance means a diminished effect that a specific medication has on your body. Your body becomes resistant to it, in a way.

Imagine that you are in a bar with your friends, and after a couple of drinks, they become visibly drunk, while you don’t really feel the effect of alcohol, even though having as many drinks as your friends. This means that your body is not as affected by alcohol as it was before.

This happens not only with alcohol or illegal drugs. This is a common problem even with medications and therapeutic drugs. Moreover, there are different types of drug tolerance.

The tolerance can develop over a long period of time or even within just a few days.
You can develop tolerance towards many substances, such as alcohol, coffee, allergy medications, drugs, painkillers, nicotine, different opiates, etc.

Developing tolerance is not always a bad thing, because it is possible to become tolerant towards some negative side effects of a specific drug. Consider the case of people with allergies, for instance. During their allergy treatment, people are exposed to allergens in small quantities. As a result, they can become less sensitive over time.

However, in most cases it has negative consequences. Getting used to medications can make it necessary to increase the dose until it becomes dangerous for your health.

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Where Can You Buy Modafinil?

The market for nootropics such as Modafinil is in constant development. Right now, there are various medications containing Modafinil. Anyone can find an option within their preferable price range.

Buying Modafinil online has become a common practice over the past years. There are a number of pharmaceutical companies manufacturing products similar to Modafinil. The most popular ones are Modvigil and Modalert.

All of these medications promote concentration, enhanced agility and alertness. The price ranges approximately from eighty cents to one dollar per pill.

Modalert 200mg Modvigil 200mg Waklert 150mg Artvigil 150mg
Company Sun Pharma Hab Pharma Sun Pharma Hab Pharma
Core Ingredient Modafinil Modafinil Armodafinil Armodafinil
Price from $0.79 pr pill $0.99 pr pill $0.79 pr pill $0.99 pr pill
Dosage Between
50-200 mg per day
50-200 mg per day
50-150 mg per day
50-150 mg per day
Safety Some Reported Side Effects Some Reported Side Effects Some Reported Side Effects Some Reported Side Effects
Good for

Mental Focus

Mental Focus

Mental Focus

Mental Focus

Effect hours

Onset: 1hr

Peak: 6hr

Drop: 2hr

Onset: 2hr

Peak: 5hr

Drop: 3hr

Onset: 3hr

Peak: 8hr

Drop: 1hr

Onset: 2hr

Peak: 6hr

Drop: 2hr


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The Existing Kinds of Drug Tolerance You Can Develop

There are several types of tolerance you can develop towards drugs. Modafinil is one of the substances that can trigger tolerance development. The most common ones are these two kinds:

1. Pharmacodynamic Tolerance

This type of tolerance can also be called functional or dispositional. This means that receptors on the cellular level gradually become resistant towards the effects of a specific drug.

This happens because the amount of receptors binding to a certain drug decreases. Thus, the substance no longer triggers the receptors to its full power.

To have a better understanding of the situation, try to imagine that you are the boss of a company, and you have made a decision to allow your employees to visit your office without an appointment.

In the beginning, you will have some workers over to discuss their problems and answer their questions. However, eventually more and more of them will be coming, making it impossible to keep up.

In order to deal with the pressure, you will have to make a rule takeoff accepting visitors only on certain days. Thus, you will be able to keep track of everything that is happening.

2. Pharmacokinetic Tolerance

The second kind of tolerance is connected directly to metabolism. All the substances that we consume will have to go through the kidneys and liver at some point in order to be removed with urine or stool later. Modafinil is also one of these substances.

The most part of the responsibility for breaking down the substances, which we consume, is placed on our liver.

There are biological catalysts in the liver, which are called enzymes. They break down these substances into the soluble particles. Next, they are filtered by kidneys, then leaving our bloodstream.

Humans can physically adapt themselves to many things, and enzymes help us in that. They take into account everything we consume and its quantities.
Pharmacokinetic tolerance makes the substance in our system wash out much quicker.

Drinking alcohol is one of many examples. It is scientifically proven that people who often drink alcoholic beverages, especially in large quantities, tend to develop resistance towards it over time. This happens because our liver starts to decompose alcohol much faster. This way, it takes a lot more drinks to finally feel intoxication.


Can Modafinil Trigger Drug Tolerance?

A lot of research has been done on the effects that Modafinil can have on our bodies. However, it is still not completely clear whether Modafinil can trigger drug tolerance or not. There are cases of developing tolerance among Modafinil users, but at the same time, many users do not experience it.

If we break down Modafinil to its components, it is easy to presume that the medicine is able to cause drug tolerance. The same receptors, which are responsible for working with other drugs, connect with Modafinil.

One of the effects of Modafinil is increasing the levels of dopamine in our brain. Other substances with the same effect often can cause tolerance.

Certain studies suggest that many people tested did not develop a tolerance towards Modafinil.

Other sources, such as social media (New Yorker), claim that there are many examples of people getting tolerant towards this cognitive enhancer to a certain extent.

How to Deal With Tolerance Towards Modafinil

Understanding pharmacodynamic and pharmacokinetic tolerance can help us to distinguish the methods for minimizing the possibility of getting them.

1. Understanding How to Deal With Pharmacodynamic Tolerance

This kind of tolerance will not develop in a matter of days. Developing such tolerance requires taking a drug regularly and for a long time. Cells should be subjected to a certain substance at length in order for them to reconfigure the receptors.

If talking about Modafinil, it works with proteins, which transport dopamine.
The most effective method for this case is drug cycling. This means that you can take it for some time and then give it a break. For example, if you take Modafinil during working days, you should refuse taking it at the weekends. This goes for longer periods of time as well.

Within these days of rest, your dopamine levels will be able to reduce to normal. This way, the receptors will function as usual, and the possibility of developing tolerance will decrease.

2. Understanding How to Deal With Pharmacokinetic Tolerance

The cases of developing pharmacokinetic tolerance towards Modafinil occur much oftener than pharmacodynamic tolerance.

In order to prevent this kind of tolerance, it is necessary to understand, which enzymes are involved in breaking Modafinil down. This is a required procedure, which is done with every medication before selling them in most parts of the world.
The studies show that the main enzyme for working with Modafinil is Cytochrome P450 2C19. Upon an extensive use of Modafinil, this protein is produced in bigger quantities in order to keep up with the substance and to process it faster.

We can avoid developing tolerance by slowing down exactly this protein. There are a few plant-based inhibitors of this enzyme, such as thyme-leafed gratiola, common barberry, golden poppy, lilac chaste tree, etc.

The most efficient one is grapefruit. Fresh grapefruit juice helped many people to prevent tolerance.

Final Thoughts on Modafinil Drug Tolerance

There is still not sufficient scientific research on the topic. Many works suggest that Modafinil does not trigger drug tolerance. However, there are just as many cases of people sharing their experience online, which involves developing some type of tolerance.

The best way to stay on the safe side while taking Modafinil is by giving it a break regularly. You can minimize the possibility of developing tolerance by having regular days of rest from the drug. The same goes with other substances.

The personal experience of each Modafinil user will be different because it depends on many factors such as age, weight, lifestyle, etc. For someone, it is enough to take a break from this smart drug every other week. The others prefer taking a day-off every three or four days.

Another helpful method is taking medications or natural supplements, which slow down the metabolism. This way our liver washes down the substance at a faster rate. For this purpose, people often choose grapefruit juice or common barberry.

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