Thomas Thorne
If you recently used Modafinil but did not achieve the promised cognitive benefits, you may have developed: Tolerance to modafinil.
A common reason for developing a tolerance to Modafinil is repeated daily use for a set period of time (+14 days), which is a common trap that many Modafinil users fall into.
For this reason, it is imperative to find the perfect settings for your Modafinil cycle and dosage. Doing so will prevent the cognition-enhancing effects of modafinil from wearing off.
Additionally, there are numerous factors that cause the nootropic effects of modafinil to wear off after taking a standard dose of 100 to 200 mg.
This detailed guide will help you do two things: (1) Prevent Modafinil tolerance and (2) combat any Modafinil tolerance that may arise with frequent use.
You can choose to read this article in depth from start to finish or simply click on a section related to your specific situation.
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What is modafinil?
Before we get too deep into the topic of modafinil tolerance, let's take a small step back and talk about what modafinil is.
Modafinil is a prescription drug approved for the treatment of narcolepsy, shift work sleep disorder, and obstructive sleep apnea. If you bought it from an American pharmacy, you would probably see it labeled with their brand name "Provigil."
The common thread between the three conditions mentioned above is excessive daytime sleepiness, which Modafinil addresses by improving wakefulness.
This is the defining characteristic of modafinil and explains why it is so popular among healthy adults seeking cognitive enhancement. Long before it developed its reputation in the world of smart drugs, researchers were already using it to treat the fatigue present in medical conditions such as multiple sclerosis.1].
Biohackers and nootropic enthusiasts were curious to see if Modafinil's fatigue-reducing and wakefulness-promoting properties would be equally present in healthy adults without any sleep deprivation issues.
In other words, is it possible that an increased focus could be on unofficial, unauthorized use of the prescription drug?
Could Modafinil be the “magic pill” that improves cognition, increases productive performance, and gives any user the ability to work all night?
When you consider the growing increase in its unauthorized use in recent years, the answer speaks for itself [2]:
“The number of patients receiving modafinil increased almost 10-fold during the study period, from 57,768 in 2002 to 555,691 in 2009. Labeled use increased less than 3-fold, while off-label use increased more than 15-fold. .
Across all years, 89% of patients prescribed modafinil had no label diagnosis, and patients with depression and multiple sclerosis accounted for 18% and 12%, respectively, of all modafinil prescriptions.
So what we have here is a drug that can supposedly "supercharge" the mind to a heightened state of peak mental performance.
But if we could take it all the time without repercussions, we wouldn't have to worry about solving the Provigil tolerance problem.Or the possible side effects associated with taking Modafinil.
Modafinil Side Effects and Safety Concerns
Fortunately, modafinil appears to be a relatively safe drug, well tolerated and with few side effects.
The most frequently reported side effects of modafinil include insomnia, headaches, nausea, and dry mouth. Experienced test subjects conclusively agree that they are more common in first-time users. If these side effects do not go away after a few doses of Modafinil, they will usually go away after reducing the daily dose.
However, there are two rare but serious adverse events that you should be aware of:3]:
“Modafinil is associated with a very rare and life-threatening rash called Stevens-Johnson syndrome (SJS). Many medications are associated with this rash; in the case of modafinil it is so rare that we do not know if the medication causes it.
Modafinil contains a warning that may reduce the effectiveness of hormonal contraceptives, which lasts a month after suspending it.”
Most of the side effects of modafinil can be avoided by simply using it responsibly and not exceeding official dosing guidelines. This means never exceeding the standard dose of 100-200 mg of Modafinil per day.
It's no surprise that modafinil was announced as "the world's first safe 'smart drug'" back in 2015 [4]!
Can you develop tolerance to modafinil?
You may have the following question: Why does tolerance to modafinil develop in the first place and how can it be avoided?
The best way to answer this question is to explain the general concept of drug tolerance.5]:
“Tolerance is a person's decreased response to a drug, which occurs when the drug is used repeatedly and the body adapts to the continued presence of the drug...increasing doses must be taken to produce the same effect.
Tolerance usually develops because drug metabolism speeds up (often because liver enzymes involved in drug metabolism become more active) and because the number of sites (cellular receptors) to which the drug binds. drug or the strength of the bond (affinity) between the receptor and the drug decreases.”
Have you ever found yourself in a situation where you needed to drink three cups of coffee to feel like you did when you first drank coffee? That's drug tolerance in action.
To make matters worse, the development of drug tolerance is independent of time. That's why each person's response to alcohol is unique [6]:
"Onset of tolerance can occur within minutes, during a single exposure to alcohol (i.e., acute tolerance), or over longer periods of time and with prolonged exposure to alcohol (i.e., rapid or chronic tolerance). ".
As you can see, drug tolerance can become a major problem unless it is treated immediately with the right solution.
But the good news is this: the development of drug tolerance can be reversible.
A proven way to mitigate modafinil tolerance (and drug tolerance for select medications) is to take a “drug holiday.” Also known as a “medication holiday,” you refrain from taking medication for a predetermined period of time.
A drug holiday aims to achieve the following results [7]:
- Allowing a medication to regain its original effectiveness by “resetting” your sensitivity to it.
- Reduce your tolerance to a medication, eliminating the need to take higher doses to get the same effect.
- Reduce the severity and frequency of side effects associated with the medication.
Once we understand how drug tolerance works, let's see what scientific research has to say about developing tolerance to modafinil.
Understanding Modafinil Tolerance
The vast majority of studies published to date have not established a clear relationship between Modafinil and drug tolerance.
As early as 2001, researchers already knew that modafinil did not have much, if any, addictive potential. And even if this were the case, the behavioral changes would be different from the changes induced by central nervous system (CNS) stimulants.8].
Many more studies published since then confirm the absence of evidence on modafinil tolerance [9]:
“There is no evidence that tolerance develops to modafinil or that the drug affects sleep quality (if taken in the morning). “It has a number of advantages including once-daily dosing, low potential for abuse, and the fact that it is not a schedule II drug.”
For readers who are concerned about tolerance to modafinil developing over time, clinical trials have shown that patients generally do not develop tolerance to modafinil after 40 weeks of treatment.10].
Surprisingly, many Modafinil users are able to moderate their consumption without developing any type of tolerance [11]:
"There were also no significant differences in the final modafinil dose between patients who had a positive history of chemical abuse/dependence (290 mg/day) and those who did not (258 mg/day)."
"Adult patients with affective disorder, whether unipolar or bipolar, can use modafinil to relieve symptoms of depression, including fatigue and drowsiness, without risking a change in their mood or developing tolerance or abuse of this medicine".
In the few cases where tolerance to modafinil was present, it was usually in people who had a history of substance addiction. They ended up taking up to 1000 mg of modafinil a day, if not more, and those doses are not representative of how nootropic enthusiasts are likely to use modafinil [12].
Which brings us to an important distinction to make when citing these studies: Modafinil was not used as a smart drug to improve cognition in any of these studies.
Put another way, modafinil tolerance could be a real problem for people who rely on this smart drug, day after day.
There are several forum posts and articles written by casual users who have realized that they need higher doses of Modafinil to feel the same cognitive effect [13].
So while modafinil tolerance is unproven in scientific circles, it appears to be a real phenomenon in the unregulated world of nootropics.
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Tolerance types
Without adding further complexity to the discussion, there are three types of drug tolerance that you should be aware of [14]:
- Pharmacokinetic clearance: The amount of drug that reaches its target site is reduced as the body eliminates more of the drug.
- Pharmacodynamic tolerance: Either the number of receptors available for the drug to bind to is smaller or they function in a way where they do not respond to the drug.
- Behavioral tolerance: The individual learns to compensate for the effect of a certain drug, which in turn decreases said effect.
These three mechanisms occur simultaneously when tolerance to modafinil develops. One mechanism may be more common than the others, depending on the individual and their use of Modafinil.
In any case, the increased focus and energy that a Modafinil user experiences are not as strong as compared to the dose they first took. All the benefits just don't seem to exist, or exist to a much lesser degree.
But as we mentioned above, the development of drug tolerance is reversible in many cases. Your tolerance to modafinil can likely be resolved with some simple tips outlined in the next section.
How to control and minimize tolerance to modafinil | 7 quick tips
If you are considering taking Modafinil or think you may be developing a tolerance to the smart drug, here are some tips to consider.
They are not ranked in any particular order, so use your best judgment to decide which of these tips may be most relevant to you. We assume that you are using high-quality modafinil from a legitimate supplier, as impure and contaminated samples can cause unwanted results.
Don't develop any tolerance
While this is much easier said than done, a preventative and proactive approach is key to ensuring that you do not develop any type of tolerance to modafinil.
This will not be relevant to people who are new to using Modafinil or related compounds, since they do not have a “modafinil tolerance” in the first place.
If you find yourself in this situation right now, please keep in mind the following tips that will be shared. Many research subjects have found them to be effective in preventing tolerance to modafinil.
Limit use
As with any other nootropic out there, the key to taking modafinil successfully without developing a tolerance is to practice moderation.
Needless to say, taking excessively high doses of Modafinil for several days or weeks in a row will likely result in the development of tolerance to this smart drug.
Here are some rules we follow to use Modafinil as a smart drug responsibly:
- We do not take Modafinil more than 4 times a week. 1 or 2 days a week works best.
- Our daily dose for best results is 100 to 200 m. We will never take more than 200 mg in a single dose.
Following the two previous rules allows us to avoid tolerance problems with Modafinil.
Never on consecutive days
Expanding on the previous recommendations, we avoid taking the drug on consecutive days. If we take Modafinil 4 days a week, we want to space our doses by at least one day.
So if we take Modafinil on a Monday, we will wait until Wednesday to take it again.
By not taking Modafinil on consecutive days, we ensure that the effects of the medication remain strong.
People who develop major problems with tolerance and smart drugs end up abusing them. This means taking the same nootropic every day at abnormally high doses and then increasing the dose even further when the drug "stops working."
Take breaks
If we have been using Modafinil 1-4 days a week for a few months in a row, we will take a break from the smart drug.
Many research subjects who use the nootropic 1 or 2 times a week for about two months straight will stop taking Modafinil completely for two full weeks.15]:
“…it takes 3 to 7 days for tolerance to halve and 1 to 2 weeks to return to baseline (in the absence of increased consumption).
Modafinil may be cross-tolerant to all benzhydryl nootropics, meaning that after consumption of modafinil, all related eugeroic compounds, such as armodafinil and adrafinil, will show a reduced effect.”
By not consuming the nootropic for two weeks in a row, your body will likely automatically reset its tolerance levels to Modafinil. After a break from modafinil, users typically feel the strength of the smart drug restored when they begin using it again.
A break of 1 to 4 weeks is usually sufficient to restore tolerance to modafinil.
Some users personally prefer a “two weeks on, two weeks off” cycle where Modafinil is used in cycles. This approach allows you to experience maximum cognitive benefits while avoiding developing tolerance to modafinil.
Alternatively, users may decide to reserve Modafinil use for emergency events (late nights, night work shifts, tight deadlines, etc.).
Smart medication cycle
Despite Modafinil's reputation as the only nootropic one may need, smart and experienced drug users will alternate using smart drugs.
This allows them to avoid becoming 100% dependent on Modafinil or any smart medication.
There are many excellent Modafinil alternatives for users looking for a different type of cognitive boost.
NOTE: If you decide to use Armodafinil (also known as Nuvigil) instead of Modafinil, know that tolerance to Armodafinil is also possible. We found that the tips in this guide are equally effective in eliminating any type of tolerance to Nuvigil.
Limit other drugs and stimulants
In addition to rotating nootropics periodically, it is highly recommended to avoid using other smart medications with Modafinil on the same day.
This means that if you are taking Modafinil one day, you should not also take something like Mind Lab Pro the same day
The same rule applies to stimulants. Combined with modafinil's wakefulness-promoting properties, the increased energy levels may be too overwhelming for some users.
Other users have had mixed results using Modafinil and fresh organic coffee (1-2 cups maximum) the same day, but that's as far as our personal recommendations end.
Magnesium supplement
There is some experimental data that suggests that magnesium supplementation can reduce tolerance levels to addictive drugs [16]:
“Magnesium reduces the intensity of addiction to opiates and psychostimulants (cocaine, amphetamines, nicotine and others).
It also reduces cocaine self-administration and relapse in cocaine and amphetamine use, in addition to reducing experimental addiction to morphine, cocaine and other substances in animals.
…Apart from the action of magnesium ions during emerging addiction, the administration of this cation after the onset of withdrawal syndrome reduces the intensity of clinical symptoms.”
If you have already developed problems with dosing and tolerance, then supplementing with magnesium and discontinuing its use may be an option worth considering to reestablish your tolerance to modafinil.
There are many ways to consume magnesium and it appears that magnesium oil may be the easiest form of administration for most people.
BONUS TIP: Be aware of which enzymes are affected by modafinil
Modafinil is metabolized in the liver by the enzyme CYP3A4, but appears to affect other enzymes during the metabolization process.17]:
“…modafinil has the potential to inhibit CYP2C19, suppress CYP2C9, and induce CYP3A4, CYP2B6, and CYP1A2.
Because modafinil and modafinil sulfone are reversible inhibitors of the drug-metabolizing enzyme CYP2C19, coadministration of modafinil with drugs such as diazepam, phenytoin, and propranolol, which are largely eliminated through that pathway, may increase circulating levels. of those compounds.”
When an enzyme is inhibited, its metabolic efficiency decreases. If a drug is normally metabolized by such an enzyme, more of the prodrug (usually the inactive form of the drug) and the active form of the drug will be present. Therefore, an individual will feel the effect of the drug "less."
Vice versa, an induced enzyme is metabolically more efficient. There will be more active drug present in your body and you will feel “more” of the drug's effect.
Check the product information with any supplements or additional medications you are taking to see if the enzyme-affecting properties of modafinil will affect its distribution in your body.
To demonstrate with an example, grapefruit is a strong inhibitor of CYP3A4. Since Modafinil itself is the active drug, it is broken down less and you are likely to experience a more powerful boost in cognition.
Modafinil tolerance | The verdict
Modafinil tolerance It may not be commonly reported in the scientific literature, however it appears to be a common occurrence among people who use the drug.
But a developed tolerance to modafinil can be reversed by using an appropriate dosage and taking it infrequently.
The tips discussed in this article will help you decide what the best course of action should be based on your circumstances.
Whether you're new to using Modafinil or have extensive experience with the smart drug, preventing tolerance is key to maximizing its benefits.
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