Modafinil Not Working? Here’s What You Need to Do

Although not a common occurrence, some modafinil users find the drug doesn’t seem to kick in as it should.

This is more common with people who use modafinil regularly — but it can also happen in new users.

Luckily, there are a few tricks you can use to get your modafinil working if this happens to you.

We’ll go over why your modafinil may not be working, and offer 5 tips you can use to fix it.

What is Modafinil?

Modafinil is a popular study drug.  It works by promoting wakefulness and boosting dopamine concentrations in the brain. The effects of modafinil can be compared to caffeine but last much longer and work better for inducing states of focus & concentration.

Modafinil is a prescription-only medication, used primarily for conditions like ADHD and narcolepsy. It’s very similar to other drugs used for this, like Adderalland Dexedrine, but comes with far fewer side effects.

Off-label use is becoming increasingly popular in developed countries. It’s used as a general productivity enhancer and to help users stay awake on long overnight work or study sessions.

People also use it to get over jet lag when traveling to other time zones and to improve many of the health issues that result from alternating day and night shift work.

How to Get Modafinil

In most countries, modafinil is technically a prescription-only medication. There are ways you can buy it online, however.

Most countries have this same classification, including; The United States, Canada, Australia, The United Kingdom, Singapore, Ireland, and a number of other countries.

Laws are different in other countries, such as India — where modafinil isn’t regulated and can be sold legally without a prescription. 

This allows users to buy their modafinil from online sources, based out of countries with looser laws on the sale of medications.

There are a couple of different reasons why your modafinil may not be working. They can be grouped into two categories depending on who is experiencing them — new users or long-term users.

1. Modafinil Not Working for New Users

Have you tried modafinil a few times and found it doesn’t give you the boost that was promised when you bought them?

There are a few things you can try before looking for a different nootropic, but first, it’s important to understand why it might not be working in the first place.

A) Poor Quality Modafinil

Depending on where you’ve purchased your modafinil, you may have received low-quality modafinil that isn’t capable of producing effects.

This is more common than you’d think and is the reason why we recommend always ordering your modafinil from high-quality, trusted vendors.

The unfortunate truth is that there are a lot of scam websites and companies with poor integrity in the modafinil space due to its unregulated nature. Companies often ship expired or inactive modafinil tablets.

How To Fix It:

If you think your modafinil tablets were faulty, the simplest fix is to order a new batch from a reputable source. Otherwise, you could try and have a friend test it to see if it works on them or not.

The best way to test if the drug is active or not is through something called Thin Layer Chromatography (TLC).

If you’re really determined, you can make your own TLC testing kits to test for the active constituents (not for the faint of heart).

We recommend this DIY TLC test kit if you want to give it a shot.

B) Insufficient Dosage

The standard dose for modafinil is 200 mg. However, some online sources are selling doses as low as 50 mg. It’s relatively common for people to order these 50 mg tablets thinking this is the standard dose — and have it not produce any noticeable effects.

In other cases, even the 200 mg dose is too small. This is especially true for people with larger than average builds.

Think of your body like a lake. When you take a medication or supplement, it gets diluted into this lake. If the lake is very small, there will be much higher concentrations of the drug in the water. Conversely, if the lake is large, the drug will become less concentrated when dissolved into a larger body of water — therefore producing fewer effects.

Learn more about dosing modafinil.

How To Fix It:

Take a look at the tablets you’re using, what’s the dose?

If the dose on the tablet is only 50 mg or 100 mg, and you’re an average sized person, you’ll likely need to increase the dose to produce any meaningful effects

Many people also find improvement when they upgrade from modafinil to the stronger version — armodafinil. The most popular armodafinil products are Artvigil and Waklert.

Aim for around 200 mg of modafinil or 150 mg of armodafinil.

Likewise, if you’re a larger person and the 200 mg dose isn’t doing enough for you, try using a larger dose. If this is the case, it’s recommended that you move up in dosage gradually by breaking a dose in half for the next one so that you’re at 300 mg, before graduating to a double dose of 400 mg.

If effects still aren’t felt at 400 mg, you most likely have either low-quality capsules, or your body needs extra help to experience the effects of the modafinil.

Which brings us on to the next point…

C) Genetic Polymorphisms (Issues With Drug Metabolism)

The field of genomics has exploded over the past several years. Since the completion of the human genome project — which mapped out the entire human genome — our understanding of how different genes affect our health has grown exponentially.

Genetic polymorphisms are unique variations of a particular gene. It’s what makes people have different hair and eye colors, and can affect many other functions of the human body as well.

Some genetic polymorphisms affect the way we metabolize drugs in the liver, some allow us to metabolize them faster (thus inactivating them quickly), and others cause metabolism to be slower than average (making the effects last much longer).

Have you ever met someone who seems to be easily affected by caffeine or alcohol? Or perhaps someone who can drink coffee or alcohol for hours and remain relatively unaffected?

These are both likely to be the result of genetic polymorphisms affecting the way they metabolize these compounds.

Like most drugs, when modafinil enters the body, we immediately begin breaking it down in the liver. Luckily, modafinil resists this breakdown, allowing it to remain in circulation for about 10-15 hours.

Eventually, all the modafinil is broken down by these enzymes in the liver and excreted in our urine. Only about 10% of a modafinil dose leaves the bladder intact; the rest is excreted as the inactive metabolite known as modafinilic acid [1].

Each of these enzymes is coded for by particular genes — some of which have well-known polymorphisms. The main genes responsible are CYP2C19, CYP3A4, and CYP2D6. [1].

How to Fix It:

We cannot change our genes. That is until technology like CRISPR become more widespread of course, but that’s a topic for another article. In general, it’s safe to say that we can’t change our genes.

What we can do, however, is combine modafinil with other supplements that slow down its metabolism.

There are many plant extracts that change the metabolic activity of our liver that can be used to boost modafinil’s effects. It should be noted that if attempting this, you are doing so at your own risk.

It’s also not recommended that you inhibit the metabolism of any particular drug for too long. Taking weekly breaks from the drug is highly recommended if using any of these methods.

1. GRAPEFRUIT JUICE

Grapefruit juice (the real stuff — not grapefruit flavored juice) has been shown to reduce the activity of all CYP450 genes associated with modafinil [2].

It’s the simplest way to reduce the rate of metabolic breakdown of modafinil.

The compounds responsible for these effects are only found in true grapefruit juice, preferably freshly squeezed from the fruit. Store bought grapefruit juice may also do this, but is of much lower quality.

2. BACOPA (BACOPA MONNIERI)

Bacopa is a popular herbal nootropic with known inhibitory effects on all 3 of the main modafinil metabolism genes [3].

It’s an excellent companion supplement for those experiencing poor effects from the medication.

3. BERBERINE-CONTAINING PLANTS

This includes Barberry (Berberis vulgaris) and Goldenseal (Hydrastis canadensis).

Berberine is a compound found in a variety of plants. It’s popular as a health supplement with mild nootropic effects. On top of this, however, berberine inhibits the CYP450 enzymes responsible for modafinil breakdown [4, 5].

Berberine is usually sold as a nootropic and for treating infections in the digestive tract due to its broad antibacterial benefits.

D) Inactivation by Other Compounds

Another reason modafinil might not be working is due to interactions with other foods/supplements/medications in the gut.

Some compounds can actually bind to medications like modafinil, and prevent them from being absorbed into the body.

Modafinil only has a 40-65% absorption rate on its own [6]. Anything that further reduces the bioavailability of modafinil can lower the effects the drug has on the body.

Many people take their supplements first thing in the morning — all at the same time. This mixes the compounds together as they dissolve in the stomach, and can neutralize them before they ever make it into the bloodstream.

A good example of inhibitory compounds are demulcents and prebiotics.

These are popular health supplements used in health promotion. They can be bought at supermarkets or over the counter at drug stores. They work by forming a slimy coating over the gastrointestinal lining. This is hugely beneficial for repairing damaged areas of the gut, but also block the absorption of other compounds — including modafinil.

If demulcents like slippery elm or inulin are taken at the same time as modafinil, it’s likely they’ll block the absorption of the drug.

Other compounds may neutralize modafinil by binding to it in the stomach and carrying it through the digestive tract unabsorbed.

When people overdose on drugs, a similar technique is used to prevent absorption of more of the drugs from the intestinal tract. Activated charcoal is used to bind to these drugs and prevent them from being absorbed into the bloodstream. The same can happen with other compounds as well.

Things like tannins from green and black tea are especially known for doing this.

EXAMPLES OF COMPOUNDS THAT MAY NEUTRALIZE MODAFINIL:

• Inulin
• Slippery elm bark
• Marshmallow mucilage
• Fiber supplements
• Licorice (Glycyrrhizin)
• Cellulose
• Green tea
• Black tea
• Many herbal teas
• Activated charcoal
• Antacids

How to Fix It:

Avoiding this problem altogether is very simple; take your modafinil at least an hour apart from all your other supplements.

Most compounds will be either absorbed or move far enough down the digestive tract to avoid complications within about an hour.

Ideally, modafinil is taken on an empty stomach first thing in the morning, followed an hour later by a nutritious meal and some water.

If you’re taking other medications, it’s highly recommended that you consult with a doctor or pharmacist before mixing modafinil.

Not only can the drugs negate the effects of modafinil, but the modafinil may negate the effects of these drugs. If you need these medications to survive, you don’t want to risk neutralizing them.

2. Modafinil Not Working for Long-Term Users

For long-term users, any of the issues described above may also happen. However, there’s another important factor to consider if taking modafinil for longer periods of time.

Drug Tolerance

Drug tolerance with modafinil is fairly controversial. There are plenty of studies published in peer-reviewed journals that have shown that modafinil doesn’t produce tolerance.

However, it’s also a common issue reported by users who take modafinil on a regular basis.

Therefore we have to consider the fact that despite a lack of scientific agreement, tolerance is possible.

Learn more about modafinil tolerance to get some tips and tricks you can try to prevent or reverse tolerance to modafinil.

How To Fix It:

Tolerance happens when the body becomes used to a drug and stops responding to it. The easiest way to fix this is to take periodic breaks from the drug.

This usually takes a few days, but can be as much as a month. It depends on the dose you were taking and how long you were on the drug without breaks.

Preventing tolerance in the first place requires the same method. Many users will take a day off per week or 1 or 2 weeks off per month.

This is usually enough to prevent tolerance from forming.

Summing it all up

In the vast majority of cases, modafinil works as advertised and is a fairly reliable drug.

If it’s not working, there are a few things you can consider and make adjustments to that will usually correct the problem.

Poor quality tablets, fast drug metabolism, other medication/supplement interactions, and insufficient doses are all suspect. For long-term users, you also need to consider the possibility of tolerance to the drug.

The best way to avoid most of these issues is to source your modafinil from a reputable supplier and take a daily 200 mg dose of modafinil at least an hour away from food and other supplements or medications.

It’s also recommended that you take periodic breaks from the drug to avoid the development of drug tolerance.

References

1. Robertson, P., & Hellriegel, E. T. (2003). Clinical pharmacokinetic profile of modafinil. Clinical pharmacokinetics, 42(2), 123-137.
2. Tassaneeyakul, W., Guo, L. Q., Fukuda, K., Ohta, T., & Yamazoe, Y. (2000). Inhibition selectivity of grapefruit juice components on human cytochromes P450. Archives of biochemistry and Biophysics, 378(2), 356-363.
3. Ramasamy S, Kiew L. & Chung L. (2014). Inhibition of Human Cytochrome P450 Enzymes by Bacopa monnieri Standardized Extract and Constituents.Molecules, vol.19(2),p.2588-2601.
4. Guo Y, Chen Y, Tan Z, Klaassen C. & Zhou H. (2012). Repeated Administration of Berberine Inhibits Cytochromes P450 in Humans.European Journal of Clinical Pharmacology, vol.68(2),p.213-217.
5. Guo Y, Pope C, Cheng X, Zhou H. & Klaassen C. (2011). Dose-response of berberine on hepatic cytochromes P450 mRNA expression and activities in mice.Journal of Ethnopharmacology, vol.138(1),p.111-118.
6. Wong, Y. N., King, S. P., Simcoe, D., Gorman, S., Laughton, W., McCormick, G. C., & Grebow, P. (1999). Open‐label, single‐dose pharmacokinetic study of modafinil tablets: influence of age and gender in normal subjects. The Journal of Clinical Pharmacology, 39(3), 281-288.