What to Do When Modafinil Doesn’t Work

Some nights, you have no other option than to burn the midnight oil. When deadlines or exams come up, sleep often falls to the wayside.

Many people look to the stimulant modafinil to get them through those times. It is, after all, a powerful wakefulness-promoting agent that can help you focus, stay on task, and be more productive than ever on very little rest (1).

You should start feeling the drug’s effects within 60 minutes after taking it (2). But what if, after that time has passed, you feel no different than before? Though rarely, modafinil not working does happen.

It this describes your experience, don’t give up yet. There is a fix for everything.

Why Doesn’t Modafinil Work?

There are a few reasons why you may find that modafinil doesn’t work for you. The causes and their solution can differ depending on whether you’re a first-time or a long-term user.

Modafinil Not Working for New Users

The vast majority of people who take modafinil for the first time will experience its benefits without any issues. That may, however, be of little comfort if you’re one of the unlucky few who don’t fall into that group.

If you don’t feel like modafinil is working, here is a list of several things which may be the cause and how you can go about fixing them.

Low-Quality Modafinil

Some people get modafinil at their local pharmacy. Others get it online. In both cases, the product should and most often will be of high pharmaceutical quality.

However, once in a blue moon, and especially if you buy on the internet, you may end up stuck with sub-par modafinil incapable of doing anything. It could be that the compound is inactive. It could also simply be that the product is expired.

Quality is the main reason why it’s critical to buy modafinil from reputable sellers, and reputable sellers alone. Sadly, at any given time, there are plenty of scam websites and vendors with zero integrity looking to take advantage of anyone they can.

How to Fix It

If you suspect the modafinil you bought is defective and are now questioning the quality of the seller, simply get another batch from a different (and this time reputable) source.

If, however, your modafinil vendor already comes highly recommended, they should stand behind their product. Most will be happy to either give you a full refund or re-ship your order. Vendors like ModafinilXL fall into this category.

And if you ever want to be absolutely sure of the level of quality before taking further action, you can use a TLC (Thin Layer Chromatography) test kit to test the modafinil yourself. It’s an easy thing to do that will tell you exactly what’s going on.

Too Small a Dose

Another frequent cause of first-time modafinil users not finding the drug being effective is taking too little of it.

The standard modafinil dose is 200 mg. It’s not unusual to find some online stores offer pills that are 100 mg or even 50 mg.

These smaller sizes are mostly sold for convenience. Many modafinil users like to fine-tune the amount they take, and buying lower dosage pills is often preferable to having to split tablets yourself.

That said, for the average person, taking a single 50 mg pill may not be enough to notice any significant effects.

Even if you’re taking the recommended 200 mg, that may still be insufficient depending on your build. People with larger frames often need to take a higher modafinil dose to experience its benefits fully.

How to Fix It

Go back to the pills you’re taking and double check how much modafinil they contain. If the amount is on the lower side (50 mg or 100 mg), try going up to at least 200 mg.

Assuming you’re already taking the recommended 200 mg but still not feeling much, try increasing the dosage in 50 mg increments per week.

However, pay attention to possible side effects (stopping if you start to experience any). Also, do not exceed 400 mg. Research shows that doses larger than that don’t give you any additional benefits, but do increase the chance of adverse effects (3).

Another option you have is to use armodafinil instead. Armodafinil is a stronger version of modafinil (4), and some people have better luck with it. Its standard dose is slightly lower at 150 mg, and the maximum you should take is 250 mg. Any online seller of modafinil will carry armodafinil too.

If even after gradually increasing the dosage of modafinil to 400 mg (or armodafinil to 250 mg) you’re still not feeling any effects, something else that could be at fault is your metabolism.

Modafinil Metabolized Too Quicky

Some people can drink vast quantities of alcohol without being affected by it. That’s genetics and, more specifically, metabolism at work. The liver is capable of metabolizing the alcohol faster than average, reducing its effects in the process.

And while having a fast metabolism sounds ideal if you want to drink your coworkers under the table, it may not be that helpful when you want a drug you’re taking to be effective.

Modafinil typically has a half-life of around 12 hours (5). It remains active in your body for that long until it is broken down by enzymes in your liver and excreted through urination.

Twelve hours is a good amount of time to get in a full day’s (or night’s) work. If you happen to have a faster metabolism, however, odds are the drug will be active for much shorter. In other words, you will not be getting its full effects.

How to Fix It

If you’re not getting the most out of your modafinil because of your fast metabolism, then the logical solution is to slow your metabolism down.

There are several substances which can do precisely that. They will decrease the metabolic function of your liver and allow you to feel stronger modafinil effects as a result.

Do note, however, that slowing down your metabolism when taking modafinil is not without its potential risks. You may end up both eating less and depriving yourself of sleep.

In general, it’s also not a great idea to alter how your body metabolizes any drug for too long. If you do end up using this method, be sure to take breaks and take them often (at least several times per week).

That all said, here are three common substances which can slow down your metabolism.

1. Grapefruit Juice

   Hands down, the simplest way to slow down the metabolic breakdown of modafinil is to drink grapefruit juice.

   What you use should be 100% pure grapefruit juice, not flavored drinks that only contain trace amounts of it. In fact, it’s preferred you squeeze the juice yourself straight from the fruit. Store bought products will often not be nearly as effective.

   As odd as this method may sound, research has show grapefruit juice to inhibit cytochrome P450 enzymes (6) which are tied to drug metabolism (7).

2. Plants Containing Berberine

   Berberine is a chemical compound found in several plants. Much like grapefruit juice, it too can slow down cytochrome P450 enzymes (8)(9) and reduce the metabolic breakdown of modafinil.

   Because berberine can increases levels of several neurotransmitters, including dopamine (10), it’s commonly available as a nootropic supplement. The compound is usually extracted from either barberry or goldenseal.

3. Bacopa Monnieri

   Bacopa, another very popular supplement, has also been shown to inhibit cytochrome P450 enzymes (11) and should slow down how quickly your body metabolizes modafinil.

   In fact, due to its unique nootropic properties, Bacopa monnieri is often stacked with modafinil to both enhance it’s benefits and reduce the chance of side effects (12).

Interaction With Other Compounds

Another reason you may not feel modafinil working is if it interacts with other compounds in your body. These could be anything from food to supplements to other medication.

On its own, modafinil has an absorption rate of around 60% (13). However, many substances can bind with it making it more difficult for your body to absorb and further lowering the strength of its effects.

It’s not uncommon to take any supplements you may be using all at once and first thing in the morning, around the same time you’re most likely also to take modafinil.

If that’s something you do, your body will process all those compounds at the same time and mix them. If any of them interact with modafinil, they may neutralize it before it ever gets a chance to do its job.

Demulcents like slippery elm, for example, may adversely affect the absorption rate of modafinil. It’s a supplement which reduces bowel inflammation by forming a soothing film on the lining of the stomach and the intestines. This lining may prevent modafinil from making it out of your digestive tract.

Activated charcoal is another substance which may inhibit modafinil (14). It can bind to it and also prevent it from being absorbed.

Plenty of other compounds may have a similar effect too. Tannins, something every type of tea contains, is another such example.

How to Fix It

The easiest way to prevent other compounds from interfering with modafinil is to take it on an empty stomach.

You don’t have to wait long after ingesting it before you can eat. An hour should be plenty. That will give modafinil enough time to be processed by your digestive system and be adequately absorbed before anything has a chance to impede it.

Alternatively, you can try to reduce the consumption of any food which can interfere. Avoiding all of the following should make modafinil more effective:

• Antacids
• Activated charcoal
• Cellulose
• Fiber supplements
• Inulin
• Licorice
• Marshmallow mucilage
• Slippery elm
• Tea (black, green, and herbal)

On a related note, if you’re using any other medication, you should talk with your physician before taking it and modafinil at the same time.

Interaction is a two-way street. Just like another substance may make modafinil less effective, it too can negate the effects of certain medication.

Since you’re probably taking the other meds for a reason, neutralizing them may not be the best idea.

Modafinil Not Working for Long-Term Users

It’s not uncommon to hear someone who’s been using modafinil for a while say it’s no longer as effective as it was when they first started using it.

Any of the reasons for reduced modafinil effectiveness with new users described above are valid for long-term users as well. But, there is also one other significant thing that may be happening.

Modafinil Tolerance

Modafinil tolerance is a somewhat controversial subject. Research concludes that it simply doesn’t happen (15). But, there is also a lot of anecdotal evidence which contradicts those studies (16)(17).

If you find modafinil is no longer working well, and have eliminated any other possible cause, tolerance is something you should consider.

How to Fix It

Tolerance to any drug happens when your body gets used to and stops responding to it. In the case of modafinil, there are several things you can do to avoid it.

1. Space out Use

   Don’t take modafinil every single day. Use it between one and four times per week or less, and try to avoid taking it on back-to-back days.

2. Use Smaller Doses

   For some people, modafinil doses as low as 50 mg may be enough to achieve the desired effects. If that’s you, there are very few reports of low doses leading to tolerance and plenty of reports to the contrary (18).

3. Cycle the drug

   After taking modafinil regularly for a while, take some time off (for example, one week off after four weeks of use). Follow this patter regularly to give your body a break.

Some of these methods will work better for you than others, but they’re all worth trying.

Even if you don’t feel you’re developing a tolerance, it may not be a bad idea to follow the above advice regardless. You may even find modafinil working stronger than ever after taking a bit of time away from it.

Conclusion

Modafinil is an immensely helpful drug that can make any time you spend studying or working much more productive. Using it doesn’t carry a lot of risks, which is why so many people turn to it.

Unfortunately, there are times when you may find modafinil not working as expected. Many things can cause that, from a poor quality product and insufficient dosage to metabolism issues and even tolerance buildup.

The good news is that each of those causes has a potential solution. Always buy modafinil from a good source, try to avoid mixing it with other supplements or certain foods, or simply take a break for it. Any and all of these things can make modafinil work better.

References

1. Dongsoo Kim. Practical Use and Risk of Modafinil, a Novel Waking Drug. Environ Health Toxicol. 2012; 27: e2012007.
2. Maddalena Mereu, et al. The Unique Psychostimulant Profile of (±)-Modafinil: Investigation of Behavioral and Neurochemical Effects in Mice. Eur J Neurosci. 2017 Jan; 45(1): 167–174.
3. Richard B Berry. Fundamentals of Sleep Medicine. 2012, Pages 451-479.
4. David E McCarty. Ready for takeoff? A critical review of armodafinil and modafinil for the treatment of sleepiness associated with jet lag. Nat Sci Sleep. 2010; 2: 85–94.
5. C. Ballas, D.F. Dinges. Stimulant and Wake-Promoting Substances. Encyclopedia of Neuroscience. 2009.
6. Tassaneeyakul W, et al. Inhibition selectivity of grapefruit juice components on human cytochromes P450. Arch Biochem Biophys. 2000 Jun 15; 378(2): 356-63.
7. Tom Lynch, et al. The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects. Am Fam Physician. 2007 Aug 1; 76(3): 391-396.
8. Guo Y, et al. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012 Feb; 68(2): 213-7.
9. Guo Y, et al. Dose-response of berberine on hepatic cytochromes P450 mRNA expression and activities in mice. J Ethnopharmacol. 2011 Oct 31; 138(1): 111-8.
10. Bombi Lee, et al. Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder. Korean J Physiol Pharmacol. 2018 Mar; 22(2): 183–192.
11. Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules. 2014 Feb 24; 19(2): 2588-601.
12. u/arch56. Bacopa and adrafinil/modafinil? Retrieved March 6, 2019, from https://www.reddit.com/r/StackAdvice/comments/3q38yf/bacopa_and_adrafinilmodafinil/
13. Seiji Nishino, Emmanuel Mignot. Wake-Promoting Medications: Basic Mechanisms and Pharmacology. Principles and Practice of Sleep Medicine (Fifth Edition). 2011; Pages 510-526.
14. Shaun D Carstairs, et al. A Retrospective Review of Supratherapeutic Modafinil Exposures. Journal of Medical Toxicology. 2010; 6: 307.
15. Mitler MM, et al. Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med. 2000 Jul 1; 1(3): 231-243.
16. u/howardroark16. Modafinil tolerance. Retrieved March 6, 2019, from https://www.reddit.com/r/afinil/comments/2ffwmj/modafinil_tolerance/
17. u/jyot5. Anyone succeeded in reversing Modafinil tolerance, specifically its nootropic effects? Retrieved March 6, 2019, from https://www.reddit.com/r/afinil/comments/8bp0kt/anyone_succeeded_in_reversing_modafinil_tolerance/
18. u/exe_calibre. Keeping Tolerance Low (Armodafinil/Modafinil). Retrieved March 6, 2019, from https://www.reddit.com/r/afinil/comments/6kwlho/keeping_tolerance_low_armodafinilmodafinil/