Modafinil is a non-stimulant wakefulness enhancer that’s used clinically to treat disorders that make you sleepy or obstruct your normal sleep cycle. It offsets the grogginess caused by obstructive sleep apnea, narcolepsy, and other related conditions. In addition to its medical use, modafinil is increasingly used by college students and entrepreneurs to increase productivity and intellectual performance.
It’s important to consider drug-drug interactions when taking modafinil. Modafinil can even interact with certain foods. In this article, we’ll discuss the effects of combining modafinil with various substances, so that you can safely get the most out of your modafinil use.
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Modafinil with Food & Drinks
Some drugs interact dangerously with specific foods. The old school class of antidepressants called irreversible MAO inhibitors (e.g.tranylcypromine) cannot safely be consumed with foods containing tyramine (like cheese) .
Unlike MAO inhibitors, there aren’t any dangerous modafinil-food pairings . The only issue you should be aware of is that consuming modafinil with foods can delay the absorption, though overall bioavailability of the drug is unaffected . It’s estimated that modafinil absorption is delayed about one hour if it’s coadministered with food .
Interestingly, consuming armodafinil with food delays the time to peak concentration by about 2-4 hours . (For the uninitiated, armodafinil is the more biologically active enantiomer of modafinil).
Modafinil With Caffeine
Caffeine the archetypal nootropic drug. It’s the most widely consumed psychoactive substance in the world. Given that so many people drink coffee, it’s worth asking: Modafinil with Caffeine; is it safe and how do the two drugs interact?
Here’s all you need to know:
Modafinil and caffeine are both stimulating, so combining the two can increase anxiety and proneness to panic attacks. For this reason you should exercise caution. If you normally drink 3 cups of coffee a day, try only drinking one cup with modafinil if you’re dead set on this combination.
Here’s what one Reddit user had to say about the combination: “Caffeine is a really good booster shot to modafinil. My recommendation is 200mg and a cup of coffee in the morning. Then if you feel like your lagging towards the end of the day, a pro plus would sort you out. Remember to stay hydrated. There will be undesired effects like head aches and dizzy spells if you dont drink alot of water. I usually drink 4L on a day with 200mg of Modaf and maybe 200mg of caffeine. Have fun.”
Interestingly, modafinil can increase the rate of metabolism of caffeine. Modafinil is a CYP3A4 inducer. CYP3A4 is an enzyme in your liver that metabolizes all kinds of drugs and toxins. Since CYP3A4 also metabolizes caffeine, and this enzyme is induced by modafinil, it makes sense that modafinil can increase the clearance of caffeine .
Modafinil and Coffee
I personally take modafinil with a cup of coffee in the morning. My verdict is that modafinil synergizes with coffee extremely well.
Some people might be overstimulated by this combination, or get heart palpitations and other undesirable cardiovascular side effects. However, my experience has been that modafinil with coffee provides the optimal level of mental stimulation.
You might know from the Yerkes-Dodson law (see above) that there’s an ideal level of arousal to facilitate learning and memory. If you’re an anxious person by nature, coffee plus modafinil could actually impair performance by shifting your arousal along the x-axis. This point is relevant because it underscores how differences in individual neurophysiology can affect responses to different drugs.
There’s an important reason I prefer to take modafinil alongside coffee instead of caffeine along (e.g. as a powder). Coffee contains a blend of numerous antioxidants, including hydroxycinnamic acids, alkylmethoxyphenols, alkylphenols and other polyphenols. You can check out the exact antioxidant composition of coffee using the Phenol-Explorer. This antioxidant blend is neuroprotective, and may prevent dopaminergic neurons from working too hard and become damaged. The evidence for this is the putative inverse relationship between lifetime coffee consumption and the risk of Parkinson’s disease [3.5].
Modafinil and Alcohol
Mixing stimulants and alcohol is generally un-wise, though there is no outright contraindication. Modafinil isn’t technically a psychostimulant (this is one of the ways that it’s different from, say, Adderall). However, modafinil does have stimulant-like effects.
The reason that it’s not a good idea to take modafinil with alcohol is that you’ll underestimate how intoxicated you are. RaroRabble on Reddit noted the following on mixing modafinil with alcohol:
“Drinking on Madafinil effectively allows me to drink as if I were 22 again. For some reason only when taking it prior to drinking. I do not get the same effect if I have been drinking then take it. I can only relate it to ya know when you take Madafinil to stay awake and you sometimes can feel that your body is tired but your mind just doesn’t want to sleep. Just like that you can feel your body is drunk but your mind doesn’t want to be. Your clear minded, smooth and articulate while drinking heavily. You most often will not feel drunk but if you pay attention you can tell you are. Definitely a blackout cure as well.”
People who use alcohol and cocaine, for example, are much more likely to get alcohol poisoning. That’s because cocaine counteracts some of the depressant effects of alcohol, which tricks your brain into ingesting more than you would overwise. Many papers have also noted that modafinil reverses some cognitive deficits associated with chronic alcoholism .
Modafinil with Drugs
As always, it’s extremely important to be conscientious of drug-drug interactions. Modafinil is actually an inducer of three hepatic (liver) enzymes: CYP1A2, CYP3A4, and CYP2B6 . This means that modafinil will increase the expression of these enzymes, which can decrease the effectiveness of drugs that are metabolized by them. Drug interactions can be complex and difficult to comment on due to individual genetic differences in the user. This is a general guide, it is not to be taken as medical advice.
Modafinil with Adderall
Adderall is probably the most prescribed medication for the treatment of ADHD. It’s a powerful dopamine releasing agent. Interestingly, there’s some promising evidence that Adderall enhances recovery from strokes .
You should think twice before combining Adderall with Modafinil. The official recommendation is that you should only take one stimulant at a time. If you think about it, taking modafinil with Adderall is like taking three stimulants. That’s because Adderall actually contains a combination of d-amphetamine and l-amphetamine in a 3:1 ratio .
In rare cases, I’ve heard of psychiatrists prescribing both Adderall and modafinil to manage ADHD. But this is clearly something that should only be undertaken with your physician’s supervision.
There’s at least one study that has investigated what happens when modafinil is combined with d-amphetamine and methylphenidate (Ritalin). They were particularly interested in pharmacokinetics (the rate of absorption and clearance of a drug and its biological half-life). Here’s what they found: volunteers given 200mg modafinil plus 10mg d-amphetamine exhibited delayed absorption of the modafinil by about one hour. It’s unknown what causes this effect .
Here’s one Longecity user’s take on the subject:
“I’ve used Provigil and Ritalin. I’ve used Nuvigil and Ritalin. I’ve always taken the Provigil/Nuvigil in the morning and a short acting stimulant in the afternoon to get me thru the work day. For years I have been on extended release Ritalin and Adderall too. If you ask me Ritalin doesn’t work as well. It burns out quickly and makes me crabby. I still feel sleepy. Even after I take it I can go to bed.”
Modafinil and Weed (Marijuana)
Taking modafinil with weed is not an unheard of recreational combination. It’s also likely that the THC in weed will offset the cognitive enhancing effects of modafinil.
Here’s one experience report from a Quora user who frequently combines modafinil with weed :
- Initially, the effect of the cannabis seems normal when you’re climbing into the high.
After about a half hour, the effects of the cannabis seem to heighten by a LOT. Your senses are heightened and you feel really in-tune with everything that’s going on.
The normal drowsiness and sleepiness that tend to come with most cannabis strains are totally absent. You feel fully awake and alert.
The cloudiness/fogginess/sluggishness often associated with cannabis are totally absent. Your body may feel a little slow but your mind will be fully alert and active.
To summarize, modafinil enhances the effect of cannabis, while decreasing fatigue. This could almost be considered an improvement on the intoxicating effects of cannabis alone.
On the other hand, cannabis also makes it easier to fall asleep after taking modafinil. This is actually a good thing, because many modafinil users report residual insomnia even 12 hours after taking modafinil. Maybe, much like Armodafinil (R-Isomer), we may finally get S-Modafinil (S-Isomer). As Armodafinil was created to last longer, S-Modafinil would have a shorter half-life, and may be more beneficial for those who find that Modafinil and Armodafinil keep them awake at night. You can find the Reddit discussion on this topic here.
One study directly investigated the safety of combining modafinil and oral THC. Twelve male and female occasional cannabis drug users participated in an outpatient double-blind, placebo-controlled, crossover study. The authors reported that oral THC raised heartbeat, and increased subjective evaluations of feeling “high” and “sedated,” in addition to self-reported euphoria. Modafinil alone raised the Profiles of Mood States (POMS) subscales of energy and tension. The study concluded that modafinil can most likely be safely taken alongside THC .
Modafinil with Piracetam
I’ve personally combined modafinil and piracetam, and can vouch for this stack. One thing to be aware of is the theoretical risk of excitotoxicity. Modafinil increases the neurotransmitter glutamate, while decreasing GABA . Piracetam is an allosteric modulator of AMPA-type glutamate receptor.
So both modafinil and piracetam boost excitatory signaling, by activating glutamate receptors. The risk with this combination is that you can become overstimulated. As always, it’s best to take it slow and take lower doses of both substances than you’d take by themselves. If your usual dose of modafinil is 200mg, and you normally take 2g of piracetam, try taking 100mg modafinil plus 1g of piracetam instead.
If you’re prone to anxiety, it’s probably best to avoid taking modafinil and piracetam together.
Vinuxito, a Reddit user, reported regularly taking 200mg of modafinil with 2.4g of piracetam. Vinuxito reported the following cognitive gains from this stack:
“I am a programmer. My focus and energy are great all day long. Even when I don’t have much sleep, which I don’t recommend. There are times when I can code for 10~14 hours straight. Procrastination is almost null. I can tell you that I am a lot more productive now. Little piece of advice: Drink a lot of water, sleep well, eat healthy and regularly (even if you don’t want to, because modafinil causes that) and exercise regularly (I do it almost every day).”
Modafinil and Ritalin
The only interaction between modafinil and Ritalin is that both drugs are cerebral stimulants. Researchers have tested this combination in healthy volunteers, and there aren’t any obvious pharmacokinetic interactions. For example, modafinil’s half-life, maximum concentration (Cmax), area under the concentration-time curve, total clearance, and volume of distribution (Vd/F) were not impacted by co-administering methylphenidate (Ritalin) .
Ritalin isn’t metabolized by any cytochrome P450 enzymes. So the fact that modafinil induces some CYP450 enzymes won’t affect the metabolism of Ritalin.
There are some scenarios that might justify combining modafinil with Ritalin. But in most cases stacking these drugs together is inadvisable.
Here’s one user’s experience taking Ritalin alongside modafinil:
“I got complete anxiety from 100mg moda + 10mg ritalin. I was trying to get better than 3 focused hours on ritalin, but somehow a 1g dose of oxiracetam calmed me down. Yeah, I’m not trying that again.” [Longecity]
Modafinil and Xanax
Xanax is one of the most prescribed benzodiazepines. It also has the greatest addictive potential of any benzo. That’s because it is rapidly cleared (has a short half-life), which prompts the user to re-dose.
Here’s what Dr. Carlo Carandang, a professional psychiatrist, had to say on the subject of combining modafinil with Xanax [ Quora]:
“I seems that they [modafinil and Xanax] would counteract one another, but they work on different neurotransmitters and brain circuits. Modafinil (Provigil) inhibits the reuptake of dopamine, and is effective for attentional problems seen in ADHD (attention deficit hyperactivity disorder). Alprazolam (Xanax) works on an entirely different neurotransmitter and circuit- it enhances the GABA neurotransmitter, and has an effect on the anxiety circuits mediated by the amygdala. Alprazolam is effective for panic disorder. A stimulant-type of drug (Provigil) combined with a benzodiazepine (Xanax) can treat both ADHD symptoms and anxiety symptoms, which can co-occur. So combining these two drugs does not counteract each other.”
The only thing I’d add is that modafinil plus Xanax can be a particularly useful combination for the treatment of social anxiety. Modafinil is a mild dopamine-reuptake inhibitor (DRI), and Xanax enhances the effect of GABA. Both of these effects on dopamine and GABA will decrease anxiety and make it easier to relate to others without being overly concerned with the impression you’re making. Social anxiety is increasingly being understood as a disorder of impaired dopamine function. That’s because dopamine tends to increase social confidence, boldness, and possibly risk-taking behaviour.
Modafinil and Noopept
Though not technically a racetam, the effects of noopept are analogous to piracetam. Noopept elicits a subtle psychostimulant-like effect that compliments modafinil’s eugeroic effects. Noopept has a couple of advantages over other nootropics. Its potent in very low doses, and increases brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).
Stacking modafinil with noopept is fairly popular, and there are numerous blog posts on the subject. One of the most viewed stacks on TrackMyStack (a website that tracks nootropic stacks) is entitled” Modafinil and Noopept – An Unstoppable Nootropic Combo.”
The author of this stack comments:
“Stacked together you feel very focused and the effects of both are enhanced and prolonged. It is actually one of my goto stacks as of now, imagine your learning ability increase, memory and focus skyrocket from Noopept and having Modafinil give you a clean energy boost which makes you feel awake and ready to get studying/work done.”
My experience has been that stacking Noopept with modafinil performs better than modafinil plus piracetam. One reason might be Noopept and modafinil’s complementary mechanism of action. Because both modafinil and piracetam affect glutamate (or glutamate receptors), combining them can be a little much.
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