Modafinil is used off-label by a lot of students, workers, scientists, and professionals that require and desire peak alertness, and for many of them, modafinil is the perfect stimulant and cognitive enhancer.
Modafinil improves wakefulness, motivation, task salience (the ability to work on boring things without finding them boring), memory formation and retrieval, selective attention (though perhaps at the expense of creative thinking), and some other aspects of executive functions. All while having little abuse potential, crash, or side effects.
Legend has it that its US approval was partially funded by DARPA, a US agency responsible for researching new military technologies, in order to provide troops with a non-addictive and less crash-prone alternative to amphetamines during long and exhausting missions.
Modafinil is approved for the treatment of narcolepsy but is often used as an augmentation agent in a wide range of disorders such as cancer, depression, ADHD, and chronic fatigue syndrome.
Personal experience
The first time I used modafinil was when I was 19. Back then it was much less known, but I was curious about its effects. At the time, I held a sales job during summer break. For retrospectively weird reasons, I limited my modafinil use to one day per week.
On the days I used modafinil, I consistently made almost double the sales. While some credit may be given to the placebo effect, I approached selling with noticeably more energy, excitement, and manipulativeness. These effects are in line with modafinil being a dopamine reuptake inhibitor. As neuroscientist Andrew Huberman likes to say, dopamine does not care about how you reach your goals, only that you do.
After entering university, I used modafinil occasionally. During my fourth year, I took a low dose of modafinil (50mg) every day. The duration of action is about 12h or so, which made modafinil a useful and subtle stimulant that lasted all day, with peak effects about 3-6 hours in.
I procrastinated less and could study for longer. I liked it much better than caffeine and I also felt that it had less tolerance build-up.
However, modafinil use had four major downsides:
- On modafinil, I was less well-rounded and more unidimensional. I would study all day and had little interest in anything else, including friends and family. All I cared about was medicine and science. While this was probably not exclusively due to modafinil, it is probable that modafinil made it worse.
- On modafinil, I did things much more thoroughly than originally intended, such as researching stupid shit for hours until I found what I was looking for. Given that time is a limited resource, I may have been less productive overall in terms of “meaningful” productivity (but not in terms of volume).
- Modafinil decreased my ability to think laterally (creativity), which is fine if I need to work on boring stuff that just needs to get done but is not fine for anything else.
- I required about one hour more sleep and I felt less refreshed the next morning before taking the next dose.
Overall, modafinil had neutral effects on my productivity. While I got more volume of work done per unit time, I slept worse, I overfocused on the wrong things, and my metacognition was poor. I discuss my approach to productivity in more detail here.
I am much less of a modafinil enthusiast than I used to be. I now take modafinil only very rarely when I need to stay up for much longer than normal or on days I need to work on something that does not captivate me. On such days, modafinil never disappoints. However, I feel that even a single dose leads to the development of counterregulation and is therefore, to some extent, “borrowed energy”, which holds true for the stimulant class as a whole.
Furthermore, whenever I take modafinil, I take an awfully long time to fall asleep, though a small dose of triazolam often helps. For this reason, I would love to try s-modafinil (one of the enantiomers), which has a half-life of only 4h compared to r-modafinil (armodafinil). Unfortunately, thus far, I was not able to find s-modafinil.
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How it works
Modafinil is a weak inhibitor of the dopamine transporter (DAT), which presumably accounts for the majority of its effects. In fact, modafinil is the only pure dopamine reuptake inhibitor in clinical use (since amineptine was taken off the market in most countries). At a dose of 100-200mg modafinil, the DAT occupancy is about 50-60%.
As discussed in The Brutal Neglect of Dopamine, dopamine controls the desire to exert effort. The increase in dopamine is also responsible for modafinil’s mood-brightening effects, cognition-enhancing effects, and appetite suppression. This also makes it a great augmentation agent added to SSRIs.
The DAT inhibition by modafinil somehow recruits histaminergic pathways, which are co-responsible for modafinil’s wakefulness-promoting effects. While there is counterregulation & tolerance to some of the dopaminergic effects, there seems to be less tolerance to the histaminergic effects.
How does modafinil recruit histamine? While many neurotransmitters serve specific functions in functionally and structurally distinct pathways, complex interactions between the different neurotransmitter systems make it impossible to target one neurotransmitter system without triggering 2nd and 3rd order effects in others.
Dense connections exist between different monoaminergic neurons. For example, dopaminergic neurotransmission regulates the activity of serotonin (5-HT) and noradrenaline (NA) in the dorsal raphe nucleus and locus coeruleus, respectively. In turn, the ventral tegmental area (DA) is regulated by 5-HT and NA. Similarly, modafinil’s effect on dopamine causes a secondary increase in not only histamine, but to various extents also serotonin, noradrenaline, acetylcholine, and glutamate. I discuss these transmitters in more detail here: An Introduction to Neurotransmitters
Of note, modafinil also slightly inhibits the noradrenaline transporter (NET) with a NET:DAT ratio of about 1:6, meaning that its effects on the dopamine transporter are about six times stronger than they are on the noradrenaline transporter. Usually, this is clinically irrelevant but if I take even low doses of modafinil (50mg) on a low dose of moclobemide, my systolic blood pressure rises by about 10-15 points, presumably because moclobemide potentiates the slight noradrenergic effect of modafinil.
Dosage-wise, armodafinil is more potent than modafinil and does not include the s-modafinil enantiomer.
Side effects
Most people I have talked to seem to tolerate modafinil well. Only two had non-standard side effects. For my brother, it caused severe headaches, and a friend lost his sense of taste and smell for three days after trying it for the first time, though to this day he still does not know whether it was actually modafinil that caused it. Understandably, he is unwilling to try it again.
For some people, the side effects of appetite suppression and a diminished experience of tiredness can be “severe” in the sense that people forget to eat (and thus start to feel like crap) or they sleep less and worse (and thus start to feel like crap).
To prevent this from happening, some friends find it useful to set an alarm for food intake and to count calories. Furthermore, I find a low dose of a sleeping pill useful to artificially counteract the wakefulness-promoting effects, which are themselves artificial.
In addition, modafinil can screw up the metabolism of other prescription drugs. The dosage of modafinil given is typically about 100-200mg, which amounts to a considerable number of molecules. Large loads of foreign molecules tend to induce or inhibit one or more enzymes of the cytochrome P450 system (CYP-enzymes), disrupting plasma levels of other medications (which is one reason I avoid herbal supplements). Modafinil specifically induces the activity of the CYP3A4 enzyme system, which participates in the metabolism of over 50% of prescription drugs.
Potential usefulness as an anti-addiction agent
Most people are just a couple of travesties away from being sent down a spiral, which sometimes ends up in drug addiction that is hard to escape. Like bupropion, modafinil might be useful for treating a variety of addictions. It has low abuse potential and increases energy, mood, and motivation – all of which are crucial to quitting and even more crucial to maintaining abstinence.
Modafinil is thought to be specifically useful for treating cocaine addiction. Interestingly, both cocaine and modafinil act on the same DAT binding site, however, what differs most is their time to peak.
Other experience reports
For a general discussion of stimulants, and links to accounts of stimulants I have experimented with, click here.
For a full list of experience reports, including non-stimulants, click here.
Sources & further reading
- Scientific review: Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review
- Scientific review: Modafinil: a review of neurochemical actions and effects on cognition
- Anecdotes: Reddit – r/modafinil
Disclaimer
The content available on this website is based on the author’s individual research, opinions, and personal experiences. It is intended solely for informational and entertainment purposes and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without the direct oversight of a qualified physician. People should never disregard professional medical advice or delay in seeking it because of something they have read on the internet.