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Modafinil for cognitive neuroenhancement: a systematic review (europeanneuropsychopharmacology.com)
135 points by molecule on Aug 22, 2015 | hide | past | favorite | 76 comments

I have recently, within the past 2 years, started to realize that I may be unintentionally self-medicating larger underlying issues and am attempting to put more trust into medical professionals.

Skipping the story book, I work rapidly changing shift-work and couldn't sleep, stay awake, or function when i was supposed to. I saw a specialist that diagnosed me with "shift-work disorder." The solution cocktail includes Ambien to go to sleep, and Modafinil/Provigil to stay awake. I only use them during the times when I'm on the odd-ball shifts (not days), and they work great. I've had no issues.

I have also recently gotten prescribed Adderall after voicing my (and former teachers) life-long concerns of possible ADHD. Low dosages did nothing, and I can "kind-of, maybe?" tell some improvements with a higher IR dose. I don't want to ask for more at risk of looking like a drug seeker, and I don't want the jitters to increase, but I'm also not really sure what I'm supposed to "feel."

Until I've recently went back onto one of those odd-ball shifts and took modafinil again. I can absolutely without a doubt tell that I'm on it. I am focused and am constantly completing something. This is what I imagined Adderall was supposed to be. The con is that it has this effect that I don't notice I'm hyper-focused until many hours later when it wears down a bit, and it's noticed in retrospect. It's weird enough that I take it as rarely as possible (I'd rather feel this then constantly falling asleep while at work, which is extremely dangerous at my job)

> I don't want to ask for more at risk of looking like a drug seeker, and I don't want the jitters to increase, but I'm also not really sure what I'm supposed to "feel."

If it's working correctly you should not "feel" anything physical, but you'll be able to concentrate and focus (within reason) on the things that previously took significant effort. It certainly isn't a 100% thing -- focusing on some things is hard with/without medication, just as it's hard for people who are not on the ADD spectrum to focus 100% of their time.

Regarding your comment about "jitters", I'll offer you a short anecdote of my own.

I was on a higher dosage schedule of Adderall XR (60 mg/day) for a couple of years before I started to experience jitters and moderate insomnia set in. After talking to my psychiatrist we decided to give Vyvanse a try (70 mg/day). A few days after taking it my jitters went away and my body's circadian rhythm started to return to normal.

Vyvanse may not be for everyone's system, but if Adderall or Adderall XR don't agree with you, it's worth talking to your doctor about it.

Happy to discuss further offline if it would be helpful, you can get in touch with me through any of the links in my profile.

> This is what I imagined Adderall was supposed to be.

It's worth noting that different psychotropic drugs work differently for different people.

For example: when I was diagnosed with ADHD a few years ago, I trialled three drugs. I definitely noticed ritalin. I certainly noticed dexedrine (and hated the experience). Strattera did nothing for me.

Other people have other experiences. YMMV.

How you noticed Ritalin? I mean, what it did that you noticed?

I was able to stay on task, at all, for more than 10 consecutive minutes. Without all the goddamn struggle and self-flagellation.

Oh, I see. That is very interesting!

I recently started to take adderall at 28 years of age. My doctor told me that they found out that at least 1/3 of the adderall will still be working the next day, and 1/3 of that the day after. And the 1/3 was the at least number. So he told me to take it intermittently and not every day. I do really like that stuff, although I have had 1 or 2 bad experiences, for the most part it makes me feel normal and relaxed.

Also, my doctor told me my diet will greatly affect how the adderall works in my body. And that really rang true to me. I usually eat pretty lean, so 10mg, or even 5mg is enough for an effective dose for me.

I tried to get provigil from the same doctor and he couldn't even believe I would ask for it, said it was too expensive to prescribe to someone like me.

I am at 20mg ir of adderall and if it weren't for the jitters I wouldn't know I have taken anything. But that low strength provigil is very very noticeable, for example.

> I'm also not really sure what I'm supposed to "feel."

Not all drugs work the same way for treating ADHD. If simply increasing the dosage isn't working, they may try (and you may suggest) switching to try out Ritalin or some of the other options.

It's well established that shift work destroys you. Don't do it.

Really? Scientific studies are now establishing that this or that "destroys you"?

I find it rather presumptive that you simply tell this person not to do something, period. They have more information about their own life and the trade-offs involved. As a straw man, maybe they earn enough from occasional shifts to pay for treatment of an otherwise deadly medical condition, or don't have other economic opportunities.

In addition, many jobs simply need to be done in shifts, and someone's gotta do it. Servers need monitoring, hospitals need staffing, power plants need running.

> Really? Scientific studies are now establishing that this or that "destroys you"?

I'm not going to go grab links for you, but yes, shift work is terribly detrimental to your health. Google "shift work health risks".

> In addition, many jobs simply need to be done in shifts, and someone's gotta do it. Servers need monitoring, hospitals need staffing, power plants need running.

Indeed. They can pay extra for the requirement, while we ensure we have regulations to keep people who have to do it as healthy as possible.

If you shift "backwards" doing shift work, you're significantly more likely to have a heart attack, accident, etc.

Take a few minutes and google it, this has been studied for 100 years or more.

You can argue about his choice of words, but shift workers fare worse on just about every measure of physical and mental well-being. There's always a choice. If I were the OP, rather than try to band-aid the symptoms with medications, I would plan and prepare to change my career to something where I don't have to do shift work. Just the same as if I had a job that I hated. It's just a job, better to find one that doesn't have so many negative impacts on your life.

Ironically, I am an operating engineer at a power plant. So, yeah, I don't have much of a choice.

I wish that were a choice! Unfortunately for me most of my career options are shift-work based at this time. Thanks for the suggestion, though.

Not everyone has the privilege to simply "n't do it".

While "cognitive enhancers" and nootropics can increase performance (caffeine is my stimulant of choice) I don't think any can really act as a substitute for proper sleep. Sleep is incredibly important to learning & memory - stimulants can only really temporarily mask the effects of sleep deprivation but they rapidly lose effectiveness if one isn't maintaining proper sleep hygiene.

The title of the article is "Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects" (emphasis mine). I don't think the article, nor anybody here in the comments, suggested that Modafinil is a good substitute for sleep.

I can't agree more. The drug that had the biggest impact on my productivity is http://www.gwern.net/Melatonin, more than modafinil or anything else.

And yes besides melatonin I follow the recommendations for improved sleep.

Totally agree. And not just from a performance perspective, the positive affect on mood in general is very important. Melatonin has helped me greatly in the last year.

Interesting. It so happens I took provigil (modafinil) more for this reason than for sleep deprivation or to cram in more all-nighters in college. The experience was like caffeine, but without jitters or noticeably increased BP/heart rate. It was more like "hyperawareness" without hyper-vigilance or anything unpleasant. ("Limitless lite.")

I tried adderall for concentration at a standard therapeutic dose, but the jitters and palpitations.

These days, I just use mirtazapine (depression) and flonase (sleep apnea) and occasional caffeine, and all is sweetness and light.

EDIT: If anyone can add peer-reviewed, reasonably-safe, well-studied neuroenhancement lifestyle choices (food, supplements, pharma, etc.) that aren't just spam/gimmicks, that would be interesting.

[Gwern](https://news.ycombinator.com/user?id=gwern) has done some interesting self-medication experiments [here](http://www.gwern.net/Modafinil), for Modafinil and [here](http://www.gwern.net/Modafinil), for nicotine. I haven't seen similar reproductions or analyses by other scientists, so peer review (or functional analog) is definitely needed here.

My experience of Modafinil is similar. I'm prescribed it for sleep apnea. It dispels the daytime somnolence and lets me function. It's been enormously helpful for me.

At my 200mg dose, I've seen no changes in vital signs (BP, heart rate), affect, or cognition.

I guess people around me might say I'm smarter on it, but only because the comparison would be to me asleep at my desk. It hasn't allowed me to reconcile gravity and quantum mechanics, at least at the 200mg dose.

I'm a little bit confused as to how you're gaining access to some of that medication. Are they not controlled? I.e. you need a prescription from a doctor to get them.

Adrafinil metabolizes into modafinil (to put it short), and it's completely over the counter and not controlled.

Told my doc that I was taking it instead of Provigil (the brand name for modafinil) and they're all for it, as long as I get my liver enzymes checked on a regular basis.

Technically, I was prescribed Provigil to deal with very bad sleep apnea, but it's also to take care of my mild ADHD. Sleep apnea / shift work disorder are the only "on label" ways that insurance will pay for it.

I tried adderall a few years ago, and it was great for ADHD / productivity / made me much more outgoing (according to my girlfriend at the time), but I'm one of the few people that has the side effect of massive uncontrollable sweating. I could be sitting in a 75F degree office and just dripping. Had to stop taking it after two weeks. The changes in prescription laws (must have a new prescription every time, no refills, and then supply issues for a while) are almost too much trouble to be worth it, anyway.

I don't know how he got adderall, but modafinal and the other drugs he mentioned are either schedule IV to Rx Only, so if you ask a pharmacist nicely they can give it to you. (That's how I got modafinil when I was in college)

> if you ask a pharmacist nicely they can give it to you.

In the US?

Yes. There is some minor paperwork involved for them, which is why you should ask nicely, and YMMV.

Can you elaborate? I worked as a pharmacy tech when I was younger and never saw drugs dispensed without a prescription from a doctor. I also can't find anything on the web about this being possible in the U.S.

the term you are looking for is "over the counter" or OTC

Modafinil is classed as a Schedule 4 narcotic. It's definitely not an OTC medication. Examples of other Schedule 4 medications: Xanax and Valium.

Actually modafinil is a schedule 4 stimulant (which matters in some states). And Pharm.D.s can get into an agreement with Physicians to dispense medication on their behalf as they see fit, it's called Collaborative drug therapy management.

Globalization is a beautiful thing.

modafinil at a very low dose might help you stay on task. But be sure not to get stuck on some random useless task. I've found that I get super focused on the details of something. But I don't think that is really the right mindset for writing good code.

That's true for all stimulants I've tried. They're better for repetitive tasks or ones that rely on motor activity. Better yet don't do stimulants unless you truly need them.

In my experience this is an effect of adderall and Ritalin, I have never experienced that on modafinil which I find allows me to 'choose' to be task orientated, or even fall asleep if I want

Same here. I have tried anything from 200mg to 25mg.

50mg daily every now and then works best for me.

Spot on. I found that Vyvance (sp? basically long release Adderall) was great for helping me stay on task far longer than I normally could, but in no way helped me pick the right task to stay on. :-)

It's no magic bullet; I still need to self discipline to pick the right things to work on. FWIW, I pretty heavily rely on todo lists for this.

I've had a similar experience using ritalin. If I have a clear task, I will feel a pressing need to execute that task.

If I don't have a clear task, I will procrastinate even harder.

I have completely unscientific evidence from watching two friends on this for a year. One took it in bursts when code was due, usually no more than 2 weeks at a time. The other took it every damn day and basically didn't sleep all year. Friend 1 is fine and now has a majorly well paying job. Dood 2 is gone, vanished in a fog of paranoia, never to be seen again by his friends.

I started taking Modafinil 3 months ago because I had to start a job which would be new & kind of difficult for me, and my prior "normal" routine involved getting really sleepy in the afternoon (yes, I was getting proper 7-8 hrs at night) and taking a nap, which wouldn't be possible at the new job.

In short, it works. I have been taking 200mg doses. I don't notice any focusing effect. I just don't get sleepy, at all, during the day. Only other effect, for me, is caffeine sensitivity -- as other posters have noted, modafinil will not make you feel wired, but add half a cup of coffee and there you go, if that's your thing.

I had tried it and it had increased the amount of focussed hours I could have in a day. Sleep deprivation wasn't an issue as I used to sleep well. I gave up as it affected my eating patterns. Good that research is being done.

Well, personally I'm not aware of anything else that can make me as productive after a bad night's sleep. I'm one of those people that are very susceptible to sleep deprivation. Cognitive enhancement issue aside - it does what it's supposed to and that's providing consistent alertness throughout the day. You can't do much if you're in a yawn-semi-coma state.

I've spent a lot of time investigating nootropics over a couple of years, and I really don't think Modafinil does much.

It is great for feeling a little more awake when you're really sleep-deprived, but the tunnel-vision effect on high doses isn't always useful.

Exercise , healthy eating, and mindfulness will yield more benefits than any smart drug.

Same here. I tried armodafinil in addition. Although I was wide awake all day, those drugs didn't address the deeper brain-foggy feeling that I was having. They just masked a little sleepiness. After taking them for a few days, I looked back and the preceding days were all in a haze. When it was painfully obvious that Modafinil was negatively impacting my memory, I stopped taking it.

I've also dabbled in a bunch of the *phetamine ADHD drugs. They were more effective, but the effects taper off after a couple of months as your brain adjusts to work around the imbalance that the drugs create. They also had nasty side effects like raising my blood pressure and making my heart feel like it was racing when I was sitting in a chair doing nothing.

My experience with oxiracetam was just money down the drain. No effect I could notice whatsoever except maybe a little more sleepiness, which was definitely not the effect I was looking for.

I've been much more satisfied with my approach the last couple of years which is as you say:

Exercise - cardio on an exercise bike every day, strength training 4 or 5 days a week, yoga a couple of times a week. Healthy Eating - low carb works for me. Carbs are my worst enemy in terms of staying clear-headed. Most of my meals are Keto Chow shakes supplemented with salads, fresh vegetables, and lean meats. Mindfulness - I try to meditate every day, typically while I'm on my exercise bike or whenever I find quiet moments shortly after waking up or before going to sleep at night.

These three things have proven to be much cheaper than the drugs and way more effective. The downside is that they aren't as easy as popping pills.

I have spent a lot of time researching nootropics too. Modafinil provides alertness/wakefulness and that is already a lot to some people. You can then add a racetam, anxiolytic or whatever else is needed. Even l-theanine is known to smooth out some negative effects of modafinil. You can use all the cognitive enhancers under the sun, but they're not gonna do squat if you're yawning your head off.

And just for the record - I work out every day, take cold showers, medidate, my diet is impeccable (macro nutrient balanced) and all that combined still doesn't give me the same level as nootropics do.

Could you point me to a good resource on nootropics?

1. LongeCity: http://www.longecity.org/forum/forum/169-brain-health/

2. /r/nootropics

From there you should be able to find other resources; but they're the best.

Devils Advocate: What about Exercise, healthy eating, mindfulness, and a smart drug?

Agreed. Unless I was sleep deprived, all Modafinil really did for me was increase my appetite (for food) and make my pee smell funny. Under sleep deprivation it's pretty good though.

Increased the appetite? One of the most reported side effects is exactly the opposite - suppression of the appetite (http://nootriment.com/modafinil-effects/) which I can personally confirm.

It could simply be because i tended to be up longer on moda and therefore ate more meals.

Reports vary. A friend of mine took some (of mine) and claimed to experience extreme jitters and paranoia, whereas I can only describe moda as giving me an extremely mild calming effect. Calm and hungry.

It took me a week of taking it before I could say definitively whether it was having an effect at all, so I eventually decided the drug as a recreational experiment wasn't worth the money.

For me Modafinil does not help me to concentrate at all, instead making me feel non-jittery-jitteriness is the only way I can describe it.

If you are looking for cognitive enhancement and focus improvements nothing will help more than yoga and meditation.

The sounds about right. I felt like I took several shots of espresso, I was just unable to sit in my chair. My gait had a spring, and if there a building to jump from without killing myself, I would've done it.

Modafinil has always made my mind feel like a jet engine out of control! And I have never managed to avoid having headaches the next morning.

Supposedly you can fix that by eating more choline beforehand.

I know this is about Modafinil, but since many of you are commenting on Adderall and the various amphetamine salt mixes out there, I wanted to comment:

20mg of instant release Adderall daily (or worse, twice daily) is not a trivial amount to be taking. The long-term effects of the increased heart-rate and sudden spikes you will get from Adderall are not yet well studied or well understood in the medical community.

Stress, arterial stress, vasoconstriction[1], increased heart rate, and high blood pressure are all just a few of the things that happen when you take amphetamine salts. It's not just the jitters.

While these side-effects are okay from time to time, the body is not used to being treated this way on a daily basis, for years and years.

If you are in a place in your life where you don't think you need to be taking it, consider not taking it. Take a break on weekends, or a week at a time.

1: This is part of why many of you get "short" or "agitated" on these drugs... drink more water to at least help.

Curious to know how the effects of "stress, arterial stress, vasoconstriction, increased heart rate, and high blood pressure" from Adderall (which I don't take) compare to caffeine and/or nicotine (current and former). Are the problems similar or the same for a daily coffee drinker/smoker or reduced?

I have thought about trying Modafinil and Adderall for those times when I just can't seem to stay on task. The results and speculation are interesting, particularly the idea that "modafinil stimulates improved performance in the range of tasks reported herein mainly as a downstream effect of enhancement of ‘top-down’ cognitive control processes." The brain is a complex beast. I think the real test, ignoring the safety concerns with altering brain chemistry, is whether you can personally observe a benefit when you take it.

Yes I'm interested in Modafinil, Amphetamines can help but they have can also be detrimental as they have all kinds of side like emotional problems. The positive effects stop working if you take too much, or too frequently and they're very addictive. Modafinil sounds milder and less harmful.

Main problem I see with Modafinil is that it's instant release.

Whenever I hear that someone takes Adderall IR, I ask them if they've tried XR or Vyvanse since the latter are superior in most ways. Mainly, IRs produce tolerance too fast and the curve is too steep.

I don't think Modafinil has an XR solution. Though, Modafinil feels like a sugar pill compared to a low dose of amphetamine.

Reminder: Sleep cleans your brain.


Off-topic but that domain name is ridiculously long!

Here is report of one life ruined by modafinil https://www.erowid.org/experiences/exp.php?ID=92932

Sounds more like a life ruined by taking twice or more the recommended dosage and taking it daily for prolonged periods of time, not looking for help and refusing to stop taking it when you notice you're oversensitive to the drug and when other people tell you you should stop. With that kind of attitude, even aspirin is dangerous.

If you have an agenda, you can find a report of one life ruined by most anything. This is a particularly egregious example of "I did basically everything wrong, but the outcome isn't my fault, it's the terrible, dangerous drug".

Well, citing my friend professional toxicologist, who spent some time working for big pharma in Swiss, and delivered relevant course at Bristol Uni, "Modafinil is not even nootropic, you can only compare it to ladasten". This guy considers piracetam useful and buys it in Russia, where it is dirty cheap.

Your appeal to authority does nothing to refute my point.

I would bet money on a huge dosage of 400mg+.

50mg is ideal IMO.

Good for mindset, but bad for soulset. A lot of people live in their heads with Modafinil, and don't take guidance from the subtle cues in nature, which they're going to have to at some point. Michael Tsarion brings this up in his talks: The War on Conciousness https://www.youtube.com/watch?v=knwyZawRse8 We have a deep fear of Nature because it's the 'final boss' we have to deal with at some point. Be this death, grief, or getting old. Any number of things are competing for your attention in Nature. Rushkoff talks about how our minds increasingly live inside a computer program and are out of sync with Nature. The internal clock is ignored and we live in a constant state of panic when checking our email and trying to game the stock market: https://www.youtube.com/watch?v=ZQHubIMP-as Alongside time being out of whack, we experience different hormones and endorphins at different times of the year. So summer might be dopamine, winter might be adrenalin filled, and autumn is some sort of smart drug like Modafinil which allows for high performance.

>Good for mindset, but bad for soulset.

Exactly. From the linked article: Modafinil "indirectly upregulates cerebral serotonin" ...a concern for those focusing on quality of life rather than quantity of output.

"To give you some perspective: the type of behavior displayed by upper classes of society; the elegance, the subtlety, the higher levels of intelligence and conscience, most likely reflect low serotonin levels (or rather, a lower ratio of serotonin to other neurotransmitters). Now take the opposite, high serotonin, say in combination with a poor immune system, low metabolic rate, chronic inflammation, and what will you have? Well, a serf/thrall."

Further discussion here:

http://www.longecity.org/forum/topic/73104-natural-serotonin... http://www.longecity.org/forum/topic/78451-symptoms-signs-of...

Anybody interested in an ebook about how to dose yourself (or your entire company) for optimal startup performance?

I've thought about putting one together by interviewing people about their non-amphetamine-based get-shit-done regimen (timings, dosages, ± side effects, results). It'll be like an Internet bad-broscience guide, but with a slant towards combining wider anecdotal evidence with results and performance benefits/drawbacks across everybody.

email me if you're interested. If there's enough seed interest, I'll make it happen.

I'm interested in you not creating such a book. While I support the idea of seeking your own improvement and taking advantage of what works for you as an individual, the view such a book espouses is not one of improving quality of life, it's one of More. Just More. Which in my mind is a really dangerous way to go about lifestyle choices. You might as well title it "How to Burn Out in 22 Hours a Day"

is not one of improving quality of life, it's one of More. Just More.

Have you seen which website you're on? More-More-More for Me-Me-Me is pretty much the MO around here.

Yup, and while in the context of business value itself I more or less agree with you, I do observe generally a more balanced view on quality of life and avoiding burnout around here than a raw selfish drive. Which is exactly why I hold a disapproving opinion of your idea, it sends that balance out the window.

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