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Modafinil-Induced Changes in Functional Connectivity of Healthy Elderly Subjects (frontiersin.org)
210 points by LolWolf on Apr 8, 2017 | hide | past | web | favorite | 163 comments

Ah, resting state functional connectivity. Still not sure I believe most of the broad-stroke conclusions, but an interesting area.

For those unfamiliar, a healthy brain has what is called neurovascular coupling where the amount of blood flow into local clusters of neurons (order of millimeters) is adjusted based on demand (order of seconds). Simple optimization strategy. With MRI T2* imaging we are able to measure blood flow because the ratio of oxy-/deoxy-hemoglobin subtly alters the magnetic field. So if you take a picture of the brain every 2 seconds you get "blood flow" and if the average signal in 2 areas have a similar shape, we say they are "functionally connected." Just good to keep in mind because it's an area of research particularly prone to misunderstanding.

> if the average signal in 2 areas have a similar shape, we say they are "functionally connected."

not so hard to understand:

The "functional" is because these analysis were usually applied to a specific task condition, thus function specific.

"similar shape" or "connectivity" is operationalized by correlation, though there are many other ways.


This feeling won't last, and you'll be worse off for it in the long term. Withdrawal from this sort of thing left me unable to get out of bed for a long period of time. Productivity went to zero. It has been several years, and I still have trouble concentrating. Please be careful.

Yeah, this is the reason I rarely take chronic doses and certainly nothing more than 1-2 pills a week. Tolerance usually doesn't build up much, but the comedown the day or two after long periods of dosing (personally >2 weeks, every day) made me somewhat more scared of the drug.

That being said, I highly recommend it, but to be used with caution.

Taking medication on a regular basis without having previously sanitized and perfected your life style (nutrition, sports, sleep, meditation, breathing...) to achieve perfect health is not very intelligent.

By the way, if you take this drug, you will notice your urine will smell differently (different chemical composition). That (logically) means that your body either retains something it should have gotten rid of or the opposite, meaning your are changing the chemical composition of your body. Science has no idea how this drug actually works (we only know that there is some kind of effect) and has no idea what its long-term effects are.

> That (logically) means that your body either retains something it should have gotten rid of or the opposite, meaning your are changing the composition of your body.

A change in the chemical composition of urine strongly suggests a change in the body, but doesn't "logically" prove it. In the simplest case you could imagine consuming some kind of dye which is simply excreted and not metabolized, which could change the appearance of your urine, kind of like in


(where the urine change itself mainly reflects what the body did not absorb).

Another possibility is that the body breaks down the drug and excretes all of the reaction products. In principle, that could occur without consuming any other substance, just by applying energy to cause a reaction to occur, or by providing a catalyst.

Also, some chemical changes in the body are beneficial (though the typical random change is most likely not).

If you ingest a bunch of extra sulfur and then expel all of it, it does not follow that you are changing the chemical composition of your body.

How long did it take for tolerance to develop?

I can't give an exact answer, but I can tell you that it happens gradually. Initially you feel great, and you're incredibly productive. Two months later you're taking the same amount, but it doesn't give you that same feeling so you increase the dose a little bit. This repeats for awhile until you start noticing side effects and try to stop. That's when you're stuck - you can't do the work you used to do unless you're medicated, and you can't stop without putting your life on hold for a very long time.

The thing to do is threshold dose, don't increase the dose, and take holidays for long enough to allow recalibration. It's simple if you understand the control system mechanisms at work.

By threshold dose I mean take no more than is needed to get an effect. I experimented a bit and found 50-100mg of modafinil (1/4 to 1/2 pill) to be effective and have never taken 200mg.

Escalation on tolerance is the exact opposite of what you want. On the first hint of tolerance, stop. Again think about the control system at work. Your body is trying to maintain homeostasis, which is usually a very good thing.

So it's months, not days. Thank you.

+1 this I have tried 100 mg (even 50 at times) and the "noise filter" is exactly what I have experienced.

It doesn't give the "alertness or kick" of coffee but it gets you in this mood of "do things".

I am a bit worried about the side effects so I haven't ever taken more than thrice a week. Unlike many others who report I don't any changes in mood. Its easy to stretch your days after so you got to be careful not to over burn yourself for the day.

Also I get a really good night sleep after a day of 'killing it' - which may just because of feeling good as a result of getting things done.

> I am a bit worried about the side effects so I haven't ever taken more than thrice a week

This sounds ideal. Like pretty much anything, I can testify that in my experience you can develop tolerance and it loses its effectiveness (at least for cognition) when taken daily.

>but it gets you in this mood of "do things".

How much of that is placebo? i.e. "You're doing things because you know you're taking something that helps you do things?" Productivity comparisons with a placebo haven't been conducted yet, but I'll bet it will be rather underwhelming as a motivational agent. Especially when you compare it to other stimulants like Coffee, it will sound even less miraculous.

The silver bullet of psychopharmacological brain-enhancement hasn't been found yet. That's the holy grail.

Anecdotally based on using it for shift-work sleep disorder (falling asleep on the job), but you definitely, definitely do not mistake it for anything else.

You know how you get "tired", and want to take a break? Still happens.

You know how you get "sleepy" and can't keep your eyes open? That's completely gone. It's a very strange feeling.

I tend to not care if its the placebo affect or not when it comes to stimulants like these. I care more when its something like "cures cancer" or not. If the medicine is supposed to make me focus then I dont care if its through a chemical reaction or placebo as long as I am focusing more

I take modafinil regularly (am on it right now) and believe me, the effect is extremely pronounced.

How long have been taking ? Can you explain your stack & schedule ?

How have managed to avoid tolerance ?

I've been taking it on-and-off for about 2-3 years. My stack is basically just modafinil 200mg unless I'm going through one of my caffeine+L-theanine phases.

I've avoided tolerance by not continuously taking it - if I'm no longer noticing the effects as much, I come off for a while until I really need it again. That seems to have stopped me from building up a lasting tolerance.

Any other side effects? I read a few people complaining fogged memories after longer cycles.

And another quick question what is ur schedule? What time do you take it?

Yeah there's a few, expect to visit the toilet on a regular basis, and you'll also retain water of you don't drink enough. Socialising can be a little awkward, and doing anything that requires broad rather than narrow focus (eg driving) can be a bit more difficult. I find my short term memory actually gets better, as does my ability to learn things long term.

I take it whenever I feel like I need a boost of concentration, it usually lasts about 6-8 hours so the latest I'll take it is 6pm if I want to sleep that night.

Believe me, this is no placebo. You feel it when it kicks in. And also dry mouth.

I can say the same thing for Dextroamphetamine. And I swear by it.

Meh. I took modafinil for about 3 months (I had a legit prescription for it) and it didn't seem to do jack shit. I stayed on it for a while just because I was waiting for it to work, plus we tried a higher dose.

Also, placebos have side effects.

Not saying it doesn't have effects for some people but it's probably mainly placebo.

I appreciate your data point, but going from "it didn't work for me" to "it's probably mainly placebo" is incredibly silly. Modafinil has been studied, and it's pretty obvious that it's doing something.

Here's a quick primer (with 73 citations): https://examine.com/supplements/modafinil/

I think there are a lot of people here underestimating the awesome power of the placebo effect.

I don't think so. It's pretty easy to do an informal single-blind trial on yourself with the help of a friend, or a double-blind with a little more ingenuity. If you're worried about the placebo effect it's a good way to put yourself at ease.

Why even invoke the placebo effect (an extremely popular thing to do here)? What's unusual about a chemical actually affecting the brain?

Why invoke the placebo effect? Because it will be having an effect. The question is, once you remove that, whether there is any remaining effect that is due to the drug.

I agree with you. I'm guessing that people are instinctively incredulous because drugs with such strong psychoactive effects are typically scheduled or hard to come by.

I suffered from serious short attention span and it started to affect my job. I convinced my doctor to prescribe me ritalin abd boom i started meetimg my deadlines. But once my dose ran out i had to visit the doctor again and that's when I realised modafinil was available otc in my country. I never abused and was using it only when my work suffered seriously. For months I didnt have any problem and the 'no side effects' of this wonder drug was too good for me. But a few months later i started getting serious rashes and blisters in my mouth, it took me a while to nail it to modafinil. I have stopped it since and the rashes have never appeared again but then my work statred to suffer again. I went into some real psycological issues too. But after much reflection i decided to quit my job and try a different field. And it made me realize a very simple lesson, which i knew as a child, there is no real prosthetic for passion. I just love what i do now and am able to do well at my job too.

A deadly rash called Stevens-Johnson Syndrome is a known (but rare) side effect of Modafinil.

I would go as far as to say "extremely rare." SJS is also an extremely rare side effect of Ibuprofen.

If you're drinking coffee for alertness, you are probably causing your own problems. Try quitting for a week, getting enough sleep for once, and consider if you're ADHD.

("Mental noise" is one of the symptoms of ADHD too.)

you're telling me the "mental noise" of coffee-induced alertness is a symptom of the very thing i'm taking caffeine to combat (adhd)? i want to hear more about this.

Oh, that was an awkward reply to a sibling comment. It's more like a symptom of being tired/overstimulated because ADHD means the brain gets tired of choosing what to pay attention to more easily.

But caffeine makes it hard to sleep and the adrenaline rush isn't so good for you.

It took me more like 2 weeks for caffeine withdrawal headaches to subside, but I was addicted to sugary soda (never drank coffee or tea) and didn't really use it for alertness or sleep cycle management. Perhaps my headaches were related to drastically reducing my sugar intake.

Yeah, addiction to caffeinated sugary soda is really two addictions.

My advice to people is to quit one at a time. Take a few days (or even a week) to taper each one down to 0 separately.

Switch up the coffee with some loose leaf Black tea, It has naturally occurring L-Theanine in it. L-Theanine has been researched fairly extensively to improve GABA production and also reduces cortisol levels caused by caffeine, which also helps calm your nerves and helps you focus. Cortisol makes your brain go heywire and induces anxiety. L-Theanine reduces anxiety by reducing the cortisol.

I have sleep apnea and so coffee is just basic and very necessary bootstrapping for me in the morning. There's no such thing as getting enough sleep for me.

Are you not treating your sleep apnea?

Trying my best using state of the art. CPAP only gets me 60% of the way there in terms of feeling rested (which is a common occurrence according to one of the best sleep surgeons in the world).

Surgery is intense and also costs 100k (it is out of network for every major PPO insurance). The most likely to be successful procedure entails painfully breaking your jaw and moving it forward with metal plates. The recovery is brutal and requires a month long Soylent diet. Other procedures involve iteratively carving out more and more soft tissue in your tonsils until there is no more obstruction.

Sleep apnea treatment is still a pretty unsolved problem in medicine. Only half of patients end up complying with wearing the very uncomfortable CPAP breathing mask for more than four hours a night, most can't even tolerate it at all.

Be certain to try all possible CPAP masks, the sleep center should Let you try one after another. Different masks work for different people. Every type of mask has unique problems, so be sure to visit various forums and search for clues.

Also there is a dental appliance that pushes the lower jaw forward to open the airways. Look into that. If your insurance doesnt cover it you can buy an off-label "anti-snore" boil-and-bite device that does the same thing.

Are you overweight? Do you eat a simple diet that takes account of possible allergies? Do you get a lot of exercise? Do you work at a desk job in a hunched position that has curved your spine and pushed vertebrae into your throat?

> Are you overweight?

No. I weigh 150 lbs (6 feet tall), same since high school.

> Do you eat a simple diet that takes account of possible allergies?

No allergies, and I'm doing better now with diet.

> Do you get a lot of exercise?

I run 2-3 days a week (2-3 miles per run). Used to be a state competitor in high school for distance running.

> Do you work at a desk job in a hunched position that has curved your spine and pushed vertebrae into your throat?

Absolutely. I sit at my desk 10+ hours a day, and my posture definitely could be a hell of a lot better.

Please if you can try , try Ayurveda intensive treatment for 10 days and then followup with 3 months medicine. I tired after Resperonics devices etc . It is gone now , habit-ed sleep on side as well as that helps too. It is was bloody cheap in India for me but you should be able to take 10 days leave if you outside India and come and get this done. Please choose good hospital.

Sounds like pseudoscience, not helpful, sorry.

Remember, obstructive sleep apnea is caused by a physical _obstruction_. You need to either address the obstruction by splinting it open using pressurized air (CPAP) or by physically making more room via surgical techniques.

Ingesting herbs doesn't address anything in terms of there being an obstruction, so it doesn't treat sleep apnea.

EDIT: Why am I getting downvoted? I am suffering from a debilitating medical disorder, and people are suggesting I need to drink snake oil or accept the flying spaghetti monster in order to heal myself. Of course, I am going to get a little upset. Please try to understand my perspective.

You are getting downvoted because you are speaking like you are the authority on truth and also comparing an ancient traditional health system to a petty joke.

The authority on truth is the data itself -- my polysomnogram that shows I stop breathing 30 times an hour in my sleep when my tongue collapses, and then this number becomes 2 with CPAP.

Like most technologists who frequent this site, I'm all for following the scientific method and gathering data through repeatable experiments that test hypotheses, and I'm against petty tradition ("we've always done it this way" is a very counterproductive/backwards way of thinking that also precludes progress -- as an entrepreneurial community, we tend to think differently and to challenge established beliefs here on HN).

Your mistake is assuming that traditional systems can't be empirical or otherwise based in efficacy.

Could you provide some links to the scientific studies that led you to your conclusions?

I'd be very interested in reading them.

My whole point is that there are systems other than modern science that are valid and effective, so the logic is a bit circular to want sceintific studies to prove that. These systems use a different epistemology and to use science as your only filter in life is extremely limiting.

Nevertheless, I will still provide you with some samples of evidence (these are high level summaries but actual studies are linked within:







I'm not denying that there might be health benefits for meditation and yoga. Indeed, you can verify them using science. Having your claims stand up to repeatable tests is establishing their very veracity. There is no circular reasoning ("but you see, my claims won't pass these tests because they are not testable" is not a valid argument).

I just don't see how any of these can _possibly_ resolve _obstructive_ sleep apnea. For example, if you have a large tongue and it collapses in your sleep, I don't see how you can solve that by meditating. That's physically impossible.

It's very easy to see whether something has any sort of effect on your apnea; you sleep every night, and the difference is readily noticeable.

By the way, the reason I asked if you are hunched over is that I took up Yoga for my spine curvature, as I was having breathing problems in my sleep due to my cervical vertebrae pushing into my throat. After about 2 months of daily practice, the breathing problems were reduced significantly.

That's really helpful, thanks.

Sorry for the confusion, these links were not intended as pointers to resolve your sleep apnea. They were to make a point, that which is that there are other systems out there besides Western science that are effective. Furthermore they were effective before they were "proven" effective by science.

So the point is to perhaps be a bit more open minded and look into someone's suggestion rather than writing them off with a snide comment. There may or may not be something more to what they are saying, but you will never know if you think you somehow have the upper hand on truth over everyone else that ever existed.

For women considering Modafinil, note that it interferes with hormonal birth control.

I did the same, but never got the same feeling as the first time I took Modafinil. First time was great. Second time was good. By the fourth of fifth time it was only okay.

Do you have the same experience each time?

I had similar experiences, effect was much weaker after 4-5 days but I think it was better for work. Initial 3-4 days were very similar to taking cocaine, I was too high to do good work.

Well, I have that first-time experience with adderall and modafinil if I've given myself a break from it. Medication "holidays" (periods of abstention) are pretty much standard practice for stimulant meds like adderall to avoid tolerance/dosage creep and anecdotally this is true for modafinil in my experience as well.

Modafinil is instant release, so it's hard to take therapeutically. Tolerance builds too quickly.

I'd be interested in an slow release format since the drug can be bought over the counter where I live.

Though it's not even in the same ballpark as amphetamine. I fly back to the States just to re-up my Vyvanse prescription.

Where do you live? For what condition is it sold over the counter?

Primarily narcolepsy.

The tolerance builds up quickly, regardless.

Well, I said "too quickly". You have to address tolerance for all drugs in this space, but some are ridiculous.

I couldn't even feel the Modafinil on day 3 without taking 5x the dose. That's a bit silly.

Instant release amphetamine ends up being more like a party drug for the same reason, though less extreme.

Compare that to a slow release amphetamine (prodrug) like Vyvanse where most people can hit a 2+ week cycle of constant use, or an indefinite cycle by only dosing a fraction of the week.

if you follow what other people do when using modafinil, they sometimes mix coffee w/ small amounts of modafinil which improves it's overall offectiveness. I personally prefer the mental zing of Loose Leaf Black Tea.

This won't help with tolerance.

I had, increase of dose didn't make a difference.

How does it compare to amphetamines or amphetamine analogs, in your opinion? I've tried armodafinil and the first time I took it I felt as you described, but only for a couple hours. Otherwise it just made me feel alert, but not focused. I find that I am much more focused and productive on amphetamines.

It doesn't force focus like amphetamines tend to do. In fact after taking it two or three times the entire pronounced stimulant effect is gone.

There are some days I wouldn't even know whether it was working until I looked back at my productivity in hindsight.

Why not just take meth? I'm half serious. At what point does using a drug to enhance your productivity go too far?

"A mathematician is a device for turning meth into theorems." ~ Paul Erdős

Side effects? Modafinil is quite benign in comparison.

We currently don't know the long-term effects of this drug. There are no studies on that subject.

Are there reputable sources online to obtain Modafinil safely? It seems to be a very popular nootropic but on the other hand is only available in the US via prescription.


Loose lips sink ships. Crackdowns are real.

When things like this get talked about outside of their focus spheres, that's when things start getting shut down because the agencies are publicly pressured to do something.

Nice try FBI

Yes, the FBI made an account 2556 days ago and invested years getting 3301 karma points.

A lot of research went into this to emulate tech knowledge enough to make it convincing.

It was worth it though and obviously is just about to pay off as they arrest some 20 people for ordering 50 Modafinil tablets and give them 2 months probation and a $500 fine (or whatever the penalty is).

We all know it had to be done however because Modafinil is in the news near daily with the wrecked communities and terrible life destroying addiction leading to violent crime.

Very smart and tricky on their part.

> invested years getting 3301 karma points.

Very low RoI. Agent should be fired.

Don't be silly. FBI agents intentionally want to fly below the radar. Duh.

You can buy Adrafinil from plenty of mainstream sites, it's not prescription, and it's metabolized into Modafinil in your body. That being said buying supplements anywhere in is coin toss, the whole industry is sketchy.

Adrafinil being sold as a supplement is actually illegal.

Look into adrafinil; it's completely non-regulated/OTC in the US and metabolizes into modafinil in your gut.

From Wikipedia:

"Adrafinil is a prodrug; it is primarily metabolized in vivo to modafinil, resulting in very similar pharmacological effects. Unlike modafinil, however, it takes time for the metabolite to accumulate to active levels in the bloodstream."

You should monitor your kidney enzymes if using it long-term; I've never had any issues.

Plenty of places selling it for $20/30 300mg caps via Google Shopping search.

In general, Adrafinil is fine, but I personally don't like stuff that messes too much with my liver.

Just be careful. Technically, modafinil and it's newer cousin armodafinil are Schedule IV controlled substances in the USA (same as many of the benzos.)

I don't think there are (m)any cases of people being busted for importing/simple possession, but if you were to get arrested for something else and had it on you, I wouldn't be surprised if you get additional charges.

Point being, this isn't a legal supplement you're ordering through the US Postal Service.

The dark net marketplaces are not a bad place to start. The pills come in blister packs from popular Indian brands that are probably more trouble to fake than just acquire. And the vendors depend on reputation to succeed.

I don't know about modafinil but if you add your email to your profile I can give you advice.

I would like to know as well - email in profile.

sure thing, added email

I'm ready but don't know where to purchase that I can trust. A message from you with some direction would be greatly appreciated.

Try r/afinil on Reddit. I found some vendors on there that worked.

- Shipments are occasionally seized by customs, so don't put all your eggs in one basket. Just a risk that's part of the game. Never happened to me though.

- Credit card theft happens, even with legit vendors... based on what I've read, sometimes (often?) it happens in the maze of overseas banks, credit card processors, etc. So general consensus seems to be that buying with bitcoin is best. While a crooked vendor could rip you off just as easily over bitcoin, anecdotally the success rate seems higher with bitcoin. Often you get a discount as well for using bitcoin!

I could ship some to you for free (not a dealer btw; just located in a country where it's cheap and available OTC)

I tried Modafinil and it just gave me a bad headache. I would be okay the first 4-5 hours, but by late afternoon, I would be edgy, anxious and fighting a searing headache.

I live in India so Moda is also incredibly cheap for me - about $0.15 per tablet. Plus, it's available without a prescription.

I live in France, it seems to cost between $50 and $60 [0] so 300 times your price! That said I certainly would not take any Modafinil.

[0] http://www.lepharmacien.fr/produitafine/medicament/vdf/231

Is it available OTC in India? I've tried a few places in Bangalore, but all of them asked for a prescription. Even online, NetMeds requires a proof of prescription before you can buy it.

Armodafinil have me a huge headache, whereas normal modafinil does not. I've heard it's different for everybody.

I took Modafinil for several years but it caused persistent dry eyes and a very dry throat. I stopped because of the negative effects.

I too experienced negative effects, terrible headaches and tremors. Severely outweighs the modest "high"/boost for me.

Ymmv but in my experience the headaches can be avoided by drinking lots of water and the tremors may be a sign that you took too high a dose for your tolerance level. If I've not taken modafinil in a few weeks then a 200mg tablet can sometimes leave me with tremors and mild anxiety.

Have you tried different brands? There is quite a bit of variation between them.

Warning personal anecdote. I briefly took this drug to help with excessive sleep and sleepiness. It had a paradoxical effect where I felt more alert but was actually experiencing micro-naps. This very nearly caused me to get into a serious car accident. Please be careful if you're thinking about this drug as part of a nootropic regimen.

Get yourself checked for sleep apnea

Thanks! Amusingly I actually ran polysomnography sessions for a while and so was tested many times as part of that training.

Apnea more than narcolepsy?

When I was taking it, it only worked first couple of days then I had to increase the dose to feel anything. Then I had a very strange effect of being tired but unable to sleep at all, as if I was sleeping awake if that makes sense. After taking 600mg to see if this fights fatigue I was not able to sleep for a couple of days. I still have not found how to tackle the fatigue. Doctors are helpless, tried almost every medication available.

check for sleep apnoea

A lot of people in this thread are exchanging advice about ibcreasing mental capacity and alertness. I have a question about this.

Do you guys honestly feel that you're not smart or concentrated enough? Or are you just trying to improve these traits to the max and beyond because they're considered to be virtious in the culture around you?

I am similarly baffled by the tolerance for (even illegally obtained) drugs which apparently exist in this community. In another discussion here¹ about a similar topic I wrote the following:

> If you have “an Everest of work”, the solution is to get less work, not to take drugs. Be the person you are.


Even if the drugs are completely safe and don't have any drawabacks, my question still stands.

I wanted to write a similar comment. I am really surprised about the lack of worry to take potent drugs. I am not a physician but experience tells that most (all?) potent drugs have major side-effects. Some even consider to buy the drug from shady websites and risk credit card theft.

> "Present findings provide functional data supporting the hypothesis that modafinil can modulate the cortico-cerebellar connectivity of the aging brain"

Did anyone doubt this at the start of the study? I bet Tylenol modulates cortico-cerebellar connectivity. Pretty weak conclusion. I hate to be so critical, but I'm not sure what is added. Drawing real-world implications is likely impossible, which admittedly may not have been the authors' goal.

Just as a counterpoint to all this "yay modafinil"; for me it's horrendous, I get a headache feel queasy immediately. It's a chemical feeling like your brain being coated in plastic. A lot like taking too much caffeine but without some of the edginess and instead a feeling of dread replaces the caffeine high.

Getting work done while feeling ill is more, not less difficult!

Considering on-label use is to combat sleepiness, would have been interesting to see more than just a placebo control. E.g. vs. caffeine or vs. a good night's rest vs. staying up all night. Maybe sleep vs. no sleep the night before provides the same thing.

The fMRI happened 3 hours after the participants dose, so sleep vs. no sleep wouldn't affect the results (you would reasonably expect the sleep vs. no sleep to be randomly distributed between participants, without being unduly biased to one cohort).

  Study participants received a single-dose of modafinil or a placebo pill.
  All subjects then underwent two fMRI scans, performed before and 3 h after
  drug (or placebo) administration.

When does Modafinil reach its full after taking a dose? I take it for sleep apnea and I don't really feel 3 hours is a sufficient time to measure its effects.

> "Present findings provide functional data supporting the hypothesis that modafinil can modulate the cortico-cerebellar connectivity of the aging brain"

I would love it if someone more knowledgeable of neuroscience explained what this meant and what the potential implications could be.

Functional connectivity is just temporally correlated neural activation (technically for fmri we are measuring blood oxygenation, but whatever). So we might have regions a, b, c and d, and find that a and b tend to be co-activated, but that c tends to de-activate when a or b are activated, while d's activity is uncorrelated with any of the others. For example, insula and dorsal anterior cingulate cortex are usually positively corellated with each other, but negatively correlated with regions of the default mode network. Modulation just means that the manipulation, in this case modafinil, changed the correlation between neural activation in different brain regions, in this case between cortical regions and the cerebellum.

So would neuroscientists.

Modafinil has changed my life - I can't even explain how it helped me setup and complete projects. I would say he best way to word the feeling is 'clarity' when one is using this. Worth a try

I am 100% an unabashed fan of Provigil/modafinil. I think it should be available OTC. Even though I have a prescription, it's $30/dose to fill it in the states. I can buy it from India for ~$1/dose.

FYI - It's about a dollar a dose at Costco.

N=24. Intriguing, but not evidence--taken alone--to effect behavioral changes by.

Also: It's mentioning a chunk of the biochemical chain yet there is no clear mention of causality regarding modafinil itself and that what is observed.

Surprisingly little is known about modafinil's activation chain, unfortunately.

I took Modafinil 200mg for a few weeks, definitely felt a boost but couldn't stand the headaches. Also Modafinil made me more sharp during the day but my work hours got too short, my brain was dead after 8 hrs of intense work. Then I went to a psychiatrist and got diagnosed with ADD. Now I take methylphenidate/ritalin 10mg, I split the tablet in two and take one starting my day and one after lunch. It's magic. I can now work for 10+ hrs a day and sometimes easily push for 14 hrs. It's really impressive.

My comment might not fly well with the long hours startup crowd here, but is 8 hours of intense work not enough for one day? I imagine most people would feel drained after working for that length of time (and 8 hours is quite a long time to pay attention to any given thing. Skeptical of the ADD diagnosis...). Perhaps your body is trying to tell you something, that it's time to do something other than work.

But I guess if you need to be working 14 hours/if you don't have a choice, then do what you gotta do.

Mate, you need to acquire a life. If you can't make do with absolutely maximum 7.5 hours of "work" a day you are entirely missing the point of living. You are not excelling, or even succeeding, you are failing.

If you insist on being a slave, be sure to charge at max for the finite hours you are selling, three to four times your normal rate beyond 7.5. And here is something you think you knew but don't: Young time is more precious than old time. Each hour before 35 is worth 3 hours after 35. This because experiences are new, senses are heightened, live is intense.

Take it from a retired high priest: Don't burn your life on this altar of bullshit.

You can't make assumptions based on a post.

For example, I make money off my own projects, I travel, I have some form of ADD, and I like to batch some of my work into 12 hour binges with the help of some medication like amphetamine.

I love my life, I don't work every day, I don't binge every day. "Work" doesn't always mean you're burning yourself on someone's pyre.

I hope you find something more fulfilling if the mere thought of 8+ hours of work must mean your are "missing the point of living".

> Young time is more precious than old time. Each hour before 35 is worth 3 hours after 35. This because experiences are new, senses are heightened, live is intense.

This is a depressing comment. Can you not have new, high intensity experiences past age 35? Is losing this an inherent part of aging? Or do many just choose to avoid new experiences after a certain point?

I don't buy it. There is so much amazing shit in this universe, and it's so difficult to get a proper perspective on it all. I honestly expect to enjoy life more once I hit 35, as my understanding and perspective should be much deeper, and I'll have made further progress on understanding how to live a balanced and fulfilling life (at least, in a way that works for me).

I will also likely have acquired more financial resources and additional connections with like minded folks, which should enable interesting projects and adventures.

I'm basing this largely on how the past 5 years have gone, and the understanding I have developed during that time (from age 22 to 27). I also fully reserve the right to adjust this forecast 5 years from now :)

>implying he isn't an entrepreneur working on his own projects

>implying he isn't enjoying it

Is this a joke? Why would you have a problem with not being able to work work such long hours? Not being able to work 10+ hours a day is called "being human."

TLDR: Finding a good doctor is really the best way to figure out what is best for you.

I also have ADD & tried Modafinil as an alternative. My doctor prescribed me 200MG as well, and it gave me splitting headaches and, until I learned to eat first, stomach aches. My doctor suggested I try 50 MGs & 100MGs instead, which didn't give me headaches but, well, just weren't as effective for me. So I went back to the old meds.

Also, Modafinil, IME, isn't like other ADD meds. Unlike, eg, Adderall or Vyvanse, doesn't keep me awake or alert, or replace caffeine. But, obviously this varies, since modafinil is also prescribed for narcolepsy & other people here clearly have a different experience with it.

Basically, chemistry varies for each of us--and there are many variables, including metabolism, medical history, weight, what your diet is, whether & what you've eaten, and so much more. Going to the doctor is not only safer, its more efficient.

W/r/t the Modafinil headaches, I've heard they can sometimes be ameliorated with choline, which is found in eggs.

As an NP, I am glad someone shared this. My husband is a computer programmer, saw this and thought, "oh this is your area of practice"

I have seen many good results with modafinil and elderly patients who are not waking up well status post stroke. It doesn't always work, especially if the stroke was huge, but there is something very heartwarming about worried family members becoming ecstatic when their loved one wakes up and people are hugging you in gratitude for prescribing it :' )

Protip: Modafinil is prescribed by doctors for ADD (& narcolepsy). Instead of risking many things (examples: counterfeit or poisoned pills, being ripped off, being arrested, or even just dealing with bitcoin), why not just go to the doctor, get a legal prescription, and fill it at the pharmacy?

> Protip: Modafinil is prescribed by doctors for ADD (& narcolepsy). Instead of risking many things (examples: counterfeit or poisoned pills, being ripped off, being arrested, or even just dealing with bitcoin), why not just go to the doctor, get a legal prescription, and fill it at the pharmacy?

FYI, Modafininil is approved for narcolepsy. It is used sometimes for ADHD, but that is an off-label use, and it's usually not used as a first-line treatment.

Lol. I had to fight my insurance for about six months through several levels of appeals to get them to pay for it for off label use. And it costs, IIRC, $700 a month out of pocket.

Woah, that's a lot more than traditional ADHD drugs from what I've heard. Is it a lot cheaper from other (illegal) sources?

Modafinil is generic. If you have a prescription, you can just buy it for cheap online from Canada.

It wasn't generic at the time and also it's a scheduled drug so it's illegal to import into the US unless the receiver is registered with the DEA.

Yes, there is a chance customs will seize your package, but even then it's still worth it and you won't get into any trouble personally.

Whats the point? In that case your just going down the "illegal" route as no legitimate Canadian pharmacy is going to ship them to you. Might as well just say "skip the doctor and buy from India with Bitcoin."

You started with the premises that there was a legitimate way to fill my prescription cheaper.

And, no, buying from an unregulated pharmacy was never "worth it" to me, that's why I didn't do it even though it was an option.

The pharmacies are absolutely in compliance with Canadian law, and they are legitimate. This works for a lot of people. You don't have to do it if you don't want to, but there is no legal risk to you.

Which site do you recommend in Canada?

I've said said elsewhere in this thread, but the cost is about a dollar a pill at Costco. (Costco is amazing.)

I haven't used any, but I found some just by googling and I'm sure you can find reviews on reddit.

It's not covered by insurance for ADHD, and the issues with grey market overseas pharmaceuticals has been overblown by vested interests.

I guess it varies? My CA doctor prescribed it for ADHD and I had no insurance challenges.

Things may have changed since I got my prescription. Also might be the carrier.

In your country.

So my wife was on modafinil for a time, due to being very sleepy for unknown reasons. The doctors figured it was better than whatever stims they had her on before. Within a year or so of starting her on modafinil, they told her to discontinue use because there are indications that long-term regular use causes neurological damage.

I don't know what their sources were for that, and it seems likely the doctors would be very conservative in prescribing experimental drugs, so there was probably an abundance of caution in play there. That said, the long-term side effects really are not well understood at all, so I'd think twice before making a regular habit of modafinil use.

I have been experimenting with moda for a few months. Started of on 100mg and was smashing through my workload, just due to being generally less chatty or interested in shooting the shit with co-workers.

My next batch I went for 200mg's to see how that affected me. Made me super moody, fidgety and I would get agitated when something didn't go right for me straight away. 100mg seems to be the right amount for me. Everyone else I asked about 200mg said they had the same side effects.

I also don't use it much now, tending to take it once every 2 weeks to crush out some work. Wary of dependence on it, and also what it's doing to my brain.

To give another anecdote about focus-related chemicals, this one from a former amphetamine (adderall)/ methylphenidate (ritalin) taker (by prescription) from high school to the first year or so post-college.

In high school I tried caffeine to get focus, but it never worked well. This was largely caffeine from soda. After seeing a therapist and a psychiatrist, and doing a combo of stimulants for ADD + good-study/work-habit-building work suggested by the therapist, was able to get through school much more successfully than before. It gave a much clearer feeling, long-lasting (with extended release variants of the drugs) focus than soda. Really quite remarkable.

But I was never super thrilled with the tolerance building. A few days cold turkey would reset things, but I was pretty useless for those days (of the lying in bed watching TV and eating cheetos all day variety). This got harder after college, when the only available times were weekends, and I wanted to be more social. I had some concerns with some of the potential long-term health effects, too.

I managed to wean myself off, and rely on the good habits it had helped me built, but work was definitely more of a chore after that. Then I got into coffee and green tea - at first, in fairly sweet sugar+creamer or latte form. This was still sort of a jittery focus, similar to from soda. Eventually, though, I started drinking black coffee and straight green tea (no rhyme or reason to which one on a given day, just my two forms of caffeine of choice).

For me, the difference between "caffeine from straight coffee or tea" and "caffeine from heavily sweetened sugary beverage" was enormous. My jitters mostly came from the sugar levels. Couple that with more and more studies suggesting potential positive health benefits from both straight coffee and tea, and I'm feeling better overall for sure now. It's not quite the same as the magic productivity pill of amphetamines, but it's good enough for me now.

The other major thing that changed for me over the years was my interest in the material. High school and first-few-years college work can be bland, and good habits were supremely helpful here as well. Don't wait until the last minute, don't do a few 14-hour day binges to get caught up or crank something out quick and dirty, etc. Between learning that, and working my first few jobs to find roles that had more natural appeal to me, I have much less need for supplements than I used to anyway.

I sometimes do Phenylpiracetam which is another nootropics to get works done (for exams for example), but when I do it while programming, by the end of the day I'm totally brain-dead, does this also happen with Modafinil ?

Sometimes you can end up with energy debt after modafinil - if you get a lot done while wired you may find yourself exhausted after it wears off.

nope. I come from one of the world's producers of coffee, Puerto Rico. Starbucks give me a break. I've seen better stuff at in the grocery aisle.


For an alternative to modafinil, I would like to take the opportunity to recommend trying ginseng.

I take it as gelatine capsules (good quality from a serious vendor), one every day. It takes a couple of weeks before it kicks in for me, but from then on it has a distinct effect - I can think about programming problems with a lot more clarity than usual, even when tired at the end of the day. Quite weird really. Traditionally one would run a three month course, then stay off for a couple of months before starting again.

There is always the possibility of placebo effect, but I've tried a lot of things and this one feels real. There are also real scientific studies showing enhanced mental acuity from using ginseng [1][2][3].

Of course is has the benefit of being a natural remedy (and legal, if you care about that).

[1] https://www.ncbi.nlm.nih.gov/pubmed/20676609

[2] https://www.ncbi.nlm.nih.gov/pubmed/16401645

[3] https://www.ncbi.nlm.nih.gov/pubmed/20737519

Ginseng is nothing like modafinil and not an alternative.

> Of course is has the benefit of being a natural remedy

Other than being non-prescription there's no benefit of it being natural. Since they're so unregulated supplement purity and potency varies significantly. Many don't contain the advertised ingredients and some are contaminated.

Great to see ginseng on HN! My startup Rareroot may be of some interest to you: We are building a web platform to let people buy wild ginseng directly from growers. We have not launched yet, but you can sign up for our mailing list. Thanks!


Can you recommend a brand?

The brand I use is from a local producer. Generally I would avoid anything that is well-advertised, those brands seem to usually contain lower grade or less active ingredient. You should look at the amount of ginsenosides. The one I use contains 16 mg per capsule.

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