Modafinil-Induced Changes in Functional Connectivity of Healthy Elderly Subjects

http://journal.frontiersin.org/article/10.3389/fnagi.2017.00085/full

by LolWolf • 9 years ago

210 65 9 years ago

journal.frontiersin.org

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

coretx• 9 years ago

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.

danielfoster• 9 years ago

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

lnanek2• 9 years ago

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.

manarth• 9 years ago

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.

johndubchak• 9 years ago

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.

hashmymustache• 9 years ago

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.

marmaduke• 9 years ago

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.

et2o• 9 years ago

"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.

kyledrake• 9 years ago

"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.

JackFr• 9 years ago

So would neuroscientists.

jonnycomputer• 9 years ago

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.

iandanforth2• 9 years ago

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.

atlas_hugged• 9 years ago

Get yourself checked for sleep apnea

iandanforth2• 9 years ago

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

rhizome• 9 years ago

Apnea more than narcolepsy?

mdekkers• 9 years ago

check for sleep apnoea

sergior• 9 years ago

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.

mrcactu5• 9 years ago

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.

contrahax• 9 years ago

congratulations

BuenosAir• 9 years ago

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 ?

beaconstudios• 9 years ago

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.

thepumpkin1979• 9 years ago

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.

Nav_Panel2• 9 years ago

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.

yoloswagins• 9 years ago

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

ageofwant• 9 years ago

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.

icelancer• 9 years ago

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

Nav_Panel2• 9 years ago

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?

always_good• 9 years ago

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".

gotothedoctor3• 9 years ago

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.

nommm-nommm4• 9 years ago

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."

johnyzee2• 9 years ago

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

mrfusion• 9 years ago

Can you recommend a brand?

johnyzee2• 9 years ago

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.

driverdan• 9 years ago

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.

rareroot• 9 years ago

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!

http://rareroot.com/

gotothedoctor3• 9 years ago

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?

chimeracoder• 9 years ago

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.

WalterSear2• 9 years ago

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

gotothedoctor3• 9 years ago

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

nommm-nommm4• 9 years ago

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.

baddox• 9 years ago

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

namlem4• 9 years ago

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

drcongo• 9 years ago

In your country.

golergka2• 9 years ago

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?

teddyh• 9 years ago

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.

① https://news.ycombinator.com/item?id=8868035

golergka2• 9 years ago

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

parasight• 9 years ago

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.

jv0010• 9 years ago

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

RyJones• 9 years ago

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.

brookside2• 9 years ago

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

majormajor• 9 years ago

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.

andy_ppp• 9 years ago

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!

AJRF• 9 years ago

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.

rebuilder• 9 years ago

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.

justlurkinNP• 9 years ago

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 :' )

Modafinil-Induced Changes in Functional Connectivity of Healthy Elderly Subjects

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