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Modafinil-Induced Changes in Functional Connectivity of Healthy Elderly Subjects
- JumpCrisscross 10y agoN=24. Intriguing, but not evidence--taken alone--to effect behavioral changes by.
- coretx 10y agoAlso: 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 10y agoSurprisingly little is known about modafinil's activation chain, unfortunately.
- lnanek2 10y agoConsidering 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 10y agoThe 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 10y agoWhen 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 10y agoAh, 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 10y 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 10y 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 10y 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 10y agoSo would neuroscientists.
- jonnycomputer 10y agoFunctional 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.
- iandanforth 10y agoWarning 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.
- davymac 10y agoGet yourself checked for sleep apnea
- iandanforth 10y agoThanks! Amusingly I actually ran polysomnography sessions for a while and so was tested many times as part of that training.
- rhizome 10y agoApnea more than narcolepsy?
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- mdekkers 10y agocheck for sleep apnoea
- sergior 10y agoWhen 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.
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- 40acres 10y agoAre 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.
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- theWatcher37 10y agoNice try FBI
- mythrwy 10y agoYes, 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.
- mrcactu5 10y agonope. 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 10y agocongratulations
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- teslaberry 10y agoconsider that much of our neuroscientific studdy is done as it was almost 20 years ago but with finer resolution. we look at MACROSCOPTIC blood flow in the brain and try and calculate metabolic consumption of macro areas of nuerons in live brain cognition. as much as we've learned a lot and continue to do so, the approach has and always had a fundamental limitation. neurons behave and then consume oxygen. their behavior is NOT the consumption of oxygen. their behavior is whatever it is, including spiking and rapid expulsion and repuptake of neurochemicals from both synapses and non-synapses junctions. they also move macro molecular proteins around inside the cell. and of course------oligodentrocytes do a whole bunch of things we do not yet really even understand. i hope and expect one day that using blood motion in the brain will be a completely obsolete method of studying the brain's underlying mechanisms of action (it will likely always be useful clinically for diagnosing certain conditions). if it's not obsolete, it means we have not made meaningful progress to other current methods. surely if those methods progress in significat ways------they will render all current fmri totally useless and show us that at least 50% of what passed for brain science with fmri studies was at best bad science, and at worse psuedoscientific garbage done because grant money was forthcoming. or because of some foolish desire to profit off of selling pharmaceutical anti-depressants, or transcranial direct stimulation or other technolgies whose underlying mechanism is not understood and might not even be effective.
- BuenosAir 10y agoI 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 10y agoSometimes 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 10y agoI 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_Panel 10y agoMy 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 10y agoW/r/t the Modafinil headaches, I've heard they can sometimes be ameliorated with choline, which is found in eggs.
- ageofwant 10y agoMate, 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 10y ago
- johnyzee 10y agoFor 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 https://www.ncbi.nlm.nih.gov/pubmed/20676609 [2] https://www.ncbi.nlm.nih.gov/pubmed/16401645 https://www.ncbi.nlm.nih.gov/pubmed/16401645 [3] https://www.ncbi.nlm.nih.gov/pubmed/20737519 https://www.ncbi.nlm.nih.gov/pubmed/20737519
- mrfusion 10y agoCan you recommend a brand?
- johnyzee 10y agoThe 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 10y agoGinseng 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 10y agoGreat 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/ http://rareroot.com/
- gotothedoctor 10y agoProtip: 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 10y 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.
- WalterSear 10y agoIt's not covered by insurance for ADHD, and the issues with grey market overseas pharmaceuticals has been overblown by vested interests.
- gotothedoctor 10y agoI guess it varies? My CA doctor prescribed it for ADHD and I had no insurance challenges.
- WalterSear 10y agoThings may have changed since I got my prescription. Also might be the carrier.
- nommm-nommm 10y agoLol. 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.
- golergka 10y agoA 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 10y agoI 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 https://news.ycombinator.com/item?id=8868035
- golergka 10y agoEven if the drugs are completely safe and don't have any drawabacks, my question still stands.
- parasight 10y agoI 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 10y agoModafinil 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
- majormajor 10y agoTo 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 10y agoJust 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 10y agoI 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 10y agoSo 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 10y agoAs 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 :' )