An Experience with Modafinil
erowid.org
erowid.org
Regulations are sticky. The FDA follows the precautionary principle. Political game theory incentivizes restricting what the electorate can do rather than giving them more freedoms, and being blamed for whatever harm may fall upon them from their licentiousness. Reversing drug laws specifically seems to require both clear evidence of benefit, and widespread support from the public and media. This leads me to believe that modafinil will takes ages to be rescheduled.
[0] https://www.gwern.net/Modafinil#fn28
[1] https://www.gwern.net/docs/modafinil/2002-deroche-gamonet.pd...
80% of people couldn't distinguish I.V. cocaine from I.V. caffeine in some study I am unable to locate at the moment, which I think involved Nora Volkow from NIH, either as PI or collaborator.
Sure, some people do fall down into the trap of doing something too much, this is true for lots of things, including video games (which I've been more addicted to than drugs at some points in my life). But if you have a kind of normal life during the week that you like too much to lose, then it's not that hard to keep your drug usage to where it's accepted, for your sake and others.
I do love cocaine, but seeing what happen to others when consuming things too much, is a great tool to avoid liking it too much so it takes over your life.
Aren't 45% of US adults obese?
But normal. The cloud of thoughts gone, I am able to make myself do anything with one thought, I have energy, the aches are gone, the tinnitus is gone, I don't second guess, I don't overthink. I just am and I do. It's amazing. This is what people like Bezos and Musk must be like lol
Amphetamine probably feels like this, too, although many say it's actually quite distinct. The price, (un)availability, very short duration and the comedown are big negatives, sadly.
But yeah, comparing it to caffeine... nah. Can't comment on IV, but I can compare it to insufflated caffeine. It has some similarities, but the important parts are missing. Or maybe I'm just desensitized to caffeine. At least I'm a good fake coke detector lol
“So, the first time you tried cocaine, were you surprised that you didn’t react the way everyone else did? Did it calm you down instead of getting you keyed up?”
“I’ve never done cocaine”
“Look, yes, some doctors might disqualify you for stimulant prescriptions for admitting to past substance abuse, but it doesn’t bother me at all. I actually do some research at $local_university specifically looking at how properly managed ADHD dramatically reduces the chance of substance abuse.”
“Serious, I’ve smoked pot, I’ve done mushrooms, but I’ve never tried coke. Had lots of opportunities if I wanted to, but it didn’t appeal to me”
“Huh! With lots of the patients that come through here, they see me for the first time after casually mentioning to a GP that they’re worried they’re weird when coke doesn’t work right for them!”
I was diagnosed twice, both times in adulthood. The first time was by a neuropsychologist who did something like 8-10 hours of testing over about 3 days. I’m not even sure if she ever asked me about any sort of drug use.
The second person to diagnose me was a physician at the student health center where I was a graduate student. Believe it or not, he was actually a pediatrician! I think he may have asked me about my caffeine consumption (excessive!), while also being impressed by my shockingly normal blood pressure (almost always between 110/70 and 125/83). I actually think going on Adderall might have lowered my BP overall, due to the increased ability it gave ume to tolerate and problem solve my way through stressful situations.
> This is what people like Bezos and Musk must be like
I would agree with you that it makes me feel normal in the sense that's what it seems I should have been. The first time I tried it, I was like "so when I'm gonna feel the effect?" for a few seconds and then I realized I feel it and thought "That's the way it [life] 's meant to be played" :D
Have you been evaluated for ADHD? This is one of the classic tells. Methylphenidate is structurally and chemically very similar to cocaine.
Vyvanse is definitely the best when it comes to duration and classical stimulants. Modafinil has even longer duration, but it isn't always as effective at targeting ADHD symptoms. Vyvanse is kind of stupid expensive, but you can get a savings card. It would be $330 for me even with a good Rx plan, and the card knocks it down to $45/month. Sounds like you would also respond well to Concerta (extended release methylphenidate). I don't like it because I apparently have the metabolism of a honeybadger and get like 4-6h of otherwise "all day" meds like concerta. I have to split my vyvanse and take it in two doses to get a full day.
> This is what people like Bezos and Musk must be like
My headcannon is both these guys are ADHD and/or on the spectrum, have a doctor's script for vyvanse, adderall, modafinil, and/or whatever else, and have figured out how to ride the tolerance curve properly to maximize productivity.
However, Ritalin is less neurotoxic than amphetamines that can indeed hike your risks of Parkinson’s (and probably few other things)
Pls send some studies, very interesting.
> We observed decreased expression of this enzyme for all applied substances.
Yeah no I'm not buying it. Amphetamine, perhaps, but atomoxetine causing DNA damage? That sets off my "spurious results" detector, hard.
I'll look into it more but I've done deep research into all things psychostimulants and I have not seen any indication of genotoxicity of methylphenidate or atomoxetine. Amphetamine has a slight risk of increased oxidative stress due to making dopamine leak places where it shouldn't, and DA's electronic structure makes it prone to generating singlet oxygen and ROS, but it's typically only observed in really high doses, like the equivalent of hundreds of mgs per dose.
Like, maybe there's some increased ROS due to any drug that boosts DA/NA (oxidizing catecholamines produces ROS in general), but like, "ritalin causes DNA damage" is the wrong conclusion to draw from that.
The chief problem I have with all stimulants is too fast of an impulse response. It comes on too fast, crashes too fast. For me, for instant release drugs, I experience the following half-lives:
- methylphenidate: 60-90m
- amphetamine salts/dexedrine: 3-4h
- caffeine: 3h
- modafinil: 6-8h
Once a drug reaches about 1.5 HLs (about one Tau/time constant, conveniently), I start fading hard. There is a hysteresis effect: peaking/crashing/re-dosing is not the same as plateauing at some in-between value. Once my brain checks out, that's kind of it for the day.
So what Concerta, Adderall XR, and similar do for me, is give me what feels like two randomly spaced doses of instant release over a 4-6h window. This is unpredictable and thrashes my mental state. It peaks too high and crashes too low. The companies market these drugs based on averaging the plasma profiles of individuals to show a nice smooth curve, but I dug into the literature and this is NOT what you see on an individual level, at all. Concerta just doesn't do it for me.
Vyvanse is way smoother. The plasma peak is already low-pass filtered by the pharmacokinetics of hydrolysis of the lysdexamphetamine. As a result, my subjective experience is basically a 6h plateau. I split my dose to basically get a nice, actually smooth profile over 8-12h with a gentle taper instead of a crash. That also means lower peak plasma conc, and peak plasma is the greatest risk factor in neurotoxicity.
If you actually dig into the literature on neurotoxicity of amphetamines, you basically don't see any until you start getting to the equivalent of 50-100mg IR, and even then it's basically within the noise floor until you get to hundreds of mg per day.
ADHD is just most likely because it’s so common, with sleep apnea being close second. I would rule out ADHD and sleep disorders first.
Potentially also, UARS, which is also form of sleep disordered breathing but not commonly detected with current technology (and also not easy to treat), some physicians do a full nasopharyngeal endoscopy under propofol anesthesia. I believe it’s incredibly undiagnosed and probably accounts for more than 10% of apnea cases, but most patients are thin instead of obese and so nobody suspects apnea-like disorder. If you needed braces or needed corrective jaw surgery UARS should be ruled out.
ADHD can be somewhat objectively measured with some tests like CPT, but that would also often show abnormalities in sleep disorders.
If your measures of attention, and sleep study, along with wakefulness maintenance test, if warranted, are all normal, and your pulse and blood pressure is normal, and by normal I mean very close to ideal 120/80, with hr below 70 - maybe you are just a mutant.
See a good neuropsych that specializes in sleep disorders. Stanford is one of the better centres for that. They will know what to do if it’s not a sleep issue also.
dx of ADHD and good response do not preclude the possibility of other disorders.
you can obtain treatment that way, and investigate other causes later, you may have to wash out from stimulants for a few weeks for the CPT and WMT, and preferably for sleep studies also, because they increase muscle tone and if your sleep issue is due to some neuromuscular issue, stimulants may partially obscure it. (This is still in research, and most physicians won’t tell you this, as it’s not yet standard of care in most places afaik)
All this tells me is that I'm clearly consuming caffeine incorrectly in the form of coffee and/or tea.
Mucosal absorption is definitely way faster than pills (unless you chew them) or drink.
One time a friend and I tried making caffeine patches with DMSO as a transport, and put it on our arms with a cotton ball and tape...NOT PLEASANT. Extreme pruritus and erythema at the administration site. Hoo boy were we alert though. Nowadays the gum is perhaps a bit too fast even, it's easy to overdue and I get palpitations.
Follow me for more horrible ideas and biohacks. /s. I don't actually have a channel for my misadventures and shenanigans...maybe I should?
I can’t imagine buying caffeine for its own sake. The effects aren’t good enough. If I didn’t drink coffee/tea I just wouldn’t get any caffeine.
Also as I understand: it is against the rules to import it so it will be stopped if caught but not against the rules to have it so you do not get fines or anything on record. Thus if you buy it abroad you can bring it into country with you unless caught in which case they confiscate it. This used to be the same case with Modafinil / Adrafinil and I suppose it is still the same.
I don’t know what I would even do with liquid caffeine. But again, I don’t want caffeine badly enough to be looking for alternative ways to get it.
The problem of course is that they want to make sure you don't take too much caffeine and have a problem, so they want to limit the strength of what you can get and my understanding from him was the strength was limited so that it was hard to get anything into you with the strength of a cup of espresso, as ridiculous as that sounds but nanny-statism is a thing.
I was absolutely lit up and it was an incredible experience. I felt utterly amazing. Like I could take on the world. I had a hard time focusing at work, because I just wanted to be talking to people (not an extrovert) or going for a 10 mile run.
I can't compare it to cocaine, because I've never tried it, but I'm guessing the reason for your perception of it is because of your tolerance to caffeine.
> I can't compare it to cocaine
Sounds like you just did.
The past being a different country, I was fortunate in the early Noughts to be able to purchase Bolivian coca tea bags from an early online drug dealer called Amazon dot com.
They were a fantastic addition to the tea shelf. I would favor a cup of the coca tea when energy was low going into an evening with social plans. Even, bright energy, short acting (duration is two hours roughly) barely feel it fading.
How does that compare to refined cocaine taken intranasally? Remarkably, I can't tell you, I don't touch the stuff. Sure wish I could still buy mate de coca though.
Coca tea is awesome.
Immediate, bright energy, short acting (duration is half hour), feel it fading within minutes (which is why you want more)
Should perhaps be insufflation
Insufflation is actually a misnomer for nasal administration, insufflation is blowing something into a person for medical reasons, not using vacuum to pull it into the body.
Now, it's a common misnomer, which I generally let pass without correction. But sauce for the goose is sauce for the gander!
That is complete bullshit.
IV bleach would also have pretty serious effects, but likely no one would confuse it for cocaine.
The onus is on inter_netuser to provide evidence for the claim, not for pennaMann to refute it. I would imagine that literally no study exists comparing the effects of intravenous caffeine and cocaine, because who would possibly fund that study, and to what end, and what review board would approve it?
> Intravenous nicotine and caffeine: subjective and physiological effects in cocaine abusers
> The subjective and physiological effects of intravenously administered caffeine and nicotine were compared in nine subjects with histories of using caffeine, tobacco, and cocaine.
> https://pubmed.ncbi.nlm.nih.gov/11160635/
Since this study exists, why is it so far off the other study exists? I don't know why it got funded, or to what end, but I'm sure happy it did. We need to study drugs more, not less.
Idk why people are so surprised. Even iv DMT has been funded and officially researched some time around 90s
Also, LD50 values are always extrapolated from single dose tests on lab animals, typically rats or mice. Not only is that not how a human would end up ingesting 10+ grams of caffeine, the LD50 varies considerably from one animal to the next.
For instance:
> [S]ome LD50s for dichlorvos, an insecticide commonly used in household pesticide strips, are listed below:[0]
> Oral LD50 (rat): 56 mg/kg
> Oral LD50 (rabbit) 10 mg/kg
> Oral LD50 (pigeon:): 23.7 mg/kg
> Oral LD50 (rat): 56 mg/kg
> Oral (mouse): 61 mg/kg
> Oral (dog): 100 mg/kg
> Oral (pig): 157 mg/kg
As you can see, these numbers don’t seem to scale up in any intuitive way when you start crossing animal species.
——-
If we imagine a study where the users have never had either I.V. caffeine nor cocaine, well, how are you supposed to reliably distinguish between two stimulants hitting your heart and brain directly, without passing through any sort of blood brain barrier, when having that experience for the first time?
Now, it would be a useless study for us. But not useless for the chucklehead who padded his or her CV with it.
[*] I'm only calling out the LDS community here because they don't consume coffee, or cocaine, generally speaking.
They just drink ephedrine instead of caffeine.
But, due to a lot of retroactive canon gymnastics, cold caffeinated beverages like soda are consumed in great quantities by Mormons. Actually, under the latest "official" stance, tea made from the "mormon tea" plant would actually be banned, as it's a "hot beverage" with mental effects.
The idea that caffeine is comparable to cocaine is pretty nuts. People murder to get cocaine. When’s the last time anyone murdered for Starbucks?
I can totally believe that if you give someone who’s never done drugs a high dose of caffeine and tell them it’s cocaine, they might believe you. But that’s not at all the same as the two actually being indistinguishable.
“I feel like my heart’s going to explode and I can’t stop moving!” “That’s the cocaine.” “Not what I would have expected, but okay!”
I am quite certain the study exists, because I recall her talking about the findings, and then reading the abstract.
But I’d love to be wrong. That would be a very interesting result.
but, like it or not, caffeine is a psychostimulant, and psychostimulant substitution is fairly well established, idk whats the controversy.
if you want to find it, you might have to crawl thru every reference of volkow's 100+ papers on cocaine.
If you want to use the reference, I suggest you find it and validate it exists before trying to make some claim.
I also don’t think anything malicious but think it’s more likely that you misunderstand something than the paper exists and you can’t find it.
As a reader trying to determine if your claim is bullshit it’s not worth the risk that you’re wrong for me to exhaustively review all 100+ papers to make sure it doesn’t exist.
As the saying goes, “If you hear hoofbeats outside your door, it’s probably a horse not a zebra.”
>Intravenous caffeine also resembles cocaine, she points out.
If you were seriously addicted but not high at the time, I expect you might feel agitated, but also kind of sorry for yourself / miserable and not so much in a murdering frame of mind.
Large amounts of money (which large amounts of cocaine can be exchanged for), on the other hand...
The DARE program told me that definitely 100% of illegal drug users eventually turn to murder to acquire more, but that might have been an exaggeration.
Someone rips you off in the drug industry you and your buddies go beat them up and take their stuff of value. Someone rips you off in above the table business you sue them.
Heroin withdrawals are quite painful (literally), and many users are also simply suffering from endogenous depression that responds to almost nothing, and in fact used to be treated by morphine.
Same goes for alcohol and benzo withdrawals that WILL give you seizures and quite possibly death.
Psychostimulants (cocaine, amphetamines, cathionines, other assorted alkaloids, including caffeine) withdrawals means being very tired, lethargic and sleeping a lot, they are not life threatening.
If people could buy cocaine at Starbucks (or get cheap stuff at a dollar store), would supply be such a problem for users that they resort to crime?
If caffeine were banned tomorrow and prices rose a thousand-fold, to what lengths would millions of addicts go to postpone the dreaded headache, constipation and lethargy for another day?
I would expect society would have a bad weekend, and then people would get over it quickly.
Honestly: easily accessible opiates are known (history) to do a lot of damage.
here is a very old one, but oral not i.v.: https://pubmed.ncbi.nlm.nih.gov/4900434/
5mg/10mg amphetamine sulphate vs 300mg and 600mg of caffeine (all oral). The study scales ended up being skewed because one subject had paradoxical response and felt relaxed instead on amphetamines, lol.
If you have access to the full text, check out page 89: fig5 and fig6.
Volkow's lecture may have referenced multiple studies, I've heard that in the context of her lecture on various findings on psychostimulants. amphetamines and cocaine have been fairly repeatedly shown fairly consistent substitutes, so it may have been a study on amp vs caffeine.
She just loves to study and talk about cocaine for some reason, has literally a hundred+ papers on it.
That happens to me and I want to research what it means but your link doesnt seem to work
Being calm and relaxed on amphetamines can potentially mean there is some arousal disorder: sleep apnea, narcolepsy, delayed sleep syndrome, or just chronic sleep deficit. Maybe concussions (mild TBI), amphetamines work for that too.
ADHD is most likely because it’s so common, with sleep apnea being close second. I would rule out ADHD and sleep disorders first.
Potentially also, UARS, which is also form of sleep disordered breathing but not commonly detected with current technology (and also not easy to treat), some physicians do a full nasopharyngeal endoscopy under propofol anesthesia. I believe it’s incredibly undiagnosed and probably accounts for more than 10% of apnea cases, but most patients are thin instead of obese and so nobody suspects apnea-like disorder. If you needed braces or needed corrective jaw surgery UARS should be ruled out.
ADHD can be somewhat objectively measured with some tests like CPT, but that would also show abnormalities in sleep disorders.
If your measures of attention, and sleep study, along with wakefulness maintenance test, if warranted, are all normal, and your blood pressure is normal - maybe you are just a mutant.
See a good neuropsych that specializes in sleep disorders. Stanford is one of the better centres for that.
I don't know, when's the last time Starbucks was selling pure caffeine injectable via IV?
on edit: another day, another downvote, but that doesn't change the fact that the whole discussed comparison is between IV versions of the drug, and as such it's ridiculous to compare cocaine against Starbucks coffee as if that disproves the assertion.
Allow me to introduce you to a bit of unpleasantness called the Opium Wars.
Which could also be called the "Give us the Tea, or Else" wars.
Sugar can't be as addictive as heroin! People give blowjobs to get more heroin, no one gives a blowjob for a chocolate bar.
But that has nothing to do with addictiveness.
I don't need to murder someone for coffee or provide oral sex for a snickers, because I can easily get those things anywhere, anyway
I just mean that it's a bad argument.
https://archive.fo/bLX94 >This is obviously worrying. “Cocaine is one of the most addictive substances of abuse,” says Volkow. “Ritalin we give to children.” She stresses, however, that taking a stimulant orally is very different to injecting or snorting it. Intravenous caffeine also resembles cocaine, she points out.
h/t to those with better google-fu than mine. all from this thread.
fwiw, caffeine is also the most common adulterant in cocaine, so chances are your iv cocaine also had a good amount of caffeine and lidocaine in it.
....but why would you even try pure i.v. caffeine though? cocaine i can understand, but caffeine?
Sometimes when you're an IV drug user and you're out of real drugs, you do weird shit. I had a tub of anhydrous caffeine, had to try it.
I get that you think you can disprove things like this with science, and that's generally a good perspective to have. But cocaine and caffeine are nothing alike. It's the difference between a kiss on the cheek and a punch in the face. You could describe those two things in the same terms if you wanted to be abstract and clinical enough, but the idea that they are indistinguishable is laughable to anyone who has experienced both.
Caffeine is a moderate boost to wakefulness. You feel a little more energetic, a little more awake. Maybe a bit happier. Cocaine is every form of success you've ever felt multiplied by 100, rolled into one, and compressed into 3 seconds. You ever win a low probability bet, or be right about something when everyone you know doubted you? That's what cocaine feels like.
Shoot up caffeine and you might work a little harder for a couple of hours. Shoot up cocaine and you might marry a stripper you don't even know yet.
EDIT: What I will say is that, perhaps at a sufficiently low dose, they may be hard to distinguish. But at the doses consumed by recreational users, they very much are not. My guess is that these studies are using very low doses of cocaine compared to what a recreational user would take, for ethical/safety reasons. So, in that context, it may be true, but you should not take that to mean that cocaine and caffeine are in any meaningful sense indistinguishable.
https://www.nytimes.com/1914/02/08/archives/negro-cocaine-fi...
https://en.m.wikipedia.org/wiki/Cocaine_in_the_United_States
however, modafinil it's actually cleaner and even safer than caffeine. That's the point. a less toxic, safer drug is illegal to possess (w/o rx).
How would you justify making a much more toxic drug completely unrestricted, what would be your argument? We'd just have cops showing confiscated bags of big bad evil drug caffeine to kids in DARE classes.
https://pubmed.ncbi.nlm.nih.gov/25414797/
or this :
https://www.beveragedaily.com/Article/2002/09/02/Coffee-acts... https://www.purdue.edu/newsroom/releases/2016/Q4/mixing-ener... https://www.purdue.edu/newsroom/releases/2016/Q4/mixing-ener...
they seem to imply something similar what you are stating
this one found no such effect on rats:
https://www.sciencedirect.com/science/article/abs/pii/S01497...
and most of the articles I found say that caffeine INCREASES the effect of caffeine
That's expected, there is a reason why it's most common cocaine adulterant, along with lidocaine.
People cutting it probably read the same studies.
>Intravenous caffeine also resembles cocaine, she points out.
If you think cocaine and caffeine are even remotely comparable in their effects, then, well, spring chicken, let me introduce you to the world.....
Most people can't answer the question "Is caffeine a xanthine or a phenethylamine" any better than chance. Good luck explaining there's a second drug that doesn't really get you high, but mildly inhibits the metabolism of a whole bunch of native 'drugs' in your brain as well as the caffeine.
No I mean that, good luck, it's fun to get as far as you can with that stuff. Just wanted to answer your second question.
Apparently the skin issues from it can be so severe it’s being warned that Stevens-Johnson Syndrome is a possible adverse effect of it.
Initially first results showed that despite the warning there had yet to be an actual case in documented literature, but scrolling further showed a case in an early 20’s patient in 2018. Scrolled back up, & the first results were from 2017… so yeah I guess.
It isn't an "extremely careful" type of situation. It's a "take 50mg first and be aware that skin outbreaks can be caused by modafinil" type of situation.
This isn't well understood because there are so few cases, but it's believed to be effectively an allergic/histamine response, and I've never heard of a case of it developing after regular use (sensitization), only initial exposure.
In terms of how often modafinil causes Stevens-Johnson Syndrome (or whatever actually happens here) it seems to be about like aspirin and Reyes syndrome, but without susceptibility being limited to the very young.
A pill is 200mg and that's a lot of molecule (I find it a high dose as well, ymmv). Everyone has to find their own risk threshold, but "take a quarter pill at first just in case you're the 1/100,000 who gets a rash" is my safe bet for risk mitigation.
For context, my first -afinil was adrafinil, which I imported from France around 2000 on the strength of some blog about how it was a preferred treatment for ADD (the H wasn't a thing yet) there. Adrafinil metabolizes to modafinil, and France is a pretty big place with a unified modern healthcare system, if this adverse effect were more than very uncommon I figure it would have shown up strongly enough to have prevented that in the first place.
That might be true but Modafinil is very dangerous compared to coffee.
It does cause accidents for instance.
If you take it medically, it can reduce accidents.
Off script you play with fire using it with heavy machinery.
Throw in alcohol that scene in Limitless becomes quite true.
Being less toxic and less addictive is meaningless comparing to something like coffee.
This is merely an anecdote, but I was prescribed modafinil for narcoleptic symptoms. Compared to traditional psychostimulants, I found it to be ineffective with a more severe side effect profile. Of course, YMMV.
My brother has narcolepsy, and finds modafinil much better than amphetamines. He says he has zero side effects with modafinil, and it makes him much less jittery than amphetamines.
I have CFS, and sometimes need a stimulant if I must stay awake. I've tried amphetamines, but they make me really jittery and a bit anxious and snappy - I feel "tweaked", and it's not pleasant. By contrast, modafinil keeps me focused and awake, with the only side effect being a small increase in blood pressure.
IMO modafinil is a wonderful drug.
Modafinil is a "wakefulness" drug. My favorite comparison is the feeling that you get when you have to pee in the middle of the night, and your body sends out that hormone to wake you up. Modfanil just kind of keeps that process going continuously. There is no "high" or any hyperactivity, just an extra layer of wakefulness.
Really? I had no idea! Thanks for teaching me something new.
Neurotransmitters tend to be context-depended, so when you wash over the whole body with a small molecule which hits in a neurotransmitter-specific rather than context-specific way, you can get some funky effects. Most of the activity comes from the coincidence that there are some domains which correlate well with context: dopamine tends to affect anything resembling taxis, so physical movement, but also goal seeking, prediction, etc.
On top of all that, receptors and enzymes are physical things, and thus different folks have different affinities for transmitters and drugs. Pharmacokinetics - how your body distributes and clears drugs - is a huge variable.
Modafinil in particular is interesting because it's what drug chemists call a "greasy brick" - highly lipophilic, low solubility, to the point where ensuring consistent bioavailability is hard. Cephalon has put in a fair bit of work ensuring a certain particle size and excipient profile (emulsifiers to facilitate absorption) and personally I've experienced quite the difference between name brand and generic, the later often does jack-all for me.
td;dr - small molecules act on broad regions and impact many subsystems at once. Biology is complicated and crufty.
There are a bunch of different aspects to being awake. Caffeine works on adenosine, which has to do with wakefulness. But also things like adrenaline have a different aspect of wakefulness that amphetamines target. Modafinil targets orexin receptors I believe, which involve wakefulness as well as eating.
The only certainty we know is it’s located in your head and weighs a few pounds. That’s pretty much it.
The absolute best neuroscience program at the absolute best university would essentially read from an outdated curriculum (which means it’s from the last semester, in neuroscience that’s ancient history), supplemented with current studies, and you will be told that you will not be penalised for using answers from six months ago that have been invalidated now, and are absolutely wrong, but were the textbook dogma last semester.
Top program in America.
It's true that we don't know everything there is to know the brain, and critically we have zero idea where consciousness actually comes from; where 'you' exist within your brain.
But we do know a whole hell of a lot of details. A bunch of the different chemicals inside of the brain, how they influence behavior and mood. We know a whole bunch about different receptors and have drugs to modify their behavior. We're now able to use transcranial magnetic stimulation (TMS) to stimulate nerve cells in the brain and are able to use that to help people suffering from depression, OCD, and to help mathematical cognition [1].
Our knowledge is hampered by the difficulty of research in this area. The cost of imaging techniques - specifically SPECT scans which use 5-7 Tesla machines which use liquid helium which is super difficult to work with. This means there's not really a way to test exactly which medication will help a given individual other than to give it to them, but don't mistake that for a total lack of knowledge about how things work. We do actually know the method of action on how those drugs work, which ones are agonists and which ones are antagonist and which don't mix.
Better real-world treatment options would be really awesome! It sucks that we can't do any better. Cheap and better imaging options would really change the status quo and allow better real-world treatment for mental illness. But what we do know takes years, if not decades for a person to learn, so even though things are still changing in the field, even though we can't answer some fundamental questions about consciousness, we understand a whole hell of a lot more than "it's located in your head and weighs a few pounds".
[1] https://www.oxfordhandbooks.com/view/10.1093/oxfordhb/978019...
And yet, despite all this, no better treatments that amphetamines have been found for so many cognitive disorders.
100 years old drug, and to prescribe which you don’t even need to know how much the brain weighs.
What is the use to the laity of all this research, if half of the time the answer is stimulants, the other have is SSRI?
I think we will be seeing the most promising area in sleep, because it’s so underserved and you can collect a lot relevant data inexpensively and un-intrusively.
CFS remains a diagnosis of exclusion, and it's quite likely that it's a label that actually represents several conditions, and people are affected to varying degrees - some are bed-bound, for example.
I don't really believe there are no side effects, ritalin and coffee certainly have some. I also wouldn't want to use cognitive enhancers to solve problems. That said, I think it shouldn't be illegal.
Once did 48 straight awake on it and felt wide awake 36 hours in…
Distinctly remember the 1st time I took it. Was perhaps 8pm at night and I swore it was 8am in the morning and I’d just had an amazing sleep: felt completely wide awake and alert.
Anyway, it took 2 days in bed for me to recover after. Brutal.
Towards the end of that time period, my brain stopped processing information in the 30 degrees at the edge of my peripheral vision on either side. We were at a restaurant celebrating being done and the waiter kept teleporting into view at around 60 degrees off my center line. Very startling. Done with it now since I don’t have anything nearly that stressful in my life, but back then, it was a godsend.
Modafinil has a 15 hour half life so my main complaint was my sleep schedule was about 26-28 hours so I was constantly shifting. Adrafinil is only the active isomer in modafinil so it’s more potent. I didn’t like it as much. Even at a half tab it still kept me up longer than modafinil. Also modafinil makes your pee smell when it’s metabolized whereas adrafinil not nearly as much.
I mean I'm not exactly anti-medication but... wow.
It took me half a lifetime to really come to grips with it, but fact is, winners absolutely do use drugs. William S. Sessions' anti-drug arcade game ads lied to me.
If the score was not an indicator, then it serves no purpose.
Not all life is competition. Ecosystems in general are a complex web of cooperation. One could say that all life is cooperation with equal merit.
The idea that competition should not exist and is some outcome of "evil" capitalism is absolute ridiculousness. I was responding directly to that asinine comment.
Life without competition doesn't exist, nor should it.
It's a natural attitude that's innate to human survival. You need competition or you will be a miserable mentally unhealthy person. You're in denial if you don't realize this truth.
This ridiculous socialist utopia where everyone is at peace doing finger painting all day doesn't exist. It's a good way for your society to collapse though. Competition is not some artificial outcome produced by capitalist economic systems.
> Anyway, it took 2 days in bed for me to recover after. Brutal.
> my brain stopped processing information in the 30 degrees at the edge of my peripheral vision on either side.
> makes your pee smell
Arnold Schwarzenegger is a prominent example.
But now I get to make cool shit for a living.
Honestly believe if you give me enough time and money I can make anything. Worth it.
Same, but it didn't take a week on modafinil to finish a crazy project for me, I just always just liked making cool shit ever since I was a kid. Currently more on the software/kernel side, but I've done my share of hardware projects.
For me, after bouncing around a few universities, I realized how much of a broken joke the system was and resolved to go the easiest route to get the piece of paper (an on-line university), which I'm glad I did because the one time in my life I needed it it was important... but uni never taught me anything I couldn't have learned more efficiently on my own.
I distinctly remember that time in a microcontrollers class where the book was wrong and teaching the exact opposite of the solution to the problem it was trying to teach, and I'd known about that one for like 7 years at that point, and when I offered to the teacher to write a little article about it so we could all learn about it, he said yes and never even read it...
Or that time where as a sophomore I was helping a team of seniors working on a project to build a CubeSat, and I designed the PCBs and all the firmware and we won the competition to get funding and actually launch... and the uni's response was to kick us out of the lab we were in because "we were using too much space" (about 1m of desk space there). That CubeSat never launched.
Also, there was one part of that board designed by a professor instead of me. It was the only part that didn't work. And I thought it was dodgy at the time, and with my current experience I can confidently say that design was utterly insane and broken and he had no idea what he was doing.
Meanwhile in Calc II they wanted me to memorize three dozen identities because... why? I liked math until I got to that class, because even though it wasn't exactly being taught in an engaging way, I could work out the underlying concepts and understand and appreciate it, and work from first principles. Then it got complicated enough that doing that at the exam was no longer viable and I was just expected to become a computer and memorize all the damn formulas (and it wasn't just a few), understanding be damned. I cheated my way through that exam ("yes professor, I promise this TI-84 emulator on my Zaurus PDA is exactly like the real thing and I don't have a little formula database app in another window"). I damn well know what integration is and how it fundamentally works and how to apply it, but storing rote trivially looked up information is what we have paper and computers for. I don't go around memorizing programming APIs, I look up what I need and whatever I use often enough comes naturally.
Chemistry was more fun. We were allowed one index card, handwritten, both sides for the exam. I developed an electrical arc sharpening mechanism for mechanical pencil lead, so I could handwrite it all in 4pt size or so. Give me limitations and I will make the best use of them :)
Yeah, the system is broken.
Don’t read too much into individual HN comments, especially those describing outlier behavior.
1) I’m not taking random pills from a stranger, let alone before the SATs
2) If it is adderall, I have no idea what it would do to me
3) If I need adderall to do well on the SATs that would get me into a better college, I’m going to need it through college
Seeing this story makes me think that, yeah, some people probably do make it through hard programs with medication…
I’m confused when I read anecdotes like this. Are you staying you literally slept for 2 hours over the course of 7 days, averaging 17 minutes of sleep per night for a week? I think that’s very unlikely!
However,
psychosis usually sets in around ~96 hours of sleep deprivation. It is however possible that this individual is unique or resistant, or maybe just his youth helped him. When I was 16 and MTV still played music-- I could survive on 2hrs sleep a day for weeks.
Please tell my brain this. Around 50% of the time my ADHD meds (Adderall) make me sleepy because, for once, my brain is calm and focused and it's a very relaxing experience as opposed to my typical state.
https://en.m.wikipedia.org/wiki/The_Dark_Fields
The book is really, really good. Much darker than the film, however. The ending is completely different, particularly the implications of the last paragraph.
If you're on a Dark Fields kick, Ted Chiang's 1991 short story Understand is worthwhile. Geekier and not as philosophically weighty, but way more fun.
Great story, as are most of his. It reminded me of the Dark Forest Theory [0] from the Remembrance of Earth's Past trilogy [1].
[0] https://bigthink.com/surprising-science/the-dark-forest-theo... [1] https://en.wikipedia.org/wiki/Remembrance_of_Earth%27s_Past
I'm not narcoleptic but somehow it just doesn't work that well for me.
Dexamphetamine worked but ooh boy the side effects like munting.
I expect you're thinking of armodafinil, the isolated r-isomer. I've taken it a few times, it's more potent by weight than modafinil but I'm unconvinced the chiral group is anywhere near so decisive as it is with amphetamine, where the laevo-rotary molecule is useless unless you have a head cold.
The lethargy and brain fog went away if I dosed again, but that only compounds the problems.
I still dose when I need a guaranteed day of focus, but I really try not to use it on consecutive days.
YMMV
As another commenter mentioned, used judiciously, it's amazing.
I have ADD, and am prescribed 60mg Adderall XR/day. OTOH, I have slept on 30mg Adderall XR a couple of times, so maybe I'm just "built differently" w.r.t. The Stimmies.
I guess this is a really nice hack he had: Has used Ritalin illegally? Increased probability of ADHD. Does it work? Even more increased probability and he know knows the person tolerates it.
This fascinates me. Some people seriously take stimulants at night to fall asleep, others in the morning to wake up..!
Recently I heard the story about how stimulants came to be used to treat ADHD and one thing that stood out except that this was an extremely suprising effect was the very simplified explanation that stimulants seems to stimulate the inhibitory parts of the brain most which seems to account for the increased self control.
I have previously used Modafinil fairly extensively and considered purchasing Ritalin or Adderall on the dark web, but was very worried about telling the doctor in case it would cause me issues getting treatment.
Two things, though.
One, that week does not exist to me. Like, I don’t remember it apart from the abstract knowledge that it happened. I learned C# and .net in the first 48 hours, having never used either before (we were a PHP shop - but some combination of naivety and hubris had us take the project on) - and a few weeks later when making some tweaks, I may as well have been looking at someone else’s code in a language I’d never worked with before.
Two, the comedown wasn’t awful, but I did sleep for about 36 hours straight, and woke up hungry enough to eat a bear.
Haven’t used it since - haven’t needed to - but I do keep a blister pack handy in case I ever find myself needing to function without cessation for a week again.
Was there any memory or retention of C# and .net at all (e.g. if you tried to learn it later, was it easier to pick up, or was the memory completely gone)?
I'm curious about what happened after, too. Were you rewarded with a raise/promotion, or was there no reward so you moved companies? Faced with an impossible deadline, I've read it's better to just let the deadline slip because it's not worth the burnout or cost to mental health (because few deadlines are truly life-or-death), so I'm wondering whether pushing through was worth it in your case.
It was my business. I was the idiot that signed us up for it - it was kinda out of necessity, as it was for the New York marathon, and their developers had evaporated on them two weeks before a critical deliverable - and we charged blood money for it.
I've run years on end on a 50/5 stack, 50mg 15 minutes after waking, 5 days a week.
Energy levels on the weekend could be low but hard to separate that from working hard all week. It was sustainable.
Now if you get a real streak going, the two days after discontinuing you'll feel like an idiot. Hyperbolic tapering is a reliable solution to this: go 200/100/50/0 instead of 200/0, give your brain a fighting chance.
There used to be a vitamin for sale in the UK called Berocca that had the slogan "You but on a good day." Modafinil for me felt like me on a really, really good day.
I wonder if some of that 'comedown' is just lack of sleep.
They told me they had read multiple studies before hand as well as personal accounts (such as from the venerable https://www.gwern.net/).
That person told me that the feeling was less intense but enough to keep the significantly longer periods of focus without feeling complete lock-in like you might experience on other similar drugs. That said, they also did say the dehydration was heavy and to keep that in mind.
They said the reason they alternated was they had found that given the longer 15 hour-ish half-life they felt effects strong enough the following day that if they dosed again it started making them feel uncomfortable. That said they are typically very sensitive to most substances. They also felt that you should do your dose early enough, 7-8am, so that by the time 1am or so rolls around you can still get mostly a normal sleep.
They also told me that one time they had done multiple consecutive doses and the come down depressive like symptoms were just as bad as the same symptoms from coming off consecutive doses of Adderall. They thought that if you're prone to dangerous depression this one might not be for you.
They did not endorse doing this but to each their own.
BUT... I later got a prescription for modafinil, which I took daily for 3 months. My experience was that you build a tolerance, just as you do with caffeine or with any other stimulant. Initially, I would take it in the morning and feel very focused for most of the day. Eventually, the stimulation would only last until noon or so, at which point I would crash and get extremely irritable. I remember the guy I shared an office with telling me to "just chill" because I kept getting frustrated at a programming issue and cursing. I was getting super pissed off at really minor things. On top of that, there were also side-effects. It made my acne quite a bit worse and my hair much more oily. This is also typical of stimulants in my experience.
I reached a point where there was zero benefit to taking modafinil anymore. It just made me have annoying mood swings, so I discontinued it, and went back to coffee, which I gradually reduced to just one coffee a day, and I felt a lot better. I haven't used modafinil in years and I don't really care to push my body like that anymore.
My general advice for people who want to try this is that there is unfortunately no free lunch with stimulants. You can use them every once in a while to get an extra boost in focus and energy, but you usually end up more tired later, like you have to pay back a debt to your system. Even just taking a stimulant for one day will lead to a little bit of tolerance buildup. You'll probably feel slightly more tired and unmotivated a day or two or three later.
I know whenever I use it I'm going to pay for it later.
Modafinil may be milder than traditional stimulants in some ways, but that doesn’t make it free of downsides or side effects. It actually has substantial effects on dopaminergic systems, despite having other additional actions.
The gentleness of Modafinil was greatly exaggerated all over the internet for a decade or more. This led some people to unhealthy use patterns. It’s definitely associated with rebound effects and extended use (especially redosing) will leave anyone in a below-baseline state the next day (even if not entirely obvious to themselves, especially with low doses)
The way I eventually settled on to 'dose' Modafinil is two pills (200mg) on Monday morning, then one pill on Wednesday morning; this kept my serum levels at a level where I got the positive effects for a whole work week, yet could still relax on the weekend.
I haven't been in a situation where I felt I needed this for a while, now.
I'm type-II bipolar, so it's not too severe, but I could tell the moda was making my manic swings worse. It was subtle, and I didn't realize it until I had a few significant(for me) manic episodes. Stopping it seems to have helped. I was a little worried about 'kindling' and causing a permanent worsening of symptoms but that doesn't seem to have happened.
To illustrate, if I got a full night sleep, then took modafinil, I would be up for easily 18 hours without feeling any urge to sleep...which seems great until it's 5am, and you need to be at work again in 4 hours.
The apparent solution to the problem is just take modafinil again in the morning. This worked for a while, but there's a limit to how much modafinil can cover a sleep debt. While modafinil had a strong effect preventing the symptoms of sleep deprivation, it had an even stronger effect blocking the capacity to sleep. Modafinil can lead to a very strange and unpleasant feeling of desperately needing to sleep and not being able to.
I'm not saying there's no way around the insomnia problem with proper planning and self-control, but for me the easiest solution was just stop taking it.
But the reason I stopped taking it is that I'm just a salaried employee. It doesn't matter if I'm super focused or not. I'm still getting paid the same amount. There's no point in artificially elevating myself.
I don't know if I would really recommend nootropics to the average person (because there is risk involved, and many of these substances have had very little in the way of human studies), but it's been an interesting journey. It was kind of a pandemic hobby I picked up.
My favorites are Aniracetam and Phenylpiracetam. (Both have become increasingly difficult to source though, despite still being legal in the US.) On top of a stack of supplements (magnesium, vitamin D, zinc, and fish oil).
The best combination I found was magnesium, ashwaganda, and green tea extract. It caused massively vivid, lucid dreams.
I've never had more fun sleeping, and my sleep health was never better. It had nothing to do with productivity, and was literally just so I could fly and shoot fire out of my hands in my dreams.
It took about two weeks of consistently taking it at the same time with the same bedtime (or as close as possible) to get the dreams going.
That being said, legit it is like living two lives, for me. You get the boring daytime life, then you can fly and turn into a horse and shoot lasers and just generally fuck shit up however you want at night. Super cool.
Is that something that happens just to some people or is there a way to avoid the headaches?
I'm curious about trying, but since I used to suffer migraines (not anymore fortunately) I am worried that I will have headaches or trigger a migraine.
Definitely will need to read more about it before considering trying it.
Same experience here. Went through a trial period of Modafinil with my doc. It's fantastic for eradicating any trace of tiredness, but it does nothing for focus
The feeling of laser sharp focus and high energy is quite pleasant and is clearly helping to work for long hours.
But it ended up with a severe burn-out in my case.
Not 100% sure it was the Modafinil, but retrospectively I think it made me drain my batteries a lot quicker.
My advice, if you need to work a lot, the best nootropic you can get is good sleep, healthy food and a bit of caffeine.
drugs have a U-shape response curve, where those who are already at their personal optimal/best, will usually find risks outweigh benefits. Some even have nothing but side-effects, happens, but rarely.
Over time I started to get panic attacks, culminating in a finaly, massive, life altering experience. I haven't touched it since. I don't think it was soley due to the drug alone--but it almost certainly didn't help.
Modafinil is awesome, but it's not a cure for whatever underlying problem you have.
Don't destroy a scholarship/career messing with stuff without knowing the consequences.
Modafinil really helped me concentrate. But sometimes it was also a "miss". That is, I would focus on something totally unrelated to my project. For instance, one day I spent 6 hours comparing Vegas hotel room prices over different days of a month.
The side effects were annoying, to say the least. Itchy ears and eyes, dry mouth, occasional anxiety, talkativeness etc.
I haven't thought about Modafinil in years but back when 'Limitless' came out and I was in my mid-twenties I experimented with it very briefly, along with a host of other "nootropics", but the risk of Stevens-Johnson syndrome put me off of it pretty quickly. It still shocks me when I think about how foolhardy I was to order this Rx drug from overseas.
It puts me much closer to who I want to be than who I would be without it: Im much more motivated to do things I enjoy doing.
I stopped taking it half a year ago because I started to get annoyed by my wife do to her slightly messines.
Now I need to find the right balance.
For me this is the same thing as glasses.
We should talk much more open about such things.
I do have adhs and hard sleep issues just as a side note.
Anyway, I feel like I was extremely productive on 400mg of Modafanil a day, and I understand why people have used it for nootropics.
I generally approve of anyone modifying their own consciousness on there own time. And I get what he did ended up harmless and even beneficial, but if you are going to experiment with psychoactive pharmaceuticals, do it on you day off for your first ever does. This guy not only went to work under the influence of drug that he didn't know what the effects on his person would be but did so in job were he is directly treating other people at a hospital. I get where we come form here there is a culture of move fast and break things but maybe not when those things are potentially other people.
Which is not an accurate statement.
Modafinil is a nootropic, which means that it can increase attention, therefore decreasing the chance of a mistake. The probability that someone will experience more wakefulness and attention is high in this regard.
And it being FDA approved lowers the probability of an adverse reaction that can cause someone to not be in the right mind and make mistakes to a very small number, which accounts for things like heart conditions.
+Plenty of people get prescribed medicine and go to work the next day even if they never tried it.
I have a good friend (who is otherwise reacting normally to stimulants) who took IIRC ~50mg of Modafinil for the first time for an exam in uni. They ended up having to go to the ER in the middle of the exam, got diagnosed with some form of allergic reaction. Doc said it can happen for many medications.
Whenever trying a new substance for the first time, do so in a way and context that minimizes impact of unexpected effects or adverse reactions.
So I agree OP was irresponsible and should at the minimum have taken one dose off work before their first work-day on it.
either that or 47 is "wind down time" for my brain
It very obviously has major negative effects, but I just can’t bring myself to change it. I’ve tried once or twice, but I always return to this.
If life was a little more flexible, I think I could pull off biphasic sleep and be ok, but when I want to sleep I usually have meetings and when I’m wide awake it’s usual the middle of the night (writing this at 3:25am).
a) be fairly rigid with it
b) turn it into a habit.
If you don't you're going to have burn out. not just emotionally but physically. I had a fit that the Dr put down to poor sleep and eating habits. It took me weeks to get over the immediate effect of the fit, I felt like I'd been worked over with a baseball bat.
I used that recovery time to go cold turkey on caffeine (if I'm going to feel like crap i might as well have a good reason for it), I limit myself to tea only now, and only 1-3 cups a day. I eat a lot better and I go bike riding a few times a week. I get at least 6 1/2 hours a sleep a night, and aim for 7-8.
its worth noting that while there is evidence for sleep debt, there is no evidence that oversleeping helps correct it.
Highly recommended podcast! https://hubermanlab.com/controlling-your-dopamine-for-motiva...
You are _awake_ but not the way caffeine or ritalin do it. You're not buzzing. Just _awake_.
However, it didn't do anything for my ADD so I didn't use it for more than a month. For a while I used my remaining supply to de-jet-lag myself after an international flight. (Pre-pandemic, I'd do an international flight about once/month.) It worked well for this. I'd use it to stay awake the first full day I landed, then my clock would be fine.
I have over half a bottle from when I was prescribed it (for MS fatigue) and I can definitely still feel in my system after a day. And yeah, if I take it more than, say, 2 days in a row, I start having a bad time.
Secondary note: I was once prescribed modafinil for severe sleeping issues before I knew it had some street/techbro value (maybe it didn't then). My experience was not great. I only took it for three days and then stopped.
I would say the effect on wakefulness was very subtle. I think I stayed up until 11 or 12 each night wherein I'd normally be up until 2 unable to sleep. I suppose the difference is I didn't get the late afternoon crash.
However, I'd wake up at 4 or 5 with significant itching. To the point that it was hard to go back to sleep. There are some serious side effects to consider that are somewhat related to skin issues and when I reported this to my doctor he seemed concerned and told me to keep an eye out for another week. I just stopped.
I've worked hard on sleep habits and it's gotten a lot better naturally. Intuitively, better sleep = better wakefulness/happiness/productivity, but we all tend to fight these uphill battles sometimes. We think if we just put in an extra few hours tonight, we'll be ahead of the game. But instead we end up putting in low-value work and being exhausted the next day, starting the cycle anew.
I really didn't find much huge exciting value in my short foray into modafinil, though. If you can work on some natural sleep training or even 5htp/melatonin/whatever works for you, you'll be better off.
There's no _kick_ whatsoever and in some ways that's kind of the appeal.
There are other modafinil analogues/prodrugs, but I’m not overly familiar with them. Flmodafinil seems relatively popular.
The funny thing is, I mostly do it because I don't want to go to the doctor every six months to say "mother may I" for a very mild and safe statin. My insurance would pay for everything, but it's such a pain to do.
My food delivery app has modafinil from any of the local pharmacies or I can get it at the mall on the way back from the gym. In fact, I can get most medications this way and I don’t have to pay the 30$ it would cost me to see my doctor if I was in my home country.
How do you know? Do they have a lab certification/ is there a regulating body?
I suppose someone could create fraudulent drugs, but honestly, it's probably cheaper just to sell you the real deal. And just like other businesses they want your repeat business.
I know they are the real drug in my case because I take them for mildly high blood pressure. It's trivial to measure blood pressure, and I can see that they have the same effect as the American drugs of the same dosage.
Then when you receive you order, you'd sacrifice a pill to carefully weigh it, check the coating matches, packaging and so on. If you ordered a whole bunch, you would check batch numbers and sample each batch for testing.
Obviously this isn't foolproof, but if someone is going to sell a counterfeit they aren't going to practically spend a lot of time in making it a perfect one.
Well, that and the potentially life-threatening skin conditions. Those are apparently rare, but I discontinued use when I saw some large purple blotches on my skin.
I think it's important to remember the hidden underlying problem won't go away just because the visible coping mechanism does. A severely depressed person using modafinil as a crutch has to treat the depression first and foremost.
If you really are worried buy a prepaid visa card with cash, and use a vpn.
I was prescribed Vyvanse but quit it (flushed the remainder of the pills in the bottle down the toilet), I had to stop when I felt the clammy hands, cold sweat and heart palpitations. On top of that, it made me feel like a zombie.
Modafinil provided me with the calmness to concentrate and ability to stick to something for hours on end without the feeling of depletion after hours of taken an amphetamine, with the only adverse reaction being a foul smell in urine.
However I stopped using it after getting into a minor motorbike accident. Another motorbike was driving on the shoulder (pretty typical in Thailand) and I didn't spot her while turning at an intersection, even after checking both directions. The tunnel vision side-effect is no joke!
Maybe there is a reason drug trials are not based on some Rando on the internet