What's remarkable to me is that modafinil is less toxic than caffeine[0], and possibly even less addictive[1], but we all know which is illegal for recreational use and which is coffee.
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.
Caffeine would be illegal to possess, if it were invented yesterday.
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.
> 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.
All this tells me is that I'm clearly consuming caffeine incorrectly in the form of coffee and/or tea.
Or, and hear me out, people outside of cocaine's traditional region are using it wrong.
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.
It should not be insufflation. Intranasal administration is a synonym for nasal administration you'll find in many papers, it's older.
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!
I quit caffeine about 8 years, only having a white tea on occasions. But I love a cup of decaf every so often. One day at work, one of my coworkers swapped the decaf pot with the regular pot and I drank a 16oz mug before I realized what was going on.
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 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.
In all seriousness, taking it sublingually might actually be extremely effective. Sublingual delivery tends to be more effective with lipophillic substances than hydrophilic substances. Caffeine is a bit weird in that it is hydrophilic, but, it is sufficiently lipophyllic to cross cell membranes and penetrate the blood/brain barrier, which is what makes me suspect it would work out well.
Huh. Technically, that would probably be considered buccal (via the cheek) delivery, but, close enough, right? I had no idea caffeinated gum kicked in significantly faster than pills or drinks.
Yep, good catch. "buccal administration" is a bit more obscure so I often just refer to sublingual unless I know the audience.
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 have a friend who can't stand the taste of coffee but of course likes caffeine as do we all, and had to import it via mail drop to Denmark in order to get his espresso-equivalent shot in the morning.
As I heard it from him, although I haven't tried anything personally, in Denmark there are some restrictions about importing liquid caffeine, he hates to drink coffee and also soft drinks, but getting caffeine from bubble gum does not provide the same level of caffeine and the water with caffeine drinks you import do not have as high a level of caffeine as soft drinks for some reason so he had to import his own and make his own.
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.
well this is second hand from him, so that also makes it about 12 years old, but I figured it seemed like the kind of thing they would keep if not get stricter about.
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.
Never done anything IV, but I do plenty of drugs (cocaine included) during basically every weekend, and have been doing so for the last ~30 years more or less.
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.
The same way you cope with anything, really: You consciously develop a personality that handles whatever you face in life. Some people call this process "growing up". I think it's more spiritual than that.
I've had cocaine a few times now and while everyone is saying it's euphoric, I keep saying it's the most normal I've ever felt. Not "euphoric", I've done other stuff that felt suuuuper good (in an actual euphoria sense) so I believe can compare.
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
> 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.
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.
I have no idea why people like Vyvanse so much. It’s just time release with a fancy mechanism and paranoia around abuse potential of instant release formulations, which work just as well in most, if not all.
However, Ritalin is less neurotoxic than amphetamines that can indeed hike your risks of Parkinson’s (and probably few other things)
Because it's been life-changing for me, and countless others? It's not just time release; that's the old school drugs like Concerta.
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.
Sure. The early history of ritalin was the first sign to me that pharmatech industry owns their regulators. Check out the follow up research on 8-hydroxyguanine glycosylase as an indicator of oxidative DNA damage in response to the 2005 nih publications asserting no increased biomarkers, its somewhat surprising on both sides for Ritalin and the popular amphetamine alternative as well.
> The aim of the present study was to examine the effects of drugs (amphetamine, methylphenidate and atomoxetine)
> 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.
Being calm and relaxed on stimulants 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. Even depression is possible.
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)
I know this is kind of an obvious follow up to your comment, but, have you been tested for ADHD? You described exactly how my brain reacts to mixed amphetamine salts (AKA Adderall). Caffeine doesn’t really do much for me, either, incidentally.
I was diagnosed last year and the psychiatrist I was seeing worked at a clinic that primarily sees inner city patients with much different health profiles than a mild mannered engineer. This is one of my favourite exchanges from the intake meeting:
“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.
I've tried cocaine and it would make me feel like the "best" or perhaps much better version of me. Improved, but subjectively not overinflated self-confidence, sharper thoughts, better concentration, high energy and motivation, easier connection to people, without apparent intoxication or affected judgement.
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
Gonna pile on with everyone else and suggest you get tested for ADHD. This is a pretty classic symptom from what I understand. This is basically how I feel with Adderall. I had no idea how "normal" things could feel.
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.
Curious - do you have something to back that up? Caffeine is pretty toxic (
I think the LD50 is something like 200 mg/KG of body weight. 20 grams would kill most people) and I don't find it surprising that an IV mix would have pretty serious effects.
The question is whether the two are somehow indistinguishable (to 80% of people, at least).
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?
Here is one similar study (I don't think is the right one though):
> 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.
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.
While it’s true that if the LD50 is 200mg/kg, you’d expect roughly 50% of humans weighing about 100kg to die from it, I kind of suspect it doesn’t quite work that way. Dose/response relationships are frequently logarithmic, which means that after a certain point, you have to increase the dose by a lot to get just a little more effect.
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.
https://pubmed.ncbi.nlm.nih.gov/7714788/
>“The mood effects but not the physiological effects of intravenous caffeine were similar to those previously observed with cocaine in studies using similar methods and subjects.”
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?
> ....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.
Shooting in the dark here, but I imagine dose size is an important variable in a study like this. At 500mg, I'm pretty sure a member of the LDS* could tell the difference between coffee and cocaine.
[*] I'm only calling out the LDS community here because they don't consume coffee, or cocaine, generally speaking.
Mormon tea / ephedrine is not commonly consumed and as far as I know it isn't consumed at all by LDS faithful. It's just a silly colloquial name for a plant.
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.
You remember the topic and the name of the PI but still can’t find this study? I am relatively certain that’s because it does not exist.
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!”
OK, I don't have any data either but I'd be pretty surprised if there were a lot of murders by people trying to acquire cocaine. I mean, it could be true?
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...
Honestly I don’t know how prevalent murdering for drug money is at all. My belief that this happens with some regularity for cocaine is based on suspect info now that I think about it.
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.
This. Drug industry has to settle disputes outside the law because it can't use the courts (and by proxy, threat of state violence) to deal with business disputes. So it's necessarily more violent because there aren't state level resources around to fund expensive stuff like due process. Being inherently criminal probably also ups the violence just from selection bias.
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.
There certainly would be very few, and likely none, murders to obtain cocaine by end users. It does not cause dependency in a way heroin and gabaergics do.
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.
> People murder to get cocaine. When’s the last time anyone murdered for Starbucks?
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?
Given now we have dedicated facilities withdrawals from social media, I suppose it is pretty addictive, maybe even as bad heroin, but at least as bad as stimulants.
>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 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.
I have high confidence that you will never find this study, and that it doesn’t exist. I’m not accusing you of malice, but I think you must be misremembering something.
But I’d love to be wrong. That would be a very interesting result.
> 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.”
I suspect the dosing might explain the equivalence. I’ve not come across the study, but if the conclusion was “a 1/100th of the normal dose of cocaine is equivalent to 3 cups of coffee equivalent” I could believe that.
dosing usually would be dialed-in to provide roughly identical autonomic effects (at least) and then graded increased doses. otherwise it would be a pointless study.
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.
It’s an old study, from 60s. No OCR. You can get the full text from other sources but it will be useless for your purposes, they don’t spend any time on that at all.
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.
Your hypothetical situation defines caffeine as being illegal and as in demand as cocaine. So basically you said if caffeine were exactly like cocaine then it would be exactly like cocaine. This is technically true but also vacuous.
Is this the study? “The mood effects but not the physiological effects of intravenous caffeine were similar to those previously observed with cocaine in studies using similar methods and subjects.”
Cocaine was isolated long before current drug laws, so I'm not sure I buy the argument "if it were invented today". Cocaine wasn't invented today and was banned.
modafinil was invented today and is scheduled, aka illegal to possess without prescription.
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.
Caffeine and modafinil shouldn’t be compared, as they have vastly different activity, history of use, and understanding of effects.
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.
I've found that the people who say Modafinil does nothing for them are people experienced with high powered stimulants who are expecting the same kick. This is mostly due to a misunderstanding of what the drug actually does.
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.
> 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.
Really? I had no idea! Thanks for teaching me something new.
Paradoxical and other unusual effects can occur with any kind of drug. Brain drugs in particular seem to be prone to a wide variance in the effect profile. I speculate that in part it is due to the heavy "reuse" of neurotransmitters for various purposes (neurotransmitters themselves being mostly reused modified amino acids). For example, dopamine modulates motor activity, reward pathways, attention, and error correction, and more. Serotonin modulates smooth muscle, appetite, uterine contraction, mood, visual salience, and more. Both can affect circadian rhythms. NMDA/AMPA and GABA are widely present and are the basic "wires" for excitatory/inhibitory signals, so drugs that affect these can do all kinds of zany things.
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.
Sorry for off-topic, but: why are there many different neurotransmitters instead of a common single one? (I mean, sure, evolution, there's no "why", but I'm asking from an hypothetic engineering standpoint.)
Neurotransmitters are often synthesized from amino acids. They have different functions in the body, often either inhibiting or exciting the neuron that it targets.
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.
If anyone tells you they understand the brain - they are lying.
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.
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".
I don’t disagree, there is of course a body of knowledge, which rapid churn implies that we are accreting that at a good pace.
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.
It's quite different in most regards: I'm super-tired all the time, need a nap every afternoon, my endurance is extremely low (lifting a kettle feels like lifting a weight, climbing the stairs feels like climbing a hill) and simple activities tire me out waaay more than they should. If I do anything remotely strenuous, then it does kind of hit me like narcolepsy - within the space of a few seconds I become extremely tired, like I've been drugged, and I have to sleep.
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.
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.
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 does seem to be a thing with Modafinil - I got a rash on my forehead after trying it. You definitely have to be careful with it, productivity gains are insane, but it's a double edged sword and will easily knock your normal sleeping patterns.
Some of my friends as well had skin issues, not severe and it subsided after stopping. If I remember correctly, it was like dry red patches. Actually, I might have experienced it as well, for me the major downside were headaches.
I doubt that people consume coffee because of its cognitive enhancing effect though.
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.
It's pretty easy to not know that coffee has monoamine oxidase inhibitors in it.
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.
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...