It seems rather likely that other neurological functions occur during that time as well. Unless we have the ability to simulate all of them, we shouldn't assume that the ones we ignore aren't important.
It would be especially harmful if we ended up suppressing the processes that make you feel sleepy when you need sleep, while the harmful effects of sleeplessness remained.
(Former neuroscientist here.) This is true of caffeine, for example, which is an adenosine analog (e.g. it has a similar shape and fits into the same receptors). Adenosine is a signal to a cell that it's running low in energy. Caffeine competitively binds to the spots on receptors where adenosine goes, effectively preventing the cell from communicating its low energy state.
Now here's the kicker. When your body builds 'tolerance' for caffeine, what this usually means* is the post-synaptic cell adjusts how much adenosine it's pumping out so that the "I'm tired" signal can cut through the caffeine. And when you go through caffeine withdrawal, it takes a while for those levels to re-adjust to normal.
* in the brain. Caffeine also has effects on your digestive tract, blood pressure, and some other non-brain parts. :)
Edit: corrected cAMP -> adenosine (simple recall error from a lecture that was 9 years ago). The gist of the reply remains the same.
This is incorrect information. (... Like so many biology/chemistry comments I see on HN.)
Caffeine is more like an adenine analog, not a cAMP (3'-5' cyclic adenosine monophosphate) analog. It binds adenosine receptors, not primarily cAMP receptors. It has indirect effects on cAMP, but I am not aware of direct ones. Also, your description of cAMP signaling sounds confused, since cAMP is an intracellular second messenger. I am not aware of an extracellular retrograde signaling process for this molecule.
Sorry, and your implication that cAMP is a byproduct of ATP consumption is totally wrong. cAMP is synthesized directly from ATP, a reaction catalyzed by the regulated enzyme adenylate cyclase.
Thank you for the correction. I mis-remembered a minor detail from a lecture that was 9 years ago, and have find/replaced cAMP -> adenosine in the above post. The gist of the post, though, remains the same. That is, caffeine competitively inhibits receptors that gate ion channels, and the mechanism of tolerance is an increase in the concentration of the thing that it competitively binds.
(My thesis was on auditory cognition and I haven't touched ion channel biophysics in that long. I have a long-ago memory that adenosine (now corrected) operated as a retrograde transmitter, though since I'm probably not going to spend my afternoon looking for the citations, I'll delete as well for now. Not because I believe it's wrong, just that I can't immediately back it up.)
Are you still doing research yourself or have you left for startup land like most of HN?
Thanks for making your corrections as well. Yes, I am in research, and I mostly come here for what's new in Python, learning algorithms, and data analysis. As an aside, it's tough to wade through the "startup land" and personal health advice and keep a straight face in all honesty, but there are few other places that aggregate the things I'm interested in on the computing side of things. An "HN" with users that specialize in bioscience would be very interesting, but I don't know of one with any level of seriousness/activity.
datatau [0] might be worth checking out, if you're not familiar.
since bioscience isn't on my radar i'm not sure if you'd find anything useful there, however, it feels like a more concentrated version of HN which specializes in some of the other stuff that interests you (e.g. learning algos, data analysis, etc.).
"Caffeine competitively inhibits phosphodiesterase, the enzyme that degrades cyclic AMP...By blocking the degradation process of cyclic AMP, caffeine indirectly affects regulation of cAMP-dependent protein kinases". TIL.
I think it's useful to think of it not as a "bad thing" but as a very high-interest loan from your future self.
In moments of weakness and pushing a deadline, I have sometimes rationalize the trade-off of future time/health to present time, and sometimes, that sticks me with tolerance that it takes time to wean off. I have made a conscious effort to quit caffeine dozens of times in my life, and the most recent time it has stuck, and I plan to stick with it. The thing is, when I gain "time" with caffeine, it's not necessarily time with high-quality cognition or productivity compared to my well-rested self, and it's easy to forget to take that into account when you're making trade-off decisions when tired. You still perform like a tired person, you're just not subjectively feeling the tiredness.
FWIW, drinking decaf gives you the health benefits of coffee with 5% (kinda negligible) amounts of caffeine.
I gave up caffeine a few years ago, for the very reasons you speak of. I feel completely different now - my thinking is broad and calm, rather than narrow and frantic.
Personally, I enjoy the flavor of Swiss water decaf more than others (and by reasoning of the "Dorito effect," that flavor may have something nontrivial to do with the nutrients left in it; it also happens to not use additional solvents).
That said, a lot of the risky solvents used in the usual methods of making decaf are no longer commercially used these days, so I don't think there's a serious health risk in drinking any ol' decaf you want.
I had heard that alcoholics who drink coffee have a markedly decreased chance of developing cirrhosis, something like a 60% reduction. But only for regular caffeinated coffee- not tea, not decaf coffee. Do you have any insight into why or is this not true?
When discussing possible mechanisms for their findings:
"We postulate that the observation of the benefit of coffee on the progression of liver disease may be due to its effects on the oxidative stress/lipotoxicity pathway, which underlie the pathogenesis of cirrhosis related to alcohol, NAFLD and possibly, in part, CHC. However, since oxidative stress is not the predominant mechanism of injury seen in CHB, coffee has no beneficial effect. Polyphenols and melanoidins, which are major components of coffee, have been shown to mediate multiple protective mechanisms in a rat model of steatohepatitis, ranging from increased fatty acid β oxidation, mitigating oxidative stress and curtailing liver inflammation (47). The other components of coffee, cafestol and kahwoel, can induce phase II detoxifying enzymes, including sulfotransferase, UDP-glucuronosyl transferase, glutathione transferase and peroxidase, and thus contribute to the anti-oxidant properties of coffee (14, 48). In addition, chemicals in coffee such as polyphenols and the diterpenes have been shown to down-regulate proinflammatory, fibrogenic cytokines such as transforming growth factor beta (TGF-β) and its downstream modulator, connective tissue growth factor (CTGF), collagen and stellate cell activation (13–16).
Epidemiologic studies on caffeine have been inconsistent in demonstrating a protective effect in liver disease since other caffeine-containing beverages such as tea have not shown to be protective (19–21). Similarly, in our study, the inverse association with caffeine became null after adjustment for coffee, suggesting that ingredients of coffee other than caffeine appear to be responsible for this beverage’s effect on risk reduction. Furthermore, other caffeine-containing beverages like green tea and black tea had no significant effects with cirrhosis mortality in this study."
Modafinil is designed for narcoleptics, people who are theoretically getting too much sleep. It is not actually intended for people to use to stay up beyond the recommended range. If you stay up for multiple days you are increasing the build up of these plaques, because the brain is not able to clear them out while you are awake.
"Is designed for" implies a lot more than what it means here. If I remember correctly, the mechanism behind Modafinil is unclear. The usage is approved for narcoleptics, but also for people who want to shift their circadian rhythm (because it [allegedly] doesn't carry the sleep debt that other stimulants do).
Is there any information (affirmative or negative) about Modafinil's effects on this plaque? Considering how recent this whole discovery seems to be, I doubt there's much conclusive info on this specific interaction.
Yeah, the "doesn't carry the sleep debt" bit is dubious at best. Maybe not at much. But it doesn't fit my experience at all. Anecdotes not being data, and all that, but for me at least I still wear down over time with a couple of uses of modafinil a week unless I actually make sure to catch up on sleep, to the point where I am careful to limit how often I use it, even though it is far easier to avoid totally crashing with than caffeine and generally feels less stressful on the body (whether that feeling reflects reality, I don't know).
Well I think you're talking about something different. From what I've heard (and in my experience), I can skip a full night of sleep with Modafinil and then fall back into my normal sleep schedule the day after.
You'll probably fall asleep earlier in the day, but you'll only sleep for 8 hours. This is why it's useful for offsetting your rhythm.
Ritalin/Adderall is very different. If you use it to stay up for 8 hours, you'll sleep for 16 hours the next time you pass out.
>Ritalin/Adderall is very different. If you use it to stay up for 8 hours, you'll sleep for 16 hours the next time you pass out.
From my subjective experience, this isn't necessarily true. All-nighters with modafinil vs. all-nighters with adderall require the same amount of catch-up sleep for me. Modafinil just gives me a less jittery wakefulness.
If you fall asleep earlier in the day, you're paying offf your sleep "debt" right away. When I use it I go to bed at roughly normal bedtime the following night. At that point 8h sleep is certainly not enough. Though I'll usually not "catch up" more than 1-2 hours extra that night. If I want to I can push through and continue as normal, and even do multiple more cycles, but over time I do end up tired enough that I need to catch up with more sleep.
I tend to prefer to use it to offset sleep for relatively short periods - e.g. get an extra night of work, and then sleep a bit longer for the next couple of nights - as I feel it's more productive to get a longer block of time where I'm fully alert, and give up late evenings when I'd feel tired anyway to recover.
Modafinil also, in my experience, does not make you likely to sleep less over time. What it does let you, similar to caffeine - but totally different feeling - let you portion out your sleep differently. Whether I delay sleeping with caffeine or modafinil, I end up wearing down until I catch up.
In my opinion, efficiently using our current methods for deferring sleep boils down to understanding that you're merely deferring it, and using it to "schedule" your most awake/concentrated periods when you need it most, rather than try to force yourself to work well all the time.
Maybe one day we have something that can let us cut sleep entirely, but we're still far away from that.
EDIT: As I've clarified in another comment below, my sleep amounts without anything are already fairly low, and that may certainly affect my ability to push it further down with modafinil over the long term.
I take armodafinil for a chronic fatigue condition that has been ruled out as any of the diagnosable sleep disorders. It absolutely causes me to sleep less, but that probably has to do with it making me want to go to sleep just a little bit later and not having room to add more sleep in the morning.
It also builds tolerance in a kind of annoying way; it prevents me from napping or sleeping even when it no longer makes me not tired.
> It also builds tolerance in a kind of annoying way; it prevents me from napping or sleeping even when it no longer makes me not tired.
Interesting. I can sleep just fine on modafinil, but I still have greatly increased focus if I just choose to stay awake. Also, I've never noticed any increase in tolerance (which I get very quickly with caffeine and alcohol), even taking it every day for two weeks, although maybe that's not very long.
I've been taking it for about two years, often skipping it on days I don't have to work, and it's definitely not as effective. Once, though, I did lose about three weeks' worth when it got accidentally tossed during a move. Insurance doesn't tend to cover that sort of thing, and the stuff is $500+/month, so I just struggled without. When I refilled it and started taking it again, I was bouncing off the walls a little bit.
Aside from the above hiccup, I come out ahead on cost if I go through my insurance rather than try to buy from India. There would also likely be some lag time involved that wouldn't have helped in that instance.
You read reviews of suppliers. Lots of reviews. And you look up images of the genuine packaging from reputable manufacturers like Sun Pharma, and compare.
You might very well be in a different situation to me if your fatigue previously made you sleep more than you necessarily need. For my part I sleep less than average already without taking anything at all, so I might very well be pushing the lower end of the viable long term sleep amounts.
Original source: asked doctor for modafinil to enable working harder for more hours. Doctor said, No, you might think it's a good idea now, but if you're back here a couple months later with depression, you'll realize it's not worth the risk.
It would be especially harmful if we ended up suppressing the processes that make you feel sleepy when you need sleep, while the harmful effects of sleeplessness remained.