Pretty much every item in the bullets at the beginning look likely to short health and lifespan with Modafinil. That’s the worry.
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People in this thread are reporting similar findings as you as well as other issues with this medication. There is one obvious commonality among you all - none of you have been clinically diagnosed with narcolepsy. I had the overnight hospital polysomnography/MSLT to diagnose it (plus I have all the symptoms: REM with sleep onset, hypnogogic hallucinations and daytime sleep attacks since childhood) though I never had the lumbar puncture to check hypocretin, but I don’t have cataplexy. Perhaps my ability to tolerate the med for over 20 years is due to my having narcolepsy, but idk. Interesting though.
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I just had labs since I’ve been dosing Modafinil daily for the last two months and my LDL (it’s still low as a result of pharmacology but 14 points higher than last time and A1C seem to be slightly higher than before. Looking at that 2020 rat study that @DrFraser posted, it could be from the modafinil but I can’t say for sure.
I think I’ll stop daily use starting tomorrow.
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I have used modafinil off and on for ~12 years. At first it was an amazing wonder-drug - I felt very motivated and focused whenever I used it. It makes you think faster and the words come out easier. Over time I have used it less and less because the effects have become less pronounced and it definitely messes with my sleep (even if I take it right after waking up).
These days, when I do take it, I only take 50 mg to minimize bad side effects, and only sporadically. Currently, the main benefits to using it are (1) ability to focus intensely on the same subject for a whole day and (2) ability to do and enjoy tasks that I normally hate (I will happily do very menial tasks that I need to do for work the whole day without getting bored).
The current drawbacks:
(1) If the day needs me to switch between tasks or engage with people I get annoyed FAST. My tolerance for frustration and patience markedly go down.
(2) If I use it for more than a couple of days I feel wired, but not rested and unable to do good work (it’s unpleasant)
(3) I often get a modafinil hangover the next day (feel less focused motivated).
All that being said, it’s a wonderdrug and worth experimenting with. I find it useful from time to time, when used sporadically, in the same way having a drink is fun if done sporadically. Everyday use leaves me feeling zombie-like.
For sourcing in the USA I’ve used www.sun-modalert.com successfully. YMMV
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mike86 , Thanks for providing your experience. Someone will find it useful and I agree 100% with the points you made. My use has also gone to 50 mg when needed, sometimes for things I want to accomplish and especially for the tasks I don’t enjoy when I don’t seem to have the energy I need. It works best with all day outdoor physical activities for me.
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Daily use is too much as it interrupts sleep in my experience but I heard of an experimental protocol from Alex Kikel that looked interesting.
Protocol to improve memory and brain function: Monday-Wednesday-Friday dosage. Start 50mg first week, then 100, then 150, then 200, etc until you get over excited from it, then increase dosage one more time the next week, then start tapering downwards by 50mg until you reach 0mg.
I tried something like that for a month but I didn’t go above 100mg a day, and I didn’t bother tapering down I just stopped. I have to say I think it did improve my mental function quite well. I get a feeling it would pair well with lithium orotate.
The benefits feel like they have lasted well after I stopped taking it. I then didn’t think to take it at all for a few months.
I’m thinking of doing it again for a month and seeing what happens, but this time combine it with lithium orotate.
Here is a video where he describes the process: https://www.youtube.com/shorts/hohB9TTClnY
There is a longer video but I can’t seem to find it.
I like to combine it with some of the “neurological reps” brain exercises he outlines in this video: https://www.youtube.com/watch?v=o0dfHfNMlB8
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I think Dave damaged his brain with using it daily and at high amounts. On one of his latest videos everyone was commenting that he seemed very sick. It was genuinely disturbing and I hope he gets better.
This is the video:
Seems to be good used sparingly, and not consistently.
There appears to be something going on in that video, but not in videos before or after it (a one off).
He could have been experimenting with some new products or partied too hard the night before.
Modafinil is safe IMO.
I noticed it in a number of videos but this was the most noticeable one.
I think over use of modafnil can be harmful. But after looking deeper into his recent activity I do remember he mentioned he was using some brain electromagnetic stimulation device he claimed allowed him to sleep much shorter durations than is recommended.
Edit: it was in the video I posted above.
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in my experience Tolerance builds up quickly, after which you need a long break (or maybe I didn’t like the comedown, idk, or maybe my HR went up too much, but I finally tried again). There is a tendency for my HR to go to 130BPM on modafinil+caffeine and maybe I should split the pill next time
I finally took one today [waited way too long]. Might synergize well with coffee.
The appetite suppression is pro-longevity, and it seems to increase dopamine by some optimal amt. Also it is antioxidant and there are a few papers on how it has mild pro-longevity effects
it seems harder to get modalert online than before…
omg i just saw dave stanley’s latest video
==
Effects on Aging Pathways
Modafinil’s actions on canonical aging pathways have been partly studied, again with mixed findings:
- mTOR/PI3K/Akt: One mouse study found that chronic modafinil downregulated hippocampal PI3K, Akt and mTOR gene expression (in a maternal‐separation stress model)j.skums.ac.ir. Conversely, in sleep-deprived mice and HT-22 neurons, modafinil was reported to reactivate the PI3K/Akt/mTOR/P70S6K pathway and suppress excessive autophagy and apoptosispubmed.ncbi.nlm.nih.gov. In other words, modafinil can modulate mTOR signaling, but context (stress, sleep loss, dose) dictates whether it stimulates or inhibits the pathway. By contrast, prototypical longevity drugs inhibit mTOR (e.g. rapamycin) to promote autophagy.
- AMPK/Sirtuins/NAD⁺: We found no evidence that modafinil directly activates AMPK or sirtuins, or alters NAD⁺ metabolism. Unlike resveratrol or NAD⁺ boosters (which target sirtuins and mitochondrial biogenesis), modafinil does not have a known direct action on these longevity regulators.
- Inflammation/NLRP3: Modafinil has exhibited anti-inflammatory effects in animal models. For example, in sleep-deprived mice modafinil reduced pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and increased the anti-inflammatory cytokine IL-10. It also attenuated NLRP3 inflammasome activity and neuronal pyroptosis, mitigating cognitive declinefrontiersin.org. Reduced neuroinflammation could be considered a pro-longevity effect.
- Mitochondrial function: As noted, one hypothesis is that modafinil targets mitochondria to boost energy production and lower ROScambridge.org. Enhanced mitochondrial ATP may improve neuronal function, but whether this translates to slower aging is unknown.
==
One theoretical model proposes that modafinil enhances mitochondrial cytochrome c activity, boosting ATP production and lowering H₂O₂ and superoxide outputcambridge.org. In sum, modafinil may mitigate oxidative stress by modulating intracellular metabolism (e.g. via CYP2C9 inhibition or mitochondrial enhancement) and by influencing neuromodulators like serotonin/adenosine that are linked to ROS levelspmc.ncbi.nlm.nih.govcambridge.org.
Preclinical and Clinical Evidence
Animal studies (preclinical): The evidence on modafinil’s oxidative effects in animals is mixed. For example, one rat study found high-dose modafinil increased lipid and protein oxidative damage in most brain regions, though it “protected the striatum against protein oxidative damage”pmc.ncbi.nlm.nih.gov. In contrast, other rodent studies report antioxidant-like effects: in young rats, modafinil prevented the oxidative damage induced by amphetamine in hippocampus (normalizing catalase activity and ROS levels)pubmed.ncbi.nlm.nih.gov. Similarly, Kumar et al. (2020) reported that subacute modafinil attenuated brain oxidative stress markers in rats – for instance, lowering lipid peroxidation – even though it caused hyperglycemia and dyslipidemiasciencedirect
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You can get modafinil really cheap and easily from Indian pharmacies.
I love modafinil. I take 100 mg daily. The normal daily dose is 200 mg. It smooths out my daily wakefulness and alertness—no ups and downs. It is not a stimulant. It does not noticeably affect HR or my RHR—one of my favorite drugs.
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For me , modafinal is uniquely satisfying , 25mg early Is more than enough
100% better focus on tasks on hand ,better motivation levels , more engaging conversations , higher energy levels
I do believe in adjusting the dosage until
You find your sweet spot
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Yeah, get a pill splitter
Modafinil has a upside downside ratio that is on the optimal frontier, and it makes aging suck way way less
What is your current stack (supps & meds) look like?
I stopped using modafinil with coffee. Too much stimulation.
Have not noticed a tolerance while using it for a few months.
Indeed.
I’ve only tried Indian brands but I can say that modafinil and armodafinil from these pharmacies feel different.
Actually, I don’t mind the tolerance buildup. This is one supplement that a new user should definitely titrate up from a small dose. After about 6 weeks, I was able to tolerate the 100 mg daily dose and occasionally a 200 mg dose if I had lost some sleep.
Now, I find the daily boost just right. I don’t want to “feel” it. I just like a day with an even cognitive alertness and no need to take an afternoon nap. Because of long-term cognitive effects that are suggested but not proven, I will keep modafinil as a regular daily supplement.
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It’s great for hangovers too
Ok I just took 100mg.
200mg was very unpleasant at times and wrecked one and almost another night of sleep