Comment · Fri, September 13, 2013 · Ceretropic
Does Anyone Else Experience Modafinil Effect Inversion with Sustained Usage?
Original post in this thread
Brukhar1 · 2 points
Disclaimer, this is anecdotal and simply based on my experience. When I first start taking modafinil after not taking it for awhile, the effects are exactly as advertised. Little bit of fuzzy head feeling first day, can't sleep for the life of me the first night, still feel refreshed the next day once it kicks in, appetite suppression, increase in cardiovascular performance when running, the works.
However, after several weeks of sustained use (4-12 weeks), at some point, the effects seem to reverse. Instead, modafinil will make me want to get more sleep, my appetite will return ravenously, and my cardiovascular performance will drop.
Now, normally, I'd chalk this up to tolerance. But when I cold turkey off modafinil, my appetite subsides back to normal levels, sleep returns to normal (no more/no less required), and my cardio performance picks back up although not to the same level as when modafinil is fully working for me.
Any one else experience this type of effect?
I know we've discussed the potential for tolerance or loss of efficacy over time before and a lot of people advise that modafinil is best used intermittently. Interestingly, it's not so much a loss of effica…
What they were answering
Brukhar1 · 2 points
Yeah, although my pharmacology background isn't what I wish it was, I don't think liver enzymes would be the cause. I was actually suspecting it's due to modafinil's neurological effects particularly in the hypothalamus. One thing I've noticed is that modafinil has the potential to treat a metric ton of things, but people only really report seeing effects in areas that were deficient.
For example, if you have hypersomnia, modafinil will keep you from falling asleep, but it won't necessarily improve your cognition or mood, unless your cognition was already impaired or your mood was already depressed. Similarly, Cephalon patented modafinil as an appetite stimulating drug because it works for that purpose, but for most people, they experience appetite suppression.
It leads me to feel that modafinil is almost an "optimizer". Not that it can optimize everything, but if there is a deficiency, impairment or underperformance in a given area that modafinil has the ability to treat, that's what it will fix, but it won't bring you to superhuman levels, instead it simply restores normal/average/optimized function. It might explain why the cognitive enhancing effects of modafinil are limited to lower performing individuals.
This ties into my initial post in the fact that, it's a bit like doing performance tweaks on your computer. If you have a bottleneck that is limiting compute…
u/MisterYouAreSoDumb · Ceretropic
I actually get very hungry on modafinil. It's not like ephedrine or amphetamine, where you lose any interest in eating. My stomach actually growls much more often when on modafinil.
Your assertion is pretty much my view as well. It does not really enhance anything on its own, unless you are deficient. We can generalize about that all day. However, there are definitely mechanism(s) that are the cause for it. Those mechanism most likely can be altered to make it more efficient. We just need to figure out what they are first.
The enzyme induction plays a larger role than you might think. I've noticed that if I take an opioid after modafinil, the effects are greatly diminished. That is most likely to the CYP3A4 induction that modafinil causes. I could see an induction like that altering levels of catecholamines over time. It doesn't just hit CYP3A4 either. It hits a lot of the CYP450 enzymes.
I don't actually think modafinil is that impressive, to be honest. It has some interesting aspects to it. We should isolate the individual mechanisms, then hit them with substances with greater affinities and less side effects. One that looks interesting is an inverse agonist of the H3 receptors, called ptolisant. Stack that with some NMDA/AMPA positive allosteric modulators, and maybe a beta adrenergic agonist/mild dopaminergic stimulant, and you could have more cognitive enhancement.