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
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb · Ceretropic
Modafinil is such a complicated drug. It induces so many enzymes, that the long-term effects are extremely variable. Who knows how it affects the expression of those enzymes after a while. Then you also have to take into consideration up/down-regulation of receptors themselves. I think histamine is the one that is causing a lot of the variability. If I take modafinil with cetirizine right when I wake up, and my BBB is more permeable, I actually get more tired than not taking it at all. I think that has to do with the inverse agonism of the H1 receptors by the cetirizine interacting with the modafinil.
So the effects you describe could be from many different things, from down-regulation of dopamine hydroxylase and histamine receptors, to induction of various CYP450 enzymes in the liver.