14 Comments

When I took modafinil 15 or 20 years ago, it made me itch terribly. More recently when I took it, that wasn't an issue but greatly increased problems with my chronic phlegm issue. Also, it focuses me, but not necessarily on what I need to be focused on! I concluded that it's not for me.

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Interesting, thanks for sharing Max.. Another commentor mentioned that in rare cases there can be severe skin reactions. At least anecdotally it seems a small percentage of people have pretty negative reactions to it. This is one of the reasons, to be honest, I doubt it would ever become equivalent to how caffeine is today.

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I wonder whether s-modafinil would be better in terms of the side-effects I experience. As far as I know, it's not generally available.

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Jan 12, 2023Liked by Dan Elton

You're correct that modafinil does have a history of generally safe clinical use. That said, you should include reports of harmful skin reactions such as Stevens-Johnson syndrome. They were the reason why modafinil was not approved by the FDA for ADHD. More recently, harmful skin reactions were part of why the European Medicines Agency restricted modafinil's approved uses.

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Feb 17, 2023Liked by Dan Elton

https://slatestarcodex.com/2015/04/25/nefarious-nefazodone-and-flashy-rare-side-effects/

> (also: ibuprofen is linked to SJS/TEN, with about the same odds ratio as modafinil, but nobody cares, and they are correct not to care.)

seems overblown

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Thanks! I added some info about this to the post.

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Jan 3, 2023Liked by Dan Elton

Now I wish I could recommend esmodafinil to my insomniac brother who does gig work on sets, sounds like the perfect solution.

FYI, the SSC link in footnote 2 is messed up and prefixed with "xn--https-hw3b". Looks like it's from an errant smartquote in a markdown link:

https://github.com/steemit/condenser/issues/2843

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Jan 3, 2023·edited Jan 3, 2023Author

By the way , it depends what’s perpetuating your brother’s insomnia. If daytime inactivity and napping are major contributing factors then it might be good. Otherwise, it could make things worse. In any case it’s a bit of a moot point since there’s nowhere you can actually get esmodafinil.

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author

Thanks. I didn't see that particular prefix, but there was an issue with the SSC link in footnote 2 which I fixed. If you notice any other bad links let me know.

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Apr 17·edited Apr 17

Might be worth mentioning that prazosin is known to diminish the wakefulness-promoting effects of modafinil, as discussed on its FDA label. In separate research, the effects of modafinil appear to be exaggerated in orexin-null mice.

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I looked up prazosin and that makes sense, because its a sedative (like clonadine). It's not directly canceling the effect of modafinil but compensating.

As far as the orexin null mice... you mean the orexin neurons are ablated so it is impossible for them to produce orexin? That is interesting I suppose -- not what would be expected.

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Yeah, it gets weird because the prazosin sedative effect oddly doesn't seem to be work in mice that don't have a certain dopamine enzyme when modafinil still does ( https://doi.org/10.1016/j.pbb.2008.07.014 ). But as long as that enzyme is around, prazosin seems to work. The effect from prazosin seems pretty strong (Table 1 from https://doi.org/10.1016/0014-2999(90)90591-S ) and the half-life of it could potentially make it appealing for nightly administration, so long as one is smartly monitoring blood pressure - perhaps with a smart watch, etc. I'm considering trying it myself because otherwise I have trouble sleeping when taking a regular dose of armodafinil. I've tried halving the dosage of armodafinil but that seems to eliminate its beneficial effects which makes sense from a pharmacokinetic perspective (I could go on but will spare you the details).

And yeah, that's right for the orexin null mice ( https://doi.org/10.1016/j.neuroscience.2004.10.005 ). I just wanted to mention it because the orexin antagonist approach may not work for reducing the wakefulness-promoting effects of modafinil. It's a shame though because the orexin antagonists of course seem to have wonderful safety and efficacy profiles.

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I’m just got confused about the s-modafinol not being a drug that is commonly prescribed? I was under assumption that normal modafinal is a hybrid of S and R enantiomers and Armodafinal is almost exclusively if not completely the R enantiomer.

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Yeah normal modafinil is a 50-50 mixture of both.

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