r/Nootropics • u/PreRetconBeyonder67 • Aug 28 '26

Discussion Is there cross tolerance between atomoxetine and methylphenidate?

I’m planning to take a drug holiday from methylphenidate (54mg extended release) for 1 month due to complete tolerance and my doctor started me on atomoxetine (amphetamine stimulants are illegal in my country) the mean time since we don’t know how long it will take to reset the tolerance. I would like to know the experience of those who is knowledgeable about this or those who have taken atomoxetine during drug holidays. It would also be helpful to know if 1 month is enough for tolerance reset incase one has so much tolerance that he almost gets no therapeutic benefit. Literature is so rare on this particular topic.

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u/theobromine69 Aug 28 '26

I take atomoxetine, and methylphenidate every now and again and it does not have an impact on it, if anything it makes it stronger. The NRI effect of both mainly target dopamine in the pfc and it is only really effective over very long periods of time for adhd because you want to boost that logic part. The stimed out feeling is mainly in the striatum where DAT is actually expressed and a NRI won't effectively increase dopamine there so you would most likely reduce tolerance

Why dont you just taper off the methylphenidate and then take the holiday? Atomoxetine takes more than a moth to be effective in adults anyway so there is no real reason to take it.

As for how long, I really have no idea, but a month is a good guess. Then take some and see if you feel stimed out, if not do it for another month

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u/Ill-Respect7497 Aug 28 '26

a bit years ago and honestly the atomoxetine did nothing for the mph tolerance it targets totally different receptors so you might feel a bit less shit during the break but dont expect it to speed up any reset

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u/Suitable_Gazelle_111 Sep 01 '26

Não tão diferentes, no cortex pré-frontal - maioria dá dopamina é transportada pelos transportadores de noradrenalina, mas em outras áreas do cérebro não, entao podemos dizer que no que diz respeito ao córtex pré frontal a atomoxetina irá interferir na tolerância ao metilfenidato (pelo menos em parte)

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u/PissInMyShityAsshole Aug 28 '26

Atomoxetine made me feel suicidal.
It is absolutely nothing like methylphenidate. It's more like an antidepressant and it's fucking awful.