“Adderall Tolerance: Much More Than You Wanted To Know” by Kurt H. Pieper

The effectiveness of amphetamine (e.g. Adderall) and methylphenidate (e.g. Ritalin) for the symptoms of ADHD, that is, lack of executive function, has been demonstrated beyond reasonable doubt in many short-term studies. (Mandatory reference) Does it last though? The literature is surprisingly sparse, but I was able to extract three main arguments:

1. (against tolerance, strong): Longer studies (RCTs) don't have worse results than shorter ones
2. (against tolerance, medium): People seem to take the same dosages for many years (i.e. no dose escalation)
3. (for tolerance, strong): In a large, long RCT with naturalistic followup (the MTA study), effects disappeared after three years. There is no evidence for a selection effect (i.e. people switching groups) explaining this.

Argument I: RCT Length vs. Effect Size

Figure can be found here

If tolerance exists, then longer studies should find smaller effects than shorter studies. They don't seem to, but note the scarcity of any kind of long-term RCT, as these are expensive to run, and suffer from dropout. This is the best kind of design: Splitting people into two groups for a time T, comparing the difference between amphetamine and normal people. In studies with longer T, this is not [...]

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Outline:

(01:08) Argument I: RCT Length vs. Effect Size

(01:55) Argument II: The Stable Swedish Doses

(02:38) Counterargument I: The MTA Study

(03:51) The Rest of the Literature Isn't Good

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First published:
July 20th, 2026

Source:
https://www.lesswrong.com/posts/iBN8uQi9zbPkdR29Q/adderall-tolerance-much-more-than-you-wanted-to-know

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Narrated by TYPE III AUDIO.

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