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Re: Amphetamine for schizohprenia? undopaminergic

Posted by linkadge on June 28, 2021, at 14:42:10

In reply to Re: Amphetamine for schizohprenia?, posted by undopaminergic on June 28, 2021, at 5:31:59

>be the underlying mechanism behind the so-called >paradoxical calming effect of amphetamines in >subjects with ADHD.

Exactly. Interestingly, mice lacking the TAAR1 receptor, become significantly more stimulated by amphetamine than normal mice. This indicates that activating TAAR1 by amphetamine offsets some of the 'stimulant' effects of amphetamines.

TAAR1 agonists seem like a very interesting target. In mice, they have antidepressant and antipsychotic effects. However, the antidopamingic effects are very region specific. (i.e. the don't induce cataplexy).

In animal models of ADHD, there is actually dopamine overactivity. In those responding to amphetamine, the TAAR1 system may be intact (and perhaps upregulated) and, like you say, the brain is responding with more of an antidopaminergic effect. Of note, antipsychotics are also occasionally used for ADHD, and they apparently work too (although less so for cognition). If ADHD was low dopamine, then they should make things worse.

This may be true too for schizophrenics. Perhaps, in a certain dose range, amphetamines may actually be doing something positive. I remember reading reports of 'bipolar' patients having clear 'antimanic' effects from stimulants.

Perhaps there is a deficiency of endogenous TAAR1 agonists in ADHD (PEA, tryptamine, octopamine, tyramine, thyroid metabolites etc).





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