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Anti-dopamine supplements to test theory for recovering reward system

mesolimbic reward system dopamine restoration dopamine inhibition

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#1 DaveX

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Posted 29 July 2019 - 03:35 PM


Part of the lasting anhedonic or other side-effects by Risperidone and similar medications is hypothesized (e.g. wikipedia, or agonist/antagonist profile) to be actually caused by dopamine overexcitation in the mesolimbic system, rather than excess serotonin. I.e., its partial agonism of dopamine receptors, along with additional overcompensation by the body, might have caused the system to downregulate significantly afterwards or even incur damage (the same as with drug abuse).

I think I have already moderate success with going the opposite route in serotonin, i.e. giving the body serotonin by way of 5-HTP, rather than depriving it of it, whereas trying to boost dopamine usually doesn't even have temporary effects, but seems to cause simultaneous exhaustion with the onset of effects (like the system can't bear it, doesn't care for it). Though this varies slightly and from time to time, but without great encouragement.

Therefore I'd like to see what dopamine-antagonism in the mesolimbic area might do, or efficiently decreasing dopamine in there. I doubt this would be risky, except to cause temporary discomfort, but it seems a more likely route to try than conventionally grooming dopamine receptors and encouraging dopamine release.
At least that is the purpose of this thread.

What are supplements which might do that? Block dopamine in the mesolimbic system or decrease it? I vaguely have assocations with licorice root doing this, but I'm not sure, and can't think of anything else.

Edited by DaveX, 29 July 2019 - 03:41 PM.


#2 DaveX

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Posted 02 August 2019 - 02:16 PM

I have to say my description of how Risperidone and others may cause super-sensitivity or excitotoxicity wasn't quite right. For one, Risperidone isn't a partial agonist, it's just an antagonist. I mistook it for Aripiprazole's activity on that part.

And I suppose a dopamine inhibitor or depleter wouldn't be so much different from those drugs' original effect.

But regardless of the explanation for the mechanism, I think dopamine depletion or inhibition can be interesting things to try.

 

And I remembered N-Acetylcysteine is actually a well-known supplement that decreases dopamine signalling (by Calcium channel blockage, I think) and is already quite popular for maintaining dopamine receptor/neuron health in addition to dopamine-increasing supplements or habits.

And then, I think Uridine is known to increase the dopamine receptor "turn-over rate", which has a balancing and health-maintaining or restoring effect.


Edited by DaveX, 02 August 2019 - 02:22 PM.


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#3 DaveX

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Posted 04 October 2019 - 12:58 PM

Berberine is actually a Dopamine D2, D1 antagonist, and it makes me feel acutely ill and nauseous, like it does many.

It is not actually an idea I still actively pursue, aside from D1 antagonism specifically, because that's how Sulbutiamine is said to cause its beneficial effects. But even so, I'd prefer any other mechanism to upregulate D1.



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Also tagged with one or more of these keywords: mesolimbic, reward system, dopamine restoration, dopamine inhibition

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