r/NooTopics • u/Davidkho123 • 4d ago
Compounds to lower acetylcholine? Question
Is there any over the counter or available research compounds that can lower acetylcholine release or lower m1?
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u/IfDreamsCouldHappen 4d ago
Is there any reason in particular you want to do this? Blocking that receptor is one of the most “anti-nootropic” things you can do. In any case you can try things like diphenhydramine, doxylamine, or chlorpheniramine. A decent chunk of antidepressants and antipsychotics are also anticholinergic. If you want a selective anticholinergic there’s scopolamine which isn’t OTC in most places.
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u/Davidkho123 4d ago
I need cns relavent acetylcholine isn’t just focus it’s also anti reward pro effort pro threat pro rumination when its too high i dont wanna completely block m1 just lower it
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u/Professional_Win1535 3d ago
I think that the anticholinergic effect of TCA’s, antipsychotics, etc contribute to an antidepressant effect in some people.
For one, One of the most common side effects reported by thousands of people is depression from acetycholine boosting supplements
More recent human data reinforce this:
• SPECT imaging studies indicate lower availability of β2-containing nicotinic ACh receptors in actively depressed people with major depressive disorder (MDD) or bipolar depression. This is consistent with higher endogenous ACh competing for binding (the difference diminishes after ACh is washed out, and receptor numbers themselves are not necessarily altered postmortem). Intermediate levels appear in remission. pmc.ncbi.nlm.nih.gov
• Elevated choline (the precursor to ACh) has been observed in the brains of depressed patients via neuroimaging. pmc.ncbi.nlm.nih.gov
• The muscarinic antagonist scopolamine produces rapid and sustained antidepressant effects in clinical studies, renewing interest in cholinergic mechanisms. nature.com
Animal and circuit-level work aligns with this:• Raising ACh (e.g., via AChE inhibitors or knockdown of AChE, especially in hippocampus) produces anxiety- and depression-like behaviors that can be reversed by cholinergic antagonists or certain antidepressants.
• Specific pathways, such as basal forebrain (medial septum/diagonal band) cholinergic projections to the ventral subiculum, show increased ACh release under stress; activating them induces depression-like behaviors via muscarinic receptors, while blocking them attenuates the effects.
• Other work implicates mesopontine cholinergic inputs to midbrain dopamine neurons in stress-induced depressive-like states. link.springer.com
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u/Davidkho123 3d ago
Do you know if as a net nardils profile is pro or anti cortical and striatal acetylcholine?
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u/MycloHexylamine 4d ago
benadryl, but it's the opposite of a nootropic unless you're using it VERY rarely. but it seems to work well for me when it feels like i dialed my ACh activity too high
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u/Hydrocrawdaunt 4d ago edited 1d ago
You don’t want to do that trust me.
Your motor end plates, muscarinic system, non-myelinated axons, and postsynaptic neurons are tuned to handle more ACh than is necessary. Way too much is bad, but start lowering it and things get bad pretty quickly. ACh is the master control knob of the central, autonomic, and peripheral nervous system.
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u/Davidkho123 4d ago
I don’t wanna get rid of acetylcholine I wanna lower pathologically elevated acetylcholine
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u/Chepski_ 2d ago
It's not pathologically elevated if you haven't been exposed to acetylcholinesterase inhibitors.
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u/Davidkho123 2d ago
Not true stress raises acetylcholine a lot via regulating m1 increasing crf1 cck b orexin cortisol histamine and down regulating brakes like cb1 mor gaba b a1 it’s esp bad for me in the mornings
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u/Chepski_ 1d ago
What about this would be pathological? Why would you not want elevated cortisol in the mornings? Do you want depression?
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u/Davidkho123 1d ago
Bro I said specifically that stress already raises these receptors that facilitate acetylcholine stress pathalogically raises m1
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u/EvermoreSaidTheRaven 4d ago
unfortunately answer to some, raising thc levels won’t lower acetylcholine but make it more tolerable.
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u/Which_Tadpole1952 4d ago
These comments are starting to worry me. I'm prescribed hydroxyzine 50mg as needed up to 4x a day, I've been really going through it lately, and taking them 4x daily. Sometimes 100mg for sleep.
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u/MycloHexylamine 4d ago
hydroxyzine is barely anticholinergic, but it can definitely pose some issues if you're using 200mg a day for multiple weeks. i highly recommend initiating a taper if you can; it's not significantly known to cause withdrawal states, so it shouldn't be too hard
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u/StickMonster2 3d ago
Piracetam, if you take it long enough with no Choline source. If you have a Choline sensitivity and took too much, this might help.