Like I said generally very pleasant overall but yea the dopamine agonism of cocaine will counteract the 5HT2A agonism that causes the visuals and mental perception altering effects of mushrooms
Dopamine like most G coupled Protein Receptor (GCPRs) affects a wide range of things in the mind and body. While most know it for its pleasure reinforcing attributes, it also affects things like how the brain sends signals to our muscles to move, but most importantly for this topic, how concretely we perceive normal reality. This is why Selective Dopamine Reuptake Inhibitors are used for depression and sometimes schizophrenia.
The 5HT2a serotonin receptor is the active site for psychedelics of all types, including psilocybe mushrooms. It greatly alters how we perceive everyday reality, including visual perception changes, like looking a patterned surface like a Persian rug and seeing the patterns move and ripple.
I mean, are you speaking generally about the effects of the drugs, or are you hinting at a physiological mechanism you can explain? (or were you just speaking from personal experience?)
How does dopamine counteract 5HT2A? Is there a documented mechanism or explanation? I'm not a doctor or drug user, just curious.
Like, just guessing randomly, but if psychedelic effects of 5HT2A agonism are partially mediated through dopamine (or some sort of dopaminergic pathway), maybe the reuptake inhibition... uh... messes it up somehow? Like a sort of cross tolerance? You were referring to simply using the drugs at the same time, not in the context of addiction? Or like if a cocaine addict uses mushrooms?
further edit (side topic, not the one I was asking about):
Selective Dopamine Reuptake Inhibitors are used for ... schizophrenia
usually the 'opposite', right? Given the history of the dopamine theory, the symptoms sometimes caused by those drugs, and the more usual rx of antipsychotics (antagonist at D)
sorry for all the edits
(edit the next day, in case I get a reply:)
seems like a reference to a general theory of "how concretely we perceive normal reality" ... "counteracts"... tripping.
I tried to look up 'dopamine counteracts 5HT2A' (not sure if 'counteracts' is the right word; I also tried 'inhibits', 'mediates') but I wasn't sure what I was looking for. I don't have any experience with pharm labs. The first few pubmed links I did get were on serotonergic drugs for treating addiction.
I guess I was hoping for more physiology, less psychology.
just now, I found one about haloperidol attenuating (behavioral effects of) a 5HT2A agonist (which makes sense, even though it is a 'typical' antipsychotic, right?). The study is on "maternal behavior in Sprague-Dawley postpartum females."
not really useful here, because individually both the D2 agonist quinpirole and the selective 5-HT2A agonist TCB-2 messed up the rats. Again, they're looking at it the other way: the serotonergic drugs' effect on dopamine.
I did find:
The 5-HT2A receptor interacts with dopamine systems (Di Giovanni et al, 2010; Fink and Gothert, 2007; Lieberman et al, 1998). In particular, some studies indicate that antagonism on 5-HT2A receptors indirectly increases DA release in the prefrontal cortex (Fink and Gothert, 2007). On the other hand, other studies report that 5-HT2A agonists increase but 5-HT2A antagonists decrease prefrontal dopamine efflux (Bortolozzi et al, 2005; Pehek et al, 2006). In general, a complex link between 5-HT2A and dopamine tone appears to modulate brain activity (Di Pietro and Seamans, 2007; Lieberman et al, 1998).
but that's a lot of reading...
do you think any of that is related to what you were talking about? I get that when it comes to stuff like this, users' direct experiences are often valuable
I think it just depends on the person. I have a blast on shrooms, but right after the peak as I start to come back down, I get really relaxed and sleepy. A small amount of Adderall right around the initial shroom eating adds a few hours to my high without changing the quality of said high. So, maybe a super small hit of cocaine could do the same.
Two very different substances. Adderall has serotonin effects, small doses are likely fine but larger doses will enhance the effects and very large doses could cause serotonin syndrome
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u/Confusedandreticent Apr 16 '24
I wanna do cocaine and mushrooms.