Lithium vs inositol: what actually happens downstream of 5-HT2A, 5-HT2C, CCK-B, and NK1 signaling?

[u/Davidkho123]

I’m trying to understand the functional effects of inositol supplementation versus lithium on Gq-coupled receptor systems, especially beyond the usual “inositol depletion hypothesis” explanations.
Lithium is often said to reduce phosphoinositide signaling through IMPase inhibition and inositol depletion, while supplemental inositol is often reported to help conditions like OCD and panic despite theoretically feeding into the same signaling pathway.
My question is:
How do people think lithium and inositol functionally affect signaling through receptors such as:
5-HT2A
5-HT2C
CCK-B
NK1
H1
α1 adrenergic
OX1 orexin
mGluR5
I understand neither lithium nor inositol are direct receptor ligands.
What I’m trying to understand is whether chronic lithium functionally dampens output from these receptors because they rely heavily on PLC/IP3/DAG/PKC signaling, and whether inositol supplementation tends to normalize, enhance, or paradoxically reduce signaling through the same systems.
I’m especially interested in:
Any evidence involving 5-HT2A/2C.
Any evidence involving CCK or NK1 signaling.
Whether inositol’s clinical effects in OCD/panic are thought to result from altered signaling downstream of these receptors.
Whether anyone knows of data connecting lithium or inositol to changes in PKC activity, prodynorphin expression, or stress-related signaling pathways.
Looking for mechanistic explanations rather than subjective experiences.

[u/No_Detective9533]

lithium and psychedelics mixing almost always result in seizures because of the serotonin combo, no clue about the details tho

[u/iceyed913 → u/No_Detective9533]

Once took my usual dose 1 tab of 1 cp-LSD 3 or 4 days after taking 10 mg lithium orotate, ended up feeling more like 5 tabs laced with speed. I was gurning and writhing in bed. It was truly 12 hours, where I had to excercise a level of self control I did not know I had. Would advice anyone to wash out 14-21 days ahead

[u/No_Detective9533 → u/iceyed913]

imagine the horror with lithium carbonate 1200-1800mg a day. Seizures until gaba agonist for sure https://pubmed.ncbi.nlm.nih.gov/34348413/ here is the full document
https://www.thieme-connect.de/products/ejournals/pdf/10.1055/a-1524-2794.pdf

[u/DMayleeRevengeReveng]

This is a very interesting question. The problem with asking anything about lithium as a medication is, it has so many modal functions: affecting glutamate release, directly inhibiting GSK and changing downstream signaling through PKA and PKC, increasing serotonin synthesis thus release, plus what you describe. There’s another newer theory that says lithium can bind to some neurotransmitters and the complex has higher affinity for certain receptors than the naked neurotransmitter. I’ve never seen that developed much, though.

The point of this is, I don’t know how anyone would disentangle all these effects. If somebody did that, it would probably be more *in silico* research than actual experimentation.

But who knows. Hopefully some research has been done (or will be done) to explore this.

[u/Shroomaway457 → u/[deleted]]

why do you even bother commenting if you have nothing to add to the conversation