Another pharmacology question of interest...

We know that psychedelics are usually 5-HT2a (serotonin subtype 2a) agonists, meaning they attach to those receptors. This is the path through which most of the action is believed to happen, since when blocking those receptors with a 5-HT2a antagonist, psychedelic effects are blocked.

That´s obviously not the whole picture because not all the 5-HT2a agonists are psychedelics.. It seems easier for me to understand this by looking at receptors and receptor action as pathway/messengers, instead of the message itself. Like imagining a tunnel where different kinds of trucks go through, for example the bread truck, so by blocking the tunnel maybe there are no more breads on the other side, but that doesnt mean that anything that goes through the tunnel is bread or that the tunnel or trucks themselves are the bread, it´s just the path. Don´t know if that´s a good or useful way of thinking about it, but serves for me

What about other receptors, what can they tell us about a substance´s actions? I´m wondering more regarding psychoactivity but any other relevant medical effects can be mentioned.

For example..

Psychedelics - 5HT2a agonists
Stimulants - Dopamine releasers but also agonists/antagonists where?
Dissociatives - NMDA antagonists
Opiates and related - opioid receptor agonists?

What else is missing in this?

What about GABA, muscarinic receptors, Sigma-1, acetylcholine, etc? What is their direct relevance to psychoactivity?

I know this is a complex subject but can we somehow get an overal picture without going too much into the complexity?

it gets pretty deep. some drugs act as sodium/potassium channel-blockers.

you also need to consider whether a ligand is competitive/uncompetitive/noncompetitive inhibitor at the active binding site, or is an allosteric affector.

also, the common stimulants are dopamine reuptake inhibitors.
some are norepinephrine reuptake inhibitors

It's a good way of understanding the principle. But what if you stop the bread truck, and another truck of different purpose takes over and collaborates with yet another truck, to produce bread? How will you differentiate between the two states? (did this substance stop the production of bread, or not?)



I feel you, but I don't think we can. It's like trying to figure out the overall picture of how a computer (human) works, by investigating the voltage terminals (receptors) on the circuit (brain) and figuring out what amounts of volts (ligands) go where (receptors). We are still looking at a microscopic field of view of a very large and dynamic system.

I do want to though!!

What about GABA, muscarinic receptors, Sigma-1, acetylcholine, etc? What is their direct relevance to psychoactivity?


HUmm gaba agonist is benzodiapazine classic anti-anxiety/ no - inhibition, sleepy floating, antagonist are gingko biloba stimulant style, more thinking hence more potential anxiety.

acetylcholine muscarinic antagonist are delirant like datura dream world this raise dopamine tush making more visual, dilate pupils, confuse, high heart rate, Agonist are cognitive enhancer,slow breathing/ heart rate more potential anxiety(less dopamine)hyperactive, movement speed+ need to move to help focus, sweaty(more adrenaline to skeletal muscle,cant focus for the amount of thought is massive and no dopamine make no focus..

Sigma is the absoluteness of cocaine, amphetamine,ibogaine ,ketamine-pcp-dxm and DMT. Never found a coumpound witch is only sigma so cant figure what it is now, but its good

Sodium channel blocker benedryl,cocaine,benzocaine, local anesthesic are sodium channel blocker, agonist i never found any yet. >Calcium channel blocker are lyrica for fiber pain, L-Type are heart slowing pill like norvacs, N-type are analgesics.

Well that all i can get out of my head right now, would love to help you comprehend more the neuropharmacologic equalizer as a neurotransmitter is more then often a neuromodulator or neuro-peptide. Ex; Acetylcholine and dopamine are yin and yang like, when one increase the other drop, more acetylcholine will modulate the adrenaline to the body and less to the heart, less acetylcholine will make you paralyze, racing heart, confused, no thought void,hallucination dream worldy. Aceylcholine will modulate glutamate and glutamate modulate acetylcholine. no im not gonna dive into this more, i gotta stop.


Equalizer because they ALL influence each other.

Ps if other find mistake please rectify im a bit to sleepy now.

Good night and may you Love all

I think this is an immensely complicated topic, and any simplifications will miss alot of whats relevant here.

One example- the mu opioid receptors in the ventral tegmentum area of the brainstem are located on GABAergic interneurones which serve to inhibit dopaminergic neurones, which project from here to the nucleus accumbens. Opiates when bound to these mu receptors inhibit the interneurones, resulting in dis-inhibition of the dopaminergic neurones resulting in dopamine release in the nucleus accumbens.To complicate matters further, the nucleus accumbens also has mu receptors.

Fascinating but intricate stuff that doesnt lend itself to easy simplification.

Sounds fascinating indeed!

Thank you all for your posts. It actually served me to understand a bit more about this, maybe other people who read this too

I found a few articles that may interest you, mainly related to psychedelic action on both 5-ht2a and 5-ht2c receptors.

http://www.plosone.org/a...Fjournal.pone.0009019#s4



http://www.sciencedirect...le/pii/S0091305798001105




http://link.springer.com...1007%2Fs00213-010-1784-0



http://www.sciencedirect...le/pii/S0163725803001657