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Comment by peanut_worm | Hacker News Reader

> Psilocybin is an agonist of 5HT2a serotonin receptors; however, unlike LSD, it has no effect on dopamine receptors

Thats surprising considering how similar their effects are.

Look at the receptor binding affinities in tables 1 and 3 (note that psilocin is the active metabolite of psilocybin, and that lower numbers indicate stronger binding) of this paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110631/

LSD has about 8 times the affinity for 5-HT2A as D3, vs 25 times for psilocin. This doesn't tell us anything about how they act on the receptors, or the affinities of the endogenous ligands they're competing with, but I think it's unlikely the dopaminergic activity is significant for either drug.

Edit: This does cite a paper from Nichols' lab[1] which claims LSD has a second phase of action after the serotonergic phase, where its dopaminergic activity dominates. This strikes me as plausible... I'd have to read it.

[1] https://pubmed.ncbi.nlm.nih.gov/17618679/

Have you done them before? LSD’s stimulating nature should make it kind of obvious. They share the 5ht2a agonism because that’s how all the classic psychs (lsd/psilocybin/mescaline/dmt) work. But LSD structurally is like a psychedelic amphetamine/phenethylamine, whereas psiloybin doesn’t have that stimulating feeling at all

I have done both about 15 times each, LSD is nothing like an amphetamine. I would say they are definitely much more similar in effect to each other than they are different.

Sorry, I'm late to the party. You can mentally place a hyphen between "psychedelic" and "amphetamine". These are substances that structurally contain the amphetamine molecule "skeleton" with some extra atoms attached. The additions change the activity from mostly stimulating to mostly psychedelic. This class includes substances such as DOM and DOB (which are mostly psychedelic), and MDMA and MDA (which are mostly entactogenic, with some psychedelic and stimulating activity). LSD is interesting because it contains both the amphetamine skeleton and tryptamine skeleton, which may be related to its incredible potency. For more information, I highly recommend the books PIHKAL and TIHKAL by Alexander and Ann Shulgin.

Lol are they?

The 5ht2a agonism is what’s similar. LSD is made unique by its strong dopamine subreceptor agonism. So no, shrooms and LSD are most different in the dopaminergic effects of lsd and the half lives (lsd 2-4x longer). LSD is more of a psychedelic amphetamine whereas psilocybin is a classic tryptamine

Actually no. LSD is a direct-acting sympathomimetic drug; it directly binds to serotonin and dopamine receptors to activate them.

Amphetamines, like all phenethylamines typically, are not direct-acting sympathomimetic, but indirect-acting; amphetamines elicit their effects through blockage and reversal of NET and DAT, the norepinephrine and dopamine transporter proteins. They are, however, TAAR1 agonists, which is currently thought to be partially responsible for regulating downstream effects on dopamine neurotransmission.

LSD is best described as a lysergamide.

Hello. Long lover of lyseragmides and novel phenethylamines, and stoner.

Why does smoking have an immediate intensification effect when combined with lysergamides? Is it because of the combination of partial antagonism and down regulation blocking of certain receptors?

Immediate effects are most likely due to smoke containing large amounts of various monoamine oxidase inhibitors.

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