• N&PD Moderators: Skorpio | thegreenhand

Why do lysergamides take a certain time to kick in even if IVed?

white55

Bluelighter
Joined
Sep 25, 2015
Messages
723
Tryptamines, 2c-x, ... all kick in basically immediately if IVed.

Lysergamides kick in in around the same regardles of roa.

Does anyone know the mechanism for this?
 
Last I heard is that it starts a cascade of various signalling molecules in your brain which takes some time to produce a trip.
 
The thing is, the same is true for other psychedelics. Still, the reason for it could totally be related. LSD does have that weird functional group that flips closed like a lid locks it into the receptor.

The latter at least could be easily tested by IVing LSD analogs that lack that functional group and comparing onset times
 
Last edited by a moderator:
I believe it is connected to the way LSD gets stuck in the receptor.

Normal psychedelics continuously bind to and dissociate from the receptor.
With LSD, we're talking about a "pseudo-irreversible" binding mechanism - once that lid on top of the receptor closes, chances are that the receptor is getting recycled before it ever releases the LSD again.
However, it also probably takes significantly longer for the molecule of LSD to get trapped in the receptor like this, than it takes for a molecule of psilocin to reversibly bind to it... consequently, you need to wait a while for a sufficient amount of "stuck" LSD molecules to accumulate before you feel the effects, while other psychs hit you pretty much as soon as they enter the brain.
 
The thing is, the same is true for other psychedelics. Still, the reason for it could totally be related. LSD does have that weird functional group that flips closed like a lid locks it into the receptor.

The latter at least could be easily tested by IVing LSD analogs that lack that functional group and comparing onset times
You mean the various R2/R3 subs such as LSZ, MIPLA, LSP, LSB, ECPLA, ....?

That would be an interesting study, if anyone is going to do it I would very much like to volunteer (assuming I wasn't in the group getting placebo).


Although I have noticed that larger doses kick in faster 250 ug ald-52 takes (or 125ug ald-52 + 100 ug eth-lad) 1 h or a bit more 500 ug ald-52 + 400 ug eth-lad more like 30 min and 1000 ug eth-lad + some ald-52 (idk 500ug? my memory is fuzzy about this one) had the ceiling morphing and swallowing me in under 15 min. Idk if the relationship is linear or logarithmic or whatever and if and when diminishing returns hit. There were dissociatives involved with the larger doses (o-pce or o-pce + 3-meo-pcp or o-pce + 3-meo-pce at around 30 mg each or 60 mg each). So that might have played a part too. 1.5 mg al-lad also kicked in quite quickly (don't remember how long since it was in 2014, but faster than 300 or 450 ug) without any dissos involved (I hadn't discovered the wonderful psy/disso combination yet) and lasted much longer than al-lad usually does, I took it around 1800 and was still tripping slightly next morning at 0900. Finally ate a bunch of benzos (etizolam, diclazepam and flubromazepam, afaik other than pyrazolam (which doesn't do anything for sleep) and phenazepam (which I didn't have since I wasn't/am not a huge fan... strangely enough I like 3-ho-phenazepam (though I wouldn't, got a free sample and liked it quite a bit... not as much as my favourites (flunitrazolam, flubromazolam and flualprazolam) these were the only rc (or sold as rc benzos (etizolam, phenazepam)) sold at that time... flubromazolam (and was extremely cheap and high quality (had it lab tested, pure flubromazolam) from a certain long gone Polish vendor) arrived a few weeks later... and drank 2-3 dl of rum (yes I know benzos and alcohol but I had tolerance to both and had taken the same or higher amount several times before so I judged it to be safe enough) around 15 min to be able to sleep later since the benzos weren't enough and I really wanted to sleep because I was exhausted and had a lot of things to do in the afternoon.
 
The latter at least could be easily tested by IVing LSD analogs that lack that functional group and comparing onset times

"LSD analogs that lack that functional group" is basically what plain old N,N-dialkyltryptamines are.

You mean the various R2/R3 subs such as LSZ, MIPLA, LSP, LSB, ECPLA, ....?

2,4-Dimethylazetitidide, N,N-methylisopropylamide, 3-pentylamide, 2-butylamide, and N,N-ethylcypropropylamide are all just bioisosteres for LSD's diethylamide moiety, though.
 
Last edited by a moderator:
I'm at work, so I can't check at the moment, but I believe Nichols tackles this around minute 19 or 20 of this video. https://m.youtube.com/watch?v=TxjCSKMbZBA
Watching now.

He's at LSZ now.

"LSD analogs that lack that functional group" is basically what plain old N,N-dialkyltryptamines are.



2,4-Dimethylazetitidide, N,N-methylisopropylamide, 3-pentylamide, 2-butylamide, and N,N-ethylcypropropylamide are all just bioisosteres for LSD's diethylamide moiety, though.
Doesn't that kill the potency making it pointless?
 
Top