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LSD molecule question

psychonautika

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i want to understand cause we have an long term argumment about this topis so their is lsd that made from ERGOT and LSD that made from something else? if the two are LSD is that possible that they make a different effect?
i understand that in ketamine their is asketamine and arketamine and the both the some molecule but different side, in LSD their is sides too?

THANKS AND LOVE!
 
https://en.wikipedia.org/wiki/Lysergic_acid_diethylamide#Chemistry

Wikipedia said:
LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride and peptide coupling reagents. Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate; or, theoretically possible, but impractical and uncommon, from ergine (lysergic acid amide, LSA) extracted from morning glory seeds. Lysergic acid can also be produced synthetically, eliminating the need for ergotamines.

And, no, whether LSD is produced entirely synethtically or from ergolines, the effects will be the same.


Wikipedia said:
LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-D-LSD, has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and are not formed during the synthesis from d-lysergic acid. Retrosynthetically, the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-tryptophan, the precursor to all biosynthetic ergoline compounds.

However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases, as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by chromatography and can be isomerized to LSD.

So by the looks of it, at least one of the optical isomers is not psychoactive. It's not entirely clear to me whether those 2 C-5 isomers which "do not exist in nature" have ever been synthesized or tested to see if they have any different effects (or even if it is possible to do so), but either way it seems to be the case that any LSD ever available so far is composed of only a single isomer, ie, (+)-D-LSD.
 
Depending on the polymorph (crystal lattice arrangement) or lsd hydrate Crystal's, it's possible that lsd could have different pharmacokinetics depending on the crystal polymorph.

This phenomena is well known in many drugs, I'm not sure whether it is known in lsd, but it is certainly possible.

This is if you are dosing straight crystal though, which is usually not how ppl take lsd....they dissolve it in a liquid, destroying the crystal structure

It's such a small amount of material I cant see this having much of an effect but stranger things have been discovered in pharmacology
 
This is from Alexander Shulgin's TIHKAL:
Let me mention in passing, that there are three stereoisomers possible for d-LSD. There are d-iso-LSD, l-LSD, and l-iso-LSD. The inversion of the stereochemistry of the attached diethylcarboxyamido group of d-LSD gives the diastereoisomer (d-iso-LSD) which is a frequent synthetic impurity of d-LSD itself. The corresponding optical antipodes l-LSD and l-iso-LSD are also known and have been tasted. All three are completely inactive: d-iso-LSD shows no psychological changes at an oral dose of 4 milligrams; l-LSD none at up to 10 milligrams orally; and l-iso-LSD none at 500 micrograms orally.

So yes, while there may be traces of d-iso-LSD occuring in virtually every batch of LSD, it does not make any noticeable difference to the trip; even if your acid was 100% iso-LSD and you ate 4000 micrograms of it, it would not produce psychoactive effects.

There are a lot of pseudoscientific bullshit claims about "needlepoint" and "fluff" LSD, and about how dealer A sells 99% pure silver LSD and dealer B is selling 99.9% pure material recrystallized straight from Jerry Garcia's kidney stones, but it's all marketing hype and dicksizing about how everyone likes to think they've got the best drugs. FFS, people can't even agree on whether "needlepoint" refers to the shape of the raw crystals, or the method the solution is transferred onto blotters.

LSD is a "classical psychedelic" (as opposed to a "dissociative" like ketamine), and as such the experience it produces is inherently highly variable, and renders the user open to suggestion. The placebo effect is an extremely powerful thing, as is the nocebo effect. For all practical intents and purposes, it is safe to say that LSD is LSD is LSD. Remember, if I were to convince you that what you were ingesting was the worlds best, purest LSD, then that would significantly affect your set&setting, and as such would obviously influence the nature of the trip.

Bottom line: LSD-25 (as in d-LSD, the active isomer) is so insanely potent at what it does (i.e. activating the 5ht2a receptor) that none of the impurities are going to have any noticeable effect at the dosage levels that LSD is normally ingested at.
 
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And, no, whether LSD is produced entirely synethtically or from ergolines, the effects will be the same.

I do not think that anyone is actually using synthetically produced lysergic acid to make LSD for commercial purposes, anyway.

These kinds of total syntheses are basically done out of scientific curiosity and for bragging rights, often to show off/try out new synthetic techniques. Sourcing ergotamine tartrate or even lysergic acid itself isn't exactly easy for an LSD lab, but it is far, far, FAR, easier than trying to make your own lysergic acid from scratch via total synthesis.

While the use of ergoline-based medications for indications like migraines and parkinson's disease has declined in recent years, a number of ergoline-based medical drugs are still in clinical and veterinary use. Therefore, ergotamine/lysergic acid remains an important precursor chemical in the pharmaceutical industry, and as such it can be diverted onto the black market.

Total syntheses of complex natural compounds involve *a lot* of synthetic steps (including protection/deprotection, work-up and purification), and each of these steps decreases your product yield to some extent; lysergic acid and its derivatives are highly fragile in the presence of oxidants, acids/bases, metal ions and light, so there is a lot that can (and will) go wrong. Even if, for some reason, use of all ergot-based medications were to cease immediately, it might be easier to "just" set up a biochemistry lab to cultivate ergot fungi, rather than doing a total synthesis of lysergic acid.
 
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^ Interesting!

Given that you seem to know what you're talking about, :) I wonder if you could shed some light on the phrasing of something I quoted from Wikipedia - specifically -
The C-5 isomers of lysergamides do not exist in nature
This sounds weird to me because surely, none of the isomers of LSD exist "in nature", ie, occur naturally, which is what I assume that to mean. Although I notice now that it does say "lysergamides" rather than LSD specifically, so assuming that naturally occurring lysergamides from plant sources have the same isomers, perhaps the C-8 isomers of these are the only ones that occur naturally - rather than isomers of LSD itself?

Still, is somewhat confusing phrasing to me, but perhaps not to someone more well versed in the chemistry.
 
This sounds weird to me because surely, none of the isomers of LSD exist "in nature", ie, occur naturally, which is what I assume that to mean. Although I notice now that it does say "lysergamides" rather than LSD specifically, so assuming that naturally occurring lysergamides from plant sources have the same isomers, perhaps the C-8 isomers of these are the only ones that occur naturally - rather than isomers of LSD itself?

Still, is somewhat confusing phrasing to me, but perhaps not to someone more well versed in the chemistry.

They are referring to natural lysergamides, such as ergotamine, ergometrine, and lysergic acid. The C5 stereochemistry is the same as is found in tryptophan, the ultimate biosynthetic precursor of these compounds, which is likely why it is consistent throughout the natural lysergamides. The C8 position, however, is fairly easily epimerized, and the C8 epimers can be found in nature. Ergotaminine, from ergot, is an example of a natural lysergamide with the opposite C8 stereochemistry of LSD:

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If you overlay LSD with the NBOMe class in ChemOffice (or similar) you will note:

-The O= oxygen of the LSD amide overlays the -O- of the NBOMe anisole ether.
-The 7-N of LSD overlays the amine N of the NBOMe
-The benzene rings of LSD & NBOMe overlay
-The N of the indole system of LSD overlays the O of 5-MeO of the PEA of the NBOMe (a 5-MeO added to the indole system of LSD may increase affinity - Dr. Dave thought so but also thought it was far, far too much work)
-The 7-position of the indole system of LSD overlays the 4-position of the PEA of the NBOMes. 7,α-DMT & 7,N,N-TMT both have higher affinity to the 5HT2a receptors than their parents and are subjectively the same as their patents

I'm sure people will have noted that many different amide analogues of LSD are active with (S,S)-2,4-dimethylazetidide being potent (rigid and appropriate space-filling) but sec-butyl, isopentyl, methylpropyl, methylisopropyl, & even piperidine derivatives. This is really useful for building training sets. As I always say - install a Linux-based OS onto your PC & download a copy of CHARMM. It's a fantastic aid to learning. The paper 'Insights into Subtype Selectivity of Opioid Agonists
by Ligand-Based and Structure-Based Methods' by Jianxin Cheng & Guixia Liu & Jing Zhang & Zhejun Xu & Yun Tang - J Mol Model (2011) 17:477–493 (DOI:10.1007/s00894-010-0745-1). It's a REAL eye-opener and it puts everyone in the position of understanding rational design.
 
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