red22
Bluelighter
- Joined
- Nov 23, 2009
- Messages
- 2,063
I get what you’re getting at — the idea that some of the “rough edges” of psychedelic amphetamines (and maybe even their after-effects) could be due to the fact that we’re almost always taking them as racemates, so we’re getting the “good” and the “bad” isomer mixed together.
Why that might be plausible
• With amphetamine itself, the optical isomers are very different:
• d-amphetamine → much more central stimulation, euphoria, focus.
• l-amphetamine → weaker for euphoria, but more potent on peripheral noradrenaline release → higher cardiovascular load, more jitter, bruxism, vasoconstriction, orthostatic hypotension.
• If you take racemic amphetamine, you get both effects at once — strong CNS stimulation and strong peripheral side effects.
• For psychedelic amphetamines (like DOM, DOB, DOC, TMA series, etc.), there’s no reason to think the isomers are equivalent in psychoactivity either — the 5-HT₂A affinity could be skewed heavily toward one, while the other could be doing more adrenergic or dopaminergic “noise” work.
Why this could matter in Shulgin’s phenethylamines
• Most of these were never clinically tested as isolated isomers — Shulgin’s synths typically yielded racemates, and that’s what the bioassays were done on.
• If, say, the active psychedelic effect is mostly from one enantiomer, and the jitter, jaw clench, cold extremities are coming from the other, then purifying to the “psychedelic-preferred” isomer could indeed make for a smoother, more “mescaline-like” experience with less of the amphetamine body load.
• In principle, this could also extend the useful dose range — right now the “side-effect ceiling” for something like DOM is often reached before the full psychedelic depth is explored.
Possible caveats
• Not all side effects are from the “wrong” isomer — some are inherent to the receptor pharmacology of the active one (e.g., 5-HT₂A agonism can itself cause vasoconstriction and jaw tension via serotonin-mediated pathways).
• Isomer separation is non-trivial in clandestine or DIY contexts, and the yields could be low.
• If both isomers are psychoactive but differently so, you might lose part of the unique character of the racemate — some users might even find the single-isomer version less satisfying or more one-dimensional.
In short:
I think your speculation is absolutely valid, and I’d bet that at least a few of the Shulgin-type psychedelic amphetamines would be far better tolerated as single enantiomers — likely with a cleaner headspace and reduced “amphetamine hangover” — but without formal testing we just don’t know which enantiomer is the “good” one for each case. The precedent from amphetamine, methamphetamine, and even MDMA suggests this is worth exploring scientifically.
If you want, I can pull what’s known about isomeric pharmacology for specific psychedelic amphetamines (DOM, DOC, etc.) — there are scattered references that might give clues as to which enantiomer to bet on.
–ChatGPT
Why that might be plausible
• With amphetamine itself, the optical isomers are very different:
• d-amphetamine → much more central stimulation, euphoria, focus.
• l-amphetamine → weaker for euphoria, but more potent on peripheral noradrenaline release → higher cardiovascular load, more jitter, bruxism, vasoconstriction, orthostatic hypotension.
• If you take racemic amphetamine, you get both effects at once — strong CNS stimulation and strong peripheral side effects.
• For psychedelic amphetamines (like DOM, DOB, DOC, TMA series, etc.), there’s no reason to think the isomers are equivalent in psychoactivity either — the 5-HT₂A affinity could be skewed heavily toward one, while the other could be doing more adrenergic or dopaminergic “noise” work.
Why this could matter in Shulgin’s phenethylamines
• Most of these were never clinically tested as isolated isomers — Shulgin’s synths typically yielded racemates, and that’s what the bioassays were done on.
• If, say, the active psychedelic effect is mostly from one enantiomer, and the jitter, jaw clench, cold extremities are coming from the other, then purifying to the “psychedelic-preferred” isomer could indeed make for a smoother, more “mescaline-like” experience with less of the amphetamine body load.
• In principle, this could also extend the useful dose range — right now the “side-effect ceiling” for something like DOM is often reached before the full psychedelic depth is explored.
Possible caveats
• Not all side effects are from the “wrong” isomer — some are inherent to the receptor pharmacology of the active one (e.g., 5-HT₂A agonism can itself cause vasoconstriction and jaw tension via serotonin-mediated pathways).
• Isomer separation is non-trivial in clandestine or DIY contexts, and the yields could be low.
• If both isomers are psychoactive but differently so, you might lose part of the unique character of the racemate — some users might even find the single-isomer version less satisfying or more one-dimensional.
In short:
I think your speculation is absolutely valid, and I’d bet that at least a few of the Shulgin-type psychedelic amphetamines would be far better tolerated as single enantiomers — likely with a cleaner headspace and reduced “amphetamine hangover” — but without formal testing we just don’t know which enantiomer is the “good” one for each case. The precedent from amphetamine, methamphetamine, and even MDMA suggests this is worth exploring scientifically.
If you want, I can pull what’s known about isomeric pharmacology for specific psychedelic amphetamines (DOM, DOC, etc.) — there are scattered references that might give clues as to which enantiomer to bet on.
–ChatGPT
