Pharmacology Does JRT get its nootropic effect from tryptamine?

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LSD-Inspired Drug Reverses Psychosis Brain Damage Without Hallucinations


ChatGPT:

"Unlike LSD, which is a lysergamide, JRT is classified as a cyclized isotryptamine. This structural modification involves replacing LSD's ergoline ring system with an indole-based structure, resulting in a compound that retains neuroplastic effects while minimizing hallucinogenic properties."

Sounds like a cross between psilocybin and lsd​

Exactly—that’s a pretty good intuition.

Structurally and pharmacologically, JRT does resemble a hybrid of LSD and psilocybin in a conceptual sense:

• From LSD: It inherits the ergoline-derived neuroplasticity effects, though its ergoline ring is modified into a cyclized isotryptamine. Like LSD, it promotes synaptogenesis and dendritic spine growth.

• From Psilocybin: Its indole-based structure (common to tryptamines like psilocybin and DMT) is what gives it that psilocybin-like backbone. This change is largely responsible for reducing hallucinogenic activity while still targeting serotonin receptors, particularly 5-HT₂A.

So, while JRT isn’t literally a mix of LSD and psilocybin, its mechanism—boosting neuroplasticity without strong hallucinations—is reminiscent of psilocybin’s therapeutic profile, combined with LSD’s potency.

If you want, I can draw a visual comparison of LSD, psilocybin, and JRT so you can see the structural similarities and differences.



Many people say that they find psilocybin and DMT (tryptamines) to be more healing than LSD…


Details about how ergolines differ from tryptamines:

"Embedded in the structures of the ergot alkaloids are conformationally-restricted variants of the phenethylamine pharmacophores of both dopamine and related biogenic amines as well as that of serotonin."

Lee K, Poudel YB, Glinkerman CM, Boger DL. 2015. Total synthesis of dihydrolysergic acid and dihydrolysergol: development of a divergent synthetic strategy applicable to rapid assembly of D-ring analogs. Tetrahedron. 71 (35): 5897–5905. doi:10.1016/j.tet.2015.05.093


Also see this:

Comparison of the molecular structures of the three types of psychedelics

 

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Many people say that they find psilocybin and DMT (tryptamines) to be more healing than LSD…

"5-MeO-DMT is a psychedelic substance with a short duration of action and intensive effects. Its therapeutic efficacy and practicality may significantly surpass those of classical psychedelics such as ayahuasca and LSD."

5-MeO-DMT in the complete resolution of the consequences of chronic, severe sexual abuse in early childhood—a retrospective case study. Mika Turkia. 2024-06-07. PsyArXiv. doi 10.31234/osf.io/bvk2f

 

[vecktor]

AI slop is here too

 

[Skorpio]

Using non-specialized AI for chemistry is pretty fraught. It’s not as good at that, and the tendency to agree with you leads to it reinforcing erroneous ideas.

 

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Claude's input:

The Dual Pharmacophore Nature of Ergolines

You've hit on something crucial here. The Bluelight forum quoted this key insight about ergolines:

"Embedded in the structures of the ergot alkaloids are conformationally-restricted variants of the phenethylamine pharmacophores of both dopamine and related biogenic amines as well as that of serotonin." bluelight

This is the key to understanding LSD's unique position: ergolines contain BOTH pharmacophores:

1. Tryptamine/indole pharmacophore - the serotonergic element

2. Phenethylamine pharmacophore - related to dopamine and other catecholamines

As one paper put it: "one can trace within the elegant structure of LSD the indole nucleus common to the tryptamines. However, it is equally true that one can find phenethylamine." PNAS

And more explicitly: "the phenethylamine structure can be found as part of the more complex ring system of the ergolines" Technology Networks

This dual nature is what gives ergolines their complexity and versatility - some researchers attribute ergoline dopaminergic properties to the pyroleethylamine moiety while others assert it's due to the indoleethylamine partial structure Wikipedia .

So What About JRT's "Phenethylamine Element"?

Here's where it gets fascinating: JRT retains this same dual pharmacophore architecture because it's built on the same overall ergoline-like framework as LSD. However, there's a critical modification:

In JRT: The tryptamine core has been swapped for an isotryptamine core (nitrogen and carbon positions switched on the indole ring)

The phenethylamine element should theoretically still be present in JRT's structure, just as it is in LSD, because both molecules share the same overall molecular weight and 3D shape. The isotryptamine substitution is a relatively subtle two-atom swap that doesn't destroy the overall ergoline-derived architecture.

Why This Matters: JRT is "More Tryptamine" Than LSD

When I said JRT is "more tryptamine-like," what I mean is:

• LSD = rigidified tryptamine with embedded phenethylamine pharmacophore

• JRT = rigidified isotryptamine with (presumably) embedded phenethylamine pharmacophore

The key insight: Converting tryptamine to isotryptamine tends to make compounds much less hallucinogenic, so researchers applied this same atom-swapping to the ergoline framework of LSD Wikipedia .

Since isotryptamines are themselves positional isomers of tryptamines, JRT's core pharmacophore is actually closer to the "simple tryptamine" scaffold than LSD's is. It's like JRT has a "defanged" or modified tryptamine core that retains neuroplastic effects but loses the intense serotonergic hallucinogenic drive.

The Bottom Line

Both LSD and JRT contain both tryptamine/isotryptamine AND phenethylamine pharmacophoric elements - this is inherent to their ergoline-derived architecture. The difference is that JRT's isotryptamine core is a modified version of the tryptamine that dramatically changes its pharmacological profile, particularly reducing hallucinogenic activity while maintaining therapeutic neuroplasticity.

So yes, in a meaningful sense, JRT is structurally "more tryptamine-like" than LSD - but paradoxically, this makes it pharmacologically less psychedelic!