Structure-based discovery of nonhallucinogenic psychedelic analogs

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Analogs of drugs like LSD show antidepressant-like activity in mice without causing hallucination, a new Science study finds, which may provide a foundation for structure-based design of safe and effective non-hallucinogenic psychedelic therapeutic drugs.

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Psychedelic drugs such as lysergic acid diethylamide and mushroom-derived psilocybin exert their effects by binding the serotonin 2A receptor . These drugs also have antidepressant effects, but the hallucinations they cause complicate their use as therapeutics. Cao. present structures of 5-HT2AR bound to psychedelic drugs, the endogenous ligand serotonin, and the nonhallucinogenic drug lisuride. The structures reveal ligand-receptor interactions that cause a bias toward arrestin recruitment.

—VVDrugs that target the human serotonin 2A receptor are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HT-lysergic acid diethylamide , as well as the endogenous neurotransmitter serotonin and the nonhallucinogenic psychedelic analog lisuride.

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Can they call them 'psychedelic' if not hallucinogenic? Just wondering.

cool!

Cool paper Probably a naive question but does 4B imply that the analogues reduce HTR rate even below baseline/saline?

Weirdly enough I was thinking about the therapeutic effects of 5HT receptor psychedelic drugs and how they were far from perfect for being used as medicine so this was a good continuation of my thought process.

I'm thinking that it above all shows how little we know about how the brain really works...

It's taking too long for science to catch up to what ancient shamans knew years ago just to make it all 'legal' again. But shamans weren't in it for financisl gain.

Interesting paper although the drugs are not analogs of LSD--they are analogs of a known antipsychotic drug lumiteperone

How do you know when a mouse is hallucinating?

How addictive it can be?

Let’s fucking go

Psychedelics belong to a more general class of compounds known as psychoplastogens, which robustly promote structural and functional neural plasticity in key circuits relevant to brain health.

I'll believe it when I see it translated to humans.

How do you tell if a mouse is hallucinating?

Well i hope these wouldn't be as weak and non effective as current anti depressives.

AdrianoAndrico If this is a real study, sign me up!

Teh_Husky Timothy Leary's ashes were sent into space such respect for the father of L. S. D. He would be proud of this.

joerogan ….you can add this to the list sir.

🤔Study my 🧠! 😂

LSD opened parts of my brain that was closed before!May critical thinking is light years ahead of most of humanity,but what do u know since Im a Genius who doesnt learn the traditional way an there for I been black balled from big uni cuz they want robots that They can program!🤖

anything to keep using caffeine & processed sugar.. sheesh eat healthy & get your metabolism going things out of your control, like: the security of having a home, a support system of people who know you, around you & a purpose, don't make you feel bad itshowyoulive

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