What is the science behind cross-tolerance?

[Th3Raz96]

I'm under the impression that it's basically you have a certain amount of specific brain reserves (serotonin?) that get used up when you trip, and you have to allow some recovery time between trips, but I'd like to know exactly what's going on, technical talk. Who's got the answers I seek? Why does taking item X one day, and then item Y the next result in a lesser experience, even though they're two entirely different substances?

Thanks!

 

[roi]

Psychedelics are serotonin agonists, not releasing agents, they don't "use up" serotonin.

Drugs that share the same mechanism of action share a cross tolerance.

 

[CrypticArc]

You're thinking of MDMA, more than psychedelics.

Okay, so serotonin psychedelics (LSD, Psilocin, Mescaline, ect.) all bind to your serotonin receptors. Your body expects a certain amount of serotonin for your brain to function normally, and your receptors can't tell the difference between LSD and serotonin, so when it gets flooded, it starts to deactivate some receptors to balance out the flooding. Naturally, if your serotonin supply was too high, this would allow you to compensate and operate normally. With psychedelics, all it does is reduce the effectiveness next time you dose.

 

[Th3Raz96]

Thanks for that Cryptic, that makes perfect sense.

Follow up question: Are there any known pure psychedelics that don't act as serotonin agonists? Note that I'm excluding dissociative NMDA-agonists and empathogens with psychedelic qualities, just pure psychedelics. I'm pretty sure there aren't (yet) but I'm not the most knowledgeable guy on the subject

 

[Yeetbeat]

What do you define as a 'pure psychedelic'? A substance that produces psychedelic effects (headspace/visuals) without releasing any monoamines (serotonin etc)?

As far as I know, that definition pretty much requires 5HT receptor agonist properties if you're going to count out dissociatives (dissociates? idk haha). I'm not too well versed on the range of psychedelic compounds out there, but as far as my knowledge goes even things like ibogaine still act on 5HT receptors (though with a quite low binding affiinity).

Salvia doesn't act on 5HT receptors afaik, though do you class it as a 'pure psychedelic'? I sure wouldn't lol

 

[Th3Raz96]

Mmmmmno, I don't think I'd consider Salvia a pure psychedelic, I think from what I've read/heard about it it's more on the dissociative/hallucinogenic side.. But its effects are akin to DMT's effects, with the short-lived mind-blast OOBE whathaveyou, and DMT is most certainly a psychedelic, so I don't know?

By pure psychedelics I just meant substances that are 100% classified as psychedelics, LSD psilocybin etc etc, and not something like ketamine that makes you trip still but has effects that lie outside of those generally classified as psychedelic effects.

 

[CrypticArc]

Then the answer to your question would probably be no. The whole reason "pure" psychedelics work is their serotonin agonism.

 

[Th3Raz96]

Gotcha gotcha, thanks Cryptic. I wonder if one will ever be discovered or synthed by some mad scientist... I mean y'know how crazy living in the future is, at some point the exact science psychedelics operate with will (hopefully) be understood, and perhaps at that point a new method will be discovered, a way to bypass the serotonin-mimicing psychedelic compounds use and straight to the effects they produce.

But maybe it's not possible

I don't really know I'm just talkin out of my ass 8)

 

[CrypticArc]

Well I mean I see what you're getting at. Iboga is pretty psychedelic if you ask me but has some weird other effects. My experience with Voacanga Africana, a close relative to iboga, was pretty purely psychedelic with a very anxious and stimulating undertone.

 

[Th3Raz96]

I'm very interested in Ibogaine, I hear it's supposed to have some amazing therapeutic value to it. I read about someone who went to an Iboga clinic in a land far far away, and he said he was completely cured of his several addictions in his time there, along with a few psychological ailments he had. All while trippin balls