Why is it still hard forexperts to correctly predict psychoactivity (if and how)?

[phew]

Even Shulgin was wrong about the supposed psychoactivity of some compounds. But that was then. This is now. We have a ridiculous amount of computing power. Why can't we use it to make accurate predictions of psychoactivity or even to tell what kinds of effects a drug will produce in the human brain?

I've been thinking so much about being able to create drugs with the exact effects you conceived. Why is this not possible? People can predict based on similarities to another existing drug, but as for a completely new experience entirely, that's quite difficult.

Will psychopharmacology ever have this power in our lifetimes? If we had large pharmaceutical companies like pfizer working on these problems, do you think they'd be able to do it within a few years?

 

[Runera46]

There are a 100 trillion synapses in the brain. We simply don't know enough to 'master' the ability to know exactly why drugs are psychoactive. However with time comes knowledge and hopefully research going on now (by a few people here and else where in the world) will soon change this!

 

[SDforever420]

I dont know much about this but wat i do know is that a drug can effect everyone differently. there for i dont think wat your asking is possible. I could be wrong tho. wait for more replies

 

[Sturnam]

We don't know the exact structure and binding site of many recreational drugs, simply put. If we did, then yeah, we could tailor new drugs instantly.

Also, look up functional selectivity. It's basically the ability of 2 agonists for a certain receptor producing vastly different downstream changes. So that complicates things as well.

 

[petebog]

Very good point SDforever420. That doesn't necessarily make it impossible, just even more incredibly harder than it is already as each persons individual brain construction would have to be taken into account.

Pretty much impossible for the forseeable future then I'd guess.

 

[seep]

Also, look up functional selectivity. It's basically the ability of 2 agonists for a certain receptor producing vastly different downstream changes. So that complicates things as well.

Reminds me of chaos theory from the 90s

 

[atara]

Partly because we don't have enough data on the action of these compounds in humans. There's nothing in the literature that mentions how 2C-T-7 feels better than 2C-T-2. It's hard to make a prediction based on nothing.

 

[AunShui]

That one's easy. The propylthio group on 2c-t-7 (either as the parent drug or an active metabolite) has MAO inhibitory properties, which causes a significant increase in plasma levels of both neurotransmitters and the drug itself, explaining why high-doses (or combination with a releasing agent like MDMA) have been known to cause hospitalization and death. 2c-t-2, which lacks this chain, does not share the same profile.

The fact remains, though: our understanding of the human brain, and the drugs that fit into it, is still in the stone ages. 50 years from now, we're going to look as sophisticated as the alchemists who thought you could synthesize mice by putting a pile of hay in a barn overnight. There won't be a "standard model" of the human brain, ever. If once person can take a drug and die, while another can take the same drug at the same dose and be cured, one brain isn't enough to account for all factors.

Bear in mind, also: it's not just about "x activates mu and y is one carbon different than x, so y should also activate mu!" As Sturnam pointed out, there are so many factors to account for here we don't even know what all of them are yet.

 

[Phener]

well I'd say we're in the decade of the brain, we're finally understanding more and more.

That said shulgin was a one off genius who was willing to risk it, test compounds on himself and PUBLISH his findings.

It's tragic anyone who does such a bold thing forgoes their oportunity to utilise all the powerful computers/equipment/labs. If such equipment was put towards finding/predicting/creating psycadelics we would quickly spawn 100x pihkals. There will be a wealth of information hiding on the computers of pfizer, glaxo etc etc - information that is not going to be made public soon (or possibly ever)

 

[atara]

That one's easy. The propylthio group on 2c-t-7 (either as the parent drug or an active metabolite) has MAO inhibitory properties, which causes a significant increase in plasma levels of both neurotransmitters and the drug itself, explaining why high-doses (or combination with a releasing agent like MDMA) have been known to cause hospitalization and death. 2c-t-2, which lacks this chain, does not share the same profile.

I said how, not why. We may understand why 2C-T-7 feels better than 2C-T-2, but the fact that it does simply does not exist in the pharmacological literature, unless you count PiHKAL as "the pharmacological literature".

See also: MBDB feels better than MDAI. This is not mentioned in any of Nichols' papers, though both act as selective serotonin releasers.

 

[AunShui]

I said how, not why.

Do you mean "how" in the sense of knowing how specific neurons cause specific reactions? I don't think we'll know that for centuries.

We may understand why 2C-T-7 feels better than 2C-T-2, but the fact that it does simply does not exist in the pharmacological literature, unless you count PiHKAL as "the pharmacological literature".

If you're getting at the fact that very little psychedelic literature is being produced today, you're dead on the money. What will it take to change this

See also: MBDB feels better than MDAI. This is not mentioned in any of Nichols' papers, though both act as selective serotonin releasers.

As I already said, it is a well-documented truth that every drug will treat every user differently. While you may find one drug mind blowing and another awful, the opposite could be true for another individual. In this particular case, however, I do feel you are correct, as MBDB appears to be pharmacologically a lot closer to MDMA than MDAI is.