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Comment · Mon, April 29, 2013 · Ceretropic

"I continue to discourage personal use until the drug is proved to be safe." - Fulvio Gualtieri, former researcher on sunifiram.

Original post in this thread

shrillthrill · 62 points

via here

Just a reminder that not everything labelled nootropic has been demonstrated safe in humans, despite it being available to buy from NSN.

What they were answering

gwern · 5 points

Just because phase 3 human trials have not happened does not mean we don't know if it's toxic or not.

It's true that it doesn't mean we don't know anything; it's also true that our confidence intervals are huge. You realize that something like 50% of drugs going into phase 3 will ultimately fail? It's not like there wasn't plenty of evidence on toxicity or not for them.

Even more importantly, in both your papers linked there, they are purely animal studies. I will point you at http://www.reddit.com/r/Nootropics/comments/1as3c9/why_i_pay_little_attention_to_animal_model/ for what this implies, but here is the summary of the various reviews and meta-analyses I compiled there: even if the animal studies concluded with infinite accuracy that sunifiram were safe and non-toxic, there is ~50% chance that those animal studies would be completely and utterly irrelevant to the question of sunifiram's toxicity and safety in humans.

Most of the nootropics we take have not undergone phase 3 human trials.

Yeah, because most of the people here are idiots looking for a quick fix and overweight tiny poorly-done studies in animal models, if they even get as far as ever reading any research. (As usual, one man's modus ponens is another man's modus tollens.)

u/MisterYouAreSoDumb · Ceretropic

Statistically, you are correct. However, given what we know about the receptor affinities, it's very unlikely that the human pharmacodynamics of unifiram and sunifiram will differ from the animal models. But yes, there is a chance they have missed something that could lead to an issue in humans. Although given what we know about the structure of the molecules, we can get a damn good idea of the possible effects by referencing human studies of similarly structured compounds.

With the known possible issues with other compounds people are trying to source, I would say sunifiram is the least of our worries. Just take a look at IDRA-21. That has known issues with exacerbating glutamate toxicity, yet people are trying to source it to try. I see it more on Longecity rather than here, though. Most people around here are fairly conservative and question new compounds.

I think a healthy level of skepticism is warranted for any nootropics; especially the new ones that are popping up. However, I also know that many people are going to chance taking those substances anyway. In those cases, I try and give beneficial information to all the parties involved about the potential dangers and risks. I even get flack for it sometimes. Everyone was arguing with me on the nefiracetam post that I was being too cautious and overstating the risks. However, given the information we know, it can have adverse effects. Those effects should be known to those thinking of taking it. In sunifiram's case, all the evidence so far points to it being perfectly safe. That's not the end all and be all of the story. However, I think that information needs to be disseminated just like I did with the nefiracetam caution.

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