FWIW: I'm looking at some binding data I have in a spreadsheet (originating from a source I've lost track of) and it shows the 5ht2a:5ht2b ratio as pretty favorable for 5-MeO-DMT, compared most of the other psychedelics on the list. LSD, and surprisingly, DOI have even better ratios though. DPT seems to have a "bad" ratio. Not sure how much to trust my numbers though, as I don't even know the source.
I'm not sure how you calculated your ratios Kaleida, but I was thinking that a meaningful way to caculate this "5ht2b safety ratio" would be: log(5ht2a)/log(5ht2b) because the closer you get to 0, the more signifigant small variations are. What do you think of this metric? Solipsis?
or maybe: sqrt(5ht2a)/sqrt(5ht2b) is better.
edit: yeah using square root gives the most sensible values.
My safety list looks like this:
(low numbers are "safer", defined as strong 5ht2a agonism compared to 5ht2b)
Interesting that some of the compounds on this list are in a very different order from Kaleidas. Show how these different studies, and different methodologies can end up with different results. Psilocin in particular.
The N/A ones were out of range of measurement in the study, or incomplete data.
Did you see the response I gave in the super long post before? I explained a little bit about how I calculated my list. This is the main chunk of it again:
"As for how the list itself was made, I know you might not be able to see the full versions of all of those studies right now, but look at least at the last one which should be the full version in HTML form. If you scroll down to the binding data, you can see that they tested many receptors, but specifically for 5-HT2A they tested for receptor binding Ki, activation potency EC50, and activation efficacy %, whereas for 5-HT2B they only tested for the last two of those. The data included in all three of the studies is like this, so given that the activation potency EC50 was the best equivalency I could get that was what I used, I just divided the 5-HT2B values by the 5-HT2A values. It would be nice to have direct binding Ki too, but I'll take what I can get. Something I'd consider an important takeaway from this though is that the list probably shouldn't be considered completely exact in its distribution of individual drugs, but the relative flow of different chemical classes and certain outliers probably do have some merit."
I am familiar with the spreadsheet you are talking about as well, it can be found here in the supporting information:
Psychedelics and the Human Receptorome.
It is interesting that some of our values are so different, but, going back to my explanation above, the thing is that we actually aren't even measuring the same data, as mine is about activation potency EC50, or the amount of the molecule required to produce half of its maximal activation of the receptor, whereas yours is measuring binding affinity Ki, so just the amount required to bind there at all. While these often do line up relatively well for certain drugs, they often don't as well. For instance, like I said the studies I used for my list don't have binding affinity values for 5-HT2B, but they do for 5-HT2A, so let me show some equivalency. Following is a list of the basic 2Cs, mescaline, LSD, and the tryptamines from before, ordered first by binding affinity and second by activation potency at 5-HT2A, all in μM.
Code:
Binding Affinity
2C-I 0.0035
LSD 0.0042
2C-T-7 0.0065
2C-P 0.0081
2C-B 0.0086
2C-T-2 0.0090
2C-E 0.0105
2C-C 0.0130
2C-T-4 0.0279
2C-D 0.0324
5-MeO-AMT 0.034
Psilocin 0.049
4-HO-MET 0.057
5-MeO-MiPT 0.163
DMT 0.237
4-HO-DiPT 0.728
DiPT 1.2
Mescaline 6.3
Activation Potency
5-MeO-AMT 0.002
5-MeO-MiPT 0.023
4-HO-MET 0.037
2C-I 0.06
DMT 0.076
2C-B 0.08
2C-T-2 0.08
2C-P 0.09
4-HO-DiPT 0.093
2C-E 0.11
2C-T-7 0.13
2C-C 0.20
2C-T-4 0.22
DiPT 0.240
LSD 0.26
2C-D 0.35
Psilocin 0.721
Mescaline 10
As you can see, while some parts of the lists are similar, others are quite different. Particularly notably, psilocin has relatively high binding affinity for a tryptamine, and even close to the range of the 2Cs, but very low activation potency, being inferior to all but mescaline in this way. So, one explanation for the discrepancies we've found between our lists that I could give, given that psilocin appears to have very low activation potency at 5-HT2B by my list, but it appears to have very high binding affinity by yours. It could be quite possible that even though it binds there easily it simply doesn't activate it much at all, and therefore might actually not really pose any danger in this way despite that. I think this kind of relationship may also be suggested, for instance, by the fact that while most synthetic tryptamines seem to have relatively high efficacy at these receptors, psilocin only has 16% at 5-HT2A. They didn't test it at 5-HT2B, but if it is similarly weak at that site, it could possibly explain this in the sense that it may just take very high doses to activate the receptors to any significant degree once its bound.
Nonetheless, psilocin is clearly an active psychedelic in doses similar to other tryptamines, so it needs to be considered that the efficacy pathway they tested may not be the only one involved in psychedelic effects through 5-HT2A, and likewise the one they tested for 5-HT2B may or may not be related at all to their heart valve effects, or to the empathogenic effects, or it could be one but not the other. It just seems nearly impossible to say at this point. I do believe that both our lists likely have their own form of merit though, and must likely be considered together along with many others to get a full image of these substances' activity. Something I do find quite tantalizing about yours, for example, is that 5-MeO-MiPT did indeed fall between 5-MeO-DMT and 5-MeO-DiPT in 5-HT2B binding as I was suspecting it might from the other list despite its low activation potency compared to non-5-substituted tryptamines.
I'm honestly not too familiar with the kinds of charts you're trying to plot, like I know I learned that stuff in school but I haven't thought it much since then, and mine was clearly just very basic math. Can you give me another simple real world example to help explain why plotting them that way is best?
It can be found here:
Regardless of the lack of information, I'm honestly not afraid of using psychedelics regularly for the rest of my life, at least the ones that are obviously not more dangerous like the NBOMes and stuff. Even just anecdotally, looking at the people who used them their whole lives and other drugs as well, it would appear to me that they're at least not really more dangerous than a lot of the types of food I eat often to enjoy myself, plenty of which will give you health problems late in life if you eat them too regularly. And again, if I have heart troubles when I'm 80 because I enjoyed 60 years of wild hedonistic fun, then I think that's a pretty darn fair trade. Bring on the heart valve surgery.
Good stuff. I like making infographics and stuff so maybe I will put my hand to some of the data.
