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Psychedelics and the Human Receptorome

^... as much as it pains me to say so. ;)

To make matters worse, Roth has said that he didn't trust one of the techs doing the work, which may explain a few of the inconsistencies. The assays were completed a few years ago. It remains a mystery as to why he would release questionable data with the PDSP stamp of approval...so much for a solid foundation for future research.


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^It's by no means a total loss.

I still find it intriguing to see that the majority of classic 5-HT psychedelics are much more promiscuous in terms of receptor affinity profiles than originally thought. My guess is that Roth's primary criticism would be some of the misleading statistical manipulation. The core discovery of the paper still stands. It is unfortunate to find out that this may not be a 100% reliable source of data, but it's the best we have.
 
Dondante said:
Anyway, I had some down time last week and made this figure showing 5-HT2A/1A affinity ratios. Obviously, this is the least surprising conclusion of the paper (since there is already evidence regarding the profiles of phens vs. trypts), but I found it satisfying to see it in graph form. It will be interesting to find out what effect other 5-HT receptors have on the phenomenology of the psychedelic experience ... and SERT and DA, alpha2, and sigma receptors too.

16246005.jpg


*These data points are from published data gathered by the PDSP, not tested by the PDSP.
Click to expand...
do I understand this right that psycedelic phenethylamines are more of 5HT1A agonists than 5HT2A agonists?
 
Enkidu said:
It's the other way around. The tryptamines have more 1A selectivity.
Click to expand...
but what is printed in the graph is -Log(Ki 5HT2A/1A), it says (first of all, what does "Ki" mean?). so greater 5HT1A activity would mean the fraction is smaller than 1, making the logarithm negative, which would yield something positive together with the other minus sign?
 
ungelesene_bettlek said:
but what is printed in the graph is -Log(Ki 5HT2A/1A), it says (first of all, what does "Ki" mean?). so greater 5HT1A activity would mean the fraction is smaller than 1, making the logarithm negative, which would yield something positive together with the other minus sign?
Click to expand...

No, Ki is the binding constant in moles/liter. The smaller the number the better the binding, so if there is 5HT2A selectivity the ratio (5HT2A/5HT-1A) is less than one. Hence, the log is negative and the -log is positive.
 
^Yep, thanks. :)

It's a bit confusing. I initially had it without the negative, but I think it makes more sense the way it is now.
 
I think this is a bit dodgy article

How can you compare affinities towards different receptors vs. different competitive ligands where some are agonists others antagonists?

Is it useful data without knowing the intrinsic activities?

If this was a 'paradigm-shifting' paper then why wasn't it published in a high-impact journal?
I had never heard of Plosone before, who are reviewing this stuff?

Author is well known for his evolution-stuff, but no prior publications in this field
 
at first glance it seemed pretty paradigm shifting, but upon closer analysis it seems to have some problems with methodology. That being said, there is still some valuable info contained in it, and I think the long term benefits of this paper will likely be the results of others trying to support or refute these results.
 
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