Has there been any research (academic, or informal) into what makes some people more susceptible to the effect of entheogens than others?

In my own experience (and this is totally anecdotal), people who are prone towards depression and melancholy seem to have much lower thresholds than those without. I know several people who have used psychedelics, both prone to depression and completely mentally healthy and the pattern seems to persist.

I myself have off-and-on bouts of depression (diagnosed, never explained), and comparatively low doses of psilocybin and DMT will absolutely floor me, when some of the other companions I know require much higher doses to get to that level of intensity.

My pet theory for this (and I'm a math person, not a neurologist, so feel free to shoot me down) is that if the brain is lacking in natural serotonin, the serotonin analogues stimulate your receptors a lot more. It's as if you have a natural tolerance, just from having endogenous serotonin, so if your body under-produces it, serotonergic compounds will trigger more reactions.

I'm highly sensitive to psychedelics, but I'm not prone to depression. It would be interesting to get some kind of quasi-empirical overview on the situation, but my guess is that you probably wouldn't find much correlations. It can seem so random. People's sensitivities will vary with increased experience as well due to plasticity. I think sensitivity is probably more of a dynamic thing than some kind of static phenomena.

I agree with Global. I am prone to depression, but I have always had a fairly high tolerance to mushrooms. Along with that, my tolerance has decreased over the years of use. I remember taking 2.5-3 g of Psy. Cyanescens and not having mush go on, and now if I take half that I'm usually pretty well set.

You may have a piece of the puzzle, which may apply to many people, though.

Also, I think you need to factor in whether your "depressives" have had an extended period of treatment with SSRIs, as I think that maybe has the opposite effect, and would make them less sensitive (again, no evidence for that - just personal observation).

I have a childhood trauma and I'm prone to depressions and I need to dose higher than most others when it comes to mushrooms and ayahuasca. Not sure about mescaline since I've tried that only once.

However, when tripping (or rolling) my trip usually lasts longer than those around me, especially with mdma my body is much much slower in the breakdown.

There is a link between childhood trauma and overactive MAO-A enzymes. This is also linked to aggression and to be honest, I had severe issues with anger management when I was a kid and I need to dose significantly higher on the MAOIs when taking ayahuasca. Might be related in my case.

yea i agree...it seems much more complex

I'm very sensitive to most psychedelics now, whereas just 5 or so years ago when i was first starting to explore them i would need much larger doses for the most part. Nowadays 100mg harmalas and 30mg freebase dmt will floor me. Back then i used to take almost twice that. Theres a number of factors that can influence sensitivity

So, not all people prone to depression and sensitive and vice versa, but is there anything to the idea that if your body doesn't produce enough serotonin, you might be more sensitive to serotonin analogues?

People with depression are known to have more serotonin receptors. SSRIs only start working after about a month of use. What happens, between the start of treatment and when it actually "kicks in" is the downregulation of certain types of serotonin receptors in response to the excess serotonin induced by SSRIs. So the idea could make sense. I've certainly had the thought that depressed people may be more sensitive to psychedelics based on this reasoning.

Everything must be tested, though, as theories are cheap. Further complicating things is that the word 'depression' is a blanket term. Treatment effectiveness varies so much that I can only conclude that diagnosis of depression encompasses several etiologically distinct conditions.

When it comes to other factors affecting psychedelic sensitivity, it's important to mind the definition. For instance, I've found that with continued use, it has become easier for me notice ever more subtle phenomena. So I can have a 'deeper trip' than before because I have a better idea of what I'm looking for and I've built for myself a sort of 'framework' in which I assigned meaning to these things. This can be construed as increased sensitivity, but I think it runs counter to intuitions if you think it through. For instance, if I can notice all these things but someone else will easily see it when I tell him what to look for, am I still more sensitive?