I am aware of this and think it's really cool. I know scientists right now seemed to be focused on the idea that the 5-HT2A-mGluR2 heterodimer might be the one "responsible for psychedelic effects" or whatever as they say, but I have to say, I'm incredibly suspicious about the 5-HT2A-CB1 heterodimer playing some critical role too given how psychedelic cannabinoids can be too. I have read a paper that said that both 5-HT2A and CB1 receptor agonists signal similarly through the heterodimer at least when applied separately (they interestingly have some antagonistic effects when applied simultaneously) so there is at least one clear plausible explanation for how 5-HT2A receptor agonists and CB1 receptors agonists could at least separately could affect the brain in the same sort of way as one another. I'm really not exaggerating when I say that a strong cannabis edible trip to me is a lot like a lysergamide.... If you gave me that first really good 50 mg oral trip I had and made it so I had no conception of what cannabis trips were like prior to that and didn't know that's what that was and you told me to guess, I think I'd almost certainly guess that it was a lysergamide of some kind that was given to me, with just the slightest suspicion of why it felt a little bit like cannabis.
As hinted at in an earlier post of mine, when I smoke cannabis within some days of weeks of a recent serotonergic psychedelic drug experience, I tend to experience a kind of simulated replay of the effects. I never understood how this was possible, and was kind of skeptical about it with myself. Once in a while the effect was so strong as to catch me off guard. A couple times when smoking someone else's weed, I had to talk myself down in my head that the weed wasn't laced. (I don't think it was---I was just seeing crazy shit and having paranoid thoughts!)
Anyway, only recently have I learned about the 5ht2a/CB1 heterodimers, and I have to wonder if they play a role in my experiences with post-trip cannabis. When I was young, I also tended to experience cannabis of providing a simulated replay of not just psychedelics but other drugs I might have recently taken. Perhaps this is enabled via heterodimers involving CB1 and other receptor types? Another question I have, but have not dug enough to figure out whether it's answered is how dynamic the expression of these heterodimers are. Like, are there just a bunch of things with 5ht2a+CB1s receptors hanging around all the time? Or is their expression highly subject to environmental changes?
On another note, last week I tried a cannabis edible for the first time in over a decade. It was only 10 mg. I don't think I liked it much. I'm a very regular but light smoker, and I wanted to test out its potential in casual/public environments. For what it's worth, it did not resemble LSD to me at all, nor has any past cannabis edible experience of mine. It definitely kept me high without having to smoke anything, which is a big plus, but the effects were much less casual and more overtly psychedelic. It's weird because I probably could have tolerated 20 mg just fine, but even at 10 mg, I just felt too edgy to want to be in most public places. In the past, I usually ate food made from lower grade weed, so I think I'll have to try different formulas to maybe find something mellower.
This is the kind of stuff I spent most of my many years using psychedelics actively thinking about. I used to try to connect the specific subjective effects I got from each one to different functional activity and signaling pathways known and documented for all the different molecules I was using in different scientific studies, but I kind of grew out of it once I realized from going through enough different ideas and enough different research papers that it was just too complicated a picture that we had too little visibility of so far for me to truly satisfactorily figure out if meaningfully figure out at all in the way that I was hoping to.
I felt that I was starting to hold back my conception of the drugs I was taking by trying them to fit them to the mold of my theories in my mind, so I decided to stop doing that (very explicitly) and start just paying more attention to the effects I get and comparing and contrasting the drugs more generally and stuff in those ways.
However, that's just me wanting to make sure I wasn't jumping to conclusions about my trips. I definitely understand the value in understanding pathways like this for the sake of making things like targeted medications. It is certainly extremely complex though. It's part of why I find the differences in each psychedelic so fascinating even when not discussing it specifically, I know there are more than just small differences amounting to those subjective distinctions.
This part has been very difficult for me to respond to because I have so many thoughts, and I can't really write them all down. I'm also constantly thinking about these things. In person, I could probably talk for many hours. I completely relate to and sympathize with what you've said here. I definitely agree that it's important to avoid allowing theoretical preconceptions to contaminate future experiences. This is much easier said than done, and I know I'm guilty of this as most of us are.
My recent experiences with 2C-B really highlight this. A long time ago, I always wanted to try 2C-B but could only find 2C-I for several years. I regarded 2C-I to be a "slightly more potent, longer lasting, more stimulating version of 2C-B", based on the chemical analogy and subjective reports. I became very familiar with 2C-I, and I looked forward to trying its mellower, short-duration cousin. In the early days, I also got to experiment with 2C-C, which I likened to a "extra mellow" version of 2C-I, but I don't feel I got to know it well despite 3 or 4 times with it. In any case, when I finally tried 2C-B, I was very disappointed. Instead of finding a superior version of 2C-I, I found an inferior one. (See what I did there?)
Only now, 1.5 decades later, I've revisited 2C-B and discovered that its effect is much less 2C-I than I'd assumed. I'm not sure it much resembles 2C-C either, but my memories of that are distant. If I didn't know better already, I wouldn't guess they were chemically very close. By evaluating 2C-B on its own terms rather than trying to compare it to 2C-I, I can now identify qualities that are unique and pleasing about it. While 2C-B is certainly not going to be my favorite, I think that in the future I will probably use it more than 2C-I.
So I guess I need to be more careful reaching conclusions by chemical analogy. Maybe 4-HO-DET can be like mescaline even though it's a tryptamine and is chemically similar to psilocin. I mean, I've always felt that of the ones I've tried, phenethylamines and tryptamines feel quite distinct as categories. And LSD seems to me a bit more phen than trypt but still very distinct. Sometimes I wonder though. It's a shame that the time courses of phens vs. LSD vs. trypts are so different (and easily identified, IMO) because it would be interesting to try to blindly test myself in my ability to discern what I've taken.
The last thing I'll say here is that I have rather suddenly found myself more interested in the pharmacology than I would have been because I'm interested in the physiological healing aspects. The interesting thing is that I think it would be easier to study 5ht2a in the peripheral body than in the brain, and such studies might lead to very interesting insights. These insights may in turn facilitate understanding of the brain being that many mechanisms may work analogously (e.g. inflammation causing both physical and psychic pain).
Something that would be very helpful to science is to discover one or more naturally occurring ligands that are 5ht2a (and/or 5ht2b/c) selective because monitoring such a ligand in physiological processes might give deeper insight into what those receptors are actually for. I'm seeing strong indications that these receptors are very important for modulating all manner of bodily processes, and therefore, it may be expected that monkeying with them using psychedelics may be producing a wide variety of interesting outcomes, even ignoring what's going on in the brain.
Most intriguing is how much 5ht2a seems to be involved in wound response including immune modulation, inflammation, and tissue regeneration. There's so much going on there, that it should be taken very seriously. That is to say that various psychedelics appear capable of exerting strong effects directly on the body and which may very directly impact physiological health. These effects could be positive, negative, or both. I'll just emphasize again that 5ht2a is multi-fuctional, and psychedelics have a balance of effects qualitatively distinct from each other and from serotonin. The history of indigenous use of certain psychedelic plants certainly suggests that most of the benefits of using these plants are positive. Regardless, these things should be investigated for as many psychedelic drugs as reasonably possible, both to improve knowledge of safe use and to learn more about how to potentially accelerate healing of the body.
Thanks for the responses again.
Thank you likewise!