I'm missing all but ~6' of my intestines, and I suspect that since most of your body's serotonin receptors are in your gut, I'm probably short quite a few. I was a daily user of ayahuasca for a while, I've tripped essentially every time my tolerance is down since I first met psychedelics, they've been an invaluable tool to me and have led to, as my medical team put it, 'unexplainable recovery' of brain damage. As far as DOx compounds go, I've used DOB and DOM (still sitting on some DOC for now), but DOB is much more interesting. I've never had what would even remotely be considered a "bad trip", I don't really think they exist honestly, it's just people trying to swim upstream when they should instead be floating with the river enjoying the view, if that makes sense. DOB nor DOM really have stunning visuals though compared to allylescaline, miprocin, LSD, 2C-B, mescaline, DMT, 25C-NBOMe, 25I-NBOMe, or 25B-NBOH imo.
For people who are trying to sci-hub the source that was mentioned above by Nichols, the doi is 10.1124/pr.115.011478.
It makes an interesting point that receptor downregulation is observed in rat brains with DOB, and while I don't doubt that administering DOB every day for a week would maybe begin to form a tolerance, I've used LSD two days after administering LSD and felt literally nothing. 1.5mg of DOB today somehow felt stronger than the 2.25mg I took two days ago, which was pretty befuddling. I'd initially taken the tabs out of hubris, thinking "Oh, I bet it doesn't share 2C-B's weird lack of tolerance formation", but alas, I was fooled and proceeded to violently vomit three pulled pork sandwiches in my office bathroom before going home. Allylescaline, miprocin and 25C-NBOMe can be redosed while still in the trip to noticeably no loss of potency, but once you come down, the tolerance hits. With 4-substituted tryptamines and lysergamides, the tolerance seems to hit the moment you feel the drug. I've noticed it in myself and others that some of these things lack the expected cross tolerance though, 2C-B/DOB are unique in that they kind of cut through other drugs' tolerances like a knife and I can't tell why. I have daily dosed 2C-B for up to 6 weeks before, and never needed to escalate dose to maintain the same effects.
There are a handful of substitutions Shulgin stumbled upon that seem interesting and underexplored, beta-MeO, N-OH and alpha-ethyl variants especially stand out.
That sounds like you've been in the wars there (possibly quite literally)... you have my sympathies.
I've only the one experience of DOB, from many years ago (it was sold as bromo-STP back then). I found it intensely visual, to the point of almost not being able to see for the patterns, but quite euphoric, if a little bit too long in duration. DOC for me was very disappointing though, which was a pity as I was hoping great things from it; orally it felt 'toxic' and not enjoyable at all, but vaping it seems to be ok, albeit not particularly interesting.
And apologies for citing a reference that's behind a paywall, that was a bit thoughtless of me.
With respect to the tolerance mechanism for psychedelics - I've tried to retread the path I followed that led me to where my present, rather muddled, thinking is at. I should emphasise that this isn't my field, and my viewpoint is about as valid as any other guy sat on a bar stool.
The 'capping' or 'lid' type model of tolerance for lsd (and by extension/implication other classical psychedelics) comes from:-
Wacker et al., Cell, 168, 377–389 e12. (
www.cell.com/cell/fulltext/S0092-8674(16)31749-4 )
The molecular cap/lid supposedly traps the lsd (or similar) at the receptor allowing for prolonged signaling/recruitment of β-arrestins which leads to increased tolerance. There's a few follow up papers on the same theme:-
McCorvy et al., Nat Struct Mol Biol, 25, 787–796. (
www.ncbi.nlm.nih.gov/pmc/articles/PMC6237183/ )
Kim et al., Cell, 182, 1574–1588 e19. (
www.cell.com/cell/fulltext/S0092-8674(20)31066-7 )
Cao et al., Neuron. 2022 Oct 5;110(19):3154-3167.e7. (
www.cell.com/neuron/fulltext/S0896-6273(22)00752-8 )
A recent paper on 2-Br-LSD that discusses the lack of tolerance build-up that it exhibits and the causative mechanisms behind that seems to also support this viewpoint:-
Lewis et al., 2023, Cell Reports 42, 112203. (
www.cell.com/cell-reports/pdf/S2211-1247(23)00214-0.pdf )
On the other hand there's also work that seems to suggest that β-arrestins aren't just simply molecules that produce tolerance but are actually integral to psychedelic activity itself:-
Slocum et al., J. Neurochem. 2022 Jul;162(1):24-38. ( onlinelibrary.wiley.com/doi/10.1111/jnc.15540 )
Jaster & González-Maeso. Mol. Psychiatry. 2023 Sep; 28(9):3595-3612. (
www.ncbi.nlm.nih.gov/pmc/articles/PMC11078317/ )
Atiq et al.
Psychopharmacology 1-26, (2024). ( link.springer.com/article/10.1007/s00213-024-06599-5 )
Frankly, I don't quite know what to make of it now, after giving it all a bit of a re-read... And I still haven't found where I picked up the idea that the standard 2C type phenylethylamines (i.e. not the NBOxs) were less 'trapped'...
Anyway, as displacement activities go, this one's been successful, I've managed to put off doing my day job for hours.
