Imo how heavily the compound desensitizes the G coupled protein receptors it signals through, tolerance won't form. That's how I currently understand tolerance formation with psychedelics at least. 25I-NBOMe can sometimes be 5-6 hours, but induces a 3-4 week tolerance, for example. Also allylescaline creates no tolerance in myself or my fiance (only administered it to one other person, once). Allylescaline is an 8-12 hour trip typically.
I think you are describing what is called receptor down-regulation. When down-regulated, receptors tend to actually physically move below the interfacial surface. Furthermore, receptors in a down-regulated state have a chance of being permanently destroyed, which leads to long-term desensitization. Technically, down-regulation leads to called tachyphylaxis but we here tend to call it "short-term tolerance" or something like that. Presumably this is why it is difficult to re-dose to boost a trip unless it's done very early on. An interesting feature of 5-HT2A is that most antagonists cause down-regulation just like agonists do. It's not clear whether any agonism is possible with down-regulation and tachyphylaxis. Another question is whether different agents can affect how long down-regulation persists, or if the timing is fixed---i.e. something like 3 days for 80% recovery or whatever.
Tolerance may be caused by many things though, and not just receptor down-regulation. Moreover, sometimes what appears to be drug tolerance is actually a more comprehensive shift in how the hormonal and signaling systems work. I.e., some tolerance manifests not just from desensitization of the particular receptor(s) but also by compensatory effects that arise throughout the various biological (sub-)systems that these drugs effect. These kinds of effects are likely to vary much more between different subjects because the drug use which induced it is taking these systems further from the state(s) that they evolved to handle.
Having said that, I want to point out that even if we consider only tachyphylaxis, any kind of model seeking to predict tolerance would necessarily factor in intensity (presumably correlating with the receptor occupancy fraction) and duration of effect. A successful model would have to be bit more complicated given that rapid-downregulation / tachyphylaxis llikely has a big impact on perceived intensity versus actual receptor occupancy fraction, but hopefully I've gotten my point across.
So I guess your contrary examples suggest that different compounds have widely different innate tendencies to induce both tachyphylaxis and longer-term tolerances. I tend to be quite skeptical of claims of any psychedelics not inducing tolerance at all. Maybe DMT is an exception? But some people do report tolerance with DMT if using repeatedly in a single day. That said, I think your examples actually suggest that tolerance is a much more complicated picture after all. Interactions at other receptors may be very important here, and it may be very difficult to untangle all the different possibilities between compounds. So does something like allylscaline really not cause down-regulation? Or is there something else going on that's counter-acting those consequences?
There's lots to think about here.
I've never tasted 2CB but am I correct in thinking it much like 2CI?
They are both 2C-series drugs, but otherwise I think they are quite different. Assuming you've had 2C-I before, I would say 2C-B is lighter, more forgiving, a lot less stimulating, and more empathogenic. I think it's maybe less visual at "typical" doses when compared to 2C-I, but I understand it can still provider strong visuals at high enough doses.
