I agree that mescaline (even synthesised mescaline HCl), mushrooms, cannabis, even nitrous I guess all have a rich/organic feel, like they are so deeply layered that you can find something new in them each time.
With synthetic psychedelics like LSD, 2cb I find they have a way more predictable effect, and can have a 'dirty' feel. I find though mainly that the naturals I basically cannot fault, but synthetics either have some magic to them that makes them unique or they just don't. For example I find LSD and MDMA feel very chemical but also simply have an obviously unique mechanism of action that makes them feel quite special and therefore in ways as good as naturals, though just with different character. 2cb though I found just felt very chemically/dirty and I didn't like it much at all, though at a half dose it was a nice enhancer of things
I didn't even notice this until after I had done quite some experimentation with all of them, and I didn't ascribe the difference to the natural vs synthetic thing for a while after that, so I don't think it's fully a placebo effect. I've never tried synthetic tryptamines though and will be trying 4-aco-DMT soon so will have to see if that follows this trend, as it may simply be that the 'stimmy'-ness of 2cb, LSD, MDMA is what gives them a chemical or dirty feel at times. Interestingly even though mescaline is a phen and definitely kept me awake for a while, not once did it feel pushy or manic like other phens and LSD can