Mind over matter, ladies. That is the number one factor here. With something like psychedelics, where experiences can vary across the entire spectrum, your set and setting can drive the effects of the drug.
If you have a belief that by taking something that came directly from nature makes you more at one with it, like it's healthier, more complete, etc., then you will most likely get much more positive effects from natural sources.
If you believe that synthetics are 'perfect' versions of nature, cleaner, more potent, better, etc., then guess what? Synths will probably have better effects for you.
Having said that, of course there is science behind it. I feel like naturals are 'better' (define better) because they include tons of other alkaloids, analogues and similar chemicals to the one you are after, which provides the 'complete' experience. Synthetics are all but one isolated chemical, which can give the experience you're looking for, but not the entire experience intended by nature.
It's not a psychedelic, but the absolute best example I can make for this is synthetic opioids vs raw poppy pods. When you take oxycodone for example, its one single man-made alkaloid and it feels like it too. With a crushed up poppy pod made into tea, you're getting thousands of opiates, all doing different but similar things. The difference in experiences is night and day, including duration of effects. ~20mg of oxy will get me going for ~4 hours. A glass of poppy pod tea will keep me high for 24+ hours, and glowing well into the next day. Also, with oxy, it leaves as fast as it comes, dropping you like an ugly baby, leaving you fiending for more. Pods will wear off slowlllyyyyy and gently leaving you glowing and happy about the nearly 2 day long euphoria experience you just got for ~$5. Try getting a similar experience using synthetic opioids and let me know how much it costs you and how you feel after you run out.
Even further into the opiate thing (sorry, not trying to de-rail, I know this is a psych discussion), I've had many poor opiate experiences with synthetics like oxy and vicodin, where I'll eat a bunch of pills and get no effects, or get disappointing effects, etc.. Then along comes kratom, not only a natural substance but a LEGAL one too, and every single time I get the effects I expect, they last long, they satisfy me, it's very cost effective, and when it wears off I don't find myself scrambling for more. I also never got a distinguishable effect from benzos and I've been prescribed nearly all of them. while Kava Kava, I get effects from.
Let's not even talk about cannabis vs JWH-XXX.
You decide.