Personal experience. Psilocybin trips vary wildly, but everybody who uses it regularly eventually encounters an episode of extreme despair. (It's not as bad as LSD, wherein you can very easily get caught in a mental loop - which if you're thinking negative thoughts will send you into an emotional deathspiral - but it's definitely a tangible risk)

It's not that it induces despair, per se, but it heightens emotional response to stimuli considerably. (Particularly in the very high dosages necessary to induce hallucinations.) It's necessary to strictly control your environment.