Ayahuasca is interesting in this respect. The effects require the co-ingestion of two different plants - one contains DMT which is usually metabolized too quic

Ayahuasca is interesting in this respect. The effects require the co-ingestion of two different plants - one contains DMT which is usually metabolized too quickly to have a psychoactive effect. The other contains a MAOI that deactivates the enzyme which deactivates DMT, allowing it to have effect. The MAOI plant does have some psychoactive effects alone - and increases the effects of many things, so that's probably how this was discovered, but still pretty amazing that people were able to figure this out through trial and error.