If you are referring to "natural" in the sense that natural = spiritual = godly or something "true" beyond this world, I'm afraid we simply don't have the answer to that.
Some people think that only mushrooms, cactus, and other living sources of drugs are able to connect your mind with the spiritual world to speak with God. Perhaps the plant or mushroom is the "guide" to help your soul journey to the other realm. In this viewpoint, LSD or 2C-I are imperfect man-made robots that are unable to truly empathize with the whole emotional release that the psychedelic experience can cause.
On the other hand, there are chemists who will say that I can compare DMT from a plant, and DMT that was built step-by-step from methane and ammonia, and find them to be 100.00% identical in every chemical test. So where is the spiritual component of the drug found? Is it possible that God exists within yourself, and the source of the chemical is irrelevant? Alexander Shulgin certainly believed that the true power of a drug was not found in its history or botanical origin-- he probably strode forward with the belief that Man and God and Intelligence are all parts of the same Truth, and if it is possible to create a drug in a laboratory using education and fire and sulphur, then it can be every bit as worthwhile of an experience as the drug that was "born from mother earth".
Personally I am of the opinion that every experience is a beautiful miracle, whether it involves a plant-derived drug, a synthetic compound, or no drug at all. I have certainly had spiritual experiences without the aid of Brother Mushroom. But I will agree that there is something (not physically detectable in the body of mushrooms themselves) tied to the whole experience of getting my body in tune with the seasons, going outside on a rainy October day, allowing my skin to become soaked and humid like the Flesh of God itself, and listening to the trees, birds, and insects to direct me where I may find the forbidden fruits waiting for me. Indeed my most intensely spiritual and emotional mushroom trips did involve this type of meditation in order to harvest the mushrooms, and I dare say that meditation was crucial in creating the set and setting! Certainly I would not have been walking around in the twilight rain sniffing the dirt and getting spores in my fingernails if I was going to swallow a vial of 2C-I!
