What is the definition of safe?
Safe from death or from mental disease?
Safe from delusions about how the life works, what role nature plays in the awakening of higher mental states and the sentiment of isolation and sadness of how the human world functions? Safe from the realization that we are all giants, raised by pygmies and don't know how getting out of this prison?
I tend to say that LSD and psilocybin are good substances to start with, under prescription that they come from a known source. They are transparent in the sense that they can be adapted to a huge spectrum of settings, LD50 is relatively low and they combine spiritual insights with that hedonistic ambience, where there is always a laughter. For starting, I think it is helpful to see that psychedelics are fun in some sense also and not only hard spiritual breakthrough -in some way it is good to see that "god" has some sense of humour, too.
DMT is safe on a physiological level, but its impact on the mind is something hard to digest. I am glad I haven't started with this molecule.
So, for me mushrooms are a good starting point, especially when grown by yourself for higher energetical exchange with the matter. LSD, you always need to buy from somebody. Mushrooms are at the forefront of independent psychedelic investigation, a real graal to autonomy.
If you want to be safe from delusions, try icecream