Hi laida222,
There are many different meanings concerning the quoted from you expression "What's he on?" besides the mentioned above from the venerable Amigos4 speculation, implying that a person may be using a mind or behaviour altering drug (we called this phenomenon referring "the person's state of mind" in similar cases "an unnatural festive, high mood" under the influence of the drug, alcohol or an agitation of soul - "He is a little bit on".)
If you ask me a riddle with the question "What's he on?" I might give you many different answers depending on circumstances and context .
1. He is on duty.
2. He is on as Hamlet.
3. He is a little bit on.
4. He is on for it.
5. He is on to it.
6. He is on to somebody.
7. He is always on to me.
8. He s on the list.
9. He's on the make.
10. He is on the mend.
11. He is on a visit.
12. He's on his beat.
13. He's on his own.
14. He's on his last legs.
15. He's on one's own.
16. He's on business.
17. He's on the "Daily Mirror".
18. He's on the program. etc......
I think, that's enough.
Regards.
V.