Psycho and Jet taken at the same time should automatically kill a person. Both are highly addictive, strong drugs that mess with the body. How does taking both of them not totally FUBAR a person's biology?
Anyway- The drugs effects should not be static, as in you will get a boost but depending upon luck or stats, it may be minimal or a surge
-The drugs duration should also be random and not static, as with static, you use it and then go do your thing knowing you'll be fine indefinitely for so long. Sometimes, you just won't get your boost. I believe the duration should even lower when you are addicted. You're an ADDICT, your body is used to the substance, how does using it constantly always give the same benefit? Bodies build up resistances, which would explain the progressively lower bonus as well as the randomized effects and duration.
-There are some minor drugs, nuka and cigs, which really don't need altering though they should be considered anyway. Not sure at hand what that would be for them, though maybe someone else does. Jov's idea about lower gains if the stat is already high might be enough of a change to those, however.
-Progressively worse withdrawal and addiction perhaps? The more you have used, the worse your stats are lowered when you are not riding your horse, which would in effect make drug-use casual, as only tactical use of them would give you the best use, with prolonged use bringing your char down to the point where you have to take it just to be normal.
-They are Drugs. They destroy the body from within.-