I like the idea of having no immediate negative effects with drugs. The idea that the downside doesn't kick in until the drug wears off would work only if you couldn't take the drug again to overcome the addiction, but had to wait for the addiction to run it's course before the drug could be ingested again. Duration of positive and negative effects would be extended or shortened by Chem Reliant/Chem Resistant, as well as Fast Metabolism.
As an example of what I'm talking about, look at Jet. This example assumes Jet has been changed to only give 2 AP, without the ST malus or CH malus.
You take a dose of Jet, and gain 2 AP for the normal duration (30 minutes?). After 30 minutes, the drug wears off and you suffer -2 AP from your base AP for another 30 minutes, and taking more Jet has no effect at all. Using Chem reliant, you could get double the duration of the positive and negative effects (60 minutes), while Chem Resistant would cut both positive effect and addiction in half (15 minutes). In addition, Fast Metabolism could maybe shorten the length of the withdrawal effect. This would probably make Chem Reliant and Fast Metabolism "needed" traits, so maybe another solution could be found there.
The same could go for Psycho and Buffout. Psycho gives +15% DR, but the withdrawal effect is -15% DR (affecting armor as well). Buffout is +2 ST, withdrawal effect being -2 ST, etc.
Drugs like Nuka and Cigs don't need as severe penalties, as they don't give as much positive benefit. Maybe a small chance of addiction, with -1 AP.
With fast relog, it may not make much difference to have severe penalties for drug use. You would still be able to cocktail drugs for PvP, but you would suffer extremely severe penalties afterwards. I know most people would just relog to another alt, so this suggestion probably doesn't mean much.
The other types of drugs are things like Rad Away, Rad-X, and Stimpaks. Since these don't boost stats, I see no reason to worry about them so much, but I do want to add my opinion on Super Stims.
The -9 HP from Super Stimpaks really doesn't do much except kill you after respawn if you've used a few of them recently. I would suggest removing the debuff effect upon death. It's not as much of a problem now with the added healing rate and 40 HP boost, but I see no reason for it. It won't do anything but cause unnecessary headaches for players.
Obviously, a lot of room to work with. It's all up for debate as far as I'm concerned.