I was just reading an interesting paper on the interaction between antipsychotic drugs, caffeine and smoking and I found this interesting snippet on how smokers need to take in three to four times more caffeine than non-smokers to get the same effect, owing to the fact that by products of increases enzymes in the liver which break-down caffeine.

Byproducts of tobacco smoking, particularly the polycyclic aromatic hydrocarbons, are metabolic inducers. These byproducts are inducers of the [liver enzyme] cytochrome P450 isoenzyme 1A2 (CYP1A2) and of the less understood UDP-glucuronosyltransferases (UGTs).The metabolic inductive effects are not specific to tobacco smoking; they can also be expected from marijuana smoking. Because inducers require the synthesis of new enzymes, several weeks are usually needed before the maximum effects of inducers are seen. Inducers’ effects may take a few weeks to disappear as well…. Additional pharmacologic support of the relevance of smoking’s inductive effects comes from caffeine intake studies. Caffeine, a drug that is more than 90 percent dependent on CYP1A2 for its metabolism and that is widely used in the United States, can exemplify smoking’s effects on drug metabolism. The C/D [concentration-dose ratio] of caffeine appears to be threefold to fourfold as high among nonsmokers compared with smokers. This higher ratio means that smokers need three to four times the caffeine “dosage” as nonsmokers on average to get the same plasma caffeine levels.

It turns out that two antipsychotic drugs, olanzapine and clozapine, are also broken down by the same enzyme, so smoking will reduce the effect of these drugs.

Hence smokers need larger doses to have the same effect, and patients on these drugs who give up smoking might find a sudden increase in side effects if the dose isn’t dropped.

We tend to think of the effect of psychotropic drugs as happening in the brain but drug metabolism happens all over the body with the liver and kidneys being particularly important and having a profound impact on the effect of the compound.

Link to ‘Atypical Antipsychotic Dosing: The Effect of Smoking and Caffeine’.