Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes.

Rationale: Studies with laboratory animals and humans suggest that dopamine may play a role in maintaining cigarette smoking behavior via its interactions with nicotine.

Objectives: This study was designed to replicate and extend previous findings showing that the dopamine D2 antagonist, haloperidol, produces blockade of smoking reward and compensatory increases in smoking.

Methods: We studied 20 subjects in a 2x3 within-subjects design, with nicotine-containing or denicotinized cigarettes crossed with oral placebo, haloperidol 1 mg, or haloperidol 2 mg. Subjects attended six sessions during which they received one of the cigarette/drug combinations, and smoked under both controlled and ad libitum conditions. Cigarette and mood ratings and smoking behavior were assessed.

Results: Haloperidol reduced the number of cigarettes smoked and the carbon monoxide boost associated with both types of cigarettes, at doses that did not appear to produce clinically significant behavioral effects.

Conclusions: Dopamine appears to play a role in mediating smoking behavior, but this may occur through a non-nicotine mechanism.