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Bupropion (BUP), which in its slow-release formulation (Zyban^®) is used as a smoking-cessation drug, increases dopamine overflow in the nucleus accumbens and serves as a reinforcer in animal experiments, both suggesting that BUP may possess some abuse liability. The present study examined if BUP produced subjective effects indicative of abuse liability in a quasi-naturalistic setting, with caffeine (CAF) serving as a positive control. In a randomized double-blind crossover design, male smokers (n = 50) ingested two doses (interdosing interval, 6 h) of placebo (PLC), 178 mg CAF, or 150 mg slow-release BUP in their normal mid-week work environment. They completed questionnaires administered by telephone at regular intervals. CAF significantly increased ratings of ‘pleasant effects’ (p = 0.008) and ‘high’ (p = 0.03), whereas BUP produced a ‘high’ of only very moderate size (p = 0.02). In 3 subjects each, BUP or CAF produced ratings of ‘pleasant effects’ that were >9-fold higher than those for PLC. Finally, BUP increased the number of cigarettes smoked by 29% (i.e., from 24 to 31 per day; p = 0.004) only in those subjects who were unable to report any effect of either BUP or CAF. CAF had no effect on cigarette consumption. These findings suggest that BUP, like CAF, might be of some abuse liability in a small subgroup of smokers (i.e., 6% each of the present sample), and it may transiently increase, rather than decrease, smoking during early phases of treatment in continuing smokers.

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