Instructions about nicotine dose influence acute responses to nasal spray

Effects of substance use are typically assumed to be related to pharmacological actions. However, beliefs about the drug content of a substance may strongly influence subjective and reinforcing responses to that substance (i.e., "placebo" effects). We examined the subjective and reinforcing effects of a nasal spray containing no nicotine as a function of instructions about the nicotine content of the spray (Told Nicotine vs. Told No Nicotine). Smokers (n=49) not interested in quitting smoking abstained overnight prior to a single session in which they were randomly assigned to one of three groups, involving one of the two instructional sets or a group that got no spray. Following dose instructions, subjects in the two spray groups were administered one set of four sprays from the spray bottle and then rated them intermittently on items related to "reward" (e.g., "liking", amount they would pay for more) and other effects. At the same time points, they also rated mood, craving, and withdrawal, and had heart rate and blood pressure measured. Reinforcement was then determined by the number of ad libitum sprays they self-administered during a 20-min period. The no-spray group simply rested quietly during the session, while measures were assessed at the same time points as subjects in the other two groups. Those in the Told Nicotine group reported greater spray ratings of "how much nicotine," "liking," "satisfying," "buzz/head rush," and "similar to smoking" compared with the Told No Nicotine group. Craving decreased more for those Told Nicotine versus those Told No Nicotine, but also decreased more for those Told No Nicotine compared with the no spray group. There were no significant differences in amount they would pay for more sprays, withdrawal, mood, cardiovascular responses, or in spray self-administration. These results show that instructions about the nicotine content of a novel delivery device (nasal spray) can influence self-reported spray ratings and reduce craving but are limited with respect to effects on other measures of drug response.