Nicotine or expectancies? Using the balanced-placebo design to test immediate outcomes of vaping

Electronic (e-)cigarette use has increased in popularity, especially among those attempting to quit smoking. Previous studies evaluating the therapeutic efficacy of e-cigarettes have suggested that non-pharmacologic factors, such as expectancies about nicotine effects, may influence the experienced effects of e-cigarettes.

The independent and synergistic influences of drug and expectancies were parsed using a balanced-placebo design, whereby 128 participants (52 dual users) were provided an e-cigarette that either contained nicotine or non-nicotine solution, while told that it did or did not contain nicotine. We hypothesized main effects of nicotine content on physiological, objective outcomes (attention, appetite, aversion, respiratory tract sensations), and main effects of the instructions on more subjective, psychosocial outcomes (affect, reward, satisfaction). Sex was included as a moderator.

Results showed that nicotine increased sustained attention, and more so among females. Nicotine delivery was associated with aversion among females, but not males. Among those who were both told and did not receive nicotine, higher enjoyment of respiratory tract sensations was reported. Nicotine with complementary instructions produced the highest reward ratings; additionally, nicotine was rewarding to males but not females.

Findings demonstrated that both nicotine content and non-pharmacologic factors impact acute outcome effects of e-cigarettes, with moderation by sex in some cases. Results are relevant to the interpretation of clinical trials of e-cigarettes and suggest a more nuanced view of reinforcement pathways.