Global tobacco-related mortality dwarfs that of all other drugs. Nicotine is believed to be the primary agent responsible for tobacco use and addiction. However, nicotine is a relatively weak and inconsistent reinforcer in nonhumans and nicotine reinforcement has not been demonstrated in never-smokers.
This study investigated the discriminative, subjective, and reinforcing effects of nicotine in never-smokers.
Eighteen never-smokers (<50 lifetime nicotine exposures) participated in a double-blind study. During a drug discrimination phase, volunteers ingested oral nicotine and placebo capsules (quasi-random order) at least 2 h apart and rated subjective effects repeatedly for 2 h after ingestion in daily sessions. Blocks of 10 sessions were continued until significant discrimination was achieved (p ≤ 0.05, binomial test; ≥8 of 10). Following discrimination, nicotine choice was tested by having volunteers choose which capsule set to ingest on each daily session. Successive blocks of 10 sessions were conducted until choice for nicotine or placebo met significance within each volunteer (≥8 of 10 sessions).
All 18 volunteers significantly discriminated nicotine from placebo; the lowest dose discriminated ranged from 1.0 to 4.0 mg/70 kg. Nine volunteers significantly chose nicotine (choosers) and nine significantly chose placebo (nicotine avoiders). The choosers reported predominately positive nicotine subjective effects (e.g., alert/attentive, good effects, liking), while avoiders tended to report negative effects (e.g., dizzy, upset stomach, disliking). Both choosers and avoiders attributed their choice to the qualitative nature of drug effects.
These results provide the first evidence that nicotine can function as a reinforcer in some never-smokers.
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Conduct of this research was supported by NIH R01DA03890 and T32 DA07209. We thank Eric Richter, Crystal Barnhouser, Samantha Gebhart, Samuel King, Kevin Strouse, Jessica Vanderhoff, Elana Schwartz, and Julia Kane for serving as session monitors, Lisa Shade for technical assistance, Linda Felch for statistical assistance, and the pharmacy and medical staff. The study was conducted in compliance with United States laws. Dr. Reissig is an employee of the U.S. Food and Drug Administration (FDA); however, the views presented in this article do not necessarily reflect those of the FDA and no official support or endorsement of this article by the FDA is intended or should be inferred.
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Duke, A.N., Johnson, M.W., Reissig, C.J. et al. Nicotine reinforcement in never-smokers. Psychopharmacology 232, 4243–4252 (2015). https://doi.org/10.1007/s00213-015-4053-4
- Drug discrimination
- Subjective effects