Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine

The potential role of nicotine in tobacco dependence was investigated using the strategies of abuse liability assessment. Eight male volunteer cigarette smokers with histories of drug abuse resided on a research ward for the duration of the study. Each subject was tested with three doses of i.v. nicotine (0.75, 1.5 and 3.0 mg/10-sec infusion) and placebo each test day, and with three doses of inhaled nicotine, in the form of research cigarette smoke (0.4, 1.4 and 2.9 mg estimated yield) and placebo (sham-smoking), given on alternate test days. Each subject was tested on 4 days with both routes of administration, according to identical experimental protocols. Physiologic, subjective and observer data were collected at intervals ranging from 15 sec to 10 min beginning 10 min before drug administration and continuing for 30 min after administration. Both i.v. and inhaled nicotine produced dose-related increases in heart rate and blood pressure, and i.v. nicotine produced a transient bradycardia in four subjects during the first 30 sec after drug administration. Skin temperature was decreased by nicotine and pupil diameter was not consistently changed. Ratings of drug dose 'strength' and drug 'liking' were directly related to dose level whereas 'desire to smoke cigarettes' was inversely related. Scores on the Morphine-Benzedrine Group (or Euphoria) scale of the Addiction Research Center Inventory were elevated by nicotine, and i.v. doses were identified frequently as cocaine. Signs and symptoms were similar for nicotine across the two routes of administration and included coughing, dizziness, nausea and relaxed feelings. Nicotine shared the pharmacologic profile of prototypic drugs of abuse. The study supports the hypothesis that the role of nicotine in tobacco dependence is equivalent to the role of other psychoactive drugs in substance abuse, e.g., to the role of cocaine in coca leaf use.