The effects of nicotine withdrawal on panic-like response to breath holding: preliminary data of a placebo-controlled, double-blind, cross-over patch study

Introduction: a growing body of literature suggests that cigarette smoking may increase the likelihood of developing panic. Different hypotheses have been proposed, the most recent suggests that smokers high in anxiety sensitivity may be more likely to attend to unpleasant, acute nicotine withdrawal symptoms. Thus, a cognitive mechanism, triggered by nicotine withdrawal symptoms, would be the pathogenetic explanation of such a co-occurrence. However, the literature on alcohol use disorders shows that alcohol withdrawals may favor the onset of panic via a biological phenomenon called kindling. In this framework, we run an experimental study to verify if the pharmacological effects of nicotine withdrawal might be the biological explanation also of the co-occurrence between cigarette smoking and panic. Methods: we conducted a cross-over design study on current smokers. Each subject received either nicotine and placebo in two different test days according to a randomized, double blind order. Thereafter, they underwent the Breath Holding test, a simple and natural method of inducing endogenous CO2 increase and panic-like responses under laboratory controlled conditions. At baseline, the level of nicotine dependence, positive and negative affectivity, anxiety, and nicotine withdrawal symptoms were measured. The response to the test was verified administering at pre- and post-test the Visual Analogue Scale of Anxiety (VAAS) and the Panic Symptom List (PSL) which assess the level of subjective and objective anxiety, respectively. Blood pressure, respiratory and heart rate, and Carbon Monoxide (CO), as an index of smoking status, were performed at baseline, pre-, and post-test. Results: participants were 20 current smokers (10 males and 10 females) with a mean age of 32.05 ± 10.13 years. Subjects under the two conditions did not differ for baseline anxiety, nicotine dependence, affectivity, or nicotine withdrawal levels as well as for the physiological measures or CO. Results indicate that the placebo patch, relative to the nicotine one, did result in higher VAAS to the respiration challenge (post- minus pre-test VAAS under placebo: 2.95 ± 3.24 versus post- minus pre-test VAAS under nicotine: 1.50 ± 8.29; p = 0.023). No statistically significant results were found for the effect of the Breath Holding test on the PSL or the physiological measures studied. Discussion: nicotine withdrawal symptoms seem to affect the response to the Breath Holding Test in current smokers in terms of higher levels of subjective anxiety. Thus, nicotine withdrawal can be the biological explanation of the co-occurrence between cigarette smoking and panic.