Acute Nicotine Gum and Tinnitus Loudness in Non-Smoking Adults

Overview

This study tested whether a single dose of nicotine gum can reduce the loudness of tinnitus (ringing in the ears) in non-smoking adults with chronic tinnitus. Nicotine acts on brain nicotinic acetylcholine receptors that regulate the balance of excitation and inhibition in auditory and attention networks, and may temporarily quiet the phantom sound while improving the ability to focus on relevant sounds. Using a double-blind, placebo-controlled, within-subject crossover design, each participant attended two sessions and received a single 4 mg dose of nicotine polacrilex gum at one session and a flavor-matched placebo gum at the other, in random order. The primary measure was the within-session change in a psychoacoustic match of tinnitus loudness; auditory selective attention was a secondary measure.

Background: Tinnitus is associated with excitatory-inhibitory imbalance across auditory, attentional, and limbic circuits. Nicotinic acetylcholine receptor modulation is a candidate dual-target mechanism, but it has not been evaluated for tinnitus in humans. Dose and protocol: The 4 mg dose and a standardized administration protocol (continuous chewing for 20 minutes at one chew per second, paced by a 1 Hz auditory cue, with saliva retained and spitting minimized to maximize buccal absorption) were established in a preceding gum optimization study in non-smokers. Trial design: Randomized, double-blind, placebo-controlled, within-subject crossover. Each participant attended two sessions on separate days, separated by a washout of at least 72 hours, receiving nicotine gum at one session and matched placebo gum at the other in randomized 1:1 order. Allocation was concealed with sequentially numbered, opaque, sealed envelopes; an independent examiner prepared the gum and participants wore a blindfold during administration. Outcomes: The primary outcome was the within-session change (post minus pre) in psychoacoustic tinnitus loudness match, compared between the nicotine and placebo sessions. The secondary outcome was the within-session change in auditory selective attention (Coordinate Response Measure percent correct). Additional pre-specified measures were pure-tone audiometry, the Tinnitus Handicap Inventory, and the Tinnitus Functional Index. Outcomes were analyzed with generalized linear mixed models.