Examining the Neural and Behavioral Impact of Accelerated Intermittent Theta Burst Stimulation in People with Opioid Use Disorder Who Smoke Tobacco Cigarettes: A Pilot Study

Background: Novel therapies are needed to improve smoking cessation outcomes in people with opioid use disorder (OUD), as they are far more likely to smoke cigarettes (70–90%) compared to the general population (11.6%) and demonstrate a poorer response to smoking cessation interventions. Methods: This pilot study, intended to be a hypothesis-generating mechanistic investigation, is the first to explore the impact of a single day (four sessions) of accelerated intermittent theta burst stimulation (iTBS) (1800 pulses/session) versus sham iTBS applied to the left dorsolateral prefrontal cortex (L-dlPFC) in people with OUD who smoke tobacco cigarettes ( n = 8 received iTBS, n = 7 received sham iTBS). Resting-state functional connectivity was acquired at baseline and after the fourth session. Attentional bias for cigarette and opioid cues, and craving assessments, were completed at baseline, and after the first and fourth sessions. Results: Connectivity between the L-dlPFC seed and a cluster comprising the left anterior supramarginal gyrus showed a significant group × time interaction, with planned comparisons showing a greater increase at follow-up in the iTBS compared with sham iTBS group ( t 12 = 6.37, β = 0.40, p < 0.001). Cigarette cue attentional bias showed a significant group × session interaction ( t 80 = 2.34 , p = 0.02), with planned comparisons showing a decrease after iTBS and an increase following sham iTBS. No effect of iTBS was observed for opioid cue attentional bias. Cigarette craving decreased in both iTBS and sham groups but did not show a significant group × session interaction. Conclusions: These results are promising but should be interpreted with caution, given the limited sample size, which precluded analyses adjusting for sex or medications for OUD. This pilot study aims to identify neural and behavioral targets for future studies of accelerated iTBS in people with OUD who smoke cigarettes. Future trials could examine the effects of increased doses of iTBS (e.g., more days of accelerated iTBS) to identify dosing to promote smoking cessation among individuals with OUD effectively.