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

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 poorer response to smoking cessation interventions. This pilot study was 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 on 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 (rsFC) 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.

Connectivity between the L.dlPFC seed and a cluster comprising the left anterior supramarginal gyrus (SMG) showed a significant group × time interaction, with planned comparisons showing a greater increase at follow-up with iTBS compared to sham iTBS ( t ₁₂ =6.37, beta =0.40, p <0.001). Cigarette cue attentional bias showed a significant group × session interaction ( t ₈₂ =2.34 , p =0.02), with planned comparisons revealing a decrease after iTBS and an increase after sham iTBS. No effect of iTBS was observed for opioid cue attentional bias. Cigarette craving decreased with both iTBS and sham iTBS but did not show a significant group × session interaction. These results are promising but need to be interpreted with caution, given the limited sample size and multiple comparisons. Future trials could examine the effects of increased doses of iTBS (e.g., more days of accelerated iTBS) to identify the dosing required to promote smoking cessation among individuals with OUD effectively.