Craving Induction and Treatment Response in Transcranial Magnetic Stimulation for Tobacco Use Disorder

Background: Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for several mental health conditions including substance use disorders. Symptom provocation before rTMS is hypothesized to activate disease-related neurocircuitry and enhance treatment effects. For addiction, craving induction is frequently used before treatment, but its clinical utility requires further exploration. To assess whether craving induction enhances treatment outcomes, we analyzed data from the pivotal multisite trial of deep TMS (DTMS) for tobacco use disorder (TUD). Methods: A total of 262 participants were randomized to 6 weeks of active or sham DTMS and instructed to set a quit date within the first 2 weeks. Craving was assessed using a 10-point visual analog scale before and after craving induction across 18 treatment sessions. Mixed-effects models tested whether craving induction increased craving across sessions and whether its magnitude predicted end-of-trial 4-week continuous quit rate (4W-CQR). Results: Craving induction produced small but significant increases in craving (b = 0.34, 95% CI 0.18 to 0.50, p < .05) without evidence of habituation across sessions (b = −0.01, 95% CI −0.02 to 0.50, p = .38). Change in craving after cue induction did not significantly predict end-of-trial 4W-CQR, and there was no interaction with study arm (p = .95). Conclusions: Craving induction reliably increased craving, although the magnitude of cue-induced craving was not associated with end-of-trial smoking cessation. This finding suggests that greater craving induction does not predict greater therapeutic effect of rTMS. Further research is needed to understand the mechanisms and clinical implications of rTMS and brain state in TUD, including potential improvements in related domains such as inhibitory control.