Isradipine Enhancement of Virtual Reality Cue Exposure Therapy is Effective for Individuals with Higher Baseline Cue-Induced Craving

Background: Evidence based treatments for smoking cessation have high relapse rates. Targeting cue-induced craving, a strong predictor of relapse, may be critical to promoting sustained abstinence. We previously found that isradipine, an FDA-approved antihypertensive, enhanced the effect of virtual reality cue exposure therapy (VR-CET) on cue-induced craving. In this secondary analysis we tested whether this augmentation strategy was more beneficial for participants with high (relative to low) baseline cue-induced craving.Methods: After a 24-h abstinence challenge, participants (N = 78) completed a single session of VR-CET with isradipine or placebo, and returned for a 24-h follow-up to repeat the procedure in a medication-free state. We conducted a moderator analysis to test the hypothesis that the effect of isradipine on cue-induced craving at follow-up would be larger among participants with higher (relative to lower) baseline cue reactivity.Results: In the model of cue-induced craving at follow-up, the Group × Baseline Cue Reactivity interaction was significant, p = .045. Among participants with higher baseline cue-induced craving, isradipine resulted in a large, significant reduction in mean craving across the 10 trials (M difference = -18.17, 95% CI [−31.38, −4.95], p = .01, d = -1.46). Among participants with lower baseline cue-induced craving were not significantly different across groups (M difference = 1.38, 95% CI [−12.98, 15.75], p = .85, d = 0.11). Conclusions: Results suggest isradipine enhances VR-CET, particularly for individuals with higher baseline levels of cue-induced craving. Future studies testing relapse-prevention strategies that target higher cue-induced craving with isradipine are warranted.