Mindfulness meditation plus transcutaneous auricular vagus nerve stimulation for alcohol use disorder: a randomized clinical trial

Abstract Background Impaired inhibitory control under negative affect is a core mechanism sustaining alcohol use disorder (AUD), but receives limited attention in treatment development. Mindfulness meditation has shown efficacy in improving this function, but outcomes differ across individuals. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation approach that targets brain–heart interplay. It may enhance neurobiological pathways underlying emotion regulation and cognitive control and thus represents a promising augmentation strategy. This randomized controlled trial examined whether concurrent taVNS augments the efficacy of mindfulness meditation on inhibitory control under negative affect and whether brain–heart interplay represents a relevant physiological pathway. Methods Sixty-three patients with AUD were randomized to receive either sham ( n = 31) or active ( n = 32) taVNS during twice-daily mindfulness meditation sessions for 10 days. Inhibitory control under negative affect was measured by no-go accuracy when angry faces were presented as distractors in a color-based go/no-go task. Tonic brain–heart interplay was quantified by heart rate variability-electroencephalography coupling at rest. Secondary outcomes include latency to any post-discharge alcohol use, craving, negative affect, emotion regulation, mindfulness, and sleep quality. Primary analyses used ANCOVA to predict post-treatment angry-face no-go accuracy from group and baseline. Additional analyses examined changes in brain–heart interplay indices and self-reported outcomes across groups. Results Mindfulness meditation with active taVNS produced greater increases in angry-face no-go accuracy than mindfulness meditation with sham taVNS ( p < 0.001). Post-treatment accuracy remained baseline-dependent in the sham group (β = 0.406; 95% CI, 0.245–0.567; p < 0.001), whereas the active group achieved uniformly high accuracy regardless of baseline (β = -0.015; 95% CI, -0.205–0.175; p = 0.798). Enhanced BHI occurred only in the active group. Reductions in anxiety and craving were greater and earlier in the active group than in the sham group. Conclusions The combination of mindfulness meditation and taVNS provides an effective and safe treatment for men with AUD. The results support the promise of targeting brain–heart interplay to develop interventions for AUD. Trial Registration ClinicalTrials.gov Identifier: NCT07036055. Registered on June 16, 2025.