Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study

Abstract

BackgroundOpioid Use Disorder (OUD) is a serious public health problem, and the behavioral and physiological effects of opioid withdrawal can be a major impediment to recovery. Medication for OUD is currently the mainstay of treatment; however, it has limitations and alternative approaches are needed. ObjectiveThe purpose of this study was to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on behavioral and physiological manifestations of acute opioid withdrawal. MethodsPatients with OUD undergoing acute opioid withdrawal were randomly assigned to receive double blind active tcVNS (N = 10) or sham stimulation (N = 11) while watching neutral and opioid cue videos. Subjective opioid withdrawal, opioid craving, and anxiety were measured using a Visual Analogue Scale (VAS). Distress was measured using the Subjective Units of Distress Scale (SUDS), and pain was measured using the Numerical Rating Scale (NRS) for pain. Electrocardiogram signals were measured to compute heart rate. The primary outcomes of this initial phase of the clinical trial (ClinicalTrials.gov NCT04556552) were heart rate and craving. ResultstcVNS compared to sham resulted in statistically significant reductions in subjective opioid withdrawal (p = .047), pain (p = .045), and distress (p = .004). In addition, tcVNS was associated with lower heart rate compared to sham (p = .026). Craving did not significantly differ between groups (p = .11). ConclusionstcVNS reduces behavioral and physiological manifestations of opioid withdrawal, and should be evaluated in future studies as a possible non-pharmacologic, easily implemented approach for adjunctive OUD treatment.