Effects of cranial electrotherapy stimulation with novel in-ear electrodes on anxiety and resting-state brain activity: A randomized double-blind placebo-controlled trial

•Home-based CES with novel in-ear electrodes has a clinical effect on state anxiety.•Increased theta activity significantly correlated with improvements in anxiety.•CES increased high-beta source activity in cuneus and middle occipital gyrus. Cranial Electrotherapy Stimulation (CES) is a promising non-invasive brain stimulation technique with the potential to alleviate anxiety. We examined the effectiveness of home-based CES with novel, headphone-like, in-ear electrodes on anxiety-related symptoms and resting-state brain activity. This study spanned 3-weeks, with randomized, double blind, and active-controlled design. Nonclinical volunteers experiencing daily anxiety were randomly assigned to either the active or the sham groups. CES provides an alternating current (10 Hz frequency, 500 μA intensity), connected to smartphone recording treatment logs. Participants treated themselves with 20 trials of CES at home. We evaluated the effectiveness using State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Wisconsin Card Sort Test (WCST), and resting-state electroencephalography (EEG). The active group showed a significant improvement in state-anxiety compared to sham, while there was a statistical trend in the WCST-Category Completed (p = .061) and no change in depression. In EEG analysis, the active group showed significantly increased relative power for theta in the left frontal region compared with the sham, and this significantly correlated with the changes in state-anxiety. The active group exhibited significantly increased high-beta source activity in cuneus and middle occipital gyrus after intervention compared with the baseline. This study had a relatively short treatment period and small sample size. Our findings provide the first electrophysiological evidence for CES for novel in-ear electrodes to improve anxiety. The modulatory effects of CES on resting-state oscillations of EEG imply that CES could beneficially affect functional brain activity.