Effects of Repeated Cranial Electrotherapy Stimulation on Physiological and Behavioral Responses to Acute Stress: A Double-Blind Randomized Clinical Trial

Kana Okano¹Marissa Marko Lee¹Hannah Hart-Pomerantz¹Marisa Smith¹Madelyn K Sandone¹Travis Harvey²Tad Brunye^1*

• ¹Cognitive Science, Center for Applied Brain and Cognitive Sciences, School of Engineering, Tufts University, Medford, United States
• ²Teamworks Innovations, Durham, NC, United States

Cranial electrotherapy stimulation (CES) is a low-intensity, pulsed neuromodulation technique widely marketed for reducing stress and anxiety. Despite its popularity, empirical evidence for its efficacy remains mixed, with few studies employing rigorous controls, standardized protocols, and repeated CES exposures. This study tested whether repeated CES sessions can attenuate physiological, biochemical, cognitive, and affective responses to an acute laboratory stressor. A double-blind, randomized, placebo-controlled clinical trial was conducted with 46 healthy participants (27 military personnel, 19 civilians). Participants were randomized to receive either active CES (250-500µA at 0.5Hz, individualized intensity) or sham stimulation for 20 sessions over approximately four weeks. At baseline and follow-up visits, participants underwent acute stress induction using torso shock; measures included physiological (heart rate, heart rate variability, respiration rate, pupil diameter), biochemical (salivary alpha-amylase, cortisol), cognitive (spatial orientation, recognition memory, decision-making), and affective (State-Trait Anxiety Inventory) indices. Stress induction reliably elevated sympathetic-adrenal medulla (SAM) and hypothalamicpituitary-adrenal (HPA) markers as well as subjective anxiety. However, across nearly all outcomes, active CES did not differ significantly from sham, nor were there interactions with session (baseline vs. follow-up). No meaningful group differences were observed in stress recovery, self-reported anxiety, or stress-related cognitive performance. These predominantly null findings challenge prevailing mechanistic accounts of CES and suggest limited efficacy in buffering acute stress responses in healthy, neurotypical individuals. Further controlled trials are needed to explore alternative parameters, populations, and neurophysiological endpoints to better understand CES's therapeutic potential.