Is there evidence that transcutaneous vagus nerve stimulators (tVNS) can lower cortisol levels?

Evidence for Transcutaneous Vagus Nerve Stimulation Lowering Cortisol Levels

Transcutaneous vagus nerve stimulation (tVNS) has demonstrated efficacy in lowering cortisol levels in response to stress, with multiple studies showing significant reductions in salivary cortisol compared to sham stimulation. 1

Mechanism of Action

• Vagus nerve stimulation (VNS) affects the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol production and release 2
• tVNS targets the cymba conchae of the ear, which is heavily innervated by the auricular branch of the vagus nerve 3
• Activation of neurons in the nucleus of the solitary tract by tVNS may activate inhibitory pathways projecting to the hypothalamic paraventricular nucleus, thus inhibiting corticotropin-releasing hormone (CRH) release 1

Research Evidence for Cortisol Reduction

• In a 2025 study, tVNS significantly reduced salivary cortisol levels during mental arithmetic stress testing compared to sham stimulation (49.5% vs 106.0% from baseline) 1
• A 2019 study found that tVNS attenuated the decline of salivary cortisol compared to sham stimulation, indicating modulation of hormonal indices of noradrenergic function 3
• A 2021 animal study demonstrated that VNS inhibited CRF-induced ACTH release (a precursor to cortisol production) for up to 1 hour compared to control groups 2
• In a case study of a psoriasis patient, daily tVNS for 3 months reduced diurnal salivary cortisol levels from 58.2 ± 35.2 (ng/mL)*h to 34.9 ± 13.8 (ng/mL)*h 1

Stress Response Modulation

• tVNS has been shown to decrease stress hormone responses during various stressful stimuli 4
• A 2023 double-blind, randomized, sham-controlled trial found that tVNS modulated stress-induced hormone levels (specifically ghrelin) in individuals with a history of exposure to traumatic stress 4
• In patients with refractory epilepsy, VNS resulted in normalization of cortisol levels, which were initially higher in epilepsy patients compared to control groups 5

Immune System Effects Related to Cortisol

• VNS appears to cause a rebalancing of the immune system, which may contribute to its effects on cortisol 5
• In responders to VNS therapy for epilepsy, pro-inflammatory cytokine IL-6 levels decreased while anti-inflammatory cytokine IL-10 increased 5
• These immune system changes occurred alongside normalization of cortisol levels, suggesting an interconnected mechanism 5

Clinical Applications

• The cortisol-lowering effects of tVNS may have implications for treating conditions associated with HPA axis dysfunction 1
• Potential applications include stress-related disorders, inflammatory conditions, and disorders involving hypothalamus-pituitary-adrenal axis dysfunction 2, 1
• The vagus nerve has been identified as a potential therapeutic target for treating disorders involving HPA axis dysfunction, such as ACTH-dependent Cushing's syndrome 2

Limitations and Considerations

• Most studies have small sample sizes, limiting the generalizability of findings 3, 1
• The timing of stimulation relative to stress exposure appears important for achieving cortisol-lowering effects 4
• Most research has focused on acute effects of tVNS; long-term effects on cortisol levels require further investigation 3, 1
• Stimulation parameters (frequency, amplitude, pulse width) may significantly impact outcomes but have not been fully standardized across studies 6