The objective of this research is the development of technologies that enable at-home non-invasive therapies for mental health, particularly within the domains of persistent acute stress elevations in healthy individuals and withdrawal in those with opioid use disorder (OUD). Specifically, this work focuses on the implementation and validation of wearable non-invasive peripheral nerve stimulation therapies. We have shown in prior work that transcutaneous median nerve stimulation (tMNS) is effective at reducing acute stress elevations as compared to sham stimulation, and likewise, we have shown that transcutaneous cervical vagus nerve stimulation (tcVNS) is effective at reducing the behavioral and physiological manifestations of withdrawal in those with OUD. To enable tMNS therapy for acute stress elevations in at-home environments, we have developed a wrist-worn hardware system capable of detecting acute stress elevations through non-invasive sensing of the photoplethysmogram (PPG) signal and onboard extraction of pulse rate (PR) and PPG amplitude (PPGamp). The system can then deliver closed-loop tMNS through a custom-designed circuit to signal the brain to counteract the stress. We have also completed work demonstrating that tcVNS modulates prefrontal cortex activity during opioid withdrawal in those with OUD. In order to demonstrate the effectiveness of tcVNS as an adjunctive therapy during active withdrawal in the transition to medication, we propose to demonstrate the effectiveness of tcVNS vs. sham stimulation at reducing the behavioral and physiological manifestations of opioid withdrawal in the context of active withdrawal in a week-long inpatient hospital setting. Finally, in prior work, we have demonstrated the importance of robust multi-modal stress detection with features from the electrocardiogram (ECG), seismocardiogram (SCG), and PPG, as well as from a combination of these three signals. As our closed-loop wrist-worn system currently only includes a single modality (PPG), we propose to develop a networked-wearable system, including a chest patch and our wrist-worn device, capable of robust multi-modal real-time acute stress monitoring and mitigation.