I am an internist and have been involved in addiction research for more than 25 years. During my first 4 years of post-graduate training after medical school, it was apparent that addiction issues were contributing to 50% of hospital admissions, either due to acute intoxication causing trauma or medical emergencies, or due to the medical consequences of chronic smoking, alcoholism, and intravenous drug use. Medical school taught how to address COPD, ascites, and reversal of overdose, but it did not provide any useful training for initiating and encouraging behavior changes in patients. Exposure to the Behavioral Pharmacology Research Unit (BPRU, Johns Hopkins University) convinced me that this field of study was the right way to study the interactions between drugs, behaviors, and the environment, while human vulnerabilities and conditioning remained the actors. Treating medical co-morbidities of substance use disorder continued to be a focus. A small study of providing on-site medical care in a methadone treatment clinic demonstrated that such medical home was more effective in nudging drug users to get needed medical care. I served as medical director of the Archway clinic of NIDA – IRP for 9 years, and continued to supervise the safety of addiction research protocols at BPRU for 13 years. While most of my research was in medication-assisted treatment context, I ran several NIDA-funded clinical trials to evaluate the utility of topiramate and zonisamide for cocaine dependence and smoking cessation. Although pharmacologic treatment has its place in addiction treatment, behavior change cannot happen if the mind continues on autopilot. For this reason, I recently shifted my focus to mindfulness. While cognitive behavior therapy helps in developing strategies to change behaviors, the thoughts and emotions preceding behaviors need to be recognized. Mindfulness teaches the skills necessary to observe the mind without judgment and helps the individual notice craving without identifying with it, creating a space where different choices can happen. Psychophysiology, or the measurement of the effects of thoughts on physiology like respiratory parameters, heart rate variability etc, can help participant identify behavioral patterns, including body response to stress that in some cases amplify distress. Distress Intolerance has been shown to be an impediment to quit smoking. Right now, I am focusing on the evaluation of End-Tidal CO2 as a marker of dysfunctional breathing and whether hypocapnia and its physiologic consequences contribute to distress intolerance and amplify the anxiety stemming from discomfort. This line of research could lead to novel therapies in substance use disorders.