The Effect of Light Intervention on Recovery in Individuals with Opioid Use Disorder (OUD) - PROJECT SUMMARY/ABSTRACT In opioid use disorder (OUD), sleep and circadian disruptions are highly prevalent, interfere with opioid mainte- nance treatment (OMT) outcomes and increase the risk of relapse. So far, the neurobiological mechanisms linking sleep/circadian disruptions and relapse remain unclear and commonly used pharmacological sleep treat- ments fail to improve sleep or decrease illicit drug use in OUD. Thus, there is an urgent need to fill this research gap. The overall objective for this proposal is to determine 1) (Aim1/K99) whether dopaminergic dysfunction underlies sleep and circadian disruptions in OUD and 2) (Aim2/R00) whether bright light therapy can reduce sleep and circadian disturbances, normalize dopaminergic transmission, and improve treatment outcomes in OUD. The primary hypotheses are that altered dopaminergic transmission in OUD plays an essential role in observed sleep/circadian disruptions in OUD. While greater sleep disturbances are expected to correlate with lower D2R availability, delayed circadian rhythms are expected to correlate with greater D1R availability. Daily exposure to bright light in the morning is expected to advance circadian rhythms, improve sleep, normalize the D1R:D2R ratio and facilitate recovery processes in OMT OUD patients. To test the hypotheses, a multi-method approach including actigraphy, polysomnography, salivary melatonin and questionnaires will be used to assess sleep and circadian rhythms and PET scans will be performed to assess striatal D1R and D2R availability. A randomized, placebo-controlled trial will be conducted to assess the effect of a home-based bright light therapy on OUD recovery. OUD patients (on OMT >1 month) will be assigned either to bright white light (10000 lux) or to dim-red light placebo (<300 lux) group for 2 weeks. Their sleep, circadian rhythms and dopamine receptor availability will be measured before and after treatment. My long-term goal is to become an independent investigator studying brain mechanisms linking sleep/circadian disturbances and drug use, and thereby facilitating the development of effective sleep and circadian interventions for patients with substance use disorders. To achieve my goal, I propose trainings that will help me 1) gain clinical experiences in addiction research, 2) expand my research toolbox with PET, which will allow me to examine brain correlates at molecular level, 3) expand my expertise and tools in clinical sleep research and interventions and 4) enhance my professional skills critical for an independent research career. I will acquire these knowledge and skills under the guidance of a group of leading experts in the field of addiction, sleep and PET imaging, including my mentors (Dr. Nora Volkow, Dr. Martica Hall and Dr. Richard Carson) and my internal and external consultants (Dr. Dardo Tomasi, Dr. Dante Picchioni, Dr. Christopher Welsh, Dr. Brant Hasler). Additionally, NIH offer me plentiful resources for successfully completing proposed research project and training plans. The pro- posed research and trainings will prepare me well for an independent tenure-track position.
