National Center for Complementary and Integrative Health (NCCIH) invites applications for a phased research approach to strengthen our understanding and utilization of the underlying mechanisms and processes associated with mind and body interventions. This FOA will support two-phased research applications to (1) uncover the underlying biological, neurological, physiological, and/or behavioral mechanisms or processes relevant to mind and body interventions (e.g. meditation, spinal manipulation, massage, yoga, tai chi, hypnosis, acupuncture) and then, (2) to utilize the results from the initial phase to improve, refine, enhance, or strengthen the identified mechanisms or processes through either rigorous validation and refinement of the intervention, or using combined approaches that, together, will modulate the underlying mechanism or process. This second phase should also be able to provide preliminary evidence that the mechanism or process modulated by the intervention is associated with a functional outcome or clinical benefit for a specific condition or disorder. The first phase in the form of an R61 will provide funding for up to two years to support hypothesis-driven pilot testing and assessment of an intervention’s mechanisms of action. The second phase in the form of an R33 will provide up to three years of support for the larger scale validation and/or optimization incorporating the initial findings. Subject to the availability of funds, transition from the R61 to the R33 phase of the award will be administratively reviewed and determined by successful completion of the “Go/No-Go Criteria” that need to be clearly specified in the R61 phase. This FOA is not appropriate for clinical trials with the primary objectives to determine efficacy or effectiveness. The ultimate goal of this R61/R33 funding mechanism is to facilitate the direct translation of basic mechanistic research to clinical application. This FOA will use the NIH R61/R33 Phased Innovation Award mechanism.