The National Institute of Neurological Disorders and Stroke, National Institute of Aging, the NIH Helping to End Addiction Long Term (HEAL) initiative, and other participating ICs seek to support applications to conduct pharmacodynamic, pharmacokinetic, and efficacy studies to demonstrate that the proposed therapeutic agent(s) have sufficient biological activity to warrant further development as therapeutics for disorders or diseases supported by participating ICs or for non-opioid analgesic therapeutics with little or no addiction liability as a part of the NIH HEAL initiative. Therapeutic agents include small molecules or biologics. Efficacy testing can be conducted in validated in vivo models and/or validated New Approach Methodologies (NAMs) as appropriate.