Opioid-related death and overdose have now reached epidemic proportions. In response to this public health crisis, the National Institutes of Health (NIH) launched the Helping to End Addiction Long-term InitiativeSM, or NIH HEAL InitiativeSM, an aggressive, trans-agency effort to speed scientific solutions to stem the national
opioid public health crisis. Herein, we describe two NIH HEAL Initiative programs to accelerate development of non-
opioid, non-addictive
pain treatments: The Preclinical Screening Platform for
Pain (PSPP) and Early Phase
Pain Investigation Clinical Network (EPPIC-Net). These resources are provided at no cost to investigators, whether in academia or industry and whether within the USA or internationally. Both programs consider small molecules, biologics, devices, and natural products for acute and
chronic pain, including repurposed and combination drugs. Importantly, confidentiality and intellectual property are protected. The PSPP provides a rigorous platform to identify and profile non-
opioid, non-addictive
therapeutics for
pain. Accepted assets are evaluated in in vitro functional assays to rule out
opioid receptor activity and to assess abuse liability. In vivo pharmacokinetic studies measure plasma and brain exposure to guide the dose range and pretreatment times for the side effect profile, efficacy, and abuse liability. Studies are conducted in accordance with published rigor criteria. EPPIC-Net provides academic and industry investigators with expert infrastructure for phase II testing of
pain therapeutics across populations and the lifespan. For assets accepted after a rigorous, objective scientific review process, EPPIC-Net provides clinical trial design, management, implementation, and analysis.