Tamper-resistant opioids are not entirely without merit, but may have at most a mild impact on making pain pharmacotherapy safer. A more consequential innovation would be to design or discover medications that do not carry risk of addiction, overdose, and other adverse effects of opioids. One route is to design opioid molecules with “biased agonism”, meaning that they relieve pain with less respiratory suppression and less activation of brain reward circuity underlying the acquisition of addiction. This approach has produced some promising preclinical findings, but these have not been replicated or rigorously tested in clinical studies as yet. A non-competing alternative approach is to develop non-opioid medications and interventions (e.g., virtual reality and nerve stimulation devices) that have significant ability to relieve pain, to ameliorate addiction, or both.

     The rapid development of effective vaccines for COVID-19 shows what is possible when governments make a massive, urgent commitment in the face of an epidemic. The same commitment is needed for the opioid crisis. Expanding National Institutes of Health initiatives such as the Blueprint Neurotherapeutics Network for Small Molecule Drug Discovery and Development for Disorders of the Nervous System and charging them with focusing more work on opioids, could be productive. Private industry could be incentivized to carry out similar work through tax credits for research and development (A prize-based competition makes less sense as the developer of any such molecule would likely reap enormous profits). Privately and publicly funded animal research is more likely to lead to life-saving innovations if guided by translational scientific models.