Opioid overdose deaths in the United States are increasing. Time to restoration of ventilation is critical. Rapid bystander administration of opioid antidote (naloxone) is an effective interim response but is historically constrained by legal restrictions.

To review and contextualize development of legislation facilitating layperson administration of naloxone across the United States.

Publicly accessible databases (1,2) were searched for legislation relevant to naloxone administration between January 2001 and July 2017.

All 51 jurisdictions implemented naloxone access laws between 2001 and 2017; 45 of these between 2012 and 2017. Nationwide mortality from opioid overdose increased from 3.3 per 100,000 population in 2001 to 13.3 in 2016, 42, and 35 jurisdictions enacted laws giving prescribers immunity from criminal prosecution, civil liability, and professional sanctions, respectively. 36, 41, and 35 jurisdictions implemented laws allowing dispensers immunity in the same domains. 38 and 46 jurisdictions gave laypeople administering naloxone immunity from criminal and civil liability. Forty-seven jurisdictions implemented laws allowing prescription of naloxone to third parties. All jurisdictions except Nebraska allowed pharmacists to dispense naloxone without a patient-specific prescription. Fifteen jurisdictions removed criminal liability for possession of non-prescribed naloxone. The 10 states with highest average rates of opioid overdose-related mortality had not legislated in a higher number of domains compared to the 10 lowest states and the average of all jurisdictions (3.4 vs 2.9 vs 2.7, respectively).

Effective involvement of bystanders in early recognition and reversal of opioid overdose requires removal of legal deterrents to prescription, dispensing, distribution, and administration of naloxone. Jurisdictions have varied in degree and speed of creating this legal environment. Understanding the integration of legislation into epidemic response may inform the response to this and future public health crises.