Naloxone is an opioid antagonist that reverses the respiratory depression, sedation, and hypotension associated with the use of heroin and other opioids; however, naloxone does not reduce the respiratory depression caused by non-opioid central nervous system (CNS) depressants such as alcohol and benzodiazepines, and it has no effect when administered to someone who has not used opioids. Whether making naloxone available for peer administration would likely result in a net reduction in harm from heroin overdoses will depend on a number of factors, including the extent to which it is used as an additional component of a peer first aid response to overdoses; whether it undermines other strategies such as airway management and calling an ambulance; whether naloxone recipients receive a medical review; and what proportion of users engage in more hazardous use if they believe their friends can keep them safe from the dangers of an overdose. For these kinds of reasons, the authors call for a carefully controlled trial of naloxone provision for peer administration before more widespread distribution is seriously considered. This paper addresses some of the methodological and medico-legal barriers to such a trial. 32 references