Page last updated August 11, 2023 by Doug McVay, Editor.

1. Overdose Education and Naloxone Distribution (OEND) Within Syringe Service Programs (SSPs)

"Among the 342 known SSPs operating at the beginning of 2019, 263 (77%) responded to the online survey; of these, 247 (94%) had an OEND program, 160 (65%) of which had been implemented since 2016 (Figure 1). With regard to phases of OEND implementation, 173 (66%) responding SSPs had been implementing OEND for 12 months or more, 74 (28%) had implemented OEND within the last 12 months, eight (3%) were actively preparing for OEND implementation, and eight (3%) were exploring OEND implementation (Table). Of the 16 SSPs not yet offering OEND, four had previously implemented naloxone distribution but stopped because of an inadequate naloxone supply or funding.

"Among the 247 SSPs with an OEND program, 191 (77%) offered OEND every time syringe services were offered, and 214 (87%) provided naloxone refills as often as participants requested them (Table). SSPs reported offering OEND for a median of 15 of the past 28 days. Only 29 (12%) SSPs entered OEND data directly into an electronic data system. During the preceding 12 months, 237 (96%) of 247 SSPs with OEND programs reported distributing 702,232 naloxone doses, including refills, to 230,506 persons (an average of 3 doses per person). Sixty-two (26%) SSPs reported distributing naloxone to >1,000 persons in the last 12 months; these programs had distributed naloxone to 186,603 laypersons, who represented 81% of all recipients in the past 12 months. Overall, 14 (6%) SSPs reported distribution of ≥10,000 naloxone doses during the last 12 months, accounting for 382,132 naloxone doses, 54% of all doses distributed by SSPs in the past 12 months. These 14 SSPs are located throughout six of the nine census divisions. Seventy-two (29%) SSPs ran out of naloxone or needed to ration their naloxone in the preceding 3 months."

Lambdin, B. H., Bluthenthal, R. N., Wenger, L. D., Wheeler, E., Garner, B., Lakosky, P., & Kral, A. H. (2020). Overdose Education and Naloxone Distribution Within Syringe Service Programs - United States, 2019. MMWR. Morbidity and mortality weekly report, 69(33), 1117–1121. doi.org/10.15585/mmwr.mm6933a2


2. Take-Home Naloxone Does Not Lead To Riskier Drug Use

"We did not find evidence that THN [Take-Home Naloxone] training was associated with risk compensation behavior in this cohort of people who inject drugs. Rather, there was no significant change in frequency of injecting any drugs, injecting opioids, or using benzodiazepines after accessing THN. There was also no change in the proportion of time that participants reported using drugs alone, a key indicator of overdose mortality risk.30,38,39

"There was no evidence of THN-associated compensatory risk behavior in this cohort. While not all overdose risk behaviors were examined in this study (eg, injecting in public, concomitant use of alcohol or benzodiazepines, and use of fentanyl),40,41 frequency of opioid injecting and frequency of benzodiazepine use are 2 of the most important risk factors for overdose. The association between knowledge of and engagement in overdose risk behaviors is complex,38 and THN is designed to be used on other people who may be at risk of overdose; therefore, it may be pertinent to examine the implications of naloxone availability for drug use in peer networks. In a qualitative study, participants with opioid use disorder residing in residential drug treatment programs in the US described both no change to their drug use and some engagement in riskier behavior by themselves or peers (eg, injecting heroin laced with fentanyl).42 However, this finding has not been borne out in empirical evidence and does not appear to correspond with increases in overdose at the population level.3,4

"Findings from this work are consistent with an emerging evidence base suggesting that concerns about risk compensation with naloxone availability are unfounded.4 Yet, these concerns continue to be raised as objections for expanding THN supply.7,11 For example, a number of pharmacists in a recent Australian study expressed concerns about distributing naloxone, as they believed that recipients would feel comfortable increasing their opioid use.43 However, because naloxone administration can be associated with opioid withdrawal and reverses the effects of any opioids that have been recently taken, the outcomes of naloxone are considered unpleasant by people who inject drugs, meaning that they are typically reluctant to administer the drug.42,44 Furthermore, it is questionable whether this concern is reason enough to withhold a lifesaving medication from people. Only 40.4% of participants in the SuperMIX study reported THN training, despite most of the sample reporting the use of opioids. There is a clear need for widespread education among health care practitioners and other key stakeholders to enable them to address this common assumption about THN, which can act as a barrier to THN supply so that coverage is increased."

Colledge-Frisby S, Rathnayake K, Nielsen S, et al. Injection Drug Use Frequency Before and After Take-Home Naloxone Training. JAMA Netw Open. 2023;6(8):e2327319. doi:10.1001/jamanetworkopen.2023.27319

3. Good Samaritan and Naloxone Access Laws Save Lives

"GAO found that 48 jurisdictions (47 states and D.C.) have enacted both Good Samaritan and Naloxone Access laws. Kansas, Texas and Wyoming do not have a Good Samaritan law for drug overdoses but have a Naloxone Access law. The five U.S. territories do not have either type of law. GAO also found that the laws vary. For example, Good Samaritan laws vary in the types of drug offenses that are exempt from prosecution and whether this immunity takes effect before an individual is arrested or charged, or after these events but before trial.

"GAO reviewed 17 studies that provide potential insights into the effectiveness of Good Samaritan laws in reducing overdose deaths or the factors that may contribute to a law’s effectiveness. GAO found that, despite some limitations, the findings collectively suggest a pattern of lower rates of opioid-related overdose deaths among states that have enacted Good Samaritan laws, both compared to death rates prior to a law’s enactment and death rates in states without such laws. In addition, studies found an increased likelihood of individuals calling 911 if they are aware of the laws. However, findings also suggest that awareness of Good Samaritan laws may vary substantially across jurisdictions among both law enforcement officers and the public, which could affect their willingness to call 911."

"Most States Have Good Samaritan Laws and Research Indicates They May Have Positive Effects," US General Accountability Office, March 2021, GAO-21-248.


4. Association of Opioid Overdose Laws with Opioid Use and Mortality

"• Naloxone access laws that ease restrictions on naloxone possession and distribution are associated with a 20% reduction overdose deaths among African-Americans.

"• Good Samaritan laws, providing immunity from prosecution for those calling emergency services, are associated with broad reductions in overdose deaths, reducing overdose deaths by 13% overall.

"• None of these harm reduction measures result in increase in opioid or heroin use.

"• These laws are effective at reducing overdose mortality without creating additional opioid use. Correspondingly, these measures should be considered an important part of the strategy used to address the opioid epidemic."

McClellan, Chandler, Lambdin, Barrot H., et al. Opioid-overdose laws association with opioid use and overdose mortality. Addictive Behaviors. March 19, 2018.


5. Protections Offered by Good Samaritan Laws Vary By Jurisdiction

"Our analysis of the characteristics of the 48 Good Samaritan laws found that they differ in the protections they offer to individuals who call for medical assistance for an overdose victim. First, there is variation in whether criminal immunity—an exemption from prosecution—is offered and, if so, for which type of drug offense, such as possessing or delivering drugs in violation of an otherwise applicable drug law. Second, there is variation in when criminal immunity takes effect—the timing can be before an individual would otherwise be arrested and charged as a criminal defendant or after these events but before an individual is prosecuted.

"Finally, because a jurisdiction retains the power to prosecute individuals who do not have criminal immunity, some Good Samaritan laws offer either an affirmative defense at trial or a mitigating factor at sentencing, or both."

"Most States Have Good Samaritan Laws and Research Indicates They May Have Positive Effects," US General Accountability Office, March 2021, GAO-21-248.


6. Naloxone As Lifesaving Intervention To Prevent Death By Opioid Overdose

"The heart of the challenge is the possibility that things could be different: overdose is a public health problem that can be solved. Unlike many of the other leading causes of death, death from opioid overdose is almost entirely preventable,21 and preventable at a low cost.22 Opioids kill by depressing respiration, a slow mode of death that leaves plenty of time for effective medical intervention.23 Overdose is rapidly reversed by the administration of a safe and inexpensive drug called naloxone. Naloxone strips clean the brain’s opioid receptors and reverses the respiratory depression causing almost immediate withdrawal.24 A growing number of harm reduction organizations in the United States are offering overdose prevention programs that provide injection drug users with resuscitation training and take-home doses of naloxone.25"

Burris, Scott; Beletsky, Leo; Castagna, Carolyn; Coyle, Casey; Crowe, Colin; and McLaughlin, Jennie Maura, "Stopping an Invisible Epidemic: Legal Issues in the Provision of Naloxone to Prevent Opioid Overdose," Drexel Law Review, Philadelphia, PA: Earle Mack School of Law, Spring 2009, Vol. 1, Number 2.


7. Naloxone Availability in Norway

"Naloxone is the most common antidote used for overdoses. It is normally ambulance personnel who administer naloxone in connection with opioid overdoses, and doses are administered by intramuscular or intravenous injection. It is now being discussed whether naloxone in the form of a mouth spray should be available to others as well, as first aid for someone who has overdosed
until the ambulance arrives."

Norwegian Institute for Alcohol and Drug Research, "The Drug Situation in Norway 2012: annual report to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)," Oslo, Norway: December 2012.


8. Barriers to Naloxone Access

"A more prosaic, but no less important, legal barrier to widespread naloxone access is the Food and Drug Administration’s (FDA) classification of naloxone as a prescription drug. This means that public health and harm reduction agencies cannot distribute naloxone like condoms or sterile syringes. Instead, naloxone must be prescribed by a properly licensed health care provider after an individualized evaluation of the patient. Because health care providers have to be involved, naloxone programs must deal with concerns about liability, which among doctors can be powerful even when they are not wellfounded in fact.31 The prescription status raises the cost of naloxone distribution and makes it illegal to give naloxone to lay people willing to administer the drug to others suffering an overdose."

Burris, Scott; Beletsky, Leo; Castagna, Carolyn; Coyle, Casey; Crowe, Colin; and McLaughlin, Jennie Maura, "Stopping an Invisible Epidemic: Legal Issues in the Provision of Naloxone to Prevent Opioid Overdose," Drexel Law Review, Philadelphia, PA: Earle Mack School of Law, Spring 2009, Vol. 1, Number 2.


9. Feasibility of Naloxone Distribution to People Who Use Injection Drugs

"This pilot trial is the first in North America to prospectively evaluate a program of naloxone distribution to IDUs [Injection Drug Users] to prevent heroin overdose death. After an 8-hour training, our study participants' knowledge of heroin overdose prevention and management increased, and they reported successful resuscitations during 20 heroin overdose events. All victims were reported to have been unresponsive, cyanotic, or not breathing, but all survived. These findings suggest that IDUs can be trained to respond to heroin overdose by using CPR and naloxone, as others have reported. Moreover, we found no evidence of increases in drug use or heroin overdose in study participants. These data corroborate the findings of several feasibility studies recommending the prescription and distribution of naloxone to drug users to prevent fatal heroin overdose."

Seal, Karen H., Robert Thawley, Lauren Gee, Joshua Bamberger, Alex H. Kral, Dan Ciccarone, Moher Downing, and Brian R. Edlin, "Naloxone Distribution and Cardiopulmonary Resuscitation Training for Injection Drug Users to Prevent Heroin Overdose Death: A Pilot Intervention Study," Journal of Urban Medicine, New York, NY: New York Academy of Medicine, 2005, Vol. 82, No. 2.


10. Price of Naloxone Has Skyrocketed Since 2006

"We contribute nationally representative evidence to help answer each of these questions, including wholesale pricing data from a proprietary drug sales database spanning January 2006 to February 2017. We find that all formulations of naloxone increased in price since 2006 except for Narcan Nasal Spray. These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 MG Evzio auto-injector. We believe that increased demand for naloxone from the opioid epidemic may explain the more gradual price increases for the 0.4 MG single-dose and 4 MG multi-dose products prior to 2012. On the other hand, we believe that the sudden, sustained prices increases occurring for all of the products since 2012 may be the result of a drug shortage for the 0.4 MG single-dose products and the fact that each naloxone product has historically been sold by only a single competitor."

Matthew Rosenberg, Grace Chai, Shekhar Mehta, Andreas Schick, Trends and economic drivers for United States naloxone pricing, January 2006 to February 2017, Addictive Behaviors, 2018, ISSN 0306-4603, doi.org/10.1016/j.addbeh.2018.05.006.


11. Benefits from Naloxone Distribution

"Naloxone distribution to heroin users would be expected to reduce mortality and be cost-effective even under markedly conservative assumptions of use, effectiveness, and cost. Although the absence of randomized trial data on naloxone distribution and reliance on epidemiologic data increase the uncertainty of results, there are few or no scenarios in which naloxone would not be expected to increase QALYs [Quality-Adjusted Life-Years] at a cost much less than the standard threshold for cost-effective health care interventions. Ecological data, in fact, suggest that naloxone distribution may have far greater benefits than those forecast in this model: Reductions in community-level overdose mortality from 37% to 90% have been seen concordant with expanded naloxone distribution in Massachusetts (7), New York City (11), Chicago (10), San Francisco (9, 67, 68), and Scotland (69). Such a result is approached in this model only by maximizing the likelihood of naloxone use or by assuming that naloxone distribution reduces the risk for any overdose. Preliminary data showing that naloxone distribution is associated with empowerment and reduced HIV risk behaviors (70, 71) suggest that future research is needed to test these hypotheses."

Coffin, Phillip O., MD, and Sullivan, Sean D. PhD, "Cost-Effectiveness of Distributing Naloxone to Heroin Users for Lay Overdose Reversal," Annals of Internal Medicine 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.


12. Rapid Effect of Naloxone

"Heroin is particularly toxic because of high lipid solubility, which allows it to cross the blood–brain barrier within seconds and achieve high brain levels.10
"Naloxone is also lipid soluble and enters the brain rapidly. Reversal of respiratory depression is evident 3–4 minutes after IV and 5–6 minutes after subcutaneous administration.11"

Etherington, Jeremy; Christenson, James; Innes, Grant; Grafstein, Eric; Pennington, Sarah; Spinelli, John J.; Gao, Min; Lahiffe, Brian; Wanger, Karen; Fernandes, Christopher, "Is early discharge safe after naloxone reversal of presumed opioid overdose?" Canadian Journal of Emergency Medicine, Ottawa, ON: Canadian Association of Emergency Physicians, July 2000.


13. Cost-Effectiveness of Naloxone Distribution

"Naloxone distribution was cost-effective in our base-case and all sensitivity analyses, with incremental costs per QALY [Quality-Adjusted Life-Year] gained much less than $50 000 (Table 2 and Appendix Figure 3, available at www.annals.org; see Appendix Table 3, available at www.annals.org, for detailed results of selected analyses). Cost-effectiveness was similar at starting ages of 21, 31, and 41 years; the greater QALY gains of younger persons were roughly matched by higher costs. In scenarios where naloxone administration reduced reliance on EMS, naloxone distribution was cost-saving and dominated (that is, less costly and more effective than) the no-distribution comparison. Cost-effectiveness was somewhat sensitive to the efficacy of lay-administered naloxone and the cost of naloxone but was relatively insensitive to the breadth of naloxone distribution, rates of overdose and other drug-related death, rates of abstinence and relapse, utilities, or the absolute cost of medical services. Naloxone was no longer cost-effective if the relative increase in survival was less than 0.05%, if 1 distributed kit cost more than $4480, or if average emergency care costs (as a proxy for downstream health costs) exceeded $1.1 million. A worst-case scenario, in which the likelihood of an overdose being witnessed, the effectiveness of naloxone, and the likelihood of naloxone being used were minimized and the cost of naloxone was maximized, resulted in an incremental cost of $14,000 per QALY gained. A best-case scenario, in which naloxone distribution reduced the risk for overdose, was dominant."

Coffin, Phillip O., MD, and Sullivan, Sean D. PhD, "Cost-Effectiveness of Distributing Naloxone to Heroin Users for Lay Overdose Reversal," Annals of Internal Medicine 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.


14. National Naloxone Program, Scotland

"The aim of the National Naloxone Programme is to contribute to a reduction in fatal opioid overdoses in Scotland. The rate of drug related deaths in Scotland remains higher than the UK average (9.17 drug related deaths per 100,000 population in Scotland in 2010, compared with 3.1 in the UK1). An earlier investigation into drug related deaths in Scotland and more recent information from Scotland’s national drug related deaths database has shown that the majority of these deaths are opioid related, the majority are ‘accidental overdoses’, the majority are ‘witnessed’ and 50% have been in prison (Zador et al, 20052; Graham et al, 2011 and 2012 3 4). As well as monitoring the supply of ‘take-home’ naloxone kits in Scotland, ISD Scotland were tasked by the Scottish Government to measure the impact of increased naloxone availability on the number of (opioid) drug related deaths in Scotland and, in particular, to monitor the number and percentage of these occurring within four weeks of prison release."

Scottish Government, "National Naloxone Programme Scotland Monitoring Report – naloxone kits issued in 2011/12," Edinburgh, Scotland: Information Services Division, NHS National Services Scotland, July 31, 2012.


15. Providing Naloxone to Prisoners at Risk of Opioid Overdose on Release in Scotland

"SPS [Scottish Prison Service] developed an intervention to provide naloxone to prisoners at risk of opioid related overdose on release from prison, as part of the National Naloxone Programme, in recognition of the increased risk of overdose in the first four weeks following release from prison custody. The naloxone is packed in with their personal belongings, which are stored at reception, then supplied to the prisoner on release from custody.
"The supply of ‘take-home’ naloxone kits by prisons was introduced, incrementally, from February 2011 and by June 2011 all Scottish prisons were participating in the programme. Approximately 100 prison staff participated in training during the introduction and implementation phase (note: HMP Inverness, along with the Inverness area of NHS Highland, as noted earlier, commenced supply of ‘take home’ naloxone from July 2009)."

Scottish Government, "National Naloxone Programme Scotland Monitoring Report – naloxone kits issued in 2011/12," Edinburgh, Scotland: Information Services Division, NHS National Services Scotland, July 31, 2012.


16. Historic Development of Naloxone Programs

"Naloxone distribution programs in the US are ongoing in Chicago, Baltimore, San Francisco, New Mexico and New York City. Additional community-based organizations interested in minimizing the adverse consequences of drug use in several cities in the US, including Los Angeles, Providence, Pittsburgh and Boston, are in the process of planning and developing naloxone administration programs for drug users."

Tinka Markham Piper, Sasha Rudenstine, Sharon Stancliff, Susan Sherman, Vijay Nandi, Allan Clear, and Sandro Galea. "Overdose prevention for injection drug users: Lessons learned from naloxone training and distribution programs in New York City," Harm Reduction Journal, January 25, 2007.