Naloxone

"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."

"Naloxone has been used as an antidote to opioids for over 50 years, and the drug has been readily available as a parenteral formula. Naloxone acts as a pure μ-opioid receptor competitive antagonist and is instrumental in preventing accidental overdose of opioids. Due to its effectiveness in preventing death due to opioid overdose, the federal government has recommended that naloxone should be available over-the-counter at most pharmacies. Naloxone can be obtained without a prescription in 43 states and can be administered by emergency medical personnel and law enforcement officials. With the availability of naloxone over the counter, it is now easier for family members and caregivers of patients with opioid use disorder to administer naloxone and potentially save lives.[1]"

"Here, we report the first xylazine dose-response locomotor study in male and female mice as well as the first assessment of adrenergic- and opioid-receptor antagonist-precipitated withdrawal symptoms following, xylazine, fentanyl, and xylazine/fentanyl administration in mice. These experiments show that male and female mice are differentially sensitive to xylazine. We find female mice are less sensitive to the motor-suppressing effects of xylazine contrary to the recent findings in rats reported by Khatri et al. (2023), potentially due to their use of repeated dosing of xylazine or species differences [27]. Using a modified version of our 3-day precipitated withdrawal model [40,41,46], we show xylazine is indeed responsive to naloxone, contrary to common assumptions made by both health professionals and in the media [7]. Both sexes exhibited some level of somatic withdrawal behaviors to xylazine and naloxone, though females showed sensitized behavioral responding. Indeed, females appear to be as sensitive, if not more sensitive to xylazine withdrawal than fentanyl withdrawal at tested doses, while males remain much more responsive to fentanyl withdrawal conditions. At the doses tested in our study, the effect of naloxone precipitated withdrawal on xylazine/fentanyl combination was synergistic as compared to each drug in isolation. This was especially apparent when examining increased bouts of paw tremors, which may represent a more passive coping behavior that we have previously observed is sexually dimorphic in opioid withdrawal [41]. In contrast, we did not observe similar findings when withdrawal was precipitated by atipamezole, an α2-AR antagonist used anesthesia reversal in veterinary medicine. These intriguing findings led us to consider the possibility of direct xylazine activity on opioid receptors. Previous studies have shown that xylazine is antinociceptive, results in a cross-tolerance to some mechanisms of opioid induced antinociception, and that these effects are naloxone-sensitive, but surprisingly not sensitive to the κOR selective antagonist nor-BNI [57–60]. Congruent with this data, we did not observe significant expression of withdrawal behavior to nor-BNI precipitated withdrawal, and pretreatment with nor-BNI exacerbated naloxone precipitated withdrawal in female mice. Until now, xylazine was thought to exert these effects through promotion of endogenous opioid release and xylazine has not been directly tested as a potential opioid agonist. We are the first to report definitive evidence that xylazine acts as a full agonist at κOR and is biased towards G-protein signaling pathways."

"As physicians, pharmacists, scientists, and specialists in poison information, we are experts in pharmacology, toxicology, and the management of opioid overdose and addiction. We applaud the effort to seek out new therapeutic strategies for the management of these patients.

"We are concerned that the use of a longer-acting reversal agent would not improve on current practice and could potentially cause harm. When withdrawal is precipitated by an opioid antagonist, there are few good management options. In most cases, the best strategy is to address and support the patient’s signs and symptoms until the effects of the antagonist wane. In the case of naloxone, which has a relatively short duration of action, severe withdrawal usually lasts less than an hour with symptoms typically persisting no more than 90 min [Citation25–27]. A longer-acting antagonist is anticipated to cause longer-lasting precipitated withdrawal and may lead to worse patient outcomes. Clinical experience with both naltrexone and nalmefene suggests prolonged withdrawal is a complication of longer-acting opioid antagonists [Citation28]. Although a longer-acting antagonist may be theoretically beneficial for the resuscitation of opioid-naive individuals in an opioid-induced mass casualty incident, this type of event has never been reported in North America and this application is unstudied.

"We are also concerned that patients who receive nalmefene may require longer periods of observation, by up to several hours, to observe for recrudescent effects as the antagonist effects wane. Patients who receive nalmefene will still need medical observation to ensure that respiratory depression does not recur after the effects of the medication subside. This will prolong emergency department visit length and challenge patient and clinician expectations, further burdening a taxed system. Further clinical study is needed to understand whether a reduction in repeat antagonist use justifies a longer length of stay or longer period of withdrawal.

"Finally, we are concerned that intranasal nalmefene has not been adequately studied for effectiveness in the actual setting and patient population: for patients with severe opioid intoxication in the out-of-hospital environment. Lack of proof of safety and efficacy in real-world use could result in significant harm if widely utilized.

"The potential benefits of nalmefene over naloxone (greater opioid receptor affinity, longer duration action) carry the risk of causing harm. These benefits, if present, should be demonstrated in the clinical environment, balanced with the risks, and compared to naloxone prior to the broad adoption of nalmefene."

"While the addition of stronger, longer-acting opioid overdose reversal agents expands the options available to combat the fatal opioid overdose crisis, their inception is perhaps without clinical grounds. Data supports continued practice without these stronger, longer acting nalmefene agents, and it is unclear whether any benefits nalmefene offers outweigh the apparent risks of its use. Nalmefene may yet find a clinical niche, but at this time, appears to be a solution designed to resolve hypothetical complications without fully understanding the unintended consequences of use. As such, without further evidence healthcare professionals should not support the use of stronger, longer-acting opioid overdose reversal agents. Further study is necessary, before nalmefene, or other naloxone alternatives should be incorporated into general practice."

"As shown above, the data supports that these stronger, longer-acting agents may be unnecessary, with other research suggesting their existence may also cause undue harm. Using a stronger or longer-acting antagonist as a one-size-fits-all approach may put patients at greater risk for experiencing more severe and/or prolonged withdrawal symptoms.(Bennett et al., 2020; Hill et al., 2022; Neale & Strang, 2015) Providers may find it difficult to manage withdrawal symptoms and comorbidities like chronic pain, forcing the patient to suffer until the reversal agent wears off. It is also notable to consider how patients who are naïve to nalmefene may react upon discharge following administration. These patients may attempt to self-manage withdrawal symptoms or cravings only to find higher opioid doses are required to overcome the nalmefene blockade, increasing their propensity to overdose as was observed when patients began adjusting to naloxone.(Neale & Strang, 2015) Alternatively, patients accustomed to opioid withdrawal symptoms subsiding within 1 to 2 h after naloxone administration may not be able to tolerate several hours of withdrawal, increasing both the likelihood of attempts to overcome the blockade and resistance to using reversal agents in the future.(Neale & Strang, 2015) Considering the average layperson likely does not fully grasp the potential harm of nalmefene, and that any opioid overdose education they may have received from an opioid overdose education & naloxone distribution (OEND) program would have been naloxone and harm reduction focused, adding these agents into the market creates opportunities for greater clinical complication. This lack of familiarity combined with the lack of clinical discretionary knowledge by the layperson who may be administering these medications in the field sets the stage for nalmefene exposure to elicit prolonged agitation and negative consequences.(Brenner et al., 2021) Furthermore, it is possible that nalmefene administration may complicate the initiation of medications for opioid use disorder such as buprenorphine/naloxone, which can be done in as little as three hours following the last opioid use when co-administered with naloxone.(Randall et al., 2023) Additionally, the FDA approved intranasal naloxone for over-the-counter use in March 2023. It is yet to be seen how this will affect its insurance coverage and medication access.(Harris, 2023b) This may especially affect vulnerable patient populations such as those with limited disposable income. Coverage for prescription nalmefene may serve some relief when naloxone is not covered or attainable by other means."

"Relevant literature on overdose response included 3 clinical guidelines,1,21,32 3 grey literature reports (a rapid review,36 an evidence brief37 and a report of a technical working group on resuscitation training38), and a pilot and feasibility study.39 The conclusions in these resources differ on overdose response, notably on the role of rescue breathing and the order in which resuscitation steps occur. An in-depth discussion of the literature is available in Appendix 1, and Appendix 3 contains more detail on findings and included studies.

"As the mandate of THN [Take Home Naloxone] programs includes overdose response training, our recommendation focuses on trained overdose response. Evidence from the Naloxone Guidance Development Group indicates that community overdose responders are effectively trained through different methods. For the purposes of this document, we recognize that people using THN programs may be trained on overdose response through their peers, using online resources, THN programs or cardiopulmonary resuscitation (CPR) training courses.

"In the literature, multiple sources identified naloxone administration and calling 911 or other emergency response numbers as critical steps in overdose response.1,21,32,36,38,39 Three guidance documents included verbal and physical stimulation to assess whether someone is experiencing overdose and to stimulate breathing.21,32,38

"For a responder trained in overdose response, guidance may differ according to whether the responder suspects respiratory depression or cardiac arrest. Overdose response must take the pathophysiology of opioid overdose into account. When someone experiences opioid overdose, regulation of breathing is impaired, respiration is depressed and insufficient oxygen reaches the brain and other organs.1 Because the person experiencing overdose is not breathing effectively, oxygen also cannot reach the heart and the individual may experience cardiac arrest (i.e., their heart stops beating or beats too ineffectively to support their vital organs).1"

"In 2021, due to the widespread availability of high-potency synthetic opioids like fentanyl, the US FDA approved two high-dose naloxone products, an 8 mg IN spray (Kloxxado) and a 5 mg IM injectable (Zimhi). The only studies reported in the FDA package inserts for both products are pharmacokinetic studies in healthy volunteers, which demonstrated substantially higher naloxone plasma levels than standard doses of naloxone (0.4 mg IM vs. 8 mg IN and 2 mg IM vs. 5 mg IM, respectively). In April 2024, based on a pharmacokinetic study of 30 healthy adult subjects, the FDA approved a 10 mg IN naloxone, Rezenopy. None of these approval trials was conducted among opioid overdose patients at risk for naloxone-precipitated withdrawal. In 2023, the FDA approved a 2.7 mg IN formulation of nalmefene (Opvee), a more potent and longer acting opioid antagonist than naloxone. The approval of nalmefene was also based on pharmacokinetic studies performed in healthy volunteers that showed higher plasma levels than standard naloxone doses and one pharmacodynamic study among opioid-experienced, but “non-depen­dent” participants which showed successful reversal of respiratory depression induced by laboratory administered remifentanil."

"Studies in two states in the US have found that there is no association between the introduction of fentanyl into the drug supply and naloxone dosing required to reverse opioid overdoses. This conclusion emerged from data collected over four years at a SSP in Pittsburgh, PA, that distributed primarily 0.4 mg IM naloxone to people who use drugs (Bell et al., 2019; Bell & Dasgupta, 2024). Although the proportion of opioid overdose deaths attributed to fentanyl grew from 3.5% in 2013 to 68.7% in 2016, the average number of doses of naloxone administered by SSP participants to reverse overdoses did not change significantly, 1.62 doses in 2013 and 1.52 doses in 2016. An additional study of the naloxone doses used in opioid reversals reported to this Pittsburgh SSP, from August 2005 to January 2023, found that from 2010 to 2023, the average dose per reversal was below two administered doses (Bell & Dasgupta, 2024). In Kentucky, Rock et al. evaluated emergency services personnel-administered intranasal-equivalent naloxone doses and observed a clinically insignificant increase from 4.5 mg to 4.7 mg over four years to reverse overdoses during which fentanyl became ubiqui­ tous in the drug supply (Rock et al., 2024). In both studies, the rate of successful overdose reversal was 99%.

"Administration of additional doses of naloxone or increasing the dose or half-life of a single product do not reverse an opioid overdose more quickly (Hill et al., 2022; Klebacher et al., 2017). In a 2018 literature review of naloxone dosing, administration, and timing, Lynn and Gal­ ankin conclude, “the interactions between the opioid agonist and the mu-opioid receptor may be the greatest determinant of the speed of recovery from the respiratory effects of many opioids, which may not markedly accelerate with increasing doses of naloxone, but rather respond to a minimum effective dose” (Rzasa Lynn & Galinkin, 2018)."

"Around the world, there is no evidence of the need or benefit of higher dose products, particularly from people to whom they would be administered (Saari et al., 2024). People who used opioids, in one qualitative study, preferred lower dose IN products (Neale et al., 2022). In 2024, the Michigan Drug User Health Alliance surveyed 108 people who use drugs about their reversal product preferences. Respondents overwhelmingly preferred standard-dose products to high dose or long-acting products (Michigan Drug User Health Alliance, 2024). Medical personnel also prefer to titrate naloxone dose based on the medical presentation of their patient (Tylleskar et al., 2020)."

"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."

"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."

"• 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."

"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."

"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"

"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."

"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."

"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."

"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."

"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"

"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."

"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."

"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."

"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)."

"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."