Interventions to increase naloxone access for undergraduate students: A systematic review of the literature

Abstract

Objective

To identify and describe interventions that increase access to naloxone for undergraduate students.

Methods

A systematic review across 4 databases identified interventions that expand access to naloxone at colleges in the United States from 2015–2023. Three reviewers extracted the following data to create a narrative synthesis and summary of program elements: setting, rationale for intervention, timeline, intervention components, study size, collaboration, sustainability, outcomes and results.

Results

Seven articles met inclusion criteria. Institutions’ implemented naloxone interventions due to concerns for student safety and/or student overdose fatalities. Three universities collaborated with their School of Pharmacy for program design and/or dissemination, while two partnered with state-based naloxone distribution programs. Most programs combined opioid-overdose/naloxone training; four distributed naloxone kits. Three studies included pre/post-outcomes, and all reported increases in participant knowledge, attitudes, and/or ability to respond to an overdose.

Conclusions

Our results indicates an opportunity for wide-scale implementation of undergraduate naloxone programs within US colleges. However, more rigorous implementation research is needed to identify barriers and facilitators to program feasibility, acceptability, and participation.

Introduction

Centers for Disease Control and Prevention (CDC) data indicate a 35% increase in opioid overdose deaths from April 2020 to 2021, which is largely attributed to increased presence of fentanyl in the illicit drug supply.¹ Deaths involving synthetic opioids, predominantly fentanyl, rose from approximately 58,000 in 2020 to 71,000 in 2021.² Two in three adults treated for opioid use disorder report first using opioids before the age of 25, underlining a meaningful opportunity for intervention during young adulthood.³ Among adolescents, fentanyl-involved fatalities nearly tripled from 2019 to 2021, with fentanyl identified in 77% of adolescent overdose deaths in 2021.⁴ This increase in overdose fatalities is in contrast to otherwise stable or decreased substance use during the COVID-19 pandemic in adolescent and young adult populations.^5,6 Overdose prevention measures tailored to the adolescent and young adult population are needed to help reduce overdoses and overdose deaths among this group.^7,8

Current estimates of lifetime prescription opioid misuse among college students range from 4% to 20%, while existing studies report that adolescents and young adults perceive low risk with opioid use.^9,10 Several recent reports highlight adolescent overdoses due to fentanyl in non-opioid drugs, such as methamphetamine, cocaine, and counterfeit pills.^4,11 Emerging evidence indicates that counterfeit pills are increasingly being sold via social media and were present in nearly one quarter of adolescent overdose deaths from 2019 to 2020.^12–14 As 97% of young adults with internet access reportedly use social media, this exposes a much broader range of this age group - beyond those who knowingly use opioids.¹⁵ This may be particularly problematic in higher education settings, where rates of stimulant and other drug use are relatively high.^16,17 Public health stakeholders continue to urge widespread provision of harm reduction measures, such as naloxone – a highly effective opioid overdose reversal agent.

One approach to address opioid overdose is expanded access to naloxone, often through naloxone access laws, standing orders, or co-prescribing policies – and currently all 50 states have a version of at least one of these policies. Widespread distribution of naloxone is an evidence-based harm reduction strategy as it is safe, easy to use, and effective in the hands of laypersons, who are typically well positioned to respond to an opioid-overdose event.^18–20 Programs and policies to improve access to naloxone, including community-level overdose education and nasal naloxone distribution programs and pharmacy standing orders have been associated with decreased overdose rates in community settings.^21,22 Despite effectiveness of naloxone interventions in the general population, naloxone is not widely available to adolescents and young adults, presenting a missed opportunity from a public health perspective. More work is needed to understand how naloxone access interventions can best reach adolescents and young adults in higher education^8,23Barriers to access may include stigma surrounding opioid use among adolescents, low levels of naloxone knowledge, pharmacist and pharmacy staff characteristics such as poor familiarity with naloxone policies and standing orders.^8,23–25 Evidence suggests that pharmacy staff may specifically limit access to minors for medications related to risk behaviors, specifically naloxone.^23,26 Additionally, while naloxone was approved for over-the-counter use in March 2023, low awareness, stigma, and cost may pose barriers to its use within this population.^27,28

With more than 16 million adolescents and young adults enrolled in United States (U.S.) higher education, undergraduate institutions provide access to a large population vulnerable to opioid misuse and therefore represent an important setting to address opioid use and prevent overdose. Within higher education, programs for suicide prevention and bystander sexual assault training are well described in the literature, and often leverage peers as key interventionists.^29–31 Further, programs which distribute reproductive and sexual health products at the campus community level have been shown to increase their use.^32–34 Further, substance use prevention programs are widely utilized on campuses for this population, but typically focus on alcohol, marijuana, and nicotine use.^35–42

Though a growing number of colleges have implemented campus-level interventions aimed at preventing opioid-overdose fatalities in their student population, the scope and characteristics of these interventions are not well described in the literature.⁴³ During this era of synthetic opioids and increased overdose fatalities, particularly among adolescents and young adults, undergraduate institutions may look to expand naloxone access for their students through overdose education initiatives or similar programs. The purpose of this systematic review is to describe existing interventions that increase naloxone access for undergraduate students and to assess the degree to which these programs are evidence-based. The results of this review can guide future decision making for the implementation of programs to reduce opioid-overdose fatalities at undergraduate institutions.

Materials and Methods

Search and retrieval

The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist for reporting was used for this study.⁴⁴ A combination of the following key terms were searched within PubMed, PsychInfo, EMBASE, and CINAHL: Naloxone or Narcan and students, or university, or college, or higher education. Articles published between 1/1/2015–2/1/2023 were included to reflect the most current prevention and harm reduction approaches for college student populations in the illicit fentanyl era.⁴⁵

Eligibility criteria

Studies were included in the systematic review if they met the following eligibility criteria:

1. The study described interventions that expand naloxone access for undergraduate students in the United States. As our intent was to review interventions for a lay college student audience, articles that described initiatives among students in dedicated medical programs, including pharmacy, nursing, and medical schools, were excluded.

2. The study was published in English.

3. The study used a primary or secondary dataset (literature reviews or meta-analyses were excluded).

Data extraction

Three independent reviewers (CEF, NM, BEB) screened articles for inclusion and extracted data about the naloxone access interventions described in each study. The data extracted from these articles include the following elements: setting, rationale for intervention, timeline, intervention components, study size, collaboration, sustainability, outcomes and results. Setting includes self-identified location of the intervention and approximate undergraduate enrollment. Rationale was defined as the reason the authors and/or affiliated institution created an intervention. Timeline refers to the study time period. Components refer to the combination of components that comprise each intervention as well as the study type (observational, descriptive, experimental). Study size refers to sample size of each included intervention. Collaboration denoted if multiple departments or groups were included in planning the intervention, as it is important to understand which types of expertise and perspectives are involved in the intervention. Sustainability included any outcomes or components to facilitate the intervention beyond the study time period.

Data for each of the extraction categories were gathered independently and three reviewers (CEF, NM, BEB) collaborated to synthesize findings. Risk of bias assessment using the modified Downs and Black checklist for assessment of methodological quality was included for all eligible studies.⁴⁶ As some questions are not relevant for uncontrolled studies, the maximum score was 20 points. Previous publications classified studies using the following score ranges: excellent (26–28), good (20–25), fair 15–19), and poor (≤14) quality.^47,48

Given the small number of included programs and the heterogeneity of program designs and outcome measures from studies meeting inclusion criteria, this review did not attempt quantitative synthesis or to calculate summary measures. We instead provide a narrative synthesis and summary of program elements, divided into three sections: intervention characteristics (study type, collaboration, study size, components, sustainability), evaluation (outcomes, results), and context (setting, time period, rationale).

Results

We identified and screened 235 unique articles from the four bibliographic databases (Figure 1). After abstract and full-text reviews by three independent researchers, seven articles met inclusion criteria.^49–55 Risk of bias assessment revealed that three studies were classified as fair quality (Panther 2017, Musco 2021, Doughty 2022), while four were classified as poor quality (Jeffrey 2017, Hill 2020, Dworkis 2022, Brown 2023).

Figure 1:

PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only

Intervention Characteristics

Of the seven included studies, three were descriptive, three were experimental, and one was observational. Of the descriptive studies, two were case reports^52,53, while one described planning for a naloxone access intervention.⁵¹ All three experimental studies utilized a pre/post survey design to assess the effect of the intervention on participants.^50,54,55 The observational study described intervention participation and uptake within their institution.⁴⁹

The most common approach (n=5) was to combine opioid-overdose education and hands-on naloxone training to undergraduate students in a single session, ranging from 30 minutes to 1 hour. Four of these interventions provided take-home naloxone kits for participants. Two institutions made naloxone available to students through a campus pharmacy standing order, which allows students to obtain naloxone without a prescription. Five studies included a peer-led component, three of which used student pharmacists to train undergrads, while two utilized students when designing the intervention. Complete results for intervention characteristics are reported in Table 1, and descriptions of each intervention are included in the Evaluation section below.

Table 1:

Characteristics of Interventions to Increase Naloxone Access for Undergraduates

Reference	Study Type	Risk of Bias	Collaboration	Study Size		Components			Outcomes	Sustainability
				Baseline	Follow-up	Peer-led	Hands-on training	Receive naloxone kit
Jeffery (2017)	Descriptive Case Report	Poor	X	-	-	✓	✓	X	-	-
Hill (2020)	Descriptive Case Report	Poor	-Wellness Network Committee on Substance Safety and Overdose Prevention -Texas Overdose Naloxone Initiative -College of Pharmacy -School of Social Work -University Police	-	-	✓	✓	✓	1. # students that use campus pharmacy standing order 2. # intranasal naloxone kits used in dorms 3. # intranasal naloxone kits used by campus police officers 4. # successful overdose reversals by students attending training session	1. # of unused naloxone kits make replacing them annually not cost effective
Panther (2017)	Experimental Pre/post survey	Fair	School of Pharmacy	150	74	✓	✓	✓	Anonymous pre/post training survey 1. Pre-survey assessing knowledge and perceptions of OUD and overdose 2. Post-survey assessing student perceptions of usefulness and quality of training method	-
Musco (2021)	Experimental Pre/post survey	Fair	School of Pharmacy	92	-	X	X	X	Anonymous pre/post electronic survey on knowledge of overdose signs, response to overdose, perceptions of campus culture	-
Dworkis (2022)	Descriptive Intervention planning	Poor	X	-	-	X	X	X	1. # BLPs on the campus 2. Average access distances to BLP locations 3. Loss/diversion of naloxone kits	1. Naloxone kits exposed to elements may affect shelf life 2. Costs and maintenance needs over time (e.g, expired kits)
Doughty (2022)	Experimental Pre/post survey	Fair	Program designed in collaboration with study, university, and community stakeholders	105	72 immediate post-test; 55 at 3-month follow up	✓	✓	✓	Pre/post surveys: 1. Opioid Overdose Knowledge Scale (OOKS) 2. Opioid Overdose Attitudes Scale (OOAS)	1. Repeated trainings may be necessary to reinforce knowledge
Brown (2023)	Observational Intervention participation	Poor	-School of Pharmacy -USC Student Health -California Department of Healthcare Services Naloxone Distribution Project	300	-	✓	✓	✓	1. Kit requests and pick ups 2. # watch educational video 3. # receiving in-depth training 4. # receiving overdose education	1. Optimal allocation of kits 2. Plans to expand into communities surrounding USC campus

Evaluation

Six studies reported outcomes for their interventions, three providing descriptive results and three employing a pre/post-test design (Table 1). One study described a protocol for training student EMS providers but did not include results. All studies that used a pre/post-test design included a survey assessing knowledge, attitudes, and/or ability to respond to opioid-overdose scenarios before and after the training sessions. One study conducted an additional follow-up with participants 3 months after the intervention.

Descriptive

Jeffery et al (2017) described the implementation of an expanded scope of practice for student EMS providers to administer naloxone on Georgetown University’s campus. Annual training on naloxone administration was provided at the beginning of the academic year through lectures, hands-on practice, and overdose simulation scenarios. A standardized protocol was provided, including an initial dose of 2 mg of naloxone intranasally, followed by a second 2 mg dose if no improvement was shown 5 minutes after the first dose. Student EMS providers were also taught to be vigilant of risks to the patient’s airway, breathing, and circulation before intranasal administration of naloxone. No results were provided in this study.

Hill et al (2020) implemented a multi-component, collaborative model for opioid overdose prevention at their institution, and reported the number of students that used the campus pharmacy standing order, number of naloxone kits used in dorms, number of naloxone kits used by campus police officers, and the number of successful overdose reversals by students attending training sessions. The authors report that no students used the campus pharmacy standing order or the naloxone kits in dorms, and no naloxone kits were used by campus police officers during the study period. However, there were 3 successful overdose reversals by students attending training sessions, with 127 students trained and 52 doses of naloxone distributed.

Dworkis et al (2022) used a geospatial analysis to explore placing naloxone kits at blue-light phones (BLPs), or call boxes topped with a light, on campus. They report the number of BLPs, average access distances to BLP locations, and the effect that loss/diversion of naloxone kits would have on student access. The authors find that with 91 BLPs across 0.65 km² of campus, 91.5% of the campus would have access to a BLP within 100 meters (100% within 200 meters), with a median campus access of 73% when accounting for possible loss or diversion at over half of the BLPs.

Observational

Brown et al (2023) describe a naloxone distribution program initiated by School of Pharmacy students, specifically referencing the model detailed by Hill et al (2020) as a guiding framework. Students could register to receive naloxone training from a 10-minute educational video and pass a subsequent quiz or attend an in-depth naloxone training workshop lasting 1 hour. Students completing the video or in-depth workshop could register to pick up a kit containing 1 box of Narcan (brand name for naloxone) nasal spray and 5 fentanyl test strips (to self-test drugs for fentanyl) from two locations on the University of Southern California (USC) campus. Naloxone kits were acquired from the California Department of HealthCare Services (CDHS) Naloxone Distribution Project free of charge. Between April 2021 and June 2022, the program (NaloxoneSC) received 327 requests for naloxone kits and estimated around 600 USC students received opioid education (327 with the 10-minute video and 290 with the in-depth training). When less than 30 kits remain or are due to expire, a follow-up application to CHDS is made for additional kits to ensure program continuity. Lastly, the authors describe the next phase of NaloxoneSC will be to expand their harm reduction kit distribution beyond the USC campus and into the surrounding communities.

Experimental

Panther et al (2017) employed a drug overdose simulation and fake crime scene to recruit interested students, administer a pre-survey assessing knowledge and perceptions of opioid use disorder and overdose, and invite them to a 1-hour training program. A post-survey assessing student perceptions of usefulness and quality of the training was given to all who completed the program. The authors report that all students viewed the training positively and at an appropriate level of difficulty, 99% found the information useful, and 97% of participants felt confident in their ability to respond to an opioid overdose situation after receiving training.

Musco et al (2021) designed an educational program for undergraduate students participating in a Greek life leadership summit and used an anonymous survey (distributed pre- and post-educational session) modeled after the Core Institute Alcohol and Drug Survey, which included questions on knowledge of substances, signs of overdose, ability to respond to an overdose, and perceptions of campus culture. The authors found higher scores in knowledge-based questions and in the confidence in participants’ ability to respond to an overdose after taking the program. They also report no changes in student perceptions of campus culture: at both time points, students felt that their campus culture encourages helping others and supports health-related issues.

Doughty et al (2022) conducted a 30-minute naloxone training program and used two validated instruments - the Opioid Overdose Knowledge Scale (OOKS) and Opioid Overdose Attitudes Scale (OOAS) - at baseline, immediate follow-up, and 3 months follow-up.⁵⁶ The authors report statistically significant improvement in OOKS and OOAS scores from baseline to follow-up at all timepoints, with the OOAS remaining higher at 3 months follow-up. After participating in the training, 87% of participants discussed naloxone with (n=240) or trained (n=52) another contact.

Context

The context surrounding implementation of the seven identified interventions, including institution characteristics, rationale for intervention, and timeline, are described below and in Table 2.

Table 2:

Context of Interventions to Increase Naloxone Access to Undergraduate Students

Reference	Setting	Undergraduate Enrollment	Time Period	Rationale
				US opioid crisis	Opioid use in college setting	Student OD deaths	Naloxone programs at peer institution
Jeffery (2017)	Georgetown University	7,598	-	✓	✓
Hill (2020)	The University of Texas at Austin	40,916	5/2016–7/2018		✓	✓
Panther (2017)	Washington State University	24,278	Fall 2014		✓		✓
Musco (2021)	Moderately-sized private liberal arts undergraduate college campus in southeastern US	~5,000–15,000	2019	✓	✓
Dworkis (2022)	Major university campus in Los Angeles, CA	~15,000	-		✓
Doughty (2022)	Medium-sized university campus in New York	~5,000–15,000	8/2019–9/2019	✓
Brown (2023)	University of Southern California	21,000	4/2021–6/2022		✓	✓

Setting

Of the seven included studies, all were conducted at a single institution. Four self-identified their institution by name (Georgetown University, The University of Texas at Austin, Washington State University, University of Southern California) while three used regional and size descriptors (major university campus in Los Angeles, CA; medium-sized university campus in New York; medium-sized private liberal arts undergraduate college campus in southeastern US). Undergraduate student enrollment of the included institutions ranged from approximately 5,000 to 41,000 students.

Rationale for Intervention

Six of the seven studies cited general opioid misuse at undergraduate institutions in the US as the reason for program implementation, with three studies specifically referencing opioid overdose fatalities within college student populations. Only one study sought to understand the magnitude and endurance of changes in students’ knowledge and attitudes after participating in a naloxone training program.

Timeline

Five studies included the timeline of their intervention, ranging from two months to two years.

Discussion

Our systematic review identified seven studies detailing opioid education and naloxone access programs for undergraduate students in the United States. First, all reviewed programs aimed to increase access, knowledge, or use of naloxone - an evidence-based intervention and the only mechanism through which to reverse an opioid overdose.^57,58 These studies were conducted across a range of geographic settings with varying institution sizes. While intervention content varied, the majority combined overdose education and hands-on naloxone training, and were delivered directly to lay undergraduate students. Other approaches included using student pharmacists from an affiliated school of pharmacy to train undergraduate students in administering naloxone, changing institution policy to allow student EMS providers to administer naloxone, or more broadly increase naloxone access through campus pharmacy standing orders, placement in residence halls, and mapping potential placement of naloxone at blue light phones on campus. The majority of these interventions endorsed collaborative approaches by including students from affiliated schools/graduate programs, community leaders, or members of student organizations. All three studies that evaluated outcomes using a pre/post-test design reported improvements in post-test survey scores for knowledge, attitudes, and/or ability to respond to opioid overdose scenarios.

Five studies included a peer-led component, most commonly using student pharmacists to train undergraduates (n=3) or directly involving students in program design/creation (n=3). College student peers are uniquely positioned to respond during a peer overdose event. A 2015 study of college-age young adults reported that one-third of respondents knew someone who experienced an opioid overdose, but more than one third would not know what to do during an overdose event.⁵⁹ From 2019–2021, two-thirds of opioid-overdose fatalities among adolescents had one or more bystanders present, but no bystander response in nearly 70% of those overdose deaths.¹⁴ This demonstrates that naloxone education within this population can be an important avenue to reversing overdoses, and campus-based opioid education and naloxone access programs may leverage the role of college peers as informed bystanders poised to intervene. Data from substance use education literature, as well as from harm reduction programs involving other substances (e.g., alcohol) suggest that peer-led interventions may be more effective in translating knowledge and fostering interest and involvement among youth than education programs delivered directly by professionals.^60,61

All but one program reviewed lacked integration of different harm reduction methods or approaches. As per our search criteria, the primary harm reduction strategy in each of the reviewed interventions was to increase use of, or access to, naloxone among undergraduate students. Other harm reduction strategies may include distributing tools such as fentanyl test strips, education about drug use practices that reduce harm (e.g., using drugs with others), or education about substance use treatment opportunities for students who use drugs.⁶² While such strategies may be implemented separately, utilizing a combination of harm reduction strategies may improve program reach or likelihood of success. While naloxone is effective for reversing opioid-related overdose, prior research indicates that people who experience non-fatal overdoses which are reversed by naloxone have high mortality rates in the following year.⁶³ As non-fatal overdoses are a strong predictor for subsequent fatal overdose, collegiate programs should consider nesting multi-pronged harm reduction approaches within naloxone-focused programs to ensure students have access to a range of options.⁶⁴

There remain several gaps in the peer-reviewed literature for undergraduate opioid education and naloxone access programs. Notably, we only identified seven studies that met inclusion criteria that have been published since 2015, highlighting a lack of recent research in this area – despite sharp increases in opioid-overdose fatalities due to fentanyl.⁶⁵ Under half include comparative pre/post outcomes, and in the studies that did have pre/post comparisons, outcomes were focused on knowledge and attitudes since follow-up periods of these studies were relatively short. Thus, studies were unable to meaningfully capture change in on-the-ground use of naloxone and intervention impact on non-fatal or fatal overdose frequency. Further, while these interventions are novel and seek to prevent opioid-overdose fatalities among their student populations, the lack of rigor in study design reveals a critical gap to be filled by future research. In addition to study design, future studies could be improved by incorporating implementation science frameworks to understand constructs such as barriers and facilitators to feasibility, acceptability, participation, and cost of programs on campuses.⁶⁶ The impact of studies reviewed in this analysis would be improved if they reported barriers and facilitators to participation in the programs on campuses. For example, one implementation study investigated the barriers and facilitators to planning and implementing naloxone training on college campuses; such methods could be applied to program evaluation.⁶⁷ None of the included studies described the proportion of students on campus who were involved or impacted by the program, or the reasons why students did or did not participate.

Limitations

Our systematic review has some limitations. First, because there were only seven included studies, each implemented at a single location with small sample sizes relative to the general student population (N=92 to 150), generalizability of the programs are limited. Second, as described above, we were unable to evaluate effectiveness of interventions for reducing overdose risk among students due to observational study designs. However, the primary purpose of our review was not to assess the effectiveness of interventions but rather to provide insight into what interventions exist and their structures and components, as well as highlight gaps and areas where future research is needed. We only included peer-reviewed published studies, but there may be unpublished or non-peer reviewed intervention or program descriptions on institution websites.

Conclusions

As the opioid crisis continues, and the presence of illicit fentanyl persists, overdose education and harm reduction interventions tailored for undergraduate students will be an increasingly important prevention strategy. In this review we have described the components of seven existing interventions. We highlight potential strengths, including increased naloxone availability and knowledge among lay students, peer-led structures, and collaborations between students and partners of varying expertise – including pharmacists, public health professionals, and clinicians. We also recognize an unmet opportunity for programs to implement various types of harm reduction strategies beyond naloxone. We identified gaps in the literature and call for more rigorous study designs and implementation research to identify barriers and facilitators to program feasibility, acceptability, and participation.