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. Author manuscript; available in PMC: 2024 May 1.
Published in final edited form as: J Subst Use Addict Treat. 2023 Mar 13;148:209005. doi: 10.1016/j.josat.2023.209005

INTEREST IN USING BUPRENORPHINE-NALOXONE AMONG A PROSPECTIVE COHORT OF STREET-INVOLVED YOUNG PEOPLE IN VANCOUVER, CANADA

Andreas Pilarinos a,b, Brittany Bingham c,d, Yandi Kwa c, Ronald Joe c, Cameron Grant a, Danya Fast a,d, Jane A Buxton e, Kora DeBeck a,f
PMCID: PMC10773610  NIHMSID: NIHMS1951772  PMID: 36921770

Abstract

Introduction

Limited research examines buprenorphine-naloxone interest among adolescents and young adults (AYA). This longitudinal study examined factors associated with initial buprenorphine-naloxone interest and the time to a positive change in buprenorphine-naloxone interest or enrollment, in addition to identifying reasons for buprenorphine-naloxone disinterest.

Methods

The study derived data from a cohort of street-involved AYA in Vancouver, Canada between December 2014 and June 2018. The analysis was restricted to AYA who reported weekly or daily illicit opioid use in the last six months but had not initiated buprenorphine-naloxone. The study examined factors associated with initial buprenorphine-naloxone interest using multivariable logistic regression, while multivariable Cox regression identified factors associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment over follow-up among AYA initially disinterested in buprenorphine-naloxone.

Results

Of 281 participants who reported weekly illicit opioid use but were not on buprenorphine-naloxone, 52 (18.5 %) AYA reported initial buprenorphine-naloxone interest, while 68 (24.2 %) AYA who were initially disinterested in buprenorphine-naloxone reported interest or enrollment over follow-up. In multivariable logistic regression, initial interest was positively associated with older age (Adjusted Odds Ratio [AOR] = 1.09, 95 % Confidence Interval [CI]: 1.03–1.15), but negatively associated with self-reported Indigenous identity (AOR = 0.22, 95 % CI: 0.07–0.68). In multivariable Cox regression, recent detoxification program access (Adjusted Hazard Ratio [AHR] = 0.85, 95 % CI: 0.73–0.98) was positively associated with the time to a positive change in buprenorphine-naloxone interest or enrollment. Common reasons for buprenorphine-naloxone disinterest included not wanting opioid agonist treatments (OAT) (initial n = 67, follow-up n = 105); not wanting to experience precipitated withdrawal (initial n = 42, follow-up n = 54), being satisfied with or preferring other OAT (initial n = 33, follow-up n = 52), not knowing what buprenorphine-naloxone is (initial n = 27, follow-up n = 9), previous negative treatment experiences (initial n = 19, follow-up n = 20), and wanting to continue opioid use (initial n = 13, follow-up n = 9), among others.

Conclusions

We documented persistent disinterest in buprenorphine-naloxone among AYA, though participants’ reasons for disinterest provide insight into the potential benefits of expanding micro-dosing induction; ensuring treatment is culturally safe; and communicating changes in buprenorphine-naloxone programming to AYA. Nevertheless, a need remains to improve the continuum of harm reduction and treatment supports for AYA.

Keywords: Adolescents, Young adults, Buprenorphine-naloxone, Opioid use, Treatment interest, Cultural safety education, Micro-dosing induction

1. INTRODUCTION

In North America, overdose from toxic illicit drugs has become the leading unnatural, preventable cause of death (Ahmad et al., 2020; Donroe et al., 2018; Lee & Mannix, 2018). This is especially true in British Columbia, Canada, where the current study is situated. British Columbia has seen significant increases in drug toxicity deaths, making it one of the epicenters of North America’s toxic drug crisis (British Columbia Coroners Service, 2022). In response to the public health emergency, the government has made efforts to improve access to opioid agonist treatments (OAT),1 which are recognized as important tools to reducing illicit opioid use and toxic drug fatalities (British Columbia Centre on Substance Use, 2018; British Columbia Centre on Substance Use; British Columbia Ministry of Health, 2017; Subramaniam et al., 2011). Buprenorphine-naloxone—which is also referred to as Suboxone©—is recommended as a first line OAT option for adolescents and young adults (AYA) with moderate to severe opioid use disorder (OUD) (British Columbia Centre on Substance Use, 2018; Committee On Substance Use Prevention, 2016). However, despite efforts to encourage buprenorphine-naloxone initiation among AYA, no existing research has sought to investigate interest in buprenorphine-naloxone among AYA. This is concerning given recent evidence from Vancouver, Canada that many AYA do not envision OAT as part of their treatment journey (Giang et al., 2020).

To date, research has found that adolescents across North America are receiving partial opioid agonists, like buprenorphine-naloxone, at higher proportions than full opioid agonists, like methadone/Methadose™ maintenance treatment (MMT), when compared to older populations (Pilarinos, Bromberg, & Karamouzian, 2022a). This is also true in British Columbia, with recent evidence also demonstrating that AYA are being prescribed buprenorphine-naloxone at higher proportions than their adult counterparts (Krebs et al., 2021). This higher rate may be because all licensed physicians and nurse practitioners are able prescribe buprenorphine-naloxone for the treatment of OUD without requiring an exemption or additional training (British Columbia Centre on Substance Use, 2017); however, as a partial opioid agonist, initiating buprenorphine-naloxone may lead to withdrawal symptoms among those who are actively using opioids, and 12 to 48 h of abstinence from opioids is typically required prior to treatment induction (British Columbia Centre on Substance Use, 2017, British Columbia Centre on Substance Use, 2018; British Columbia Centre on Substance Use; British Columbia Ministry of Health, 2017; Maremmani & Gerra, 2010).

Despite this, buprenorphine-naloxone has an improved safety profile in comparison to MMT and take-home dosing is more likely to be permitted, providing more flexibility and independence (British Columbia Centre on Substance Use, 2018; British Columbia Centre on Substance Use; British Columbia Ministry of Health, 2017). This added flexibility is favorable to many AYA, who have previously reported the logistic challenges associated with attempting to access other OAT, such as MMT, which requires daily witnessed dispensation (Giang et al., 2020). This is evidenced from a study examining buprenorphine-naloxone interest among adults within the study setting, which found a significant association between previous MMT access and buprenorphine-naloxone interest, though overall interest in buprenorphine-naloxone was low (Weicker et al., 2019).

For this reason, this study sought to examine factors associated with an initial interest in using buprenorphine-naloxone among AYA. This also includes identifying factors associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment over study follow-up. By gauging AYA’s interest in using buprenorphine-naloxone, the intent of this analysis is to better characterize the potential reach of buprenorphine-naloxone, identify ways to improve the provision of buprenorphine-naloxone, and better engage AYA in treatment programming with the goal of enhancing the health and well-being of AYA who use opioids.

2. MATERIALS AND METHODS

2.1. Study sample

The study derived data from the At-Risk Youth Study, which is an open prospective cohort of street involved AYA who use drugs in Vancouver, Canada (Wood et al., 2006). Participants are recruited through street-based outreach and snowball sampling, and eligibility requirements include being between ages 14 and 26 at recruitment, reporting illegal drug use in the past 30 days (excluding cannabis), and providing informed consent. At intake, participants complete an interviewer-administered questionnaire. Following their baseline interview, participants are invited back for an interview at six-month follow-up intervals. Participants have access to nursing care and infectious disease testing and are reimbursed $40 CAD at each study visit. The University of British Columbia/Providence Health Care Research Ethics Board approved the study.

Participants who, for the first time, responded affirmatively or negatively to the question of “Would you like to go on Suboxone?” and who reported weekly or daily illicit opioid use in the last six months were included in the analysis of initial buprenorphine-naloxone interest, while we excluded participants who reported “not using opiates” or “already on buprenorphine-naloxone”. The study period was between December 2014 and June 2018, which is when the question regarding participants’ interest in using buprenorphine-naloxone was introduced on the study questionnaire.

Participants who initially indicated that they were disinterested in buprenorphine-naloxone were asked to select one or more reasons for their disinterest. These included: “Satisfied with Methadose™ program”; “Don’t want to go into withdrawal”; “Unable to find a doctor to prescribe Suboxone”; “Would like to, but cost is a barrier”; “Don’t know what Suboxone is”; “Need more information about Suboxone”; “Not interested in opioid maintenance program”; and “Other” (open-ended), which were categorized using thematic analysis. Additionally, participants who indicated that they were “Satisfied with Methadose™ program” or other OAT were retained in the analysis given that clinical guidelines recommend de-intensifying OAT programming by transitioning people to buprenorphine-naloxone (British Columbia Centre on Substance Use; British Columbia Ministry of Health, 2017). Participants who reported initial buprenorphine-naloxone disinterest, and who provided a subsequent study follow-up interview during the study period, were included in the secondary analysis of factors associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment in the last six months regardless of whether they reported ceasing illicit opioid use or not as they would still be eligible to receive, and potentially benefit from, buprenorphine-naloxone. This is particularly relevant in the context of an increasingly toxic drug supply, where AYA who recently ceased opioid use could still benefit from having access to buprenorphine-naloxone instead of having to source drugs from the illicit market.

2.2. Measures

Self-reported variables hypothesized to be associated with the outcomes of interest included: age (per year older); study follow-up period, defined as the time period when participants conducted a study follow-up interview (per additional six month period) and which are numbered according to the first ARYS follow-up questionnaire administered in 2005 (e.g., December 2014 refers to follow-up period #13); sex (female vs. male); self-reported Indigenous identity, defined as First Nations (Gadacz et al., 2022), Inuit (Freeman et al., 2020), or Métis peoples (Gaudry & Welch, 2019) (Indigenous vs. white); other self-reported racialized or ethnic identities, defined as an affirmative response to being Black, South Asian, Chinese, Other Asian, Latinx, and Middle Eastern, which were aggregated due to low counts and to protect participants’ privacy and confidentiality (Other vs. white); education level (>highschool vs. other); years of drug use (per year longer); ever any injection drug use (yes vs. no); non-fatal overdose, defined as an overdose or acute reaction following drug use (yes vs. no) (Brugal et al., 2002); recent daily illicit opioid use (yes vs. no), a combined variable that includes daily injection and non-injection heroin, fentanyl, or non-medical prescription opioid use (NMPOU); recent weekly heroin or fentanyl use (yes vs. no); recent weekly NMPOU, defined as acquiring prescription opioids and using them for reasons other than prescribed (yes vs. no); recent weekly cocaine use (yes vs. no); recent weekly crack cocaine use (yes vs. no); and recent weekly crystal methamphetamine use (yes vs. no). Other variables included: recent employment (yes vs. no), defined as legal self-employment, regular or temporary work; recent incarceration, defined as being in detention, prison or jail overnight or longer in the past six months (yes vs. no); recent homelessness, defined as sleeping on the street, having no fixed address, staying with friends or staying in a shelter or hostel (yes vs. no); recent difficulty accessing services, defined as needing health or social services but not being able to obtain them (yes vs. no); ever accessing MMT (yes vs. no); recent MMT access (yes vs. no); accessing a detoxification program (yes vs. no); accessing a recovery house, defined as a communal living environment that supports participants’ recovery goals (yes vs. no) (Government of British Columbia, 2020); accessing a substance use treatment center, defined as a short-term, intensive program that provides treatment and recovery supports (yes vs. no) (Government of British Columbia, 2020); accessing a counsellor (yes vs. no); accessing Narcotics Anonymous, Cocaine Anonymous, Alcoholics Anonymous, or Self-Management and Recovery Training (NA/CA/AA/SMART) (yes vs. no); accessing residential treatment, defined as longer-term, live-in treatment settings where medical or other treatment are provided (yes vs. no) (Hadland et al., 2009); accessing outpatient treatment, defined as accessing community health clinics that provide OAT (yes vs. no) (Prangnell et al., 2016); and drug court involvement (yes vs. no). The study lagged all substance use variables to the previous follow-up to address potential reverse causation, which has been used and described within the ARYS cohort previously (Feng et al., 2013; Hadland et al., 2012).

2.3. Statistical analysis

2.3.1. Baseline comparisons

The study compared baseline characteristics of participants who reported initial buprenorphine-naloxone interest to participants who were initially disinterested in using buprenorphine-naloxone. For this, we used Mann-Whitney U test to make comparisons for continuous variables and Pearson’s χ2 test to compare variables with binary outcomes. The study also collected reasons for initial buprenorphine-naloxone disinterest and disinterest over follow-up, and participants were able to provide multiple explanations for their disinterest. We tabulated reasons for buprenorphine-naloxone disinterest and categorized open-ended responses using thematic analysis.

2.3.2. Logistic regression

The study team employed multivariable logistic regression to identify factors associated with initial buprenorphine-naloxone interest. Covariates that were significant at p < 0.10 at the bivariate level were subsequently included in the full model, which we then subjected to a backward selection model building approach. This approach involved removing explanatory variables with the largest p-value, except for age, sex, and race or ethnicity variables that were forced into the final model, until we identified a reduced model with the lowest Akaike Information Criterion. This technique has previously been employed with ARYS (McAdam et al., 2022; Mittal et al., 2019). Last, we conducted a subanalysis whereby the study excluded participants who indicated they were currently on MMT or other OAT from the analytic sample.

2.3.3. Cox regression analysis

To identify factors associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment in buprenorphine-naloxone among participants who were initially disinterested, the study identified a multivariable Cox regression using a backward model building approach (Maldonado & Greenland, 1993; Rothman et al., 2008). We adjusted for variables that were found to be statistically significant between those who were excluded and included in this subanalysis in the multivariable Cox regression model, along with age, sex, and race or ethnicity variables. The reduced model was assessed using variance inflation factors, but the study observed no collinearity. Previous ARYS studies have used and described this approach (Feng et al., 2013; Hadland et al., 2012; Pilarinos, Fast, Nosova, Kwa, et al., 2022). Last, we conducted a subanalysis whereby the study excluded participants who indicated they were currently on MMT or other OAT from the analytic sample.

3. RESULTS

Between December 2014 and June 2018, a total of 685 participants completed at least one study questionnaire. Of these, 180 (26.3 %) participants reported not currently using opioids, 166 (24.2 %) participants reported less than weekly frequency of illicit opioid use, 42 (6.1 %) participants were missing data on the outcome variable, and 16 (2.3 %) participants were already on buprenorphine-naloxone and excluded from the analysis. Of the remaining 281 (41.0 %) participants, 52 (18.5 %) participants reported initial buprenorphine-naloxone interest and 229 (81.5 %) participants were initially disinterested, as outlined in Fig. 1. A total of 12 (4.3 %) participants were adolescents under age 19 years, and the characteristics of this sample, measured at their first study visit during the study period and stratified by initial interest in using buprenorphine-naloxone, are presented in Table 1. Additionally, reasons for initial buprenorphine-naloxone disinterest included not being interested in an OAT program (n = 67, 28.2 %), not wanting to go in withdrawal (n = 42, 17.6 %), being satisfied with or preferring other OAT programs (n = 33, 13.9 %), not knowing what buprenorphine-naloxone was (n = 27, 11.3 %), having a previous negative treatment experience (n = 19, 8.0 %), wanting to continue to use opioids (n = 13, 5.5 %), needing more information on buprenorphine-naloxone (n = 12, 5.0 %), preferring detoxification (n = 8, 3.4 %), mistrust in the health care system or medication (n = 6, 2.5 %), and the inconvenience of pills or daily medications (n = 6, 2.5 %), with additional reasons presented in Table 2.

Fig. 1.

Fig. 1.

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Flow-chart of disinterest in using buprenorphine-naloxone or enrolling in buprenorphine-naloxone among adolescents and young adults in Vancouver, Canada between December 2014 and June 2018.

Table 1.

Baseline characteristics of adolescents and young adults in Vancouver, Canada stratified by an interest in using buprenorphine-naloxone when first asked between December 2014 and June 2018 (n = 281).

Characteristic Total (%) (n = 281) Buprenorphine-naloxone interest p-Value
Yes (%) (n = 52) No (%) (n = 229)
Age (med, IQR) 24 (22–27) 24 (21–28) 24 (22–26) 0.4811
Study follow-up period (med, IQR) 20 (18–22) 20 (18–21) 20 (18–22) 0.4421
Years drug use (med, IQR) 8.8 (6–12) 8.9 (6–12) 8.8 (6–12) 0.6881
Sex (female) 92 (32.7) 20 (38.5) 72 (31.4) 0.331
Indigenous identity 73 (26.0) 10 (19.2) 63 (27.5) 0.103
Other race/ethnicitya 27 (9.6) 1 (1.9) 26 (11.4) 0.0482
Highschool education 125 (44.5) 20 (38.5) 105 (45.9) 0.322
Employment 109 (38.8) 19 (36.5) 90 (39.3) 0.712
Injection drug useb 224 (79.7) 40 (76.9) 184 (80.3) 0.580
Non-fatal overdoseb 99 (35.2) 18 (34.6) 81 (35.4) 0.918
Daily illicit opioid useb 195 (69.4) 41 (78.8) 154 (67.2) 0.105
Weekly heroin or fentanyl useb 273 (97.2) 51 (98.1) 222 (96.9) 0.660
Weekly NMPO useb, c 44 (15.7) 10 (19.2) 34 (14.8) 0.434
Weekly cocaine useb 31 (11.0) 4 (7.7) 27 (11.8) 0.398
Weekly crack useb 35 (12.5) 5 (9.6) 30 (13.1) 0.494
Weekly CM useb, d 187 (66.5) 35 (67.3) 152 (66.4) 0.898
Incarceration2 61 (21.7) 6 (11.5) 55 (24.0) 0.052
Homelessness2 173 (61.6) 26 (50.0) 147 (64.2) 0.050
Difficulty accessing servicesb 104 (37.0) 17 (32.7) 87 (38.0) 0.476
Ever MMTe 138 (49.1) 23 (44.2) 115 (50.2) 0.436
MMTb, e 95 (33.8) 17 (32.7) 78 (34.1) 0.851
Detoxificationb 57 (20.3) 13 (25.0) 44 (19.2) 0.350
Recovery houseb 22 (7.8) 4 (7.7) 18 (7.9) 0.8582
Treatment centreb 15 (5.3) 6 (11.5) 9 (3.9) 0.048
Counsellorb 33 (11.7) 9 (17.3) 24 (10.5) 0.172
NA/CA/AA/SMARWb, f 37 (13.2) 10 (19.2) 27 (11.8) 0.156
Outpatient treatmentb 2 (0.7) 0 (0) 2 (0.9) 0.9912
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a.

Other self-reported racialized or ethnic identities include Black, Latinx, Middle Eastern, South Asian, and ‘other’ Asian.

b.

Refers to activities in the last six months.

c.

Denotes non-medical prescription opioids.

d.

Denotes crystal methamphetamine.

e.

Denotes methadone maintenance treatment or Methadone™.

f.

Denotes narcotics anonymous, cocaine anonymous, alcoholics anonymous, and self-management and recovery training.

1.

p-Value is generated using Mann-Whitney U test.

2.

p-Value is generated using Fisher's Exact Test because of small cell count.

Table 2.

Reasons for an initial disinterest in using buprenorphine-naloxone at first response (n = 229, 238 observations), as well as disinterest over follow-up (n = 107, 272 observations), among a prospective cohort of street-involved adolescents and young adults in Vancouver, Canada between December 2014 and June 2018.

Reasons for not being interested in using buprenorphine-naloxone Initial (n, %) Follow-up (n, %)
Not interested in OAT program 67 (28.2) 105 (38.6)
Don't want to go into withdrawal 42 (17.6) 54 (19.9)
Satisfied with or prefer other OAT programa 33 (13.9) 52 (19.1)
Don't know what buprenorphine-naloxone is 27 (11.3) 9 (3.3)
Previous negative treatment experience 19 (8.0) 20 (7.4)
Would like to continue opioid use 13 (5.5) 9 (3.3)
Need more information about buprenorphine-naloxone 12 (5.0) 7 (2.6)
Prefer detoxification 8 (3.4) 5 (1.8)
Mistrust in healthcare system or medication 6 (2.5) 6 (2.2)
Inconvenience of pills or daily medications 4 (1.7) 2 (0.7)
Didn't work for peers or family 2 (0.8) 0 (0)
Not effective for pain management 2 (0.8) 1 (0.4)
Would like to, but cost is a barrier 2 (0.8) 2 (0.7)
Only addresses physical cravings 1 (0.4) 0 (0)
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a.

Other OAT includes methadone, injectable diacetylmorphine, hydromorphone, and morphine

Bivariate and multivariable logistic regression of factors associated with an initial buprenorphine-naloxone interest are presented in Table 3. Self-reported Indigenous identity (adjusted odds ratio [AOR] = 0.22, 95 % confidence interval [CI]: 0.07–0.68) was negatively associated with initial willingness to use buprenorphine-naloxone, while older age (AOR = 1.09, 95 % CI: 1.03–1.15) was positively associated after adjusting for female sex (AOR = 1.08, 95 % CI: 0.49–2.33), recent incarceration (AOR = 0.42, 95 % CI: 0.15–1.22), and recent treatment center access (AOR = 3.18, 95 % CI: 0.98–10.4). Additionally, a subanalysis that excluded participants who reported current MMT or other OAT enrollment (n = 109, 38.8 %) found that daily illicit opioid use (AOR = 4.46, 95 % CI: 1.34–14.9) was positively associated with initial buprenorphine-naloxone interest (results not shown).

Table 3.

Bivariate and multivariable logistic regression of factors associated with an initial interest in using buprenorphine-naloxone at first response among street-involved adolescents and young adults between December 2014 and June 2018 (n = 281).

Characteristic Unadjusted Adjusted
Odds ratio (95 % CI) p value Odds ratio (95 % CI) p value
Age (per year older) 1.03 (0.95–1.11) 0.481 1.09 (1.03–1.15) 0.005
Study follow-up period (per later period) 0.95 (0.82–1.09) 0.442
Years drug use (per year longer) 1.01 (0.95–1.08) 0.688
Sex (female vs. male) 1.37 (0.73–2.56) 0.331 1.08 (0.49–2.33) 0.865
Indigenous identity (Indigenous vs. other)a 0.53 (0.25–1.13) 0.103 0.22 (0.07–0.68) 0.008
Highschool education 0.73 (0.40–1.36) 0.322
Employmentb 0.89 (0.48–1.66) 0.712
Injection drug useb 0.82 (0.40–1.68) 0.580
Non-fatal overdoseb 0.97 (0.51–1.82) 0.918
Daily illicit opioid useb 1.82 (0.88–3.73) 0.105
Weekly heroin or fentanyl useb 1.61 (0.19–13.4) 0.660
Weekly NMPO useb, c 1.37 (0.63–2.98) 0.434
Weekly cocaine useb 0.62 (0.21–1.87) 0.398
Weekly crack useb 0.71 (0.26–1.92) 0.494
Weekly CM useb, d 1.04 (0.55–1.98) 0.898
Incarcerationb 0.41 (0.17–1.01) 0.052 0.42 (0.15–1.22) 0.111
Homelessnessb 0.54 (0.30–1.00) 0.050
Difficulty accessing servicesb 0.79 (0.42–1.50) 0.476
Ever MMTe 0.79 (0.43–1.44) 0.436
MMTb, e 0.94 (0.50–1.78) 0.851
Detoxificationb 1.40 (0.69–2.85) 0.350
Recovery houseb 0.90 (0.29–2.82) 0.858
Treatment centreb 3.03 (1.01–9.06) 0.048 3.18 (0.98–10.4) 0.055
Counsellorb 1.79 (0.78–4.11) 0.172
NA/CA/AA/SMARTb, f 1.78 (0.80–3.96) 0.156
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a.

Other includes white, and other self-reported racialized or ethnic identities, such as Black, Latinx, Middle Eastern, South Asian, and ‘other’ Asian, which were combined due to small cell count.

b.

Refers to activities in the last six months.

c.

Denotes non-medical prescription opioids.

d.

Denotes crystal methamphetamine.

e.

Denotes methadone maintenance treatment or Methadose™.

f.

Denotes narcotics anonymous, cocaine anonymous, alcoholics anonymous, and self-management and recovery training.

Among 229 participants initially disinterested in using buprenorphine-naloxone, 54 (23.6 %) participants were not seen over follow-up and we excluded them from the analysis. Participants who were lost-to-follow-up were older (p = 0.024) and more likely to be seen at a later study follow-up period (p < 0.001), and we adjusted for these variables in the multivariable Cox regression model. The remaining 175 (64.1 %) participants contributed 439 observations over a median study follow-up of two study visits (IQR = 1–4), and 5 (2.3 %) participants were adolescents under age 19 years. Of these, 68 (38.9 %) participants reported a positive change in buprenorphine-naloxone interest (n = 55, 31.4 %) or enrollment (n = 13, 7.4 %), accounting for 322.5 person-time risk years per person per year and an incidence rate of 0.29 (95 % CI: 0.24–0.34) per person. Reasons for buprenorphine-naloxone disinterest over follow-up included not being interested in an OAT program (n = 105, 38.6 %), not wanting to go into withdrawal (n = 54, 19.9 %), being satisfied with or preferring other OAT programs (n = 52, 19.1 %), not knowing what buprenorphine-naloxone was (n = 9, 3.3 %), having a previous negative treatment experience (n = 20, 7.4 %), wanting to continue to use opioids (n = 9, 3.3 %), needing more information on buprenorphine-naloxone (n = 7, 2.6 %), preferring detoxification (n = 5, 1.8 %), mistrust in the health care system or medication (n = 6, 2.2 %), and the inconvenience of pills or daily medications (n = 2, 0.7 %), with additional reasons presented in Table 2.

The results of the bivariate and multivariable Cox regression analysis of factors associated with time to a positive change in buprenorphine-naloxone disinterest or actual enrollment are presented in Table 4. In the multivariable model, recent detoxification program access (adjusted hazards ratio [AHR] = 1.98, 95 % CI: 1.04–3.77) was positively associated with time to a positive change in buprenorphine-naloxone interest or actual enrollment over follow-up after adjusting for older age (AHR = 1.00, 95 % CI: 0.94–1.07), later study follow-up period (AHR = 0.92, 95 % CI: 0.82–1.04), female sex (AHR = 0.78, 95 % CI: 0.46–1.32), self-reported Indigenous identity (AHR = 1.27, 95 % CI: 0.75–2.17), other self-reported racialized or ethnic identity (AHR = 0.68, 95 % CI: 0.31–1.50), and employment (AHR = 1.49, 95 % CI: 0.93–2.39). Additionally, a subanalysis that excluded participants who reported current MMT or other OAT enrollment over follow-up (n = 84, 48.0 %) found that recent employment (AHR = 3.52, 95 % CI: 1.37–9.03), recent homelessness (AHR = 3.12, 95 % CI: 1.26–7.76), recent crystal methamphetamine use (AHR = 2.53, 95 % CI: 1.08–5.93), and recent daily illicit opioid use (AHR = 2.33, 95 % CI: 1.04–5.21) were positively associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment over follow-up (results not shown).

Table 4.

Bivariate and multivariable Cox proportional hazard model of factors associated with time to a change in interest in using or actual buprenorphine-naloxone enrolment among street-involved adolescents and young adults who first reported that they were disinterested in using buprenorphine-naloxone between December 2014 and June 2018 (n = 175).

Characteristic Unadjusted Adjusted
Odds ratio (95 % CI) p value Odds ratio (95 % CI) p value
Age (per year older) 1.01 (0.96–1.07) 0.748 1.00 (0.94–1.07) 0.956
Study follow-up period (per later period) 0.90 (0.81–1.02) 0.091 0.92 (0.82–1.04) 0.199
Years drug use (per year longer) 0.99 (0.94–1.04) 0.666
Sex (female) 0.80 (0.49–1.32) 0.380 0.78 (0.46–1.32) 0.350
Indigenous identity (Indigenous vs. white) 1.13 (0.66–1.92) 0.662 1.27 (0.75–2.17) 0.375
Other race/ethnicity (other vs. white)a 0.76 (0.35–1.66) 0.485 0.68 (0.31–1.50) 0.346
Highschool education 1.45 (0.93–2.26) 0.102
Employment 1.59 (1.01–2.50) 0.043 1.49 (0.93–2.39) 0.095
Injection drug useb, c 1.23 (0.60–2.54) 0.568
Non-fatal overdosedb, c 1.27 (0.71–2.25) 0.423
Daily illicit opioid useb, c 0.99 (0.55–1.78) 0.975
Weekly heroin or fentanyl useb, c 1.33 (0.75–2.39) 0.332
Weekly NMPO useb, c, d 1.10 (0.52–2.35) 0.797
Weekly cocaine useb, c 0.38 (0.06–2.68) 0.334
Weekly crack useb, c 1.42 (0.62–3.27) 0.408
Weekly CM useb, c, e 1.50 (0.85–2.62) 0.159
Incarcerationb 0.81 (0.46–1.40) 0.441
Homelessnessb 1.45 (0.92–2.27) 0.107
Difficulty accessing servicesb 1.46 (0.89–2.41) 0.135
Ever MMTf 1.54 (0.92–2.58) 0.102
MMTb, f 1.22 (0.75–1.98) 0.417
Detoxificationb 1.79 (0.98–3.29) 0.060 1.98 (1.04–3.77) 0.037
Recovery houseb 1.96 (0.72–5.31) 0.187
Treatment centreb 1.66 (0.62–4.42) 0.314
Counsellorb 1.78 (0.87–3.64) 0.116
NA/CA/AA/SMARTb, g 1.24 (0.56–2.77) 0.599
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a.

Other racialized or ethnic identities include Black, Latinx, Middle Eastern, South Asian, and ‘other’ Asian.

b.

Refers to activities in the last six months.

c.

Refers to activities lagged to the previous, available follow-up.

d.

Denotes non-medical prescription opioid use.

e.

Denotes crystal methamphetamine.

f.

Denotes methadone maintenance treatment.

g.

Denotes narcotics anonymous, cocaine anonymous, alcoholics anonymous, and self-management and recovery training.

4. DISCUSSION

Overall, our findings indicate a low level of interest in using buprenorphine-naloxone among AYA despite evidence from the study setting that AYA receive partial opioid agonists, like buprenorphine-naloxone, at a higher proportion in comparison to adult populations (Krebs et al., 2021). Findings are, however, consistent with previously documented lower levels of engagement with OAT among AYA compared to older populations (Alinsky et al., 2020; Chavez et al., 2020; Feder et al., 2017; Hadland et al., 2018), which may be explained by AYAs’ satisfaction with MMT and other OAT identified in this study.

Although this study was conducted prior to the implementation of youth-specific clinical treatment guidelines in the study setting (British Columbia Centre on Substance Use, 2018), recent research among AYA in Vancouver, Canada, conducted during and after the implementation of these guidelines, indicates many AYA do not envision OAT as being part of their long-term treatment journey (Giang et al., 2020). Additionally, evidence suggests that perceived pressure and coercion to initiate buprenorphine-naloxone, as well as excluding AYA from treatment decision-making, can lead to treatment disengagement (Pilarinos, Kwa, Joe, Thulien, et al., 2022). Our finding of a positive association between older age and initial interest in buprenorphine-naloxone also suggests that this pressure may be particularly impactful on younger AYA, which emphasizes the importance of practicing patient-centered care with adolescents who use illicit substances (Pilarinos, Bromberg, & Karamouzian, 2022b). Given suggestions that buprenorphine-naloxone may be less effective in the context of high frequency use of potent opioid analogues (Bruneau et al., 2018), treatment programs should ensure AYA have access to a broad range of meaningful and purposeful harm reduction, health, social service, and treatment supports.

Our finding that Indigenous AYA were less likely to report an interest in using buprenorphine-naloxone is also concerning. Given recent findings of widespread anti-Indigenous racism within British Columbia’s health care systems, the lower interest in buprenorphine-naloxone may be attributed to discrimination or prejudice that Indigenous and other racialized or ethnic groups may experience when attempting to access health care (Goodman et al., 2017; Turpel-Lafond & Johnson, 2021). This assumption is further supported by participants’ reasons for being unwilling to use buprenorphine-naloxone, where 19 (8.0 %) initial responses and 20 (7.4 %) responses over follow-up included mention of a previous negative health care experience. To remedy this, research has made recommendations for the expansion of Indigenous cultural safety and anti-racism education programming throughout the health care system (Guerrero et al., 2018; Russell et al., 2019). This education programming can include addressing clinicians’ biases toward Indigenous peoples and other racialized or ethnic groups, as well as incorporating culturally based practices and traditional medicine within treatment settings and programs, which previous research among Indigenous AYA has indicated is an important treatment component (Russell et al., 2019).

Given the need to refrain from opioid use prior to buprenorphine-naloxone induction, fear of experiencing withdrawal symptoms (initial: n = 42, 17.6 %; follow-up: n = 54, 19.9 %) was another common reason for initial buprenorphine-naloxone disinterest. Buprenorphine-naloxone causes precipitated withdrawal if opioids were recently used (Ahmed et al., 2020) and so patients must remain abstinent from opioids for 12 to 48 h prior to initiating buprenorphine-naloxone (British Columbia Centre on Substance Use, 2017, British Columbia Centre on Substance Use, 2018; British Columbia Centre on Substance Use; British Columbia Ministry of Health, 2017; Maremmani & Gerra, 2010). This is an impactful treatment deterrent and so an alternative method to treatment induction—known as the Bernese method—has demonstrated promising results (Ahmed et al., 2020; Hämmig et al., 2016; Moe et al., 2020). One study provided evidence of its use in the study setting (Brar et al., 2020) and micro-dosing induction onto buprenorphine-naloxone is increasingly being used by physicians and nurse practitioners since the completion of this study. This approach involves gradually titrating patients onto buprenorphine-naloxone while patients continue to use prescribed or illicit opioids, in turn avoiding the need for detoxification prior to treatment initiation (Ahmed et al., 2020; Brar et al., 2020; Hämmig et al., 2016; Moe et al., 2020). Considering the number of AYA who reported experiencing withdrawal as a reason for being disinterested in using buprenorphine-naloxone, expanding access to this micro-dosing induction may be an effective approach to engage AYA who fear precipitated withdrawal.

Additionally, many participants reported that they did not know what buprenorphine-naloxone was (initial: n = 27, 11.3 %; follow-up: n = 9, 3.3 %), or that they required more information about buprenorphine-naloxone (initial: n = 12, 5.0 %; follow-up: n = 7, 2.6 %). Although the proportion of participants who reported not knowing what buprenorphine-naloxone was decreased over follow-up, findings point to potential gaps in communicating advances or improvements in treatment approaches to AYA who use opioids, such as the Bernese method, and the need for identifying novel and impactful ways to reach AYA. One evidence-based approach to improving awareness of advances in research and treatment is working with peers with lived and living experience of substance use to understand appropriate messaging and ways to effectively disseminate information through their respective networks (Hoffman et al., 2013; Mackesy-Amiti et al., 2013). To date, limited research examines the use of peer networks to disseminate information about improvements and advances in treatments, and so future research into how peer networks can be mobilized for knowledge dissemination may be beneficial.

Consistent with previous literature that some AYA want detoxification programs and do not consider OAT as part of their treatment journey (Giang et al., 2020), this analysis found that a small number of participants were disinterested in using buprenorphine-naloxone as they preferred detoxification (initial: n = 8, 3.4 %; follow-up: n = 5, 1.8 %). However, concerns exist that detoxification might increase the risk of harm arising from a reduced tolerance for illegal opioids upon discharge, which increases overdose risk (Chang et al., 2018; Strang et al., 2003). Nevertheless, our finding that attending a detoxification program was positively associated with buprenorphine-naloxone interest or enrollment over follow-up complements existing research suggesting that buprenorphine-naloxone should be made available to patients within detoxification settings (Friedmann & Suzuki, 2017), therefore decreasing the likelihood of relapse and overdose upon discharge. This approach has been employed within the study setting and has demonstrated positive results (Danilewitz & McLean, 2020).

Our finding of a positive association between recent crystal methamphetamine use and buprenorphine-naloxone interest or actual enrollment over follow-up among participants who were not currently enrolled on MMT or other OAT suggests that buprenorphine-naloxone may be favorable to AYA who report polysubstance use. Given that recent research from Vancouver, Canada, has demonstrated that crystal methamphetamine use is positively associated with the time to MMT discontinuation (Pilarinos, Kwa, Joe, Dong, et al., 2022), the positive association between crystal methamphetamine use and buprenorphine-naloxone interest or enrollment we observed among AYA who were not currently on MMT or other OAT may be attributable to the added flexibility of take-home dosing permitted with buprenorphine-naloxone in comparison to MMT or other OAT (British Columbia Centre on Substance Use, 2018). This flexibility may also explain the positive association between recent homelessness and the time to a positive change in buprenorphine-naloxone interest or enrollment, where recent qualitative research has found that the daily witnessed dispensation required for MMT or other OAT make it difficult for AYA to remain on MMT or other OAT while also navigating poverty, homelessness, and the broader risk environment (Pilarinos, Kwa, Joe, Thulien, et al., 2022). Nevertheless, recent evidence has found high rates of crystal methamphetamine initiation and re-initiation among adults receiving OAT (Cui et al., 2022), which highlights the potential benefits of co-prescribing stimulants alongside OAT, as well as providing ready access to stable and safe housing, to simultaneously support reductions in illicit opioid and crystal methamphetamine use.

Lastly, the positive relationship between recent employment and the time to a positive change in buprenorphine-naloxone interest or actual enrollment over follow-up suggests that buprenorphine-naloxone may be more favorable for AYA who have secured employment. Buprenorphine-naloxone has an improved safety profile and take-home dosing is permitted, which may be more favorable to AYA who prefer greater flexibility in their treatment programming (Kenney et al., 2018; Mendelson & Jones, 2003; Yokell et al., 2011). Hence, while buprenorphine-naloxone is listed as a first line treatment and MMT as a second line treatment within the study setting (British Columbia Centre on Substance Use, 2018), based on our current study findings, the option of buprenorphine-naloxone should not be overlooked for AYA who are currently on or previously attempted MMT (Chung et al., 2019; Rosado et al., 2007). Conversely, several participants reported disinterest in buprenorphine-naloxone due to being satisfied with or preferring other OAT (initial: n = 33, 13.9 %; follow-up: n = 52, 19.1 %), highlighting the importance of ensuring that AYA who are stabilized on OAT are not transitioned off or onto buprenorphine-naloxone without their consultation and consent. Instead, providing greater flexibility around the prescription of other OAT, such as through take-home dosing, may support AYA in maintaining employment while reducing illicit opioid use (Pilarinos, Kwa, Joe, Thulien, et al., 2022).

Research has noted and previously described several limitations to the ARYS study, including the generalizability of findings, unmeasured confounding, and recall and social desirability bias (Cheng et al., 2018; DeBeck et al., 2016; Pilarinos et al., 2020). Additionally, changes to the illicit drug supply since the completion of this study also limit the generalizability of the study findings, where the increasing presence of opioid analogues and benzodiazepines have challenged response efforts to the toxic drug crisis and treatment effectiveness (Silverstein et al., 2019); hence, future research into the use of buprenorphine-naloxone in the context of an increasingly toxic and changing drug supply would be valuable. The study period for this analysis preceded the introduction of clinical treatment guidelines for OUD among AYA (British Columbia Centre on Substance Use, 2018), which limits our ability to assess the impact of these guidelines on buprenorphine-naloxone. Nonetheless, qualitative research from the study setting has sought to understand how AYA navigate OAT in the context of these clinical guidelines and provides some insight into how these guidelines influenced AYAs’ experiences and perspectives on buprenorphine-naloxone and other OAT (Fast, 2021; Giang et al., 2020; Pilarinos, Kwa, Joe, Thulien, et al., 2022). Adding to this, while existing guidelines suggest that transitioning to buprenorphine-naloxone may beneficial for those who are stable on OAT due to the added flexibility (British Columbia Centre on Substance Use; British Columbia Ministry of Health, 2017), we were unable to measure participants’ suitability to transition to buprenorphine-naloxone and future research examining suitability to transition from other OAT to buprenorphine-naloxone would be beneficial. Another limitation is that a small proportion of the analytic sample included adolescents under age 19 years, and so future research that is specific to adolescents is needed. Additionally, the study instrument did not collect information on participants’ gender, and so we were unable to account for this in the analysis. Lastly, although substance use–related variables were lagged to the previously available follow-up, treatment-related and other variables were not lagged, and the study could not infer a temporal relationship.

5. CONCLUSION

The low levels of buprenorphine-naloxone interest observed in this study suggest that many AYA are not interested in buprenorphine-naloxone treatment, although participants’ reasons for being disinterested in buprenorphine-naloxone provide insight into ways to improve treatment willingness. Nevertheless, the high risk of mortality for AYA who use drugs in the study setting emphasize the importance of providing AYA with access to a continuum of culturally safe harm reduction, treatment, health, and social supports and services, and understanding ways to reduce barriers to and improve buprenorphine-naloxone uptake and retention among AYA who use opioids.

HIGHLIGHTS.

  • Young people reported low interest in buprenorphine-naloxone (BUP-NAL).

  • Race-based factors were negatively associated with initial BUP-NAL interest.

  • Recent detoxification was positively associated with BUP-NAL interest or enrolment over follow-up.

  • A continuum of harm reduction and treatment supports for young people is needed.

Acknowledgements

We would like to acknowledge and extend our sincere gratitude to the Xwməθkwəy̓əm (Musqueam), Sḵwx̱wú7mesh (Squamish), and Səlílwətaʔ (Tsleil-Waututh) Nations on whose land this research was conducted. We also wish to thank the study participants for their contribution to the research, as well as current and past researchers and staff. Lastly, we thank Lizzy Ambler for supporting this work.

Funding

The At-Risk Youth Study is supported by the Canadian Institutes of Health Research (CIHR) [SKF-149507; MOP-286532] and US National Institutes of Health [U01DA038886]. Andreas Pilarinos is supported through a Four-Year Fellowship from the University of British Columbia. Dr. Kora DeBeck is supported by a Michael Smith Foundation for Health Research/St. Paul’s Hospital Foundation-Providence Health Care Career Scholar Award and a CIHR New Investigator Award.

Footnotes

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Andreas Pilarinos: Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing – review & editing.

Brittany Bingham: Writing – review & editing. Yandi Kwa: Writing – review & editing.

Ronald Joe: Writing – review & editing.

Cameron Grant: Investigation, Data curation, Writing – review & editing.

Danya Fast: Conceptualization, Writing – review & editing, Supervision.

Jane A. Buxton: Conceptualization, Writing – review & editing, Supervision.

Kora DeBeck: Conceptualization, Writing – review & editing, Supervision, Funding acquisition.

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