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Crystal methamphetamine use and methadone maintenance treatment dissatisfaction: A prospective cohort study in Vancouver, Canada

  • Zishan Cui
    Affiliations
    British Columbia Centre on Substance Use, 400-1045 Howe Street, Vancouver V6Z 2A9, BC, Canada

    School of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, BC V6T 1Z3, Canada
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  • Kanna Hayashi
    Affiliations
    British Columbia Centre on Substance Use, 400-1045 Howe Street, Vancouver V6Z 2A9, BC, Canada

    Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby V5A 1S6, BC, Canada
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  • Paxton Bach
    Affiliations
    British Columbia Centre on Substance Use, 400-1045 Howe Street, Vancouver V6Z 2A9, BC, Canada

    Department of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
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  • M.-J. Milloy
    Affiliations
    British Columbia Centre on Substance Use, 400-1045 Howe Street, Vancouver V6Z 2A9, BC, Canada

    Department of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
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  • Thomas Kerr
    Correspondence
    Corresponding author at: BC Centre on Substance Use, 400-1045 Howe Street, Vancouver, BC V6Z 2A9, Canada.
    Affiliations
    British Columbia Centre on Substance Use, 400-1045 Howe Street, Vancouver V6Z 2A9, BC, Canada

    Department of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
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Published:January 17, 2023DOI:https://doi.org/10.1016/j.josat.2023.208956

      Highlights

      • The increasing crystal meth use poses challenges for methadone maintenance treatment.
      • Frequent crystal meth use is associated with increased methadone dissatisfaction.
      • Improved care options are needed for patients engaging in frequent crystal meth use.

      Abstract

      Background

      Patient satisfaction is key to the success of methadone maintenance treatment (MMT), and yet how MMT satisfaction is affected by the increasingly common use of crystal methamphetamine among people receiving opioid treatment remains poorly understood. We aimed to assess the association between crystal methamphetamine use and MMT dissatisfaction.

      Methods

      We employed generalized estimating equations to examine the relationship between crystal methamphetamine use and MMT dissatisfaction among patients receiving MMT within two prospective cohorts in Vancouver, Canada, between December 2016 and March 2020.

      Results

      Of the 836 participants receiving MMT, the median age was 47 years, and 55.3 % self-identified as male at baseline. In a multivariable model, those reporting more than weekly crystal methamphetamine use were more likely to report MMT dissatisfaction (Odds ratio: 1.40, 95 % confidence interval: 1.05–1.86) compared to those reporting less than monthly crystal methamphetamine use.

      Conclusions

      Among our sample of people receiving MMT, we noted a positive association of frequent crystal methamphetamine use with MMT dissatisfaction. Our study suggests a need for novel strategies to better understand and address frequent methamphetamine use among those receiving MMT, particularly given recent shifts in substance use patterns involving the rising co-use of methamphetamines and opioids.

      Keywords

      1. Introduction

      In the context of the ongoing overdose crisis in the United States (US) and Canada, opioid-related overdose remains a leading cause of accidental death (NIDA, 2021;
      Government of Canada
      Opioid- and stimulant-related harms in Canada.
      ), driven in large part by illicitly manufactured fentanyl and its analogues in the unregulated drug supply (
      • Coroners Service B.c.
      ). The province of British Columbia (BC), Canada, has experienced an unprecedented number of overdose deaths in recent years and the provincial government declared a public health emergency in April 2016 (
      BC Centre for Disease Control
      The BC public health opioid overdose emergency. Observatory: Population and public health.
      ).
      Opioid agonist therapy (OAT) remains the first-line treatment for opioid use disorder (OUD) and research has shown it to be superior to withdrawal management in treatment retention and reduction of illicit opioid use, morbidity, and all-cause mortality (
      • Bahji A.
      • Cheng B.
      • Gray S.
      • Stuart H.
      Reduction in mortality risk with opioid agonist therapy: A systematic review and meta-analysis.
      ;
      National Institute on Drug Abuse
      How effective is drug addiction treatment? Principles of drug addiction treatment: A research-based guide.
      ). The provincial OUD guidelines in BC recommend that medically supervised OAT, including buprenorphine-naloxone or methadone, should be offered to patients with OUD in the absence of contraindications (
      • Bruneau J.
      • Ahamad K.
      • Goyer M.È.
      • Poulin G.
      • Selby P.
      • Fischer B.
      • Wild T.C.
      • Wood E.
      Management of opioid use disorders: A national clinical practice guideline.
      ). Methadone maintenance treatment (MMT) has historically been the standard of care for OUD in BC and is still considered first-line treatment in patients using high daily doses of opioids or with a history of severe withdrawal symptoms (
      • Lu Z.
      Appraisal of clinical practice guideline: CRISM National Guideline for the clinical management of opioid use disorder.
      ). In 2019, nearly 70 % of individuals on OAT were on MMT in BC (
      British Columbia Centre for Disease Control
      ).
      Research has shown that treatment satisfaction is key to the success of MMT, including promoting retention in MMT and reducing unregulated opioid use (
      • Kelly S.M.
      • O’Grady K.E.
      • Brown B.S.
      • Mitchell S.G.
      • Schwartz R.P.
      The role of patient satisfaction in methadone treatment.
      ;
      • Perreault M.
      • White N.D.
      • Fabrès É.
      • Landry M.
      • Anestin A.S.
      • Rabouin D.
      Relationship between perceived improvement and treatment satisfaction among clients of a methadone maintenance program.
      ). Understanding the factors that promote or undermine patient satisfaction is critical to optimizing OAT outcomes. Past research has identified stigma, side effects, demanding programmatic requirements, and unmet social and other medical needs as being associated with lower satisfaction with MMT (
      • Alcaraz S.
      • Trujols J.
      • Siñol N.
      • Duran-Sindreu S.
      • Batlle F.
      • Pérez de los Cobos J.
      Exploring predictors of response to methadone maintenance treatment for heroin addiction: The role of patient satisfaction with methadone as a medication.
      ;
      • Muller A.E.
      • Bjørnestad R.
      • Clausen T.
      Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications.
      ). Additionally, studies have suggested that patients may use methamphetamine to counter the sedating effects of methadone (
      • McNeil R.
      • Puri N.
      • Boyd J.
      • Mayer S.
      • Hayashi K.
      • Small W.
      Understanding concurrent stimulant use among people on methadone: A qualitative study.
      ). Given the noted rising prevalence of methamphetamine use among people receiving opioid treatment (
      • Ellis M.S.
      • Kasper Z.A.
      • Cicero T.J.
      Twin epidemics: The surging rise of methamphetamine use in chronic opioid users.
      ;
      • Fischer B.
      • O’Keefe-Markman C.
      • Lee A.
      • Min H.
      • Daldegan-Bueno D.
      ‘Resurgent’, ‘twin’ or ‘silent’ epidemic? A select data overview and observations on increasing psycho-stimulant use and harms in North America.
      ), that the use of methamphetamine may be associated with reduced retention in MMT is concerning (
      • O’Connor A.M.
      • Cousins G.
      • Durand L.
      • Barry J.
      • Boland F.
      Retention of patients in opioid substitution treatment: A systematic review.
      ). However, an understanding of the relationship between methamphetamine use and MMT satisfaction is lacking.
      Our study aims to evaluate the relationship between crystal methamphetamine (“crystal meth”) use and MMT satisfaction. We hypothesize that patients reporting crystal meth use will be more likely to report MMT dissatisfaction. As such, we aim to contribute to a better understanding of the challenges presented by rising crystal meth use among patients receiving opioid treatment and thereby inform integrated treatment strategies for people who co-use methamphetamines and opioids.

      2. Methods

      2.1 Study sample

      The Vancouver Injection Drug Users Study (VIDUS) and the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS) are two open prospective cohort studies of adults who use unregulated drugs in Vancouver, Canada. Details of these cohorts have been described in previous studies (
      • Kerr T.
      • Tyndall M.
      • Li K.
      • Montaner J.
      • Wood E.
      Safer injection facility use and syringe sharing in injection drug users.
      ;
      • Wood E.
      • Hogg R.S.
      • Bonner S.
      • Kerr T.
      • Li K.
      • Palepu A.
      • Guillemi S.
      • Schechter M.T.
      • Montaner J.S.G.
      Staging for antiretroviral therapy among HIV-infected drug users [4].
      ). In brief, participants of VIDUS and ACCESS are recruited through self-referral, word of mouth, and street outreach primarily in the Downtown Eastside neighborhood of Vancouver, which is characterized by high rates of unregulated drug use (
      • Friedel B.
      • Staak M.
      Drug situation in Vancouver.
      ). VIDUS enrolls HIV-negative adults who report having injected unregulated drugs in the month preceding enrollment and ACCESS enrolls HIV-positive individuals who report having used unregulated drugs other than or in addition to cannabis in the month preceding enrollment. Once enrolled, at baseline and semi-annually thereafter, participants complete an interviewer-administered questionnaire obtaining information on socio-demographic characteristics, drug use patterns, risk behaviors, and health care utilization. The study instruments and follow-up procedures for these cohorts are harmonized to allow for combined analyses. Participants receive a $40 (CDN) honorarium for each study visit. All eligible participants provided written informed consent. The studies have been approved by the University of British Columbia/Providence Health Care Research Ethics Board.
      For the current study, we restricted our analysis to participants who completed a study visit between December 2016 and March 2020, given that the OAT satisfaction question was added to the questionnaire as of December 2016. We further restricted our sample to those visits in which participants reported to have received MMT in response to the question “in the last 6 months, have you received any medications (such as Methadose or Suboxone) for the treatment of your alcohol or drug use?”

      2.2 Study variables

      The study outcome was MMT dissatisfaction, measured by asking “how satisfied were you with the medication treatment you received?” A five-point Likert scale was dichotomized as “very unsatisfied” or “unsatisfied” versus “neutral” or “satisfied” or “very satisfied”. The main exposure was crystal meth use frequency by any route, categorized as “none to less than monthly use”, “monthly to weekly use”, and “more than weekly use”. Based on existing research, we considered explanatory variables that could be associated with crystal meth use frequency or MMT satisfaction (
      • Alcaraz S.
      • Trujols J.
      • Siñol N.
      • Duran-Sindreu S.
      • Batlle F.
      • Pérez de los Cobos J.
      Exploring predictors of response to methadone maintenance treatment for heroin addiction: The role of patient satisfaction with methadone as a medication.
      ;
      • Damon W.
      • McNeil R.
      • Milloy M.J.
      • Nosova E.
      • Kerr T.
      • Hayashi K.
      Residential eviction predicts initiation of or relapse into crystal methamphetamine use among people who inject drugs: A prospective cohort study.
      ;
      • Lake S.
      • Kerr T.
      • Buxton J.
      • Walsh Z.
      • Cooper Z.D.
      • Socías M.E.
      • Fairbairn N.
      • Hayashi K.
      • Milloy M.-J.
      The cannabis-dependent relationship between methadone treatment dose and illicit opioid use in a community-based cohort of people who use drugs.
      ;
      • Mackay L.
      • Bach P.
      • Milloy M.J.
      • Cui Z.
      • Kerr T.
      • Hayashi K.
      The relationship between crystal methamphetamine use and methadone retention in a prospective cohort of people who use drugs.
      ;
      • Muller A.E.
      • Bjørnestad R.
      • Clausen T.
      Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications.
      ). These variables included: age, self-identified gender (male vs. non-male), sexual orientation (heterosexual vs. other), self-reported ethnicity/ancestry (white vs. Indigenous vs. other), cohort designation (VIDUS vs. ACCESS), unstable housing (hotel/shelter/recovery house/street/other vs. apartment/house), Downtown Eastside residence, drug-dealing involvement, incarceration, and MMT dose (>100mg/day vs. ≤100 mg/day). Substance-use variables other than crystal meth use include crack or cocaine, cannabis, alcohol, and unregulated opioids use (i.e., heroin or fentanyl), and were categorized as “none to less than monthly use”, “monthly to weekly use”, and “more than weekly use”. As patients who were dissatisfied with MMT would likely engage in unregulated opioid use, we used unregulated opioid use frequency collected during the visit immediately preceding the ascertainment of MMT dissatisfaction. In addition, we also controlled for new initiates of MMT, defined as a participant reporting not being on MMT in an immediately preceding study visit. All variables except for ethnicity were time-varying and dichotomized as yes vs. no unless otherwise noted.

      2.3 Statistical analysis

      First, we compared the baseline sample characteristics stratified by ever being dissatisfied with MMT at any point during the study period, using the Pearson's χ2 test for categorical variables and the Wilcoxon Rank Sum test for continuous variables. Second, we conducted univariable and multivariable GEE models to study the relationship between crystal meth use frequency and MMT dissatisfaction. All explanatory variables of interest were included in the multivariable GEE model. The amount of missing data was minimal (<1 % for each variable and overall), and thus the study removed missing data from the multivariable model. All statistical tests were two-sided and considered statistically significant at p < 0.05. The study team used SAS version 9.4 to conduct all analyses (SAS Institute, Cary, North Carolina, United States).

      3. Results

      Between December 2016 and March 2020, 836 participants who reported receiving MMT in the previous six months were included in this study. The median follow-up time per individual was 2.2 years (1st to 3rd quartile [Q1-Q3] = 1.1–3.1). During the study follow-up, our participants contributed a median of 3 visits (Q1-Q3 = 2–6), resulting in 3009 visits included in this analysis.
      Table 1 presents the baseline characteristics of all participants stratified by MMT dissatisfaction. During our study period, more than half (50.7 %) of participants reported ever being dissatisfied with MMT. As shown, 555 (66.4 %) participants were from VIDUS (i.e., HIV negative) and 281 (33.6 %) were from ACCESS (i.e., HIV positive). Among all participants, the median age at baseline was 47 years (Q1-Q3 = 37–54); 462 (55.3 %) self-identified as being male; 479 (57.8 %) self-identified as white and 316 (38.1 %) identified as being of Indigenous ancestry. At study baseline, 170 (20.3 %) participants reported daily use of crystal meth and 327 (39.1 %) reported daily use of unregulated opioids, 129 (15.4 %) of whom reported daily use of both crystal meth and unregulated opioids.
      Table 1Baseline sample characteristics stratified by ever reported treatment dissatisfaction during the study period among participants receiving methadone maintenance treatment in Vancouver, Canada (N = 836).
      Treatment dissatisfaction
      TotalNoYes
      (N = 836)(N = 412)(N = 424)
      VariablesN (%)N (%)N (%)p-value
      Crystal meth use frequency
      Variables refers to the last six months prior to the interview date.
       Less than monthly use497 (59.5 %)244 (59.2 %)253 (59.7 %)0.968
       Monthly to weekly use69 (8.3 %)35 (8.5 %)34 (8.0 %)
       More than weekly use270 (32.3 %)133 (32.3 %)137 (32.3 %)
      Crack or cocaine use frequency
      Variables refers to the last six months prior to the interview date.
       Less than monthly use529 (63.3 %)272 (66.0 %)257 (60.6 %)0.194
       Monthly to weekly use98 (11.7 %)48 (11.7 %)50 (11.8 %)
       More than weekly use209 (25.0 %)92 (22.3 %)117 (27.6 %)
      Alcohol use frequency
      Variables refers to the last six months prior to the interview date.
       Less than monthly use589 (70.5 %)310 (75.2 %)279 (65.8 %)0.004
       Monthly to weekly use133 (15.9 %)49 (11.9 %)84 (19.8 %)
       More than weekly use114 (13.6 %)53 (12.9 %)61 (14.4 %)
      Cannabis use frequency
      Variables refers to the last six months prior to the interview date.
       Less than monthly use326 (39.0 %)162 (39.3 %)164 (38.7 %)0.177
       Monthly to weekly use474 (56.7 %)227 (55.1 %)247 (58.3 %)
       More than weekly use36 (4.3 %)23 (5.6 %)13 (3.1 %)
      Unregulated opioid use frequency
      Variables refers to the last six months prior to the interview date.
       Less than monthly use308 (36.8 %)162 (39.3 %)146 (34.4 %)0.199
       Monthly to weekly use104 (12.4 %)54 (13.1 %)50 (11.8 %)
       More than weekly use424 (50.7 %)196 (47.6 %)228 (53.8 %)
      Age (median (Q1-Q3))47 (37–54)45 (35–53)48 (39–55)<0.001
      Cohort
       ACCESS281 (33.6 %)133 (32.3 %)148 (34.9 %)0.422
       VIDUS555 (66.4 %)279 (67.7 %)276 (65.1 %)
      Ethnicity/ancestry
       White479 (57.8 %)230 (56.5 %)249 (59.0 %)0.766
       Indigenous316 (38.1 %)160 (39.3 %)156 (37.0 %)
       Other person of color34 (4.1 %)17 (4.2 %)17 (4.0 %)
      Male gender462 (55.3 %)229 (55.6 %)233 (55.0 %)0.855
      Sexual orientation - heterosexual130 (15.6 %)64 (15.5 %)66 (15.6 %)0.990
      Unstable housing
      Variables refers to the last six months prior to the interview date.
      563 (67.4 %)283 (68.9 %)280 (66.0 %)0.385
      Living in downtown eastside
      Variables refers to the last six months prior to the interview date.
      619 (74.2 %)305 (74.0 %)314 (74.4 %)0.901
      Drug-dealing
      Variables refers to the last six months prior to the interview date.
      73 (8.7 %)41 (10.0 %)32 (7.6 %)0.218
      Incarceration
      Variables refers to the last six months prior to the interview date.
      169 (20.2 %)84 (20.4 %)85 (20.1 %)0.902
      New methadone initiates186 (22.3 %)104 (25.3 %)82 (19.4 %)<0.001
      High methadone dose
      Variables refers to the last six months prior to the interview date.
      256 (35.7 %)131 (38.0 %)125 (33.5 %)0.213
      a Variables refers to the last six months prior to the interview date.
      We present the results of the univariable and multivariable GEE analyses in Table 2. The univariable GEE model shows that compared to those reporting less than monthly crystal meth use, patients reporting more than weekly crystal meth use were more likely to report MMT dissatisfaction (odds ratio: 1.34, 95 % confidence interval [CI]: 1.07–1.67). After adjusting for confounders and other predictors, the multivariable model shows that patients reporting more than weekly crystal meth use were more likely to report MMT dissatisfaction (adjusted odds ratio: 1.40, 95 % CI: 1.05–1.86) compared to those reporting less than monthly crystal meth use. The odds of reporting MMT dissatisfaction between patients reporting monthly to weekly crystal meth use were not significantly different from those reporting less than monthly crystal meth use.
      Table 2Univariable and multivariable GEE analyses of the relationship between crystal meth use frequency and treatment dissatisfaction among participants receiving methadone maintenance treatment in Vancouver, Canada. (N = 3009).
      Treatment dissatisfaction
      ORc (95 % CI)aORc (95 % CI)
      Crystal meth use frequency
      Variables refer to the last six months prior to the interview date.
      (Ref: less than monthly use)
       Monthly to weekly use1.16 (0.85–1.58)0.99 (0.70–1.41)
       More than weekly use1.34 (1.07–1.67)1.40 (1.05–1.86)
      Crack or cocaine use frequency
      Variables refer to the last six months prior to the interview date.
      (Ref: less than monthly use)
       Monthly to weekly use1.05 (0.80–1.36)1.14 (0.86–1.52)
       More than weekly use0.91 (0.71–1.17)0.95 (0.71–1.27)
      Alcohol use frequency
      Variables refer to the last six months prior to the interview date.
      (Ref: less than monthly use)
       Monthly to weekly use1.32 (1.04–1.68)1.23 (0.95–1.61)
       More than weekly use1.28 (0.99–1.65)1.09 (0.83–1.45)
      Cannabis use frequency
      Variables refer to the last six months prior to the interview date.
      (Ref: less than monthly use)
       Monthly to weekly use1.00 (0.81–1.22)1.07 (0.85–1.33)
       More than weekly use0.91 (0.70–1.18)1.02 (0.76–1.38)
      Unregulated opioid use frequency
      Variables refer to the last six months prior to the interview date.
      Variable collected on the lagged visit of the treatment dissatisfaction outcome.
      (Ref: less than monthly use)
       Monthly to weekly use1.30 (0.96–1.77)1.30 (0.93–1.83)
       More than weekly use1.50 (1.18–1.92)1.58 (1.20–2.10)
      Age (per year increase)1.00 (0.99–1.01)1.02 (1.01–1.04)
      Calendar year (per year increase)0.86 (0.80–0.93)0.81 (0.72–0.90)
      Cohort (VIDUS vs. ACCESS)1.09 (0.86–1.38)1.03 (0.79–1.35)
      Ethnicity/ancestry (white vs. other)1.12 (0.89–1.41)1.14 (0.87–1.49)
      Gender (male vs. non-male)1.08 (0.86–1.35)1.06 (0.82–1.37)
      Sexual orientation (other vs. heterosexual)1.45 (1.11–1.88)1.61 (1.20–2.15)
      Unstable housing
      Variables refer to the last six months prior to the interview date.
      1.09 (0.89–1.34)1.20 (0.93–1.54)
      Living in downtown eastside
      Variables refer to the last six months prior to the interview date.
      0.76 (0.62–0.94)0.61 (0.46–0.79)
      Drug-dealing
      Variables refer to the last six months prior to the interview date.
      1.29 (1.02–1.63)1.24 (0.94–1.63)
      Incarceration
      Variables refer to the last six months prior to the interview date.
      1.18 (0.79–1.76)1.08 (0.69–1.70)
      New methadone initiates1.04 (0.77–1.40)1.06 (0.71–1.58)
      High methadone dose
      Variables refer to the last six months prior to the interview date.
      0.81 (0.65–1.00)0.79 (0.64–0.99)
      OR: odds ratio; aOR: adjusted odds ratio; CI: confidence interval.
      a Variables refer to the last six months prior to the interview date.
      b Variable collected on the lagged visit of the treatment dissatisfaction outcome.

      4. Discussion

      Using data from two large prospective cohort studies, we found a positive association between frequent crystal meth use and MMT dissatisfaction among individuals receiving MMT between late 2016 to early 2020 in Vancouver, Canada. Specifically, we found that, compared to patients who reported less than monthly crystal meth use, those who reported more than weekly crystal meth use were significantly more likely to report MMT dissatisfaction, and those who reported monthly to weekly crystal meth use were similarly likely to report MMT dissatisfaction.
      In our study setting, the increasing prevalence of crystal meth use, especially in combination with opioids, poses challenges for MMT (
      • Mackay L.
      • Bach P.
      • Milloy M.J.
      • Cui Z.
      • Kerr T.
      • Hayashi K.
      The relationship between crystal methamphetamine use and methadone retention in a prospective cohort of people who use drugs.
      ;
      • O’Connor A.M.
      • Cousins G.
      • Durand L.
      • Barry J.
      • Boland F.
      Retention of patients in opioid substitution treatment: A systematic review.
      ). In a qualitative study published in 2020, McNeil et al. suggest that some patients receiving MMT use crystal meth to counter the sedating effects of methadone (
      • McNeil R.
      • Puri N.
      • Boyd J.
      • Mayer S.
      • Hayashi K.
      • Small W.
      Understanding concurrent stimulant use among people on methadone: A qualitative study.
      ). Additionally, crystal meth use could be a marker of ongoing unregulated opioid use among patients receiving MMT. Especially, as potent synthetic opioids have become increasingly available in our local unregulated drug supply, crystal meth may be used to prevent over-sedation caused by potent synthetic opioids (e.g., fentanyl) (;
      • Ellis M.S.
      • Kasper Z.A.
      • Cicero T.J.
      Twin epidemics: The surging rise of methamphetamine use in chronic opioid users.
      ). In turn, crystal meth use could make it more challenging to stabilize some patients on MMT.
      • O’Connor A.M.
      • Cousins G.
      • Durand L.
      • Barry J.
      • Boland F.
      Retention of patients in opioid substitution treatment: A systematic review.
      systematic review summarized that three of five studies conducted in the United States and Canada show a significant association between methamphetamine use and reduced methadone retention (
      • O’Connor A.M.
      • Cousins G.
      • Durand L.
      • Barry J.
      • Boland F.
      Retention of patients in opioid substitution treatment: A systematic review.
      ). Furthermore, a recently published analysis conducted using the same cohorts as our analysis noted a dose-dependent relationship between the frequency of methamphetamine use and methadone discontinuation (
      • Mackay L.
      • Bach P.
      • Milloy M.J.
      • Cui Z.
      • Kerr T.
      • Hayashi K.
      The relationship between crystal methamphetamine use and methadone retention in a prospective cohort of people who use drugs.
      ). Our study adds to the existing research to help explain the noted relationship between frequent crystal meth use and reduced methadone retention by suggesting a relationship between frequency of crystal meth use and MMT dissatisfaction.
      Our study provided a better understanding of crystal meth use among patients receiving MMT, which might allow care providers to more accurately predict the treatment effects of MMT. The positive relationship between frequent crystal meth use and MMT dissatisfaction points to the need for regular and consistent assessment during MMT visits to improve MMT success overall, including treatment satisfaction and retention. For example, care providers could carefully explore patients' crystal meth use frequency. If patients report more-than-weekly crystal meth use, providers should assess MMT treatment satisfaction and should explore other opioid treatment options. Moreover, in addition to the urgent need for the development of pharmacologic treatments to treat methamphetamine dependence, a timely response is also needed to counter the rapidly rising methamphetamine use patterns among patients receiving opioid treatment (
      • Ellis M.S.
      • Kasper Z.A.
      • Cicero T.J.
      Twin epidemics: The surging rise of methamphetamine use in chronic opioid users.
      ). In a systematic review published in
      • Brown H.D.
      • DeFulio A.
      Contingency management for the treatment of methamphetamine use disorder: A systematic review.
      , Brown and DeFulio summarized the broad benefits of contingency management intervention programs that offer treatment for methamphetamine use disorder (
      • Brown H.D.
      • DeFulio A.
      Contingency management for the treatment of methamphetamine use disorder: A systematic review.
      ). Care providers could consider incorporating contingency management programs into regular OAT visits for patients who concurrently use methamphetamines and opioids (
      • Morley K.C.
      • Cornish J.L.
      • Faingold A.
      • Wood K.
      • Haber P.S.
      Pharmacotherapeutic agents in the treatment of methamphetamine dependence.
      ). However, given the limited durability of the benefits of such interventions (
      • Morley K.C.
      • Cornish J.L.
      • Faingold A.
      • Wood K.
      • Haber P.S.
      Pharmacotherapeutic agents in the treatment of methamphetamine dependence.
      ), work needs to continue to focus on identifying novel strategies to address crystal meth use.
      Our study has several limitations. First, the participants in both VIDUS and ACCESS were recruited with nonrandom sampling, and our study sample is characterized by a high proportion of participants living in the Downtown Eastside of Vancouver, a unique neighborhood with high rates of polysubstance use (
      • Friedel B.
      • Staak M.
      Drug situation in Vancouver.
      ). Therefore, the generalizability of our findings could be limited. Second, self-reported data used in this study could be subject to reporting biases. However, prior research has suggested that self-reported data were generally accurate among drug-using populations (
      • Darke S.
      Self-report among injecting drug users: A review.
      ). Third, we could not account for MMT adherence or differentiate reasons for MMT dissatisfaction due to data limitations. However, considering the complex nature of MMT engagement, the broad nature of our sample could better speak to the issues of MMT in practice. Future research should build on richer quantitative data or qualitative interviews to understand meaningful factors causing MMT dissatisfaction. Last, we cannot infer causation between crystal meth use and MMT satisfaction in this observational study due to the concerns of unmeasured confounding and reverse causation. The study could not establish temporality as patients could have been dissatisfied with MMT before they start to use crystal meth.
      In conclusion, our study noted the potential challenges to treatment satisfaction presented by rising crystal meth use among people receiving MMT. In response to the recent shifts in substance use patterns where methamphetamine-opioid co-use is rapidly rising, our study highlights the need for improved care options for patients engaging in frequent crystal meth use while receiving OAT. Such efforts have the potential to help increase MMT satisfaction. Future research needs to depict the direct and indirect pathways between crystal meth use and MMT success to better inform effective integrated strategies targeting patients who use crystal meth while receiving MMT.

      CRediT authorship contribution statement

      Zishan Cui: Conceptualization, Methodology, Software, Formal analysis, Data curation, Writing – original draft. Kanna Hayashi: Methodology, Writing – review & editing, Funding acquisition. Paxton Bach: Conceptualization, Writing – review & editing. M.-J. Milloy: Writing – review & editing, Funding acquisition. Thomas Kerr: Conceptualization, Methodology, Writing – review & editing, Supervision, Funding acquisition.

      Uncited reference

      (
      (NIDA) National Institute of Drug Abuse
      Drug topics: Opioid overdose crisis.

      Declaration of competing interest

      MJM's institution has received an unstructured gift from NG Biomed, Ltd., to support his research. MJM is the Canopy Growth professor of cannabis science at the University of British Columbia, a position created by unstructured gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia's Ministry of Mental Health and Addictions. Funding sources had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. All authors declare no conflict of interest.

      Acknowledgments

      The authors thank the study participants for their contribution to the research, as well as current and past researchers and staff. The study was supported by the US National Institutes of Health (NIH) (U01DA038886, R01DA021525). This research was undertaken, in part, thanks to funding from the Canadian Institutes of Health Research (CIHR) Canadian Research Initiative on Substance Misuse (SMN–139148). TK is supported by a foundation grant from the CIHR (20R74326). KH holds the St. Paul's Hospital Chair in Substance Use Research and is supported in part by the NIH grant (U01DA038886), a CIHR New Investigator Award (MSH-141971), a Michael Smith Foundation for Health Research (MSFHR) Scholar Award, and the St. Paul's Foundation. PB receives funding from the MSFHR. MJM is supported by the NIH (U01DA0251525), a CIHR New Investigator Award, and an MSFHR Scholar Award.

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