Comparative effectiveness of urine drug screening strategies alongside opioid agonist treatment in British Columbia, Canada: a population-based observational study protocol.

INTRODUCTION: Urine drug tests (UDTs) are commonly used for monitoring opioid agonist treatment (OAT) responses, supporting the clinical decision for take-home doses and monitoring potential diversion. However, there is limited evidence supporting the utility of mandatory UDTs-particularly the impact of UDT frequency on OAT retention. Real-world evidence can inform patient-centred approaches to OAT and improve current strategies to address the ongoing opioid public health emergency. Our objective is to determine the safety and comparative effectiveness of alternative UDT monitoring strategies as observed in clinical practice among OAT clients in British Columbia, Canada from 2010 to 2020. METHODS AND ANALYSIS: We propose a population-level retrospective cohort study of all individuals 18 years of age or older who initiated OAT from 1 January 2010 to 17 March 2020. The study will draw on eight linked health administrative databases from British Columbia. Our primary outcomes include OAT discontinuation and all-cause mortality. To determine the effectiveness of the intervention, we will emulate a 'per-protocol' target trial using a clone censoring approach to compare fixed and dynamic UDT monitoring strategies. A range of sensitivity analyses will be executed to determine the robustness of our results. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.

Differential effect of cannabis use on opioid agonist treatment outcomes: Exploratory analyses from the OPTIMA study.

INTRODUCTION: Conflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone. METHODS: We analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6. RESULTS: The mean maximum dose taken during the study was 17.3 mg/day (range = 0.5-32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10-170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aß ± standard error (SE) = -0.06 ± 0.04; p = 0.15), craving (aß ± SE = -0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aß ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3). CONCLUSIONS: The current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.

Methadone Dose, Cannabis Use, and Treatment Retention: Findings From a Community-based Sample of People Who Use Unregulated Drugs.

OBJECTIVES: Lower daily methadone dose is negatively associated with retention in methadone maintenance treatment (MMT). Cannabis use during MMT is common, with many patients reporting its use for opioid withdrawal mitigation. We sought to test whether the association between lower MMT dose and treatment retention differs by concurrent high-frequency cannabis use in a community sample of people on MMT. METHODS: We obtained data from participants initiating MMT in 2 community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We built multivariable Cox frailty models to estimate the relationships between MMT dose (<90 mg/d vs ≥90 mg/d) and time to treatment discontinuation. We included an interaction term to test whether high-frequency (≥daily) cannabis use modified the measured effect of lower treatment dose on treatment retention. RESULTS: Between December 2005 and December 2018, 829 participants (54.1%) initiated at least 1 MMT episode and were included in the analysis. Lower MMT dose was strongly positively associated with treatment discontinuation regardless of concurrent high-frequency cannabis use (interaction P > 0.05). Structural factors including homelessness and incarceration were significantly and positively associated with treatment discontinuation. CONCLUSIONS: Although we previously found the magnitude and strength of the relationship between lower MMT dose and high-frequency unregulated opioid use to be tempered during high-frequency cannabis use periods, this effect measure modification does not appear to translate to time retained in treatment. Cannabis-based interventions to promote retention in MMT are unlikely to produce long-term benefit without addressing external factors that place MMT patients at increased risk of treatment discontinuation.

The Cannabis-Dependent Relationship Between Methadone Treatment Dose and Illicit Opioid Use in a Community-Based Cohort of People Who Use Drugs.

Background: Methadone maintenance treatment (MMT) is an effective treatment for opioid use disorder. However, subtherapeutic dosing may lead to continued opioid use by failing to suppress opioid withdrawal and craving. Preclinical and pilot experimental research suggests that cannabinoids may reduce opioid withdrawal and craving. We sought to test whether the association between low methadone dose and illicit opioid use differs according to concurrent cannabis use patterns. Methods: Data for this study were derived from two community-recruited cohorts of people (≥18 years old) who use illicit drugs in Vancouver, Canada. We used generalized estimating equations to estimate the adjusted association between lower daily MMT dose (<90 mg/day) and daily illicit opioid use, testing for interaction between dose and daily cannabis use. Results: Between December 2005 and December 2018, 1389 participants reported MMT enrolment and were included in the study. We observed a significant interaction (p<0.01) between daily cannabis and lower MMT dose on concurrent daily illicit opioid use: lower MMT doses increased the odds of daily illicit opioid use by 86% (adjusted odds ratio [AOR]=1.86, 95% confidence interval [CI]=1.61-2.16) during periods of no or low-frequency cannabis use and by 30% during periods of daily cannabis use (AOR=1.30, 95% CI=1.01-1.67). Discussion: This study provides preliminary observational evidence that cannabis may mitigate some of the negative effects of subtherapeutic MMT dosing, guiding future clinical investigations into the safety and efficacy of cannabis and cannabinoids as adjunct treatment for MMT.

Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis.

BACKGROUND: The ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT. METHODS: Data were drawn from two community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We used generalized linear mixed-effects modeling, adjusted by relevant confounders, to investigate the relationship between cannabis use and recent fentanyl exposure (both assessed by urine drug testing) among participants on OAT between 2016 and 2018. RESULTS: Among the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 - 0.99). CONCLUSIONS: Participants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.

Integrated models of care for people who inject drugs and live with hepatitis C virus: A systematic review.

BACKGROUND: Despite the key role that people who inject drugs (PWID) play in the hepatitis C virus (HCV) epidemic, HCV treatment rates among this population have been historically low. Integrated models of HCV and substance use care have the potential to overcome some barriers to access; however, the evidence base is uncertain. This systematic review assesses the impacts of integrated HCV and substance use services on engagement in HCV care among PWID. METHODS: We searched five databases up to December 2018 to identify original quantitative studies evaluating the impacts of co-location of HCV and substance use services on engagement in the HCV cascade of care among adult PWID. We conducted a narrative synthesis, categorizing models based on patient entry point (a: HCV facility, b: substance use disorder (SUD) facility, and c: other facilities), and levels of integrated services offered (a: HCV/substance use testing only, b: HCV/substance use treatment, and c: testing/treatment + other services). RESULTS: A total of 46 articles corresponding to 44 original studies were included. Almost all studies (n = 42) were conducted in high-income countries and only six studies in the Direct-Acting Antiviral (DAA) era. Twenty-six studies discussed the integration of services at SUD facilities, one at HCV facilities, and seventeen at other facilities. Analysis of included studies indicated that overall integrated care resulted in improved engagement in HCV care (e.g., testing, treatment uptake and cure). However, the quality of evidence was predominantly low to moderate. CONCLUSIONS: Available evidence suggests that integration of HCV and substance use services may improve engagement along the continuum of HCV care among PWID. Given limitations in data quality, and very few studies conducted in the DAA era and in low- and middle-income settings, further research is urgently needed to inform strategies to optimize HCV care access and outcomes among PWID globally.

Substance Use and Adherence to Antiretroviral Therapy: What Is Known and What Is Unknown.

PURPOSE OF REVIEW: People who use drugs face multiple challenges to achieve optimal HIV treatment outcomes. This review discusses the current knowledge in substance use and antiretroviral therapy adherence, highlighting recent findings and potential interventions. RECENT FINDINGS: Studies continue to demonstrate the negative impacts of substance use and related disorders on antiretroviral therapy adherence, with the exception of cannabis. Evidence-based addiction treatment, in particular, opioid agonist therapy, appears to improve adherence levels. Most individual-level adherence specific interventions did not provide sustained effects, and no studies evaluating structural-level interventions were found. Findings suggest the urgent need to scale-up opioid agonist therapy, as well as to simultaneously address multiple structural barriers to care to optimize HIV treatment outcomes among people who use drugs.

Intentional cannabis use to reduce crack cocaine use in a Canadian setting: A longitudinal analysis.

BACKGROUND: No effective pharmacotherapies exist for the treatment of crack cocaine use disorders. Emerging data suggests that cannabinoids may play a role in reducing cocaine-related craving symptoms. This study investigated the intentional use of cannabis to reduce crack use among people who use illicit drugs (PWUD). METHODS: Data were drawn from three prospective cohorts of PWUD in Vancouver, Canada. Using data from participants reporting intentional cannabis use to control crack use, we used generalized linear mixed-effects modeling to estimate the independent effect of three pre-defined intentional cannabis use periods (i.e., before, during and after first reported intentional use to reduce crack use) on frequency of crack use. RESULTS: Between 2012 and 2015, 122 participants reported using cannabis to reduce crack use, contributing a total of 620 observations. In adjusted analyses, compared to before periods, after periods were associated with reduced frequency of crack use (Adjusted Odds Ratio [AOR]=1.89, 95% Confidence Interval [CI]: 1.02-3.45), but not the intentional use periods (AOR=0.85, 95% CI: 0.51-1.41). Frequency of cannabis use in after periods was higher than in before periods (AOR=4.72, 95% CI: 2.47-8.99), and showed a tendency to lower frequency than in intentional cannabis use periods (AOR=0.56, 95% CI: 0.32-1.01). CONCLUSIONS: A period of intentional cannabis use to reduce crack use was associated with decreased frequency of crack use in subsequent periods among PWUD. Further clinical research to assess the potential of cannabinoids for the treatment of crack use disorders is warranted.