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.

Suboptimal nonmedical qualities of primary care linked with care avoidance among people who use drugs in a Canadian setting amid an integrated health care reform.

BACKGROUND: People who use unregulated drugs (PWUD) often face significant barriers to-and thereby avoid seeking-health care. In Vancouver, Canada, a neighborhood-wide health care system reform began in 2016 to improve health care delivery and quality. In the wake of this reform, we sought to determine the prevalence of health care avoidance and its association with emergency department use among PWUD in this setting and examine patient-reported nonmedical qualities of health care ("responsiveness"). METHODS: The study derived data from two prospective cohort studies of community-recruited PWUD in Vancouver in 2017-18. Responsiveness was ascertained by the World Health Organizations' standardized measurements and we evaluated seven domains of responsiveness (dignity, autonomy, communication, confidentiality, prompt attention, choice of provider, and quality of basic amenities). The study used Pearson chi-squared test to examine differences in responsiveness between those who did and did not avoid care. The study team used multivariable logistic regression to determine the relationship between care avoidance due to past mistreatment and emergency department use, adjusting for potential confounders. RESULTS: Among 889 participants, 520 (58.5%) were male, 204 (22.9%) reported avoiding health care, most commonly for chronic pain (47.4%). Overall, 6.6% to 36.2% reported suboptimal levels (i.e., not always meeting the expected quality) across all seven measured domain of responsiveness. Proportions reporting suboptimal qualities were significantly higher among those who avoided care than those who did not across all domains, including care as soon as wanted (51.0% vs. 31.8%), listened to carefully (44.1% vs. 20.4%), and involved in health care decision-making (27.9% vs. 12.7%) (all p < 0.05). In multivariable analyses, avoidance of health care was independently associated with self-reported emergency department use (adjusted odds ratio = 1.49; 95% confidence interval:1.01-2.19). CONCLUSION: We found that almost a quarter of our sample of PWUD avoided seeking health care due to past mistreatment, and all seven measured domains of responsiveness were suboptimal and linked with avoidance. Individuals who reported avoidance of health care were significantly more likely to report emergency department use. Multi-level interventions are needed to remedy the suboptimal qualities of health care and thereby reduce care avoidance.

Latent patterns of polysubstance use among people who use opioids: A systematic review.

BACKGROUND: A mounting body of evidence suggests that polysubstance use (PSU) is common among people who use opioids (PWUO). Measuring PSU, however, is statistically and methodologically challenging. Person-centered analytical approaches (e.g., latent class analysis) provide a holistic understanding of individuals' substance use patterns and help understand PSU heterogeneities among PWUO and their specific needs in an inductive manner. We reviewed person-centered studies that characterized latent patterns of PSU among PWUO. METHODS: We searched MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Google Scholar from inception, through to June 15, 2020, for empirical peer-reviewed studies or gray literature that reported on latent classes of PSU among PWUO. Two independent reviewers completed the title, abstract, full-text screening, and data extraction. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale, and quality of reporting was evaluated using the Guidelines for Reporting on Latent Trajectory Studies checklist. Studies' findings were summarized and presented in a narrative fashion. RESULTS: Out of the 3372 initial unique studies identified, 30 were included. PSU operationalization varied substantially among the studies. We identified five distinct PSU latent classes frequently observed across the studies: Infrequent/low PSU, PSU primarily involving heroin use, PSU primarily involving heroin and stimulant use, PSU primarily involving stimulant use, and frequent PSU. Belonging to higher frequency or severity PSU classes were associated with frequent injection drug use, sharing needles and paraphernalia, high-risk sexual behaviours, as well as experiences of adversities, such as homelessness, incarceration, and poor mental health. CONCLUSION: PSU patterns vary significantly across different subgroups of PWUO. The substantial heterogeneities among PWUO need to be acknowledged in substance use clinical practices and policy developments. Findings call for comprehensive interventions that recognize these within-group diversities and address the varying needs of PWUO.

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.

Treatment of stimulant use disorder: A systematic review of reviews.

AIMS: Stimulant use disorder contributes to a substantial worldwide burden of disease, although evidence-based treatment options are limited. This systematic review of reviews aims to: (i) synthesize the available evidence on both psychosocial and pharmacological interventions for the treatment of stimulant use disorder; (ii) identify the most effective therapies to guide clinical practice, and (iii) highlight gaps for future study. METHODS: A systematic database search was conducted to identify systematic reviews and meta-analyses. Eligible studies were those that followed standard systematic review methodology and assessed randomized controlled trials focused on the efficacy of interventions for stimulant use disorder. Articles were critically appraised using an assessment tool adapted from Palmeteer et al. and categorized for quality as 'core' or 'supplementary' reviews. Evidence from the included reviews were further synthesized according to pharmacological or non-pharmacological management themes. RESULTS: Of 476 identified records, 29 systematic reviews examining eleven intervention modalities were included. The interventions identified include: contingency management, cognitive behavioural therapy, acupuncture, antidepressants, dopamine agonists, antipsychotics, anticonvulsants, disulfiram, opioid agonists, N-Acetylcysteine, and psychostimulants. There was sufficient evidence to support the efficacy of contingency management programs for treatment of stimulant use disorder. Psychostimulants, n-acetylcysteine, opioid agonist therapy, disulfiram and antidepressant pharmacological interventions were found to have insufficient evidence to support or discount their use. Results of this review do not support the use of all other treatment options. CONCLUSIONS: The results of this review supports the use of contingency management interventions for the treatment of stimulant use disorder. Although evidence to date is insufficient to support the clinical use of psychostimulants, our results demonstrate potential for future research in this area. Given the urgent need for effective pharmacological treatments for stimulant use disorder, high-quality primary research focused on the role of psychostimulant medications for the treatment of stimulant use disorder is needed.

Changes in substance use in relation to opioid agonist therapy among people who use drugs in a Canadian setting.

BACKGROUND: Although previous studies have shown that opioid agonist therapy (OAT) is linked to reductions in illicit opioid use, less is known about how OAT impacts the use of other psychoactive substances. We aimed to examine the changes in use of different substances by comparing patterns before and after initiating OAT. METHODS: Data for this study was derived from three ongoing prospective cohorts involving people who use drugs in Vancouver, Canada from 1996 to 2018. We assessed use patterns for heroin, illicit prescription opioid, cocaine, crack cocaine, crystal methamphetamine, cannabis, daily alcohol use, and benzodiazepines. Segmented regression was conducted to compare the trends of substance use between pre-treatment and post-treatment periods. RESULTS: The study included 1107 participants. After OAT engagement, we observed an immediate decline in the proportion as well as a decreasing trend for heroin (Adjusted Odds Ratio (AOR): 0.80, 95% confidence interval (CI): 0.77, 0.83), illicit prescription opioid (AOR: 0.87, 95% CI: 0.83, 0.90), and benzodiazepines (AOR: 0.73, 95 % CI: 0.67, 0.80). There was no significant difference comparing the pre-treatment and post-treatment trends for cocaine, crack cocaine, crystal methamphetamine, and cannabis. However, higher growth slope was noted during the post-treatment period for daily alcohol use (P = 0.016). CONCLUSIONS: We observed significant reduction in illicit opioids use following OAT initiation, but not for stimulant and cannabis. The increasing problematic use of alcohol may pose challenges to the safety and effectiveness of OAT. Development of comprehensive and tailored treatment strategies is needed for poly-substance users accessing OAT.

High-intensity cannabis use is associated with retention in opioid agonist treatment: a longitudinal analysis.

BACKGROUND AND AIMS: Cannabis use is common among people on opioid agonist treatment (OAT), causing concern for some care providers. However, there is limited and conflicting evidence on the impact of cannabis use on OAT outcomes. Given the critical role of retention in OAT in reducing opioid-related morbidity and mortality, we aimed to estimate the association of at least daily cannabis use on the likelihood of retention in treatment among people initiating OAT. As a secondary aim we tested the impacts of less frequent cannabis use. DESIGN: Data were drawn from two community-recruited prospective cohorts of people who use illicit drugs (PWUD). Participants were followed for a median of 81 months (interquartile range = 37-130). SETTING: Vancouver, Canada. PARTICIPANTS: This study comprised a total of 820 PWUD (57.8% men, 59.4% of Caucasian ethnicity, 32.2% HIV-positive) initiating OAT between December 1996 and May 2016. The proportion of women was higher among HIV-negative participants, with no other significant differences. MEASUREMENTS: The primary outcome was retention in OAT, defined as remaining in OAT (methadone or buprenorphine/naloxone-based) for two consecutive 6-month follow-up periods. The primary explanatory variable was cannabis use (at least daily versus less than daily) during the same 6-month period. Confounders assessed included: socio-demographic characteristics, substance use patterns and social-structural exposures. FINDINGS: In adjusted analysis, at least daily cannabis use was positively associated with retention in OAT [adjusted odds ratio (aOR) = 1.21, 95% confidence interval (CI) = 1.04-1.41]. Our secondary analysis showed that compared with non-cannabis users, at least daily users had increased odds of retention in OAT (aOR = 1.20, 95% CI = 1.02-1.43), but not less than daily users (aOR = 1.00, 95% CI = 0.87-1.14). CONCLUSIONS: Among people who use illicit drugs initiating opioid agonist treatment in Vancouver, at least daily cannabis use was associated with approximately 21% greater odds of retention in treatment compared with less than daily consumption.

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.

The Impact of Enrolment in Methadone Maintenance Therapy on Initiation of Heavy Drinking among People Who Use Heroin.

BACKGROUND: There is equivocal evidence regarding whether people who use heroin substitute heroin for alcohol upon entry to methadone maintenance therapy (MMT). We aimed to examine the impact of MMT enrolment on the onset of heavy drinking among people who use heroin. METHODS: We derived data from prospective, community-based cohorts of people who inject drugs in Vancouver, Canada, between December 1, 2005, and May 31, 2014. Multivariable extended Cox regression analysis examined the effect of MMT enrolment on the onset of heavy drinking among people who used heroin at baseline. RESULTS: In total, 357 people who use heroin were included in this study. Of these, 208 (58%) enrolled in MMT at some point during follow-up, and 115 (32%) reported initiating heavy drinking during follow-up for an incidence density of 7.8 events (95% CI 6.4-9.5) per 100 person-years. The incidence density of heavy drinking was significantly lower among those enrolled in MMT at some point during follow-up compared to those who did not (4.6 vs. 16.2; p < 0.001). MMT enrolment was not significantly associated with time to initiate heavy drinking (adjusted relative hazard (ARH) 1.27; 95% CI 0.78-2.07) after adjustment for relevant demographic and substance-use characteristics. Age and cannabis use were the only variables that were independently associated with the time to onset of heavy drinking (ARH 0.74; 95% CI 0.58-0.94 and ARH 2.06; 95% CI 1.32-3.19, respectively). CONCLUSION: In this study, MMT enrolment did not predict heavy drinking and may even appear to decrease the initiation of heavy drinking. Our findings suggest younger age and cannabis use may predict heavy drinking. These findings could help inform on-going discussions about the effects of opioid agonist therapy on alcohol consumption among people who use heroin.

Pain Among High-Risk Patients on Methadone Maintenance Treatment.

The complexity of treating concurrent pain and opioid dependence among many methadone-maintained individuals presents a major challenge in many clinical settings. Furthermore, recent expert guidelines have called for increased research on the safety of methadone in the context of chronic pain. This study explores the prevalence and correlates of pain among a prospective cohort of people who use illicit drugs in Vancouver, British Columbia, Canada, who reported enrollment in methadone maintenance treatment (MMT) between 2011 and 2014. Among the 823 participants eligible for this analysis, 338 (40.9%) reported moderate pain and 91 (11.1%) reported extreme pain at the first study visit. In multivariable, generalized, linear mixed model analyses, higher pain severity was positively and independently associated with self-managing pain (adjusted odds ratio [AOR] 2.15, 95% confidence interval [CI] 1.77-2.60), patient perception of methadone dose being too low (AOR 1.82, 95% CI 1.41-2.34), older age (AOR 1.31, 95% CI 1.13-1.51), having a physical disability (AOR 4.59, 95% CI 3.73-5.64), having ever been diagnosed with a mental illness (AOR 1.44, 95% CI 1.13-1.84), white ethnicity (AOR 1.42, 95% CI 1.10-1.83), and marijuana use (AOR 1.25, 95% CI 1.02-1.52). These findings suggest several areas for clinical intervention, particularly related to patient education and alternative analgesic approaches for MMT patients experiencing pain. Perspective: To better understand the complexity of concurrent pain and opioid dependency among individuals on methadone maintenance treatment, this article describes the prevalence and correlates of higher pain severity among methadone-maintained people who use illicit drugs. Patients on methadone with comorbid pain may benefit from education and alternative analgesic approaches.