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.

The relationship between cannabis use and patient outcomes in medication-based treatment of opioid use disorder: A systematic review.

Despite high rates of cannabis use during medication-based treatment of opioid use disorder (MOUD), uncertainty remains around how cannabis influences treatment outcomes. We sought to investigate the relationship between cannabis use during MOUD and a number of patient outcomes. We searched seven databases for original peer-reviewed studies documenting the relationship between cannabis use and at least one primary outcome (opioid use, treatment adherence, or treatment retention) among patients enrolled in methadone-, buprenorphine-, or naltrexone-based therapy for OUD. In total, 41 articles (including 23 methadone, 7 buprenorphine, 6 naltrexone, and 5 mixed modalities) were included in this review. For each primary outcome area, there was a small number of studies that produced findings suggestive of a supportive or detrimental role of concurrent cannabis use, but the majority of studies reported that cannabis use was not statistically significantly associated with the outcome. No studies of naltrexone treatment demonstrated significantly worse outcomes for cannabis users. We identified methodological shortcomings and future research priorities, including exploring the potential role of adjunct cannabis use for improving opioid craving and withdrawal during MOUD. While monitoring for cannabis use may help guide clinicians towards an improved treatment plan, cannabis use is unlikely to independently threaten treatment outcomes.

Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

BACKGROUND: Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. METHODS AND FINDINGS: This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. CONCLUSIONS: We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

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.

High-intensity cannabis use and HIV clinical outcomes among HIV-positive people who use illicit drugs in Vancouver, Canada.

BACKGROUND: Reforms to the legal status of medical and non-medical cannabis are underway in many jurisdictions, including Canada, as are renewed efforts to scale-up HIV treatment-as-prevention (TasP) initiatives. It has been suggested that high-intensity cannabis use may be associated with sub-optimal HIV treatment outcomes. Thus, using data from a setting with a community-wide treatment-as-prevention (TasP) initiative coinciding with increasing access to medical cannabis, we sought to investigate the possible impact of high-intensity cannabis use on HIV clinical outcomes. METHODS: Data was derived from the ACCESS study, a prospective cohort of HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. Cohort data was confidentially linked to comprehensive clinical profiles, including records of all antiretroviral therapy (ART) dispensations and longitudinal plasma HIV-1 RNA viral load (VL) monitoring. We used generalized estimating equations (GEEs) to estimate the longitudinal bivariable and multivariable relationships between at least daily cannabis use and two key clinical outcomes: overall engagement in ART care, and achieving a non-detectable VL among ART-exposed participants. RESULTS: Between December 2005 and June 2015, 874 HIV-positive PWUD (304 [35%] non-male) were included in this study. In total, 788 (90%) were engaged in HIV care at least once over the study period, of whom 670 (85%) achieved non-detectable VL at least once. In multivariable analyses, ≥ daily cannabis use did not predict lower odds of ART care (Adjusted Odds Ratio [AOR]: 1.02, 95% confidence interval [CI]: 0.77-1.36) or VL non-detectability among ART-exposed (AOR: 0.96, 95% CI: 0.75-1.21). Upon testing for potential interactions, ≥ daily cannabis use was found to be negatively associated with ART engagement during periods of binge alcohol use (p<0.05). CONCLUSION: With the exception of frequent cannabis use during periods of binge alcohol use, our results showed no statistically significant impact of daily cannabis use on the likelihood of ART care or VL non-detectability among ART-exposed HIV-positive PWUD. These findings are reassuring in light of the impending legalization of cannabis in Canada and ongoing efforts to expand TasP initiatives.

Prescribing medical cannabis in Canada: Are we being too cautious?

There has been much recent discussion and debate surrounding cannabis in Canada, including the prescribing of medical cannabis for therapeutic purposes. Certain commentators - including the Canadian Medical Association (CMA) - have denounced the prescribing of cannabis for medical purposes due to a perceived lack of evidence related to the drug's efficacy, harms, and mechanism of action. In this commentary, we present arguments in favour of prescribing medical cannabis in Canada. We believe the anti-cannabis position taken by CMA and other commentators is not entirely evidence-based. Using the example of neuropathic pain, we present and summarize the clinical evidence surrounding smoked or vapourized cannabis, including recent evidence pertaining to the effectiveness of cannabis in comparison to existing standard pharmacotherapies for neuropathy. Further, we outline how the concerns expressed regarding cannabis' mechanism of action are inconsistent with current decision-making processes related to the prescribing of many common pharmaceuticals. Finally, we discuss potential secondary public health benefits of prescribing cannabis for pain-related disorders in Canada and North America.