There are an estimated 33 million opioid users globally [1], which is markedly contributing to the global burden of disease [2]. Illicit opioid use is associated with significant personal health risks, such as accidental injury, dependency, infectious disease [3], and potential for fatal overdose, in addition to its effects on the social concerns of healthcare costs, criminal activity, and employment [2]. Although the prevalence of heroin use has remained constant in Canada, a dramatic rise in the use of prescription opioids has resulted in a surge in opioid detoxification admissions from 2000 to 2004 [4]. In both the USA and Canada, illicit use of prescription opioids has become a significant contributor to emergency room visits and mortality [5]. This changing landscape and steady increase in problematic opioid use in North America signals an urgent need for evidence-based treatment practices.

Canada has witnessed a fivefold increase in patients on methadone maintenance treatment (MMT) since the mid-1990s [6]. MMT is an opioid substitution therapy and is the most widely researched pharmacological treatment for opioid use disorder [7]. Methadone is a long-acting synthetic opioid intended to reduce cravings and withdrawal symptoms without producing the euphoric effects associated with illicit opioids [8]. Studies have shown this treatment to be effective in decreasing illicit opioid use, reducing criminal activity, and reducing mortality rates among patients [7]. Although an overall efficacious treatment for reducing illicit opioid use, MMT is limiting in that it has high attrition rates [9] because it often requires patients to be on the treatment for life [10].

Polydrug use is common among MMT patients [11, 12], with cannabis consistently being the most commonly used illicit drug in this population [13–15]. This may be due to the fact that cannabis is generally perceived as harmless [16]. While it may be the case that mortality directly resulting from cannabis use is unlikely [2], associations with other adverse health outcomes have been found. In particular, regular cannabis use increases the risk of motor vehicle accidents and respiratory problems and poses a risk for dependency [17]. Long-term use is also associated with lower school performance and decreased life satisfaction [16]. Furthermore, cannabis use is associated with adverse mental health outcomes. The strongest evidence comes from studies on psychotic disorders, with a systematic review showing a strong, positive relationship between incidence of psychosis and cannabis use, which increases as frequency of cannabis use increases [18]. Studies have also found associations with other psychiatric illnesses including mood disorders (unipolar and bipolar) [19–21] and anxiety (particularly panic disorder and social anxiety) [22, 23]; however, evidence for a directional association with these disorders is inconclusive. Nonetheless, it remains a possibility that cannabis use during the treatment of opioid addiction could influence its outcome.

Studies on the association between cannabis use and MMT outcomes have produced conflicting results, with some demonstrating beneficial effects on outcomes [14] and others showing an association with adverse treatment outcomes. For example, Wasserman et al. [24] found that cannabis use at baseline and throughout the study period was significantly associated with subsequent heroin use during treatment, whereas Scavone et al. [14] found that patients using cannabis during the study reported significantly less daily expenditure on acquiring opioids. Most studies, however, have failed to produce a statistically significant association between cannabis use and MMT retention or illicit opioid use [13, 25–28]. Epstein and Preston [26] found that cannabis use increased other outcomes such as jail time and family conflict, suggesting that its use during MMT may act indirectly via social and lifestyle risk factors. The relationship between cannabis use and MMT outcomes may also include complex interactions with health behaviors. For instance, depressive symptoms and illicit substance use during MMT is significantly associated with a lack of HIV medication adherence [20], which may in turn affect MMT outcomes and overall health status among patients.

It remains unclear whether there is a true association between cannabis use and MMT outcomes and to what degree this association may be mediated by other confounding variables. A systematic investigation and evaluation of the studies is necessary, as well as the identification of any gaps in the literature. We hypothesize that the use of cannabis in patients with opioid use disorder treated with methadone is associated with poor response to MMT as defined by illicit opioid use and length of treatment retention. Evidence indicates that treatment retention is a critical factor in MMT success, with research suggesting that those in treatment for less than 90 days resemble those receiving no treatment at all [29]. Indeed, MMT dropout is significantly associated with drug use relapse and other high-risk health behaviors [11] and is a useful indicator of treatment response. We will also consider secondary outcomes to evaluate risky health and social behaviors including criminal activity, jail time, polydrug use, injection drug use, needle sharing, and unprotected sex. Isolating each outcome and controlling for potential confounders will help to clarify the association between cannabis use and MMT outcomes.