Friend or foe? Cannabis use among those with opioid use disorder (OUD)

Abstract

The global prevalence of opioid use disorders (OUD), particularly heroin dependence, has substantially increased over the past 30-years (+47.3%), accounting for more death and disability than any other illicit drug class. In response to the opioid crisis and growing recognition of cannabis as a therapeutic product, there have been recent attempts to understand the impact of cannabis use among those with OUD, with studies reporting a mix of beneficial and detrimental effects. However, studies have been limited by brief follow-up durations and inadequate measures of cannabis use (e.g., concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)), overlooking long-term heterogenous patterns of substance use and health outcomes. This thesis aims to increase our understanding of the longitudinal course and relationship between cannabis and opioids use to better inform public health responses. The following chapters present findings from four studies examining the impact of cannabis use on several pivotal stages throughout the life course of OUD, including the initiation of opioid use and development of OUD, and longitudinal patterns of ongoing use, treatment use and health outcomes relating to heroin dependence.

Despite long-standing debate over the relationship between cannabis use and the onset of opioid use and OUD, Study 1 presented in Chapter 2 is the first systematic review of the likelihood of transitioning from cannabis use to opioid use and OUD (including abuse and dependence). A synthesis of the results indicates 2.76 times greater odds of initiating opioid use, and 2.52 times greater odds of developing an OUD, dependence, or abuse, given prior cannabis use compared to no prior cannabis use.

Studies 2, 3, and 4 presented in Chapters 3, 4 and 5, use data from the Australian Treatment Outcome Study (ATOS), an 18-20-year longitudinal cohort study of people with heroin dependence, an opioid responsible for the highest number of opioid-induced deaths in Australia. Study 2 further supports findings that cannabis use remains common beyond the development of an OUD. Results of a random intercept cross-lagged panel model (RI-CLPM) suggests that the relationship between cannabis and heroin use was not consistent across time, with only a few associations observed between time points. Specifically, an increase in heroin use at 3-months and 24-months post-baseline was associated with a reduction in cannabis use at subsequent time points, whereas an increase in cannabis use at 24-months was associated with an increase in heroin use at 36-months.

Using group-based trajectory modelling, Study 3 identified five distinct patterns of treatment use among the ATOS cohort throughout the 18-20-year period, yet cannabis use was not associated with treatment trajectory group membership. Finally, Study 4 demonstrates that although those with a history of heroin dependence use a range of cannabis products, high potency/indoor grown herbal was the most common type used. Furthermore, frequent use of high potency cannabis was predicted by younger age at baseline but was not associated with health outcomes at 18-20-years post-baseline.

Cannabis use was found to often precede, be associated with, and continue beyond the initiation of opioid use and development of OUD. Despite a rising interest in cannabis-based interventions for those with OUD, there was no evidence to suggest that cannabis use was associated with a reduction in heroin use, impacted treatment use, or was related to health outcomes among those with OUD. These findings highlight the need for cannabis intervention and prevention programs to be designed around preventing the initiation of more harmful substances such as opioids, and for policymakers to be cautious when designing legislation relating to cannabis use. Further research should adopt improved causal inference methods (e.g., mendelian randomisation) to gain a greater understanding of the relationship between cannabis and opioid use.