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Association Between Cannabis Use and Methadone Zielinski et al. Biology of Sex Differences (2017) 8:8 DOI 10.1186/s13293-017-0130-1 RESEARCH Open Access Association between cannabis use and methadone maintenance treatment outcomes: an investigation into sex differences Laura Zielinski1, Meha Bhatt2, Nitika Sanger3, Carolyn Plater4, Andrew Worster4,5, Michael Varenbut4, Jeff Daiter4, Guillaume Pare6,7, David C. Marsh4,8, Dipika Desai6, James MacKillop9,10, Meir Steiner9,11,12, Stephanie McDermid Vaz9,13, Lehana Thabane7,14 and Zainab Samaan6,7,9,10* Abstract Background: Cannabis will soon become legalized in Canada, and it is currently unclear how this will impact public health. Methadone maintenance treatment (MMT) is the most common pharmacological treatment for opioid use disorder (OUD), and despite its documented effectiveness, a large number of patients respond poorly and experience relapse to illicit opioids. Some studies implicate cannabis use as a risk factor for poor MMT response. Although it is well established that substance-use behaviors differ by sex, few of these studies have considered sex as a potential moderator. The current study aims to investigate sex differences in the association between cannabis use and illicit opioid use in a cohort of MMT patients. Methods: This multicentre study recruited participants on MMT for OUD from Canadian Addiction Treatment Centre sites in Ontario, Canada. Sex differences in the association between any cannabis use and illicit opioid use were investigated using multivariable logistic regression. A secondary analysis was conducted to investigate the association with heaviness of cannabis use. Results: The study included 414 men and 363 women with OUD receiving MMT. Cannabis use was significantly associated with illicit opioid use in women only (OR = 1.82, 95% CI 1.18, 2.82, p = 0.007). Heaviness of cannabis use was not associated with illicit opioid use in men or women. Conclusions: This is the largest study to date examining the association between cannabis use and illicit opioid use. Cannabis use may be a sex-specific predictor of poor response to MMT, such that women are more likely to use illicit opioids if they also use cannabis during treatment. Women may show improved treatment outcomes if cannabis use is addressed during MMT. Keywords: Cannabis, Opioid, Opioid use disorder, Methadone maintenance treatment, Sex differences * Correspondence: [email protected] 6Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada 7Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Zielinski et al. Biology of Sex Differences (2017) 8:8 Page 2 of 10 Background Because of the ongoing opioid epidemic in Canada, we Canada is currently developing legislation for the legalization must remain mindful of how increasing accessibility of of cannabis [1]. The rationale is that legalization would have cannabis will impact this population, in particular. Cur- social and economic advantages by generating revenue and rently, the most commonly prescribed treatment for deterring such crimes as illegal drug dealing [2]. Prohibition OUD is methadone maintenance treatment (MMT), an has been ineffective, with data suggesting that this policy op- opioid substitution therapy [12]. MMT has proven to be tion has created more societal costs by way of excessive incar- effective in retaining patients in treatment and reducing ceration, largely involving already marginalized individuals opioid use and mortality [13], and this effectiveness has [3], and no evidence to suggest that these criminal penalties led to a steep increase in patients on MMT. In Ontario, have any substantial effect on public health [4]. Canada, the number of patients receiving MMT has Colorado, USA, has recently legalized cannabis, and nearly doubled since 2010 [12]. Despite its effectiveness, while it remains premature to assess the public health im- a significant number of patients respond poorly to treat- pact of this policy, data show that the commercialization ment and experience relapse [14]. Illicit opioid use in of medical marijuana in 2009 led to a 20% increase in combination with MMT is of immense concern, as it is college age (18–25 years) monthly marijuana use and a a substantial risk factor for overdose and death [15]. 36% increase in adult (26+ years) monthly marijuana use Recent studies point to a changing landscape of OUD in the following 3 years [5]. Legalizing cannabis will and those in treatment, one that includes a higher almost certainly increase its availability and accessibility; percentage of women, older aged patients, and more plausible mechanisms for increasing recreational use individuals abusing prescription opioids rather than include reduced prices, ease of access, criminal penalties heroin [16]. These sociodemographic changes warrant no longer acting as a deterrent, and increased social ac- a re-evaluation of risk factors associated with poor ceptability [6]. It is reasonable to expect that Canada will MMT outcomes. observe a similar increase in the prevalence of cannabis Compared to the general population, patients on use, though its public health impact remains uncertain. MMT show a higher prevalence of cannabis use [16], Despite the commonly held perception that cannabis and because of its documented association with polysub- is relatively harmless [7], its use has been linked to ad- stance use [9, 17], psychiatric disorders [18], and overall verse consequences such as cognitive impairment, lower worse quality of life [19], represents a potential risk life satisfaction, respiratory problems, and increased risk factor for poor MMT outcomes. Several studies have in- of developing psychotic episodes and disorders [8]. vestigated the influence of cannabis use on MMT out- Those with a history of psychiatric or substance-use dis- comes in humans, though the results are mixed. Some orders can experience worsened symptoms from canna- studies have indicated cannabis use is associated with bis use [1]. Cannabis users are also at heightened risk for poorer treatment outcomes [20–22] while others looking developing other substance-use disorders [9]. However, at illicit opioid use found no significant association the current system of criminalization is similarly associ- [23–26]. Although this is the case, confidence in these ated with individual and public risks. For example, indi- diverging results is reduced by methodological limitations viduals with a criminal record from minor possession such as small sample size and subjective outcome mea- charges often experience considerable difficulties in find- sures, making further investigations merited. ing employment or housing leading to further social and Furthermore, few studies have considered sex as a po- health risks [1]. Public costs of criminalization are also tential moderator. It is well established that substance- substantial, with an estimated $2.3 billion spent annually use behaviors differ by sex and different social and on enforcement and prosecution [1]. biological factors contribute to the development of While public health risks of cannabis legalization may substance-use disorders between men and women [27]. by and large be minimal, certain vulnerable populations Although a higher proportion of men use cannabis, are more susceptible to the deleterious effects of its use. women who use cannabis are more likely to experience One such population are those with substance-use disor- adverse outcomes such as development of cannabis use ders. North America is currently in the midst of an disorder, and may also be more likely to show negative opioid crisis [10], in which we are witnessing a dramatic outcomes from cannabis in other domains such as more increase in non-medical use of opioids and subsequently severe cannabis withdrawal symptoms and [28] and the incidence of opioid use disorder (OUD). While worse mental health and social functioning [29]. A large opioid abuse is associated with serious adverse out- survey of cannabis users, for example, found that a comes, it has been shown that the development of addic- larger proportion of men use cannabis for recreational tion is a major driver in the increase in opioid-related purposes while more women reported using it for pur- morbidity and mortality [11], indicating the extent to poses of self-medication [30]. Thus, motivational pro- which OUD negatively impacts public health. cesses for drug use may differ between men and women. Zielinski et al. Biology of Sex Differences (2017) 8:8 Page 3 of 10 The objective for this study is to investigate sex differ- were provided with a written consent form to read and ences in the association between cannabis use and illicit sign. Eligible participants provided informed written opioid use during methadone maintenance treatment. consent, upon which they underwent
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