According to the United Nations Office on Drugs and Crime (UNODC), 228 million adults worldwide used cannabis in 2022 (1). There is a historical sex/gender gap in the prevalence of cannabis use, where men and boys are consistently more likely to use cannabis than women and girls across different metrics of use (e.g., lifetime use, past-month use, daily use) and in many countries globally (2-4). We refer to this as a “sex/gender” gap, as differences in cannabis use are likely driven by both biological and sociocultural factors (2). Importantly, the sex/gender gap seems to be narrowing. For example, the gap in past-month prevalence of cannabis use in the United States (US) declined from a high of 2.125 men to women using cannabis in 2002 to a low of 1.25 men to women in 2020 – which seems to be largely driven by an increase in women’s cannabis use (5). Youth data from the Canadian province of Ontario show that, as of 2023, girls actually have a higher prevalence of cannabis use than boys do (6). Changes in the sex/gender gap in prevalence of use may be driven in part by cannabis legalization and will likely lead to changes in cannabis-related harms, such as prevalence of cannabis use disorder (CUD) (2). CUD is characterized by an inability to cease or reduce cannabis use despite persistent physical and/or psychological harm (7), as defined in the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). While men are more likely to meet criteria for CUD and have greater symptom severity (8-11), women may escalate their use of cannabis faster than men (e.g., fewer years between age of first use and CUD symptom) (8, 10, 12, 13). Recent data-driven work has suggested that there are sex/gender differences in the factors underlying CUD – individual risk factors (e.g., mental health or cognitive factors) had stronger associations with CUD in men, while social-structural risk factors (e.g., low education level) had stronger associations in women (14). More work is needed to better understand how sex and gender impact CUD trajectories, correlates, and treatment and how to integrate this knowledge clinically to improve care for individuals with CUD.

Sex is an umbrella term that refers to complex biological traits and processes necessary for sexual reproduction, including genes and gene expression, hormones, body parts, and all the downstream biological impacts of sex-related gene expression and hormone production. Sex is thus a property of bodies and affects the way that drugs interact with bodies (3). A growing literature has found that gonadal hormones like estrogens, progestins, and androgens (which are essential for sex-related biological processes) can influence drug-seeking behaviours in rodents and the experience of subjective drug states in humans (15-18). For example, female rodents show greater self-administration of cannabinoids than male rodents, yet this sex difference is reduced by ovariectomy (removal of the ovaries, and thus dramatic reduction in ovarian hormone production) (19). The modulation of drug experiences by ovarian hormones is thought to contribute to variability in the risk of progression of drug use in humans (20). Moreover, human laboratory experiments have found that adult female participants experience greater subjective effects of cannabis than male participants under certain conditions (21-23).

Gender is a term that describes the sociocultural context and correlates of sexed bodies – it is a social construct that describes the social meaning of sexed bodies and the organization of that meaning into socially relevant categories. Gender is typically used as an umbrella term to refer to multiple concepts, including gender identity (individual experiences of gender), gender roles and norms (expectations placed on individuals based on their presumed gender), gender relations (how individuals of different genders interact, especially as it relates to power), and institutional gender (the translation of gendered meaning into social institutions, e.g., laws and regulations dictating the distribution of power and resources) (3). Gender roles and norms can influence drug use and harms, e.g., stigmatization and devaluation of women’s drug use partially explains lower drug use and more experiences of sociocultural harms associated with persistent drug use among women (2). The historical association between substance use and masculinity (24) has likely had an important role in shaping sex/gender differences in cannabis use, where men and boys have a higher prevalence of use than women and girls across cultures (2). Performative aspects of gender (i.e., engaging in behaviours to shape or reinforce one’s gender identity or expression) can influence how and why drugs are used and in which contexts (3). In quantitative studies, greater adherence to traditional masculine norms is associated with increased use of cannabis, while adherence to feminine norms is associated with decreased use of cannabis (2, 25). Several studies have focused on initial opportunities to use cannabis, finding that boys can more easily access cannabis than girls (2).

Some nuances about sex and gender are worth noting. First, the scientific literature is increasingly acknowledging that neither sex nor gender are binary (26, 27). Further, there is a distinction between an individual’s gender identity (e.g., woman, man, or non-binary) and their expression or performance of gender (e.g., femininity and/or masculinity) (26, 27). Second, there is an increasing focus on using an intersectional framework in the health sciences to understand how multiple social categories (e.g., gender, race, sexuality) intersect at the individual level to influence health (28). For example, while sexual and gender minorities have a higher prevalence of cannabis use than cisgender, heterosexual people, bisexual women appear to have the highest prevalence of use when examining intersections of gender and sexual identity (29). Complex three-way intersections between gender, sexual, and racial identities have been documented for lifetime substance use (30). To the extent possible, our review will keep these nuances in mind when synthesizing and interpreting the results of the identified literature.

There are no currently approved pharmacological treatments for CUD, so CUD treatment primarily involves psychological and psychosocial interventions (31). The current evidence favours both motivational enhancement therapy (MET) and cognitive behavioural therapy (CBT) for treatment of CUD, while contingency management has shown promise in some studies as well (32). Gender likely influences psychosocial interventions. For example, previous studies have found that women with anxiety disorders attend more psychotherapy sessions, are more engaged in therapy, and view psychotherapy as more helpful when compared to men (33). Meta-analysis has identified that women with psychiatric disorders are more likely to prefer psychotherapy over pharmacotherapy when compared to men (34). Pharmacological interventions for CUD have been tested in clinical trials, with the strongest evidence in favour of drugs that target the endocannabinoid system, though the evidence is still weak and more randomized controlled trials are needed to establish efficacy (31). Importantly, there are sex differences in the endocannabinoid system. For example, circulating levels of endocannabinoid ligands fluctuate across the rodent estrous cycle (a hormonal cycle analogous to the human menstrual cycle) (35) and ovariectomy causes a change in density of the cannabinoid type-1 receptor (CB1R) that is reversed by administration of exogenous estradiol (36). Thus, both sex and gender have the potential to influence various CUD treatment approaches. Furthermore, sex/gender differences in comorbidities have the potential to influence CUD treatment. For example, studies have consistently documented a stronger association between CUD and poorer mental health among women than among men, particularly mood and anxiety symptoms (37-41).

Previous narrative reviews have highlighted broad relationships between sex, gender, and cannabis (e.g., 2, 15). Systematic reviews have each provided a specific piece of the puzzle – how sex interacts with cannabis use to impact the brain (42), changes in the sex/gender gap in the prevalence of cannabis use (43), and sex differences in the comorbidity of CUD with mental illness (44). Finally, a large scoping review was undertaken pre-2020 that broadly covered the influence of sex and gender on cannabis use and related outcomes (3, 25), including one paper that specifically focused on sex- and gender-based analysis in trials of pharmacological interventions for CUD (45). However, what is currently missing is a structured overview of all clinically relevant literature relating sex, gender, and intersecting social categories to problematic cannabis use and CUD to inform prevention and treatment of CUD. We chose a scoping review to account for the breadth of evidence that is necessary to be clinically meaningful, and to help us organize the existing evidence to identify significant knowledge gaps necessary to advance care. We chose to use the Arksey and O’Malley (2005) framework for scoping reviews (46) as this is the most commonly used scoping review methodology (47).