The use of cannabis for therapeutic purposes is legal in 39 U.S. states, three U.S. territories, and the District of Columbia, while 24 states, three territories and the District of Columbia have enacted measures to regulate cannabis for non-medical, recreational use (National Conference of State Legislatures (NCSL), 2025). Research on the therapeutic benefits of cannabis is mixed, with the most support for chronic pain, chemotherapy-induced nausea and vomiting, and patient-reported spasticity symptoms associated with multiple sclerosis (National Academies of Sciences, Engineering, and Medicine, 2017). Potential undesirable effects associated with cannabis use include addiction, adverse brain changes, and impaired attention, memory, and learning (Volkow et al., 2014).

Adverse effects of cannabis use may be exacerbated in the context of the co-use of cannabis with other substances (Tucker et al., 2019; Yurasek et al., 2017). In fact, cannabis, cigarette, and alcohol consumption have been shown to increase the odds of same day co-use (i.e., using one of the other substances) and tri-use (i.e., using both of the other substances; Roche et al., 2019). Moreover, cannabis and cigarette co-use has been associated with cannabis use disorder onset, persistence, and relapse over time (Weinberger et al., 2021). In addition, cannabis and alcohol co-use has been associated with higher odds of alcohol use disorder (Waddell, 2022).

Individuals who use cannabis and cigarettes tend to report heavier cigarette and cannabis use in addition to worse overall physical and mental health compared to individuals who use only one or the other (Tucker et al., 2019). Additionally, co-use of cannabis and cigarettes may result in increased exposure to carbon monoxide, toxicants, and carcinogens, depending on the product and method of administration (e.g., smoking combustible products). Cannabis and alcohol co-use has also been associated with a number of adverse consequences, including impaired cognitive performance, behavioral and social consequences (e.g., legal issues, lower academic achievement, high-risk sexual behaviors, driving while intoxicated), risk of abnormal brain development in adolescence, and poor mental health (e.g., co-occurring substance use disorders, anxiety disorders, mood disorders; Yurasek et al., 2017). Cannabis use disorder, cigarette dependence, and alcohol use disorder are highly comorbid with one another and their co-use can interfere with efforts to reduce or quit each substance (McClure et al., 2020). For these reasons, it is important to understand potential modifiable risk factors that may contribute to the use of other substances, including cigarettes and alcohol, among people who use cannabis for therapeutic purposes.

Psychological inflexibility is characterized by an unwillingness to experience distressing feelings, emotions, or sensations, with attempts to avoid or control them (Hayes-Skelton & Eustis, 2020) and is one such modifiable factor. Specifically, this refers to one’s ability to “be present,” or to fully engage in whatever you are doing, to “open up,” or to allow oneself to experience one’s thoughts and feelings, and to “do what matters,” or to act in accordance with one’s values (Harris, 2022). Psychological inflexibility, a promising target in the treatment of substance use disorders (De Groot et al., 2014; Gloster et al., 2020), is the opposite of psychological flexibility and refers to one’s inability to fully experience the present moment without trying to change it or its accompanying thoughts and emotions (Hayes et al., 2006).

This inability has been associated with increased substance use (Farris et al., 2015a, 2015b; Luoma et al., 2020) as individuals commonly use substances to try to avoid or distract themselves from uncomfortable internal experiences (e.g., negative thoughts, feelings, sensations). In addition, it has been linked to a number of alcohol-related problems (e.g., problematic alcohol use, academic difficulties, interpersonal problems, high risk or illegal behavior, health consequences; Luoma et al., 2020) and cigarette smoking-related problems (e.g., cigarette dependence, difficulty quitting smoking, perceived barriers to quitting smoking, lower motivation to quit smoking, positive smoking expectancies, greater withdrawal, worse cravings; Buckner et al., 2015; Farris et al., 2015a, 2015b). Thus, psychological inflexibility represents an important risk factor and treatment target for the persistent use of substances, such as alcohol and cigarettes.

Despite research highlighting increased substance use severity and difficulties quitting among individuals who co-use cannabis with other substances (e.g., cigarettes, alcohol), there is minimal research on psychological inflexibility and substance co-use. Most existing research in this area has examined the role of psychological inflexibility and use of individual substances (e.g., cigarettes or alcohol) or substance use disorders in general as opposed to co-use of specific substances (e.g., cannabis and cigarettes; cannabis and alcohol). Moreover, to the authors’ knowledge, only one study has examined psychological inflexibility and cannabis use. Bordieri and colleagues found that psychological inflexibility moderated the relationship between cannabis use severity and posttraumatic stress symptom severity such that higher levels of posttraumatic stress were associated with greater risk of cannabis use disorder only among individuals with psychological inflexibility (Bordieri et al., 2014). Although this sample recruited individuals from a residential substance use treatment program, the authors did not specifically report on participants’ co-use of other substances. Nonetheless, this study highlights that one’s level of psychological inflexibility may differentially impact the relationships between other variables (e.g., posttraumatic stress) and cannabis use among individuals with substance use disorders.

Distress tolerance may also impact the relationship between psychological inflexibility and the co-use of cannabis with cigarettes or alcohol. Distress tolerance is considered conceptually distinct from psychological inflexibility. Distress tolerance refers to one’s perceived or actual ability to withstand negative internal states (Zvolensky, 2011), whereas psychological inflexibility refers to one’s unwillingness to contact the present moment and attempts to avoid, alter, or control negative emotional states. Thus, it is possible that an individual who views negative internal states as intolerable (i.e., low distress tolerance) may be highly motivated to avoid, reduce, or control them (i.e., demonstrate high psychological inflexibility) through various means, including by engaging in substance use. Distress tolerance is commonly associated with smoking cessation lapse (Veilleux, 2019), and is associated with problematic alcohol use both directly (Zegel et al., 2021) and indirectly through coping motives (Pilatti et al., 2022), physiological stress reactivity (Holzhauer et al., 2017), cognitive schemas (Simons et al., 2018), depressive symptoms (Brooks Holliday et al., 2016), and posttraumatic stress symptoms (Brooks Holliday et al., 2016).

Due to the high prevalence and negative consequences associated with the co-use of cannabis with cigarettes and alcohol, it is important to identify factors (e.g., psychological inflexibility, distress tolerance) that may relate to greater cigarette smoking and alcohol use among individuals who use cannabis for medical purposes. By identifying these factors, mental health professionals can design interventions to reduce the likelihood of substance co-use and be aware of potential therapeutic targets that may serve as a focus of psychotherapy to reduce distress and increase life satisfaction (Karekla et al., 2025; Weststrate et al., 2023). It is especially important to examine these factors in samples using cannabis for therapeutic purposes because policy changes have increased the use of cannabis among individuals already suffering from physical and psychiatric distress (Rhee & Rosenheck, 2023).