August 2025

Cannabis and cognition: does gender make a difference?

According to the 2024 Canadian Cannabis Survey, cannabis is currently the most widely used and socially accepted psychoactive substance in Canada, after alcohol and tobacco (2024 Canadian Cannabis Survey). This social acceptability, stemming from its recent legalization, has opened the door for research to explore its benefits and reduce its potential harms, even though cannabis remains one of the most extensively documented and long-recognized substance. Among its many pharmacological and health effects, several studies have examined its link to cognition. Cognition encompasses all mental processes involved in perception, understanding, reasoning, etc. Cannabis thus plays a major role in working memory, sustained attention, and other executive functions that have been described repeatedly in humans (Kroon 2021). But do these effects differ by sex and gender ?

A recent systematic review by Matheson et al. examined this subject and summarizes that women may be more sensitive to the acute effects of cannabis, particularly regarding memory and attention (Matheson 2025). Thus, for a given dose of cannabis, females appear to have greater difficulty maintaining information in working memory. In contrast, males appear to experience more persistent cognitive impairments (psychomotor and cognitive speed) associated with chronic use (Schnakenberg Martin 2022). Other previous studies exploring these factors have also reported that women report more pronounced subjective effects from cannabis than men (Cuttler 2016).

These variations in effects depending on gender and sex can be partially explained by the differential modulation of the endocannabinoid system by sex hormones interacting with the environment. More specifically, estrogen interacts with CB1 cannabinoid receptors by modulating their density in certain brain regions, acting on synaptic plasticity regulation systems via intracellular pathways and therefore influencing the cognitive response to THC (Simons 2024). Interaction with the environment (stress factors, diet, social environment) can be observed through epigenetic mechanisms that impact the expression of CB1 receptors and the activity of enzymes in the endocannabinoid system (Machado 2024). Furthermore, taking into account the higher fat composition in women and the strong lipophilicity of THC, the metabolism, distribution within tissues, and elimination of cannabis may be influenced, leading to greater storage of THC in women and prolonged continuous release compared to men, affecting plasma cannabinoid levels and, potentially, some of the functions of the ECS. Finally, other factors such as gender-related social and psychological determinants (cannabis use patterns, contexts of use) may accentuate or attenuate these observed differences in effects.

These results, although preliminary, highlight the importance of systematically incorporating an analysis that includes sex and gender into studies measuring the acute and chronic effects of cannabis use. In an even broader context, these data underscore the importance of adopting a personalized approach to research on the effects of cannabis and cannabinoids, considering interindividual differences that may explain their variability and open new avenues for exploration. In a public health context, these findings can strengthen prevention messages by refining content and target audiences to reduce the risks associated with non-therapeutic cannabis use. Sexual differences, which are still not fully understood, open a crucial field of research that could lead to the adaptation of clinical and public health recommendations.

Article by Amani Mahroug