Sex-specific responses to cannabis exposure: Implications for behavior and beyond

Cannabis is one of the most widely used psychoactive substances worldwide, with a growing interest in its potential therapeutic applications. In recent years, there has been a significant increase in cannabis use, driven by the progressive legalization and acceptance of recreational usage. Despite the expanding legalization and use of cannabis, the effects of this substance on various physiological systems and behaviors are not fully understood. Accumulating evidence suggests that cannabis exposure may elicit sex-specific effects, highlighting the importance of considering sex as a biological variable in cannabis research. Sex can affect many behavioral outcomes, thus these differences should be considered when looking at the continuation of cannabis legalization. Despite the growing recognition of the importance of sex differences in research, the current literature on cannabis use and its effects has not adequately addressed these differences. Understanding sex differences in cannabis use is crucial for developing treatment strategies and informing public health policies. This scoping review aims to address these gaps and highlight instances of sex-specific behavioral responses to cannabis exposure. The purpose of this review is to: 1) give an overview of cannabis, the endocannabinoid system, and sex-differences in scientific literature, 2) provide an overview of the current state of knowledge regarding sex differences in cannabis use, 3) examine how sex differences can influence the behavioral effects of cannabis use. This review will predominantly focus on tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis. By synthesizing the available literature, this scoping review seeks to identify gaps in our understanding and guide future research efforts in this field.