Review articleSex differences in cannabinoid-regulated biology: A focus on energy homeostasis

- Sex differences are fundamental to cannabinoid-regulated biology.
- Males are more sensitive to the appetite-stimulating properties of cannabinoids.
- Sex steroid hormones have divergent roles in determining cannabinoid sensitivity.

Considerable strides have been made over the past 20 years in our understanding of the ligands, receptor subtypes, signal transduction mechanisms and biological actions comprising the endocannabinoid system. From the ever-expanding number of studies that have been conducted during this time, it has become increasingly clear that sex differences are the cornerstone of cannabinoid-regulated biology. Available evidence has demonstrated that these sex differences endure in the absence of gonadal steroids, and are modulated by the acute, activational effects of these hormones. This review focuses on select aspects of sexually differentiated, cannabinoid-regulated biology, with a particular emphasis on the control of energy balance. It is anticipated that it will lend impactful insight into the pervasive and diverse disparities in how males and females respond to cannabinoids - from the organismal level down to the molecular level. Additionally, it will furnish a newfound appreciation for the need to recalibrate our thinking in terms of how cannabinoids are used as therapeutic adjuvants for a broad range of clinical disorders and associated comorbidities, including body wasting and obesity.