The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity

Abstract

Cannabis is the most commonly used illicit drug worldwide. Although its use is associated with multiple adverse health effects, including the risk of developing addiction, recreational and medical cannabis use is being increasing legalized. In addition, use of synthetic cannabinoid drugs is gaining considerable popularity and is associated with mass poisonings and occasional deaths. Delineating factors involved in cannabis use and addiction therefore becomes increasingly important. Similarly to other drugs of abuse, the prevalence of cannabis use and addiction differs remarkably between males and females, suggesting that sex plays a role in regulating cannabinoid sensitivity. Although it remains unclear how sex may affect the initiation and maintenance of cannabis use in humans, animal studies strongly suggest that endogenous sex hormones modulate cannabinoid sensitivity. In addition, synthetic anabolic-androgenic steroids alter substance use and further support the importance of sex steroids in controlling drug sensitivity. The recent discovery that pregnenolone, the precursor of all steroid hormones, controls cannabinoid receptor activation corroborates the link between steroid hormones and the endocannabinoid system. This article reviews the literature regarding the influence of endogenous and synthetic steroid hormones on the endocannabinoid system and cannabinoid action.

Investigating the cumulative effects of Δ9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats

“…The sex-dependent THC effects in time to right and open field, do however suggest that females may be more sensitive to the effects of THC at this time period. This finding is consistent with accumulating evidence demonstrating that sex is an important modulator of cannabinoid sensitivity resulting in a sexually dimorphic endocannabinoid system ( Struik et al , 2018 ). Overall however, we failed to support our hypothesis that THC prior to RmTBI conferred neuroprotection.…”

Anabolic androgenic steroid abuse in the United Kingdom: An update

“…It is actually possible that anabolic androgenic steroid use creates a vulnerability in the user to develop a dependence syndrome. Animal studies have highlighted the importance of sex hormones as modulators of drug sensitivity (Marusich, Craft, Lefever, & Wiley, ; Struik, Sanna, & Fattore, ). Chronic anabolic androgenic steroid use is understood to suppress the endocannabinoid system (Struik et al, ), with consequent reduction in reward function (Seitz et al, ; Wallin, Alves, & Wood, ).…”

Sex and Gender Interactions on the Use and Impact of Recreational Cannabis

“…Studies examining the neural regions of rats have reported greater CB1 receptor desensitization and downregulation in females, which may in part explain cannabis telescoping among females [33]. In addition, sex hormones may modulate cannabinoid sensitivity [34][35][36]. However, studies on the influence of sex hormones on responses to cannabinoids in humans are lacking [21].…”