Cannabinoid Regulation of Murine Vaginal Secretion

Tearing and salivation are wholly dependent on the activity of exocrine (lacrimal and salivary) glands, whereas vaginal moisture and secretion rely on a combination of exudation and exocrine secretion. Exocrine gland disorders impact millions, and women with Sjögren's Syndrome often experience dry eye and mouth as well as vaginal dryness. Cannabis users' complaints of dry eye and 'cottonmouth' are well-known, but some female cannabis users also report vaginal dryness. The regulation of vaginal secretion by the cannabinoid signaling system is essentially unstudied. We recently reported that despite their small size and nocturnal nature, laboratory mice have measurable basal vaginal moisture and pheromone-stimulated secretory responses that are regulated by circadian and estrous factors. We tested the regulation of vaginal moisture by cannabinoid CB1 receptors in this model. We now report that the cannabinoid receptor agonist CP55940 does not alter baseline vaginal moisture but prevents a stimulated secretory response due to a local peri-vaginal effect. Chronic intermittent CP55940 reduces basal vaginal moisture but also unmasks or induces a potentiating effect for CP55940, suggesting multiple sites of action. The acute and chronic effects likely occur via CB1 receptors. Δ⁹-tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, a partial agonist at CB1, has no acute or chronic effects. In summary, strong acute activation of CB1 receptors in a murine model does not reduce vaginal moisture but does prevent a pheromone-stimulated vaginal secretory response. In contrast, chronic intermittent CB1 activation reduces baseline vaginal moisture. The extent to which these findings translate to humans remains to be determined.