Murataeva Natalia, Mattox Sam, Yust Kyle, Straiker Alex
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47401, USA.
Gill Institute for Neuroscience, Indiana University, Bloomington, IN 47405, USA.
Biomolecules. 2025 Mar 24;15(4):472. doi: 10.3390/biom15040472.
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. Δ-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.
流泪和流涎完全依赖于外分泌腺（泪腺和唾液腺）的活动，而阴道湿润和分泌物则依赖于渗出和外分泌的共同作用。外分泌腺疾病影响着数百万人，干燥综合征女性患者常出现干眼、口干以及阴道干燥。大麻使用者抱怨干眼和“口干”是众所周知的，但一些女性大麻使用者也报告有阴道干燥的情况。大麻素信号系统对阴道分泌物的调节基本上尚未得到研究。我们最近报道，尽管实验室小鼠体型小且活动具有夜行性，但它们具有可测量的基础阴道湿润度以及受昼夜节律和发情因素调节的信息素刺激分泌反应。我们在这个模型中测试了大麻素CB1受体对阴道湿润度的调节作用。我们现在报告，大麻素受体激动剂CP55940不会改变基础阴道湿润度，但由于局部阴道周围效应会阻止刺激分泌反应。慢性间歇性给予CP55940会降低基础阴道湿润度，但也会揭示或诱导对CP55940的增强作用，表明存在多个作用位点。急性和慢性效应可能通过CB1受体发生。Δ-四氢大麻酚（THC）是大麻的主要精神活性成分，是CB1的部分激动剂，没有急性或慢性效应。总之，在小鼠模型中强烈急性激活CB1受体不会降低阴道湿润度，但会阻止信息素刺激的阴道分泌反应。相比之下，慢性间歇性激活CB1会降低基础阴道湿润度。这些发现转化到人类的程度还有待确定。
