Cannabidiol as a potential reversal treatment for anxiety in an experimental model of menopause and prospective case translation considering racial differences in women

Abstract

Studies have indicated that estrogen depletion, marked by the period of menopause in women, can lead to the appearance of mood disorders, such as anxiety, which probably involves the serotonergic system. Cannabidiol (CBD) is the main non-psychotropic constituent of the Cannabis sativa plant, and there is already evidence in the literature about its anxiolytic properties. However, the mechanisms of action that may be associated with it have not yet been fully described. Because CBD modulates pathways in common with estrogen, it is hypothesized that it may be responsible for reversing the anxiety associated with the hormonal decline observed during the menopause. Therefore, this study aims to evaluate CBD as a potential reversal treatment for estrogen depletion-induced anxiety in an animal model of menopause and to investigate whether the associated mechanism of action may be related to the modulation of key targets of the serotonergic system. In addition, this work proposes a brief discussion on racial differences in symptomatology and treatment of menopausal women. Experimentally, groups of adult female wistar rats were submitted to bilateral ovariectomy and subsequent pharmacological treatment with CBD or vehicle. The elevated plus maze and the open field behavioral tests were performed to evaluate the animals' anxiety. Afterwards, the rats were euthanized and the hippocampi were collected for molecular analysis. The results showed that ovariectomized rats have anxiety-like behavior related to estrogen depletion, and that treatment with CBD helps to reverse this condition, potentially by regulating the 5-HT1A receptor and the SERT transporter mRNA expression, thus acting as a possible therapeutic alternative. Furthermore, it is important to consider race in health studies, as well as to start this debate in pre-clinical research.