Melatonin mitigates hormonal toxicity in cannabis-treated female Wistar rats: involvement of cannabinoid receptor

Abstract Background Consumption of Cannabis sativa (CS), a well known psychoactive substance may impose threat on the hormonal activities of the body, hence, a protective measure is needed to prevent this threat. This study investigates the effects of melatonin and CS together with its receptors (cannabinoid receptors 1 and 2) on hormonal toxicity in female rats. Methods Fifty female rats were assigned into ten groups of five animals each, such that the rats in groups 1,2,3,4, 5, 6, 7, 8, 9, and 10 received orally 1mL distilled water, 2 mg/kg of ethanolic extract of Cannabis sativa (EECS), 2 mg/kg of cannabinoid one receptor (CB 1 R) blocker (rimonabant hydrochloride), 2 mg/kg of cannabinoid two receptor (CB 2 R) blocker (am630), 2 mg/kg of CB 1 R blocker + 2 mg/kg of EECS, 2 mg/kg of CB 2 R blocker + 2 mg/kg of EECS,2 mg/kg of CB 1 R blocker + 2 mg/kg of CB 2 R blocker + 2 mg/kg of EECS,4 mg/kg of melatonin,2 mg/kg of CB 1 R blocker + 2 mg/kg of EECS + 4 mg/kg of melatoninand2mg/kg of CB 2 R blocker + 2 mg/kg of EECS + 4 mg/kg of melatonin, respectively for 14 days. Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E), progesterone, and prolactin were quantified according to the instruction provided by assay kit manufacturers, using microplateimmunoenzymometric (EMA/ELISA) assays. Results CS significantly ( p  < 0.05) decrease GnRH, FSH, LH, E, progesterone, and prolactin levels respectively when compared with the control. However, blockage of either cannabinoid receptors 1 or 2 significantly ( p  < 0.05) increase the levels of all these reproductive hormones when compared to the CS-treated group. Although, that of the former was more than the latter. All these effects were ameliorated by melatonin when the cannabinoid receptors (1 and 2) were stimulated and blocked. Conclusion This study concluded that the gonadotoxic effects of CS could be mediated by endocrine disruption caused by cannabinoid receptors 1 and 2. In addition, CB 1 primarily disrupts hypothalamic-pituitary-gonadal axis. Thereby causing more hormonal toxicity than CB 2 which mainly influence hormonal imbalance indirectly through immune modulation. However, these effects could be ameliorated by melatonin. The study suggests that melatonin could be used as a supplement to prevent the gonadotoxic effects of CS.