Melatonin supplementation reversed cannabis-induced disruption of reproductive hormones in female rats, with effects mediated primarily through CB1 receptors.
Researchers studying cannabis and reproductive health, and women interested in how cannabis may affect hormonal balance.
CB1 causes more hormonal disruption than CB2
What the researchers found
Cannabis extract significantly altered levels of GnRH, FSH, LH, estradiol, progesterone, and prolactin in female rats. Blocking CB1 receptors caused more hormonal disruption than blocking CB2, suggesting CB1 primarily disrupts the hypothalamic-pituitary-gonadal axis. Melatonin ameliorated these effects even when cannabinoid receptors were blocked.
Why it matters
This study provides mechanistic evidence for how cannabis might disrupt female reproductive hormones and identifies a potential protective strategy. The finding that CB1 receptors play a larger role than CB2 in hormonal disruption adds specificity to our understanding.
The numbers in context
50 female rats in 10 groups of 5. Treatment lasted 14 days. Cannabis extract dose: 2 mg/kg. Melatonin dose: 4 mg/kg. CB1 blockade caused more hormonal toxicity than CB2 blockade.
How the study worked
Fifty female Wistar rats were divided into 10 groups receiving various combinations of cannabis extract, CB1 blocker (rimonabant), CB2 blocker (AM630), and melatonin over 14 days. Reproductive hormones were measured using ELISA assays.
What this study cannot tell us
Animal study with only 5 rats per group, limiting statistical power. Short 14-day treatment period. Rat reproductive physiology differs from humans. The cannabis extract dose may not reflect typical human consumption patterns.
How to read the evidence
Small animal study with 5 rats per group over a short treatment period. Findings are mechanistically interesting but far from clinical application.
When this study was published
2026 animal study.
The bigger picture
With rising cannabis use among women of reproductive age, understanding how cannabis affects reproductive hormones is increasingly relevant. The melatonin finding, while preliminary, opens a line of inquiry into protective supplementation.
Questions still open
- Would melatonin supplementation have similar protective effects in humans? Are the hormonal changes observed at this dose relevant to typical human cannabis consumption levels?
Common questions
Does cannabis affect female reproductive hormones?
Could melatonin actually protect against these effects in people?
Read the original research
Melatonin mitigates hormonal toxicity in cannabis-treated female Wistar rats: involvement of cannabinoid receptor.
Journal of cannabis research, 8(1), 27
Citation
Oluwasola, A. (2026). Melatonin mitigates hormonal toxicity in cannabis-treated female Wistar rats: involvement of cannabinoid receptor.. Journal of cannabis research, 8(1), 27. https://doi.org/10.1186/s42238-025-00375-8
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