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Estrogen

Why Women Benefit More From Cannabis Use

Pain relief may be linked to estrogen levels.

Key points

  • Women respond differently to cannabis than men.
  • The behavioral and neurobiological effects of cannabis in females have different magnitudes depending on the level of sex hormones.
  • Females may be more sensitive to the pain-relieving and euphoric effects of cannabis than males.

Women respond differently to cannabis than men. Females report experiencing a greater "High" than male participants when given a relatively low dose of THC (0.015 mg/kg). Females tend to progress to tolerance and dependence faster than males after initiation of regular cannabis use.

Cannabis use is associated with improved sexual function among females, but not males. A recent study demonstrated that cannabis helps women orgasm who have difficulty having orgasms, enhances the frequency and quality of women's orgasms, and, of clinical relevance, helps women orgasm who have a female orgasmic disorder.

The behavioral and neurobiological effects of cannabis in females have different magnitudes depending on the level of sex hormones. Recent studies have investigated the interaction between fluctuations in the levels of the female sex hormones estrogen and prolactin and exogenously administered cannabinoids.

It is well known that cannabis increases prolactin release in males, causing gynecomastia (aka, man-boobs); in contrast, cannabis has no direct effect on prolactin levels in females. Female sex hormone fluctuations, especially estrogen, alter the function of the brain’s endocannabinoid system in a region-dependent manner.

While the number of cannabinoid receptors in the limbic system (a collection of brain regions that control emotional responses) does not fluctuate, the responsiveness of the CB1 receptor, the receptor responsible for allowing us to experience euphoria, becomes much greater when estrogen levels are increasing.

When estrogen levels in the blood become elevated, the pituitary levels of the brain’s endocannabinoid transmitters, 2-AG and AEA, are also significantly elevated. Taken together, these neurobiological changes might explain why women experience a greater level of euphoria at lower doses of THC.

No one currently understands the neurological mechanisms underlying these region-specific changes, and less is known about the effects of administering exogenous cannabinoids to cycling females.

One recent study reported that administration of a relatively small dose of THC induces a greater degree of anti-nociception (pain reduction) when estrogen levels are elevated. This anti-nociceptive action also correlates with a time when the endocannabinoid receptors in the PAG (a brainstem region responsible for blocking incoming pain signals) are more responsive, and endogenous levels of endocannabinoid neurotransmitters are elevated.

Estrogen does not bind directly to the brain’s endocannabinoid receptors; however, it clearly interacts with how cannabinoids, both exogenous and endogenous, influence brain function. For example, 2ithin the hippocampus, a brain region responsible for forming new memories, estrogen acts at its receptor to increase the release of the endocannabinoid AEA, which, paradoxically, increases the activity within this brain region.

The importance of these changes remains on how the brain consolidates memories to be determined. Overall, due to the regular fluctuation in sex hormones, particularly estrogen, females may be more sensitive to the pain-relieving and euphoric effects of cannabis than males.

Facebook image: Canna Obscura/Shutterstock

References

Mulvehill S, Tishler J (2022) Four theories support a hypothesis that cannabis may be a treatment for female orgasmic disorder. The Journal of Sexual Medicine, 19(5):S209-S210

Nia AB et al (2022) Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC). Psychopharmacology 239 (5):1621-1628

Kim HJJ et al (2022) Impact of the mouse estrus cycle on cannabinoid receptor agonist-induced molecular and behavioral outcomes. Pharmacological Research Perspectives 10:e00950

Kasman AM et al (2020) Assessment of the association of cannabis on female sexual function with the female sexual function index. Sexual Medicine 8(4):699-708

Click on these links if you would like to learn more about the endocannabinoid system or PAG.

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