How Estrogen Increases the Body’s Sensitivity to Cannabinoids

Scientific research shows that the structure of the female and male brain has certain differences. These differences are observed not only in humans but also across the entire animal kingdom. This phenomenon, known as “sexual dimorphism,” is also present in other parts of the body, from the reproductive organs to the structure of brain nerve cells and overall behavioral patterns. For this reason, psychoactive substances—including the active components of marijuana—affect male and female bodies somewhat differently.

For many years, scientists studying the therapeutic properties of marijuana paid little attention to these physiological differences between the sexes, mostly conducting cannabinoid trials on male animals. This approach was chosen not only for convenience but also to avoid the influence of natural hormonal fluctuations on the effects of the substances. As a result, until recently, most medical knowledge about the effects of THC and CBD was based on studies of male organisms and brains. Now, recognizing this oversight, researchers have begun actively studying how sex hormones affect the activity of endocannabinoid receptors. New studies conducted in early fall show that the “female” hormone estrogen directly interacts with cannabinoid metabolites, significantly enhancing their effects. This may explain why women can be not only more sensitive to the therapeutic and recreational properties of marijuana but also more susceptible to negative consequences from frequent and prolonged use.

Increased Sensitivity of Females to Cannabinoid Effects

According to a number of laboratory studies conducted on both male and female mice and rats, scientists found that, overall, females are more sensitive to both the positive and negative effects of cannabinoids—with one exception: compared to males, female animals showed less interest in food after receiving doses of cannabinoids.

It’s important to note that the female body is more sensitive not only to the intoxicating effects of marijuana but also to its therapeutic properties. Female rats experienced the pain-relieving effects of THC and CBD for noticeably longer than males. Additionally, researchers observed another interesting pattern: while cannabinoids somewhat suppressed sexual desire in male animals, they significantly increased libido in females. Of course, this phenomenon also applies to the negative side effects of cannabinoids, such as the risk of panic attacks from THC overdose and the development of depression after abruptly stopping marijuana use.

This pattern is also seen in the formation of psychological dependence on marijuana. One study notes that the increased effect of THC on CB1 receptors is likely the main factor explaining why female rats are more prone to frequent use compared to males. Currently, doctors believe that these differences in cannabinoid effects are due to the influence of sex hormones on the expression and sensitivity of endocannabinoid receptors in different areas of the brain.

The Interaction of Cannabinoid Receptors and Estrogen

As mentioned earlier, sex hormones (testosterone in men and estrogen in women) play a major role in differentiating the physiology of all sexually reproducing animals. It’s logical that, as with other biological systems, estrogen determines the development and sensitivity of the endocannabinoid system, which in turn explains the observed differences in cannabinoid effects between males and females.

Research shows that, on average, female organisms have a noticeably higher concentration of endocannabinoid receptors throughout their organ systems. Additionally, the level of these receptors in women can fluctuate due to hormonal changes during menstrual cycles and pregnancy.

Accordingly, a high concentration of estrogen makes CB1 receptors—which modulate the function of all biological systems—certain areas of the brain more sensitive to cannabinoids. Doctors have also noticed that increased estrogen levels significantly boost the production of anandamide, an endogenous cannabinoid compound that affects the sensitivity of CB receptors to active substances. As a result, THC, which directly activates CB1 receptors, has a stronger and longer-lasting effect on the body when estrogen levels in tissues are high.

Why Estrogen?

At the earliest stages of development, even in the womb, the release of estrogen or testosterone triggers the differentiation of the body’s structure into female or male, respectively. In addition to influencing the overall physiological structure, these hormones also affect the brain’s organization, predisposing each sex to certain behaviors and heightened sensitivity to specific emotions. During puberty, the female body begins to actively produce estrogen, making it especially sensitive to all effects of cannabinoids during this period.

For this reason, early exposure to marijuana can potentially have a negative impact on the development of brain structure in females. Scientists suggest that the psychoactive effects of certain cannabinoids, particularly THC, alter the natural balance of anandamide in brain regions responsible for motivation and emotional regulation, changing their structure to some extent. (It’s worth noting that cannabinoids similarly affect male brain development, which is why doctors advise young people to avoid marijuana use until brain formation is complete—a process directly regulated by the endocannabinoid system.)

Since THC is a direct stimulant of CB1 receptors, which are abundant in the brain, it can disrupt the natural developmental processes. Therefore, estrogen’s ability to enhance the effects of cannabinoids greatly increases the risk of structural abnormalities in various brain regions. This is confirmed by another study, which found that young women who regularly use marijuana have a larger amygdala compared to non-users. Since this brain region is responsible for regulating and expressing emotions, abnormalities in its size were associated with a higher tendency toward anxiety or depression.

It’s important to note that these studies measured only the effects of THC on development. It’s possible that other cannabinoids, particularly CBD, may balance these effects by blocking CB1 receptors. To date, scientists have already confirmed CBD’s ability to suppress the negative side effects of THC in both humans and animals, suggesting that CBD may help protect the developing brain from structural changes.