As cannabis grows in popularity, many are turning to established research to get an idea of how the drug will affect their body. However, the research contains a gap: most studies on the effects of cannabis have been conducted on males. This is because scientists have long considered male rats better research subjects than females, as their hormones fluctuate less.

As such, we’re now in a situation where our understanding of how cannabis affects the body is biased towards men. This is not ideal, especially as research shows that cannabis interacts directly with the oestrogen pathways of the female body. With women’s interest in cannabis growing at a far faster rate than men’s, we need better information on how sex differences influence the effects of cannabis. Here, we’ll be exploring the chemical dance between cannabinoids and oestrogen, and what that means for female users.

MECHANISM OF ACTION

Oestrogen and cannabinoids interact with many of the same pathways in the human brain and body. One study showed that males and females have different cannabinoid type 1 receptor (CB1) densities in different parts of the brain. They isolated oestrogen as a likely causative factor in this difference. Women have a greater CB1 density in the amygdala, which is involved in emotion, and a lower density in the hypothalamus, which is involved in hunger. Receptor difference in the hippocampus—involved in memory—also seems to be influenced, but the interaction is complex.

This altered neural landscape produces a state of affairs where cannabis affects female or oestrogen-treated brains differently than male brains. In many ways, it makes female brains more sensitive to the effects of cannabis.

The Influence Of Estrogen And Cannabis

PAIN RELIEF AND TOLERANCE

A recent study from the University of Washington has shown that oestrogen makes female rats 30% more sensitive to the pain-relieving effects of cannabis, and that they also develop tolerance much more quickly. Female rodents are much more likely to compulsively self-administer THC than males, suggesting a lower threshold for dependence.

What does this mean for us humans? It could be good news for female pain sufferers looking to find relief with cannabis—it’s likely they’ll benefit with significantly less than the standard dose. That being said, female smokers need to keep an eye on their tolerance—they may need to up their dose much more quickly than their male counterparts to maintain the same effects. Researchers warned that this could mean women are more susceptible to the negative effects of cannabis, including anxiety, paranoia, and even addiction.

The same research found that female rats' sensitivity to THC fluctuates along with their menstrual cycle. The rats were most sensitive around ovulation when the oestrogen level was spiking.

EMOTION AND MEMORY

The higher concentration of CB1 receptors in women’s amygdala may be responsible for the differing emotional effects that men and women experience with cannabis. The amygdala is associated with fear and negative emotion, and women who smoke THC-rich cannabis are more likely to get anxious than men. However, more women seek out CBD-rich strains, which have the opposite effect on CB1 receptors and may act to reduce anxiety. Moreover, studies have shown that women who engage in chronic cannabis smoking in their teen years have a larger amygdala, and are more sensitive to anxiety and negative emotion.

Cannabis also interacts with the female hormonal system where it acts as an aphrodisiac—many women report feeling more sexual and easily aroused while high. This is the opposite of men, for whom cannabis sometimes causes sexual dysfunction. However, very high levels of cannabis may flood out the oestrogen system and inhibit sexsyual functioning in females.

Finally, women seem to be more sensitive to the detrimental effects of cannabis on memory. This is likely related to the effects of oestrogen in modulated CB1 density in the hippocampus.

Cannabis And Female Hormonal System

ONE EXCEPTION

Remember the hypothalamus? It turns out it's responsible for one of the few areas where females are less sensitive than males to the effects of cannabis. The hypothalamus regulates hunger, and males experience the munchies much more severely than females. A study on guinea pigs showed that males consumed 62% more than usual, while females only consumed 23% more.

Why is this? Cannabis activates CB1 receptors in the hypothalamus, which prompt the release of hunger-promoting hormones. Oestrogen partially blocks CB1 activation in this part of the brain, thereby reducing the munchies. The munchies will be at their lowest during ovulation when oestrogen level is at its peak.

Men are also more likely to get the chills from cannabis—studies have shown that females experience less of a drop in body temperature than males. This may also be down to oestrogen and the hypothalamus.

EFFECTS OF CANNABIS ON THE UTERUS

We’ve seen how oestrogen could influence the effects of cannabis, but could the causality run the other way? Could cannabis have an effect on the female reproductive system?

Research has shown that condensed marijuana smoke does seem to influence the behaviour and appearance of uterine and other reproductive cells in women, mainly by competing with oestrogen for binding sites in the uterus. Interestingly, pure THC did not demonstrate this effect, nor did most cannabinoids. Only CBD and certain flavonoids demonstrated this behaviour in isolation.

Whatever this interaction means, it may be beneficial. Many women report using cannabis strains high in CBD to treat PMS, cramps, and other painful menstrual symptoms.

Can cannabis disrupt the female menstrual cycle? The research is mixed. Animal studies have shown that cannabis can influence hormone levels in a way that causes increased rates of ovulation, but the research in humans is less clear. Chronic use seems to normalise disruption of the reproductive cycle, but not necessarily to the level of pre-use. Further, timing might be key; a toke during the luteal phase may cause a massive effect, while one in the follicular phase might not.

Oesstrogen Influence The Effects Of Cannabis

VARIATION IN STRAIN PREFERENCE

Given all we’ve seen about how cannabis interacts with female biology, it’s no surprise that women have different strain preferences. Research from Leafly has shown that the three most searched strains by women are Blue Dream, Girl Scout Cookies, and Sour Diesel. Women seem to prefer sativas and uplifting hybrid strains to the “chiller” indica family. It seems that women also prefer strains high in CBD; this could be linked to CBD’s anxiolytic effects—given that women are almost twice as likely as men to experience an anxiety disorder—or perhaps due to CBD’s ability to relieve some menstrual symptoms. Overall, women seem to prefer uplifting, fruity strains that are also high in CBD.

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