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Sex, drugs and estradiol: Why cannabis affects women differently

Cannabis use is riding high on a decade-long wave of decriminalization, legalization and unregulated synthetic substitutes. As society examines the impact, an interesting disparity has become apparent: the risks are different in females than in males.

A new review of animal studies says that sex differences in response to cannabis are not just socio-cultural, but biological too. Published in Frontiers in Behavioral Neuroscience, it examines the influence of sex hormones like testosterone, estradiol (estrogen) and progesterone on the endocannabinoid system: networks of brain cells which communicate using the same family of chemicals found in cannabis, called ‘cannabinoids’.

Animal studies

“It has been pretty hard to get laboratory animals to self-administer cannabinoids like human cannabis users,” says study co-author Dr Liana Fattore, Senior Researcher at the National Research Council of Italy and President of the Mediterranean Society of Neuroscience. “However, animal studies on the effects of sex hormones and anabolic steroids on cannabinoid self-administration behavior have contributed a lot to our current understanding of sex differences in response to cannabis.”

So how does cannabis affect men and women differently? Besides genetic background and hormonal fluctuations, the paper highlights a number of important sex differences.

Men are up to four times more likely to try cannabis — and use higher doses, more frequently.

“Male sex steroids increase risk-taking behavior and suppress the brain’s reward system, which could explain why males are more likely to try drugs, including cannabis” explains Fattore. “This is true for both natural male sex steroids like testosterone and synthetic steroids like nandrolone.”

But despite lower average cannabis use, women go from first hit to habit faster than men. In fact, men and women differ not only in the prevalence and frequency of cannabis use, pattern and reasons of use, but also in the vulnerability to develop cannabis use disorder.

“Females seem to be more vulnerable, at a neurochemical level, in developing addiction to cannabis,” explains Fattore.

“Studies in rats show that the female hormone estradiol affects control of movement, social behavior and filtering of sensory input to the brain — all targets of drug taking — via modulation of the endocannabinoid system, whose feedback in turn influences estradiol production.

“Specifically, female rats have different levels of endocannabinoids and more sensitive receptors than males in key brain areas related to these functions, with significant changes along the menstrual cycle.

“As a result, the interactions between the endocannabinoid system and the brain level of dopamine — the neurotransmitter of “pleasure” and “reward” — are sex-dependent.”

Human impact

The inconsistency of conditions in these studies greatly complicates interpretation of an already complex role of sex hormones in the endocannabinoid system and cannabinoid sensitivity.

“The effects varied according the specific cannabinoid studied, as well as the strain of animals tested and duration of hormone exposure,” admits Fattore. However, the human data so far are consistent with the idea that estradiol regulates the female response to cannabinoids. As in animals, human males and females are diverse in their genetic and hormonally driven behaviour and they process information differently, perceive emotions in different ways and are differently vulnerable to develop drug addiction.

“Blood levels of enzymes which break down cannabinoids fluctuate across the human menstrual cycle, and imaging studies show that brain levels of cannabinoid receptors increase with aging in females — mirroring in each case changes in estradiol levels.”

Fattore believes that deepening our understanding of the interactions between cannabinoids and sex steroids is crucial in assessing the impact of increasing cannabis use, and tackling the fallout.

“Gender-tailored detoxification treatments and relapse prevention strategies for patients with cannabis addiction are increasingly requested. Optimizing personalized evidence-based prevention and treatment protocols demands further research on the source of sex disparities in cannabis response.”

Sex differences in cannabis use are beginning to be explained with the aid of brain studies in animals and humans.

Does Cannabis Affect Hormone Levels?

Marijuana can help regulate many things in the body from mood to pain management due to its interaction with the endocannabinoid system. This has many cannabis consumers wondering: Does cannabis affect hormone levels? And if so, how? Here’s what we know so far about cannabis and your hormone levels.

The Endocannabinoid System

There is room for a lot more research on marijuana’s hormonal impact. Despite this, it’s safe to say that something with such a powerful influence on the endocannabinoid system would also have hormonal repercussions.

This is largely due to THC, the cannabinoid we understand best. THC can reportedly alter neurotransmitters that are either linked to or located in the hypothalamus. The hypothalamus is the portion of the brain that connects the nervous system to the endocrine system, which produces the body’s hormones.

We have a good grasp of cannabis’ effect on the endocannabinoid system, the body’s network of neurons responsible for a host of critical bodily functions.

These interactions are what make cannabis an effective painkiller, appetite stimulant and mood regulator.

As the body’s nervous system operates in relation to other bodily functions, cannabis would also produce an effect on hormone levels.

Cannabis’ Effect On Men’s Hormones

There is more conclusive research on how cannabis affects men’s hormones than women’s. And research suggests that it impacts reproductive hormones, for the most part.

Preclinical studies show that THC blocks the release of GnRH, a hormone that triggers the production of other hormones.

This can ultimately lower testosterone production. The same study also found that THC limited growth hormone release, which is responsible for growing bone and muscle.

Another study published in the American Journal of Epidemiology found that using marijuana more than weekly, along with other drugs, contributed to a 55 percent total sperm count reduction.

It also found that that marijuana use increased testosterone production. It should be noted that using other drugs could have an effect on this study’s results.

Cannabis’ Relationship to Female Hormones Is A Little More Complicated

Does cannabis affect hormone levels in women? The scientific community knows less about cannabis’ effect on women’s bodies than on men’s.

To dive deeper into this issue, The Cut interviewed cannabis expert and nurse Eloise Theisen. Theisen credits Sexxpot‘s effectiveness—the famous aphrodisiac weed—to lower levels of THC.

“[…] High levels of THC can promote anti-estrogen activity, though science is still very limited … My guess is that Sexxpot, with the lower THC, regulates the body’s endocannabinoid system (the group of brain receptors that are involved with processes like pain, sensation, mood, and mediating effects of cannabis) and helps bring back the balance of hormones, but without sacrificing the therapeutic properties,” Theisen says.

Research Shows That Estrogen Largely Affects Cannabis’ Potency

Additionally, new studies confirm that the female body absorbs marijuana differently depending on estrogen levels. According to research conducted by Professor Rebecca Craft of Washington State University, female rats are approximately 30 percent more sensitive to THC than male rats.

This mainly resulted in higher pain tolerance.

“What we’re finding with THC is that you get a very clear spike in drug sensitivity right when the females are ovulating,” Professor Craft explains.

Estrogen can also have another effect on women’s experience with marijuana. Over just ten days, the female rates became much more tolerant of the effects of THC than the male rats. This would indicate that women are more likely to build up a tolerance to marijuana than men.

Craft also observed that cannabis did not disrupt the female rats’ reproductive cycles. It would appear that hormone levels determine cannabis’ potency for women, not the other way around.

Final Hit: Does Cannabis Affect Hormone Levels?

Though we need to further study cannabis’ effects on all genders, preliminary research shows that the answer to “does cannabis affect hormone levels?” is yes. Studies show that consuming cannabis does indeed have hormonal consequences.

These effects are largely on reproductive hormones like testosterone and estrogen, and on growth hormone. This information, while relevant to everyone, is especially useful for those going through or seeking hormone replacement therapy.

As cannabis use increases, we’ll have more time, and a larger sample pool, to study its impacts on a grand scale.

If you're going through any sort of hormonal treatment, you've probably asked your doctor: does cannabis affect hormone levels?