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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.

How Does Cannabis Use Affect Glands and Hormone Production?

Cannabis is a plant, that is used for a variety of anti-inflammatory, pain-relieving purposes. However, very little is known about how cannabis interacts with the endocrine system. While some research shows that THC suppresses hormone secretion from the pituitary gland and hypothalamus, not many definitive conclusions can be drawn.

Human research is difficult to navigate because each patient will have a different reaction depending on many varying factors including diet, chemical exposure, endocannabinoid system (ECS), and general health. In addition to affecting vital sex hormones, evidence suggests that chronic cannabis use may also affect the adrenal, prolactin, thyroid, and growth hormones.

What is the Endocrine System?

The endocrine system is the communication department of your body. It’s made up of the pancreas, sex organs, hypothalamus, as well as pineal, thyroid, and adrenal glands, which communicate to other parts of the body by making hormones, the messengers of the endocrine system. These hormones regulate immunity, influence mood, proliferate growth, adjust metabolism, and even assist fertility. Some of the hormones you’ve probably heard of are fertility hormones (estrogen, progesterone, testosterone, prolactin), thyroid, cortisol, and insulin.

The ECS has an integrated role within the endocrine system. Endocannabinoids influence mood, hunger, and energy , among other things, by interacting with hormones. Cannabis can influence the ECS by enhancing or altering its receptors, commonly known as CB1 and CB2 , that can bind to hormones but are also an essential regulator of the hypothalamic-pituitary-adrenal (HPA) axis . The HPA axis is one of the main endocrine system conductors that sends critical messages, by the use of hormones, to the body . These different processes of cannabis, found both in rat and human studies, affect the body by suppressing or engaging with hormones or the glands that secrete them and, ultimately, the multifaceted endocrine system.

Adrenal Hormones

The adrenal hormones are the main puppeteers of stress, energy, adrenaline, and blood pressure. They are a topic of interest in a healthy body, especially when they can be influenced by endocannabinoids found in cannabis. The adrenal glands also secrete a small amount of sex hormones, but not nearly enough to rival those produced in the reproductive organs. Cannabis suppresses adrenal activity , according to the 2009 study in the German journal Psychopharmacology study on the effects of cannabinoids on humans.

The suppression of the adrenal glands lowers blood sugar, which may raise cortisol in the short-term . Ongoing adrenal suppression can interfere with blood sugar regulation, raising cholesterol , and suppressing the immune system.

Prolactin

Prolactin is the hormone most people know as the breast-milk-producing hormone, though it has many other functions in the body, especially related to fertility. Prolactin increases with stress and age and affects most tissues in the body, such as skin and hair. High amounts of prolactin contribute to infertility and lowered sexual desire. If in fact, THC has been recorded to suppress pituitary hormones, one of which is prolactin.

High prolactin levels enhance stress in women as well as estrogen dominance, aggression, anxiety, depression, infertility, and osteoporosis, according to studies in the American Journal of Psychiatry and Psychotherapy and Psychosomatics . While lowered prolactin reduces the risk of breast and testicular cancer . In addition to reducing stress, less prolactin allows for more dopamine , which provides for feelings of elation and happiness. Though keeping prolactin low seems desirable, suppressing pituitary hormones such as prolactin and other reproductive hormones can negatively affect fertility and postpartum.

Thyroid

It is unclear exactly how cannabis affects the thyroid . Research shows that cannabinoids can have beneficial effects for those with Graves’ disease and Hashimoto’s disease but can also lower thyroid-stimulating hormone (TSH), which regulates thyroid function. The thyroid is a very sensitive yet powerful gland that controls hormones that regulates mood, digestion, metabolism, and brain function. Cannabis suppresses pituitary hormones, which could cause changes in thyroid function, the consequences of which have yet to be determined by researchers.

Human Growth Hormone (HGH)

The human growth hormone (HGH) is one of the many hormones released via the pituitary gland, which is heavily influenced by the endocannabinoid system and CB1 receptors, those which are affected by THC consumption. The suppression of HGH is beneficial to suppress growth proliferation of a cancerous cell . This is one reason why cannabis is a wonderful prescription for cancer patients. On the other hand, they are crucial for female fertility and the support of the delicate female cycle. Also, as their name suggests, they’re very important for growth and development both physically and mentally. For underdeveloped children, suppressing these hormones is not a wise decision.

Endocannabinoids play a crucial role in the endocrine system between hormone-producing organs and glands to the hormones themselves. Because the endocrine system is so complex and not enough controlled human research has been conducted, it’s still not fully understood how cannabis exactly affects hormones and its impact on health.

How Does Cannabis Use Affect Glands and Hormone Production? Cannabis is a plant, that is used for a variety of anti-inflammatory, pain-relieving purposes. However, very little is known about how