Does CBD Increase Estrogen?

 

We get this question from both sides of the aisles.

Women who do or don't want an increase and men who don't want to increase.

For women, estrogen is an incredibly powerful player across many pathways.

Learn all about estrogen's full power here.

Of course, there's the question of estrogen levels and certain cancers.

Researchers know that the endocannabinoid system is intimately wrapped around steroidal hormones.

What about CBD?

Let's get into it.

We'll cover these areas: 

• The endocannabinoid system and estrogen
• CBD versus THC for estrogen levels
• Does CBD increase estrogen
• Can CBD help balance estrogen
• Can CBD help with estrogen dominance
• CBD and estrogen-positive cancer
• Does CBD contain estrogen

 

Here we go!

The endocannabinoid system and estrogen 

Researchers are only now unraveling the complex and many relationships between our endocannabinoid system and steroidal hormones (including estrogen, testosterone, and progesterone).

Clues have been found along the way and the effects can be different between the genders.

That's our first clue since estrogen has brain modulating effects in males but is a superstar in the female body across almost every system.

For example 

Completely opposite effects have been seen in sexual behavior such that cannabinoids facilitate female but impair male sexual activity. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933663/

Let's first take a step back to understand the role of the endocannabinoid system and then introduce estradiol (E2 - our most prominent flavor of estrogen).

The endocannabinoid system dates to about 600 million years ago in evolution and every animal you see has one.

It's generally tasked with balancing other key systems from stress: 

• Nervous system - neurotransmitters like serotonin, GABA, and dopamine
• Immune system - inflammatory response agents like microglia and cytokines
• Endocrine system - both steroidal (estrogen) and metabolic

 

Did you catch the last one?

By stress, we mean the general type...anything internal or external that pushes a given system one way or the other.

The endocannabinoid system works like a feedback system to right the ship.

What about steroidal hormones like estrogen? 

While the ECS is known to modulate pain and neurodevelopment, it is also known to impact the female reproductive system where it affects folliculogenesis, oocyte maturation, and ovarian endocrine secretion.  

https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-018-0478-9

"Ovarian endocrine secretion".   That's estrogen and progesterone!

There's a direct tie between one of our most powerful endocannabinoids called Anandamide and estrogen.

A bi-directional relationship really. 

There was a significant correlation between plasma AEA and E2 (P = 0.022), but not between plasma AEA and serum P4, in non-pregnant women. 

https://academic.oup.com/humrep/article/24/8/1989/646929

So progesterone is off the hook (for non-pregnant women) but estradiol is intimately tied to anandamide.

In fact, anandamide levels ebb and flow during the monthly cycle just like estrogen.

FAAH breaks down anandamide so this would result in an inverse relationship with estradiol.

There are two kinds of endocannabinoid receptors in the body: 

• CB1 - prominent in the nervous system
• CB2 - prominent throughout the body including the immune system

 

If we go up to the hypothalamus, the master controller of estrogen production, we see a direct effect via these receptors.

Let's go up the chain to GnRH (gonadotropin-releasing hormone).

It's a mouthful but this is the manager of estrogen production (as well as progesterone and testosterone).

Here's the connection that's important to us.

CBs block the pulsatile release of GnRH. When a CB receptor agonist is delivered into the third ventricle of adult female mice, estrous cycles are prolonged by at least 2 days. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1237039/

Translation please.

Basically, direct stimulation of CB1 receptors will downregulate the whole steroidal hormone (including estrogen) process.

Anandamide is the main driver of CB1 activity.

Guess what cannabinoid can imitate anandamide in the body?

THC!

CBD versus THC for estrogen levels 

It's been established for a while that THC can interfere with the entire steroidal hormone system including the net effects on reproduction.

THC directly stimulates (like lock and key) the CB1 receptor just like anandamide.

Actually it hits much harder and stays to long compared to THC which is why you have different effects including the "high" and tolerance with longer term use.

There are definite differences in response by gender.

Consistent with this, females are more sensitive than males to the adverse effects of escalating THC exposure during adolescence on emotional behavior and stress reactivity in adulthood. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933663/

Estrogen is a powerful mood balancer (see CBD and perimenopause anxiety or CBD and perimenopause depression).  We did a huge review on CBD and mental health here. 

In fact, THC interferes with the process at the very top of the chain...pregnenolone.

Pregnenolone is the raw material for ALL our steroidal hormones.

THC's effect there?

THC also inhibits steroidogenesis by preventing the conversion of pregnenolone to progesterone.  

https://www.zrtlab.com/blog/archive/the-effects-of-cannabis-on-your-hormones/

Steroidogenesis is the process of making hormones like estrogen.

See our full review on pregnenolone to see why this is so important.

There's lots of research on THC's effect in this process.

What about CBD?  Does it directly stimulate CB1 receptors in the same way as THC?

No.

This is beauty of CBD we see across different pathways.

Here's the distinction: 

• THC is a direct agonist (driver) of CB1 receptors
• CBD is an inverse agonist of CB1 and CB2 receptors
• CBD is also a negative agonist modulator

 

Goodness.what does all that mean?

Agonist just means that it promotes (as opposed to blocks) activity.

THC is a partial agonist for CB1-R and CB2-R; CBD is an inverse agonist for both. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479799/

That third one is important.  It basically says that CBD will slow down other chemicals that push in one direction.  

A dampening field if you will.

Okay...what does all that mean?

Basically, THC directly spurs activity in one direction.

CBD works as a restraint on activity...like a rubber band.

It's a signal backwards like a feedback mechanism.

This is why we don't see overdoses on CBD.  

 

You can definitely overdose (get too much) on THC (see CBD and greening out) or any chemical that pushed in one direction  (see CBD versus benzos or CBD versus SSRIs).

This speaks to the heart of the endocannabinoid system in finding "homeostasis"...a fancy word for balance.

Interestingly, THC itself may reduce estrogen but cannabis smoke appears to be estrogenic: 

MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did.

https://www.ncbi.nlm.nih.gov/pubmed/16499939

MSC is short for marijuana smoke condensate.

Just a head's up if you use cannabis (male or female).  More estrogen.

So let's get into directly based on research.

Does CBD increase estrogen 

In most pathways, CBD has the opposite effect of THC.

CBD acts as a partial agonist for GPR18 and GPR55 and antagonizes the effects of THC. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479799/

Check out why you must use CBD if you use THC to go through some of the big items.

Back to CBD.

Can we find specifically on CBD and estrogen?

One very old study found a reduction in estrogen but at very high levels.

We prefer newer research since the techniques are so much more sophisticated now.

Above, we referenced the study that showed marijuana smoke was estrogenic but CBD itself was not.

This is generally attributed to the other substances found in cannabis (and potentially full-spectrum CBD in hemp oil).

The direction may be the other way (more prominently).

Estradiol directly influences the levels of endocannabinoids. 

One study found no binding of CBD to estrogen receptors in living things (as opposed to in a test tube): 

Neither Δ9-THC, desacetyl levonantradol, nor cannabidiol stimulated transcriptional activity.  

https://www.sciencedirect.com/science/article/abs/pii/S0006295296006594

What we do know is that estrogen has powerful effects on cannabinoids and their receptors.

A recent report has demonstrated that protein levels of the CB1 receptor are significantly lower in females relative to males. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933663/

They even found that women will use cannabis more after having ovaries (and hormones) removed.

It even goes right down to receptor activity present which can fluctuate during the cycle: 

Our data are in accord with those of Mize & Alper (2000) who reported that estradiol replacement in OVX females decreased CB1 receptor-mediated G-protein activation in the hippocampus 2 hr following estradiol administration.

 

This has a huge impact on many other systems...especially mood and cognition (see CBD and perimenopause mood or CBD and perimenopause brain fog).

So...the research is pointing to Anandamide and THC's direct effect on reducing estrogen levels: 

Lower concentrations of GnRH [and consequently a decrease in LH and follicle-stimulating hormone (FSH) concentrations] result in lower circulating estrogen levels.  

https://www.spandidos-publications.com/10.3892/ijmm.2016.2779

Estrogen in turns increases the levels of cannabinoids.

CBD does not appear to have a direct effect on estrogen levels.

We'll look at this further in our CBD and estrogen-positive breast cancers where there's more research.

Can CBD help balance estrogen 

We've looked at CBD's effects across many pathways with interesting results but asking for CBD to balance estrogen levels (to progesterone or testosterone) is not yet supported in the research.

We're all about research.

There is research for balancing of other hormone pathways (insulin, metabolic, etc).

PCOS (polycystic ovarian syndrome) is a disease born out of hormone imbalance but it also has a metabolic bent (insulin figures strongly) so we can't fall back on that.

 

Check out our reviews on fisetin and berberine as there's interesting research for both on PCOS.

It's important to get a Dutch test or equivalent to really understand your hormone profile.

In the end, hormone balance is driven by many factors (weight, genetics, stress, etc).

CBD can definitely have an impact there (see CBD and perimenopause weight or CBD and stress for anxiety).

We'll keep an eye out for new research on the complicated relationship between our endocannabinoid system and steroidal hormones.

Here's a graph of just a few pathways between the two: 

https://academic.oup.com/view-large/figure/59384298/zee0031263180002.jpeg

There are tantalizing clues that endocannabinoids partially regulate the hormone pathway.

Let's go upstream to GnRH which manages estrogen levels: 

These lipids, in turn, could bind to CB receptors on neighboring cells, and perhaps GnRH neurons, to exert feedback control over GnRH function.  

https://www.ncbi.nlm.nih.gov/pubmed/16020480?dopt=Abstract

Goodness...this goes directly to balancing estrogen and other steroidal hormone levels.

Feedback control is the key there as we find throughout the literature.

A slightly different way of asking this question...

Can CBD help with estrogen dominance 

This is a common question and usually speaks to estrogen's relationship with progesterone.

There's a fine balance between the two as progesterone is generally a calming agent against estrogen's pro-growth effects.

As with the section above, we have not seen research where CBD directly affects this balance. 

We have a huge review on progesterone here since it's so important (immune, mood, calm, sleep, etc) and drops by 50% at age 40.

 

Also, check out our review on pregnenolone which is the precursor for all steroidal hormones but with a strong effect on progesterone.

This doesn't imply that it will substitute for supplementation of progesterone, however.

If you check our estradiol review, you'll see just how important these hormones are to every pathway we have.

Dutch test (to see how the body ACTUALLY processes these hormones) and adjust accordingly is my baseline these days (in perimenopause).

Let's look at the cancer angle now.

CBD and estrogen-positive cancer 

This really requires a separate full article (here for CBD and cancer pathways) as there's a great deal of research.

Some cancers are driven by estrogen levels.

The effects of CBD and cannabinoids may be more about the birth/death cycle of cells than the actual impact on hormonal pathways.

CBD's effect on cancer is fascinating and speaks to its role in supporting balance in other key systems.

First, the direct effects: 

Finally, a recent study showed that CBD induces concentration-dependent cell death of both oestrogen receptor-positive and oestrogen receptor-negative breast cancer cells through a mechanism involving a CB1-, CB2-, and TRPV1-independent receptor activation. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863507/

Here's the really fascinating piece.

CBD's effect will depend on the state of the cell (again, about balance).

Researchers put it this way: 

Although CBD was found to reduce the formation of ROS and NO in various cell lines and animal models of inflammation, there are also reports showing that CBD can induce ROS formation in cancer cells, leading to cytotoxicity. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479799/

ROS is short for reactive oxygen species...oxidation (see CBD and oxidative stress).

Basically, the effects were threefold: 

• Normal cell with low oxidative stress - no effect
• Normal cell with high oxidative stress - reduce oxidation
• Cancer cell - INCREASE oxidation!

 

This is amazing.  Here's why…

The body (and chemo or radiation) uses oxidation to kill cells that appear faulty.

We have an entire system for detecting and killing pre-cancerous or cancerous cells.

The coolest part?   This study came from breast cancer studies.

The study is here: 

https://www.ncbi.nlm.nih.gov/pubmed/21566064

CBD unleashed a slew of cellular damage on cancerous cells but not on surrounding healthy cells.

This may be one of our favorite studies as it points to the true role of the endocannabinoid system.

Also, check out the full reviews of fisetin and berberine for cancer.

Finally, one question that comes up.

Does CBD contain estrogen

CBD does not contain estrogen.

Similarly, it has not been shown to increase estrogen.

THC may suppress estrogen levels while cannabis smoke may be estrogenic.

CBD operates as a constraint on THC's effects (see CBD versus THC).

Technically, a reverse negative modulator.

That's fancy talk for….feedback mechanism!

Related reviews here:

CBD and progesterone

Estrogen and mental health

My estrogen journey

Estadiol safety review

Bijuva study on oral estrogen safety

 

Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.