Can You Take CBD With HRT?

by Indigo Naturals December 05, 2019

I originally had this very same question.

In the throes of a brutal perimenopause (that story is here), bioidentical estradiol and progesterone literally pulled be back from the depths.

It's not surprising once you read our review on estradiol here or progesterone here.

Estradiol (E2 - our primary estrogen) is tied into almost every cell in your body and after the crazy swings during perimenopause, it drops to almost nothing.

Most importantly, it drives serotonin which governs mood, sleep, and inflammatoin.

Check out the perimenopause versus menopause for more insight on this whole process.

Then there's progesterone which you start to lose in your late 30's and early 40's.

It helps to balance and protect from estradiol's pro-growth strategy in the body.

We're probably preaching to the choir so let's get to the question at hand.

Can we take CBD with HRT?

There's also a very fascinating tie between CBD and expanding the window in which HRT is effective.

It might the most important piece of this entire article.

We'll get into all of it.

These are the areas we'll cover:

Can CBD increase estrogen
Can CBD increase progesterone
Can CBD replace HRT
Can I take CBD with HRT
Does CBD interfere with HRT
Can CBD extend the age range of when HRT is effective
How much CBD to take with HRT
What's the best CBD to take with HRT

Let's get started!

Can CBD increase estrogen

CBD has shown powerful antiinflammatory and neuroprotective effects across many systems.

It operates in the endocannabinoid system which is tasked with balancing other key systems in our bodies:

Nervous system - neurotransmitters such as serotonin, GABA, and more
Immune system - inflammatory agents such as microglia and cytokines
Endocrine system - Hormones!

Did you catch the last bit?

Since HRT is usually used to either increase or level out hormones, let's look specifically at estrogen first.

It's definitely the more dynamic of the two.

Again, we go deep into estradiol supplementation and its effect here.

The question is...what interaction will CBD have with estrogen (estradiol usually) via HRT?

Most of the research comes from hormone driven cancers such as estrogen positive breast cancer which we'll touch on below.

First, understand that our hormones and the endocannabinoid system are intimately intertwined:

Sex steroid hormones regulate the endocannabinoid system and the endocannabinoids prevent tumour development through putative protective mechanisms that prevent cell growth and migration, suggesting an important role for endocannabinoids in the regulation of sex hormone-dependent tumours and metastasis.

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

Did you catch that piece..."endocannabinoids prevent tumor development".

CBD supports our endocannabinoid system directly when running low (see CBD and endocannabinoids).

There's a lot of research on how Estradiol controls certain endocannabinoids such as Anandamide and FAAH (see the woman who can't feel pain, anxiety or depression because of FAAH).

It's harder to find the opposite.

There is research on THC potentially reducing estrogen signalling but counterintuitively, it can increase sex drive.

CBD generally has opposing effects in the body (see CBD versus THC here).

That being said, there's very little research on CBD's effects directly on estrogen.
We'll have to a step up the ladder to GnRH.

Gonadal Releasing Hormone - the substance that starts off the whole cascade of sex hormones.

Let's take baby steps as this gets pretty complicated fast.

First…

As is the case for androgens, the endocannabinoid system appears to modulate the release of estrogens via the central down-regulation of LH and GnRH.

https://academic.oup.com/endo/article/153/3/1016/2423624

Okay...so basically, the system that CBD helps balance has some control over estrogen pathways.

That's a start but...which way!

Research is showing that THC which directly acts on CB1 receptors can interfere with estrogen signalling.

But CBD does not directly act on those receptors (hence, no "high" feeling or normalizing).

Instead, it works as a contraint on activity.

The term is a reverse agonist!

This just means that it boosts the returning signal to act as a buffer. A feedback mechanism!

Again, this is why we don't see overdoses (although a study just tried to use scary headlines based on giving rats CBD at the equivalent of 40% of their body weight!! Nice one, Big Pharma. sarc)

If the endocannabinoid system controls hormone levels, especially in women with reproductive complexity, we would expect to see benefits where hormones are out of balance.

Something like….PCOS (poly cystic ovarian syndrome).

Researchers found a gene tied to risk for that and the commonly adjoined fatty liver:

Our preliminary results suggest the potential role of CNR1 polymorphisms in the etiology of NAFLD, especially in PCOS women.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127238/

What's CNR1?

Oh...just the gene for CB1 receptors (primary endocannabinoid receptor in the nervous system).

Now, we have to be a bit of a detective since we can't find exact studies on CBD's effect on estrogen (which is really surprising to us).

THC has been shown to reduce estradiol levels although smoking cannabis can increase estrogen.

This makes sense since it substitutes for Anandamide in the endocannabinoid system.

High levels of endocannabinoids and exogenous cannabinoids suppress the release of gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), estrogen and progesterone.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332911/

The research points to THC and CBN (cousins of CBD) for this effect.

THC directly boosts CB1 (our main receptor) activity as if it were Anandamide.

CBD, works quite differently as we saw above.

It sends a message backwards from the receptor to reduce the activity or receptivity for this action.

This dampening occurs based on levels.

We know this because higher doses of CBD would basically reduce anandamide, our "bliss" molecule and we would definately feel that effect (depression, psychosis, etc).

In fact, research is showing CBD has the opposite effect (see CBD and depression or CBD and schizophrenia).

Let's dig deeper...what about actual estrogen receptor activity?

CBD actually shows some interaction with these receptors but at very high levels:

Of several other common cannabinoids tested, only cannabidiol showed any estrogen receptor binding. This was evident only at very high concentrations of cannabidiol.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332911/

Interestingly, CBD operates the same way as the mother of all our steroidal hormones, pregnenolone.

We covered pregnenolone here in detail since it's so important as we get older.

In fact, the brain naturally responds to too much THC (CB1 activity) by blocking this excess with pregnenolone much like CBD does:

However, in 2014, Vallée et al.29 identified pregnenolone as an allosteric inhibitor at CB1Rs decreasing Δ9-tetrahydrocannabinol (Δ9-THC).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576597/

So...back to our original question.

CBD does not appear to increase estrogen levels from the research and may help to set a range of levels.

This is just a complicated way to say balancing but we need more research.

THC appears to reduce estrogen but cannabis smoke may be estrogenic. Muddy water indeed.

What about progesterone, the other key component of HRT?

Can CBD increase progesterone

Progesterone is incredibly powerful as a counterbalance to estradiol's pro-growth agenda.

Studies show that CBD can reduce progesterone but only at very (very) high doses:

High CBD concentrations (1 mM) inhibited progesterone 17-hydroxylase, which creates precursors for sex steroid and glucocorticoid synthesis, whereas 100 μM CBD did not in an in vitro experiment with primary testis microsomes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/

Keep in mind that these levels are not really obtainable by supplementation.

You have to be careful.

Some studies have shown that CBD and cannabinoids can affect the entire streroidal process including reproduction.

For example...this scary headline:

Chronic cannabidiol exposure promotes functional impairment in sexual behavior and fertility of male mice.

https://www.ncbi.nlm.nih.gov/pubmed/29936126

You dig deeper and you find out it was based on 15 or 30 mg per kg of weight.

A 160 pound person weighs approximately 72 kg.

That would be about 1000 mg or 2000 mg for that person….chronically. daily.

Sleep studies are showing help around 160 mg
Neurogenesis peaks at about 300 mg
The public speaking study for social anxiety was at 600 mg
Even the schizophrenia and psychosis study was at 800 mg

Even at the extreme levels, progesterone wasn't affected:

Body weight gain and circulating progesterone concentration did not significantly change in CBD-treated animals.

Again, CBD doesn't appear to significantly impact hormone levels unless at extreme levels not recommended anyway:

However, CBD exhibits only weak efficacy as 10 mM CBD is required to inhibit ~20%, 49%, and 67% of progesterone 17α-hydroxylase, testosterone 6α-hydroxylase, and testosterone 16β-hydroxylase, respectively.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604182/

Their conclusion…

Thus, it is unrealistic to propose that these enzymes are meaningfully involved in the therapeutic effect of CBD in neurological disorders

Let's get to some practical questions that arise from all above.

Can CBD replace HRT

NO!

Read our Estrogen journey or progesterone review.

Estrogen and progesterone are tightly woven into the machinery of your brain and body.

Those machines keep running long after estrogen and progesterone flee the scene but without key missing pieces.

Let's take one example.

CBD has been shown to "normalize" or "modulate" serotonin, our critical feel good neurotransmitter.

The problem is that estrogen controls both its creation (from tryptophan) and its removal (MAO enzyme).

CBD can only normalize what's there to begin with.

The body will desparately shift to making estrogen elsewhere (see CBD and perimenopause weight gain) but nothing does the job like ovaries.

Serotonin is just ONE pathway of 100's. Almost every system has estrogen and progesterone receptors.

CBD can help support the system tied to stress response (in all its many meanings) but your steroidal hormones (estradiol and progesterone) are primary building blocks.

Can I take CBD with HRT

As we saw above, there is little interaction between CBD and the HRT hormones, estrogen and progesterone.

CBD can help with a range of issues which probably led you to look at HRT to begin with.

We've covered these in detail here:

Take a look at any of those and you'll see we don't mess around with research.

We still need more research on the complicated interaction with the endocannabinoid system and hormones.

As it comes in, we'll add it here.

There are some tips on how to use them together.

Let's look at that now.

Does CBD interfere with HRT

One note...if you take oral progesterone (very popular) or estrogen, you want to take CBD opposite to when you take those.

CBD can use the liver pathways that are used for metabolizing progesterone.

I actually found this out personally.

Bio-identical oral progesterone was working fine at night before bed.

I would take CBD (150 morning and 150 mg at night) but the progesterone wasn't putting me to sleep like it did before.

I moved my CBD to the morning - 300 mg.

I'm aiming for 300 mg which is shown as best for neurogenesis (see CBD and neurogenesis here).

Progesterone has a powerful pro-sleep and calming effect.

It puts me right out and it's the first thing that really started to help me through the dark days of perimenopause (that story is here).

I moved the CBD to 4 hours prior to the progesterone and its effects were restored.

The general rule is at least 4 hours apart between CBD and hormones (oral) and/or medications.

Always work with your doctor or naturopath of course.

Basically, if the liver is busy processing CBD, it can affect the progesterone matabolism and it turns out that the metabolites (what the oral progesterone is broken down into) is where the magic happens.

Now, let's turn to a very fascinating effect.

Can CBD extend the age range of when HRT is effective

No one's really talking about this but then again, few are spending a few hours each day buried in NIH studies on CBD.

Let's go back to 2002.

That's when the study came out which scared women silly about hormone replacement.

Risk of cancers and blood clots, etc.

Turns out this was a highly flawed summary of the study.

What the study did find was that when women waited till much later to start HRT, they didn't reap the protective benefits.

There appeared to be a window to start HRT and benefit from it.

Follow up studies also bare this out:

Here, we found that facilitation of memory extinction and long-term depression by 17β-estradiol (E2) was normal in mice 1 week after ovariectomy (OVXST), but it was impaired in mice 3 months after ovariectomy (OVXLT).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546454/

The researchers found that women age 56-65 had lower levels of two substances, one of them, our prominent endocannabionid 2-ag.

When they bolstered these levels or supported CB1 activity, HRT would work again.

Their summary:

The present study demonstrates that an HT time window in mice can be prolonged by cotreatment with a CB1 agonist, implying a potential strategy for HT in long-term menopausal women.

What's the effect of CBD on these substances?

CBD blocks FAAH, the primary enzyme that breaks down Anadamide.

It has also been shown to break down…..2AG!

What's CBD's effect there?

Biochemical studies indicate that cannabidiol may enhance endogenous anandamide signaling indirectly, by inhibiting the intracellular degradation of anandamide catalyzed by the enzyme fatty acid amide hydrolase (FAAH).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/

Okay...your eyes are probably glossing over.

Here's the important piece.

2-AG can re-open the period during with HRT actually conveys benefits if we start later.

And CBD's effect there:

There is also evidence that CBD reduces MAGL-mediated degradation of 2-AG.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486906/

Let's look at another important piece from that same 2002 study which sent millions of women spiraling ever since.

Can CBD help protect from HRT risk

There was a panic after 2002 with millions of women coming off of Hormone Replacement Therapy.

Headlines of cancer and blood clotting risk among others.

Really read through the safety and history section of our estradiol article.

First, they were using synthetics or horse derived hormones.

More importantly, the risk appeared to occur with the women who waited too long to start HRT!

We described how the endocannabinoid system can "re-open" this window and CBD is a tool there.

That being said, we're about being smart here.

Estradiol is pro-growth in the body. That's part of why we suffer when it leaves.

Are there ways to protect from cancer risk in general?

We're so glad you asked.

CBD has shown powerful anti-tumor effects especially for hormone related cancers.

In fact, many of the SERM's (selective estrogen receptor modulators) like Tamoxifen used for estrogen driven cancers have a fascinating hidden story:

Furthermore, selective estrogen receptor modulators (SERMs), including tamoxifen, bind to CB-Rs; this process may contribute to the growth inhibitory effect of SERMs in cancer cells lacking the estrogen receptor.

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

Did you catch that?? They operate through the CB receptors. Our endocannabinoid system.

Why would this be?

CBs block cell cycle progression and cell growth and induce cancer cell apoptosis by inhibiting constitutive active pro-oncogenic signaling pathways, such as the extracellular-signal-regulated kinase pathway.

This system is critical to our cell birth/death governance which is at the heart of cancer.

We did a massive review on CBD and cancer here.

Now...the coolest attribute of CBD:

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.

So...CBD can have three effects depending on the state of the cell:

Healthy cell with low inflammation - no effect
Healthy cell with high inflammation - anti-inflammatory
Cancerous cell - increase inflammation to kill it!

We've seen this effect across many pathways but it really speaks to the beauty of CBD and more importantly, the endocannabinoid system.

It's all about homeostasis...a fancy word for balance.

We did a full review on Siberian Rhubarb because of its focus on the estrogen receptor B which can be protective as well.

Also, we take Fisetin and Berberine not only based on longevity studies but also as a form of cancer insurance.

Check out the reviews through the links...they're pretty amazing.

Practical questions now.

How much CBD to take with HRT

There isn't exact research on this.

A starter level is around 25-30 mg to test how it works on your system.

As we mentioned above, research is pointing to the following:

Sleep benefits - 160 mg daily
Neurogenesis for anxiety, depression, and cognitive health - 300 mg max

There's probably not a reason to go higher than the 300 mg aside from acute situations (social anxiety, panic attacks, etc).

The general range is approximately from 50 - 300 mg depending on needs.

As we get more information with current studies, we'll make sure to add those here.

We do have some guidance on the type of CBD.

What's the best CBD to take with HRT

First, we must have the highest quality and verified CBD as there's lots of junk out there.

We just did a big review of CBD on Amazon. It's not promising.

Here's the basic list of requirements:

Organically grown in the US at an FDA registered farm
CO2 processed (cleanest option)
3rd party tested for:
No THC
No pesticides
No heavy metals
No bacteria
No mold

We actually test IndigoNaturals twice: once for the biomass and once for the finished product.

Our entire family uses it and I'm taking 300 mg a day to get me to the other side of perimenopause.

We're very serious about research on this front.

There's another interesting component that 90% of the market isn't talking about.

Histamines and allergies.

We covered it in our CBD and perimenopause allergies and histamines.

Everyone out there is pushing full spectrum CBD.

That's basically CBD added back to hemp oil.

Here's the issues…

40-60% of the population has allergy and histamine issues.

Big shocker..this number goes up as we get older and for women. Progesterone is a major player in calming immune response.

Sound like a cross-over for hormone replacement folks??

I tried 3-4 of the biggest brands at first and immediately had allergic response.

That all went away with CBD Isolate.

That's why we focus on isolate.

Check out the research at our CBD full spectrum versus CBD isolate for allergies.

It's a big wake up call. Just look at our reviews to see how people respond differently to Isolate.

We know the estradiol article is a big read but it's really important.

My doctor told me, "Your levels are fine" when I was starting to spiral down.

Progesterone and estrogen immediately rescued me from that period.

CBD was basically a lifeline during that period and continues to be going forward.

Be well. Be informed. Take care of yourself!!

This glimpse into perimenopause is just the beginning. 'Dre's Story' offers our complete, research-rich journey into hormones, tools to feel better, and safety. The full Perimenopause Toolkit with new additions can be found Here . Please review so other can learn. Feeling better starts with understanding what is happening.