Turns out...hormones are important.
Especially for mood.
It's estimated that 25% of women will have debilitating perimenopause these days.
My perimenopause experience was right up there.
Aside from crazy blood pressure and heart rate fluctuation, the mood changes were front and center.
Rolling anxiety 24-7 and accompanying panic attacks.
Weird, temporary bouts of depression that could pass in an hour.
This was completely out of sorts (I promise!!).
That whole story is here including how the doctors sent me reeling down the medication path.
It started with benzos. Wrapped up with SSRI's.
I was in the ER after 3 nights of no sleep for Lexapro.
It's so unsettling to think that flux in hormones can totally change the you-ness of you.
We'll get into why this happens and more importantly, what we can do about it.
We'll look at CBD for perimenopause mood changes as well as other powerful tools we found along the way.
These are the topics we'll cover:
- Why perimenopause affects mood
- Estrogen and mood changes
- Estrogen, serotonin, and mood
- Can CBD help with perimenopausal mood changes and balance
- Other tools for perimenopause mood
- How much CBD for perimenopause mood changes
- What's the best CBD for perimenopause mood shifts
Let's get started.
Why perimenopause affects mood
First, we have to understand what perimenopause is.
Most women (and doctors for that matter) just assume it's a gradual loss of our steroidal hormones, estrogen, and progesterone.
They slowly drop, we lose our period and welcome to menopause.
Over half of the women who go through the transition have serious issues as a result.
As we mentioned above, roughly 25% are walloped by the process.
I count myself in that lucky bunch.
Where do we and our medical field have it wrong?
Here's the lay of the land.
Progesterone has been dropping since your late 30's and early 40's.
As a result, you'll see gradual reductions in basic mood balancing.
I noticed slight panic responses about 4-5 years prior to perimenopause at PTO meetings and doctor visits.
Just out of nowhere!
Progesterone really drops when your period starts to go away and it may even plunge before then as you may have periods and no egg release.
It's the egg release that drives progesterone production.
So…. a slow, steady drop of progesterone and then off a cliff in early perimenopause.
Estrogen's a whole different animal.
There can be a disconnect between estrogen and it's upstream controllers...FSH and LH.
These two groups of hormones are supposed to counterbalance each other but for some women, they're not responding correctly.
This drives big spikes and drops in estrogen as the body is trying to create one more egg (the role of estrogen).
It's this flux in estrogen that really drives significant changes in mood during perimenopause (or periods for that matter).
This sums it up well:
Most notably, a number of studies have found an increased incidence of depression (10–12) and anxiety (13) in women across the menopausal transition, a period characterized by drastic fluctuations in estrogen levels before overall levels drop to approximately 10% of estrogen levels experienced premenopausal.
Let's look at the two hormones for mood specifically.
You'll quickly realize that estrogen and progesterone are not just for making babies!
We'll start with the heavy hitter for mood.
Estrogen and mood changes during perimenopause
Estrogen is a master communicator that has its hands in almost every pie across your body and brain.
Check out our full review on estradiol here to understand why and how.
Let's dive into estrogen's effect on mood since it's in flux during perimenopause.
First, women are more at risk than men to have mood issues.
Worldwide epidemiological studies report that the prevalence of major depressive disorder (MDD) among women is 1.5 to 3 times higher than in men.
This is directly tied to hormones (hint 1):
The increased risk is associated with fluctuating estrogen levels that occur during reproductive cycle events, particularly during the menopausal transition, a time characterized by drastic fluctuations in estrogen levels and increases in new-onset and recurrent depression.
So...we showed our cards too early.
"Fluctuations in estrogen".
In our CBD and HRT review, we looked at estrogen's role in more detail.
What about when they give HRT (hormone replacement therapy) to women in perimenopause and menopause?
Transdermal estradiol and micronized progesterone administered at the time of menopause are generally associated with cognitive and effective benefits.
So what gives….what exactly is estrogen doing to affect mood?
First, know that estrogen and estrogen receptors are everywhere in the brain.
They're also intimately tied into the anxiety circuit (see CBD and anxiety benefits here).
Scientists have done studies where they remove the ovaries (and thus estrogen production) from rats.
The rats then display anxiety and depression-like behaviors.
What happens when they give back estrogen to the main areas in our anxiety circuit?:
Administration of E2, compared to vehicle, subcutaneously or to the hippocampus or amygdala of ovariectomized rats decreases anxiety and depressive behavior.
The Amygdala is our emotional response area and the hippocampus is the seat of our memories...including emotional colorings.
We dive deep into the two different estrogen receptors (A and B) but a clue can be found when they "knock-out" each one and watch the results:
Studies utilizing ER knockout mice or selective ER modulators suggest that ER-mediated effects of E2 on anxiety and depressive behavior may require ERβ.
We'll circle back to that below in our tools for perimenopause mood. Very exciting!
Let's now introduce the biggest (of many) effects that estrogen has on mood during perimenopause.
Estrogen, serotonin, and mood
Serotonin may be the workhorse of our brain's communication system.
It's called the "feel good" neurotransmitter but that may only be because you feel so bad when it's too high or too low.
It's the target for SSRI's (see CBD versus SSRI for serotonin), the go-to class of drugs for depression and even anxiety.
I was put on Lexapro after the benzos were causing issues.
That's what landed me in the hospital after 3 nights of no sleep.
SSRIs boost serotonin levels but doctors can't really test to see if you're low or not.
Hence all the nasty side effects.
Then there's Serotonin Syndrome, an excess of serotonin which is quite dangerous.
That's where I was...insomnia, flatline effect, suicidal thoughts.
SO….why is this class used if they have all this baggage?
They boost serotonin!
What's the connection with estrogen and serotonin?
Estrogen directly controls both the creation (from tryptophan) and removal (MAO) of serotonin.
Yes... it governs serotonin levels and function.
We can't put it better than this:
Estradiol is especially nurturing towards serotonin – it stimulates TRPH expression to ensure that enough serotonin is made and suppresses MAO A levels to prolong the longevity of the neurotransmitter.
Did we mention that estradiol is spiking (to levels higher than during pregnancy) and dropping during the perimenopausal transition.
And then during menopause….
It's going away!
Goodness...we are sending millions of women adrift out to sea ever since that bogus 2002 study scared everyone from HRT.
The problem with the doctor's goto remedy of SSRI's:
- They generally work for about 30% of people
- They normalize (effect goes away as the brain adjusts for artificial boosting)
- Nasty side effect
- Brutal to come off of (see how I used CBD to wean off of SSRI's)
The good news is...we have other ways that don't carry the hefty toll of suicidal thoughts.
That's just an inkling of estrogen's role in mood disorders.
Estrogen is everywhere! Till it isn't.
Next up, progesterone.
Progesterone and perimenopause mood changes
Estrogen's a big player but not the only one.
You can't mention estrogen's yin without progesterone yang.
Estrogen is highly involved in the management of serotonin.
What about progesterone?
GABA is our main inhibitory neurotransmitter which slows things down in the brain.
In fact, it's key to being calm and able to sleep!
The biggest class of medications for anxiety, benzodiazepines (Xanax, Valium, Ativan, etc) work primarily by boosting GABA levels.
It's THE lever for anxiety.
Opposing GABA is Glutamate, our gas pedal in the brain.
There's a delicate balance between these two that drive every type of behavior or mood we have.
What does progesterone do there?
By both means of administration, progesterone significantly enhanced inhibitory responses of Purkinje cells to GABA and suppressed glutamate excitation within 3-10 min post-steroid.
In general, progesterone has a calming effect on our mood.
It also helps with sleep since increases on the GABA scale goes from calm to sleepy.
The real star here may be a little known metabolite called allopregnanolone.
Progesterone breaks down into this substance which is the star behind the new postpartum depression medication (see our pregnenolone review for more info).
So for anxiety and depression:
There is a dramatic potential for the therapeutic anxiolytic activity of pharmacological compounds derived from powerful anxiolytic agents, such as the progesterone derivative, allopregnanolone.
Anxiolytic just means anti-anxiety.
Amazingly, that synthetic version of allopregnanolone costs $25K and requires hospitalization.
Pregnenolone (which drives allopregnanolone) is $10 and you can get it here.
Let's turn our attention to CBD now for perimenopausal mood changes.
Can CBD help with perimenopausal mood changes and balance
We've also looked at the two main pathways addressed by the most common medications that doctors will prescribe:
- Serotonin pathways for depression (and anxiety although with less effect)
- GABA pathways for anxiety
What does CBD do for either if anything?
Serotonin is tricky since it's so integral to a range of different pathways.
Too much or too little is bad.
- Too little and you may have depression and poor brain repair (BDNF).
- Too much and you may have Serotonin Syndrome with a host of nasty side effects
The key here is balance.
Studies have definitely pointed toe serotonin function as being key to CBD's effect on depression:
Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).
When they chemically blocked serotonin creation, the antidepressant effect of CBD goes away.
We've dug deeper to show that the real star of this serotonin effect is BDNF (see CBD and BDNF) and it actually operates through CB1 receptors! That's our endocannabinoid receptor that CBD supports.
Let's go deeper into CBD's effect on the serotonin pathway.
We'll start with this recent study:
Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT1A receptors.
The key there is that CBD doesn't just juice up serotonin availability like SSRI's.
This causes the brain to go the other way with naturally produced serotonin (hence, normalization).
It actually improves "function" by making the receptors more balanced.
You'll see this throughout the research with descriptions like "normalize" or "modulates".
Not increase. Reduce.
Serotonin does many different things depending on the brain area (hence the increase of anxiety/depression with new SSRI prescriptions).
By affecting its function in the DPAG, CBD has an effect on panic attacks (critical during perimenopause).
Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG.
By the way, 5HT is the scientific name for serotonin function.
Again, lots of studies and they all point to balancing or improvement of serotonin function:
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
That's important with estradiol in flux during perimenopause.
What about GABA?
A study on GABA and autism helped to clear the air as anxiety commonly coincides:
Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant.
Interestingly, the effect on autism was reversed in one pathway.
Another study looked at a disease with a pronounced imbalance between GABA and Glutamate (the brake and the gas pedal). Schizophrenia.
The effect of CBD there:
Overall, these findings show that CBD can restore cannabinoid/GABAergic signaling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure.
We'll leave off with this one.
In contrast to the effects of delta 9-THC, mice treated with cannabidiol and nabilone spent a greater amount of time in the open arm of the maze, an effect similar to that produced by diazepam, the reference anxiolytic agent. In this test situation.
Two very important pieces come out of this.
- First, THC can cause anxiety depending on the dose.
- Secondly, CBD had the same effect on anxiety as diazepam.
You know...Valium! The Godmother of all benzos (since women have borne the brunt of their damage...especially as we get older).
We've covered perimenopause irritability separately but it's all about balance during this transition since the key managers are on vacation (unless we supplement).
Let's look at other supplements that I've found to be helpful for mood during perimenopause.
Other tools for perimenopause mood
Think of perimenopause as a period of intense stress.
Stress is really anything that pushes the system one way or the other and estrogen doing cartwheels definitely meets that requirement.
Here are things that I have found (out of 100's of supplements) to be helpful if not essential:
- Siberian Rhubarb (full review here) - substitute for estradiol with focus on ERb receptor where mood issues are affected- Purchase here
- Pregnenolone (review here) - mother of all steroidal hormones including progesterone and allopregnanolone- Purchase here
- Berberine - (review here) alternative to metformin with longevity, mood, and gut benefits- Purchase here
- Fisetin - (review here) powerful antioxidant and remover of senescent cells (zombie cells) - Purchase here
- Magnesium Glycinate - especially for migraine with aura or stress response - Purchase here
- B complex - essential to support various pathways- Purchase here
- Vitamin D- Make sure to check with your doctor on your levels before starting. D is very important in supporting hormone production.
- Turmeric- This one is the all-around workhorse of supplements. Who doesn't love their turmeric? It decreases my anxiety! It's an adaptogenic that goes into fine-tune your body! It's great for the mind as well as the body. Purchase here
- Fish Oil- Your endocannabinoids are made out of Omega's. Purchase here
- Choline- Game changer for me personally. I was forgetting appointments right before I took this supplement. My brain loved this stuff and don't forget to eat your eggs!! Purchase here
- DHEA- Very important to take to support your hormone levels! DHEA is a primary source of hormones! Have your doctor test your levels and go from there! Purchase here
- Vitamin C and E- Helped with lessening my hot flashes. Great support of the immune system For C purchase here For E purchase here
Our review of supplements for perimenopause can be found here.
In the end, you have to look at the gaps left by hormones falling. The new research on this is pretty stark if you just let them go down. See the estradiol review as an example.
Now, more practical questions.
How much CBD for perimenopause mood changes
We don't have hard research on hormone-driven changes but we do have information on anxiety.
Remember how serotonin's effect on anxiety and depression is primarily driven by boosting BDNF, our brain's fertilizer.
This whole process is called neurogenesis and it's critical to anxiety and depression under the onslaught of whatever is doing the damage (stress, lack of hormone protection, over-active immune, gut issues, etc).
Studies show that neurogenesis for CBD peaks at 300 mg and then starts to go down.
The anxiety effect (calming) may increase but the long term brain support function is optimal at 300 mg.
This applies to both depression and anxiety (plus a range of mood and mental health issues).
A starting dose is usually 25-30 mg to test on your body.
Always take at least 4 hours away from medications and work with your doctor and naturopath with any supplement of course.
What's the best kind of CBD for perimenopause mood issues?
What's the best CBD for perimenopause mood shifts
Our system is already in flux during perimenopause so we don't want to add more to it.
For this reason, we must insist on the following:
- Organically grown in the US at an FDA registered farm
- CO2 processed
- 3rd party tested
- No THC
- No Pesticides
- No Solvents
- No Heavy Metals
- No Bacteria
- No Mold
This is essential and we post 3rd party testing on every page for this reason.
That's the start of it, however.
Most of the market is pushing full-spectrum CBD.
We tried 3-4 of these big brands early in our testing of CBD for my perimenopause.
I had bad allergic reactions.
If you read our CBD and perimenopause allergies, you'll realize that hormone flux is a nightmare for histamines and allergies.
We are at the top of the range for issues (between 40-60%).
The last thing we need is a bunch of plant material which is essentially what full-spectrum CBD in hemp oil is.
Histamine is a powerful excitatory hormone in the brain and directly counters the effects of GABA (our key antianxiety neurotransmitter from above).
If you read our reviews, many people say how they had issues with other CBD products which go away with ours.
We're not surprised. Check CBD full spectrum versus CBD isolate for anxiety to get the full picture here.
Be well. Be informed. Feel great!
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.
Get specific links for CBD and Perimenopause symptoms and questions here.
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.