One of the most common searches when we researched anything and everything with this transition was "perimenopause and divorce".
That's a good lead-in for this whole review.
From talking with my friends going through perimenopause, there appears to be two ways to go (beyond anxiety and depression).
Anger and irritability or outright crying.
It's not unusual to bounce between both!
Mind you, I had been on this earth for a good four decades with a pretty calm demeanor and suddenly, I was being hit by waves of these different emotions.
We covered the big mood changes with perimenopause at our CBD and mood changes but let's zero down into anger.
Angrily.
As you'll see below, the root of this is pretty clear now from research.
Furthermore, we'll look to see if CBD can help with this pathway.
These are the topics we'll cover:
- Can perimenopause cause anger and irritability
- Estrogen and serotonin for irritability
- Serotonin and irritability or anger during perimenopause
- Inflammation and perimenopause anger
- Can CBD help with perimenopause irritability or anger
- How much CBD to take for perimenopause anger
- What's the best CBD for perimenopause irritability
Can perimenopause cause anger and irritability
Yes!
First, understand what perimenopause is.
We go into it with detail at our perimenopause versus menopause but a quick recap.
We're basically losing our key steroidal hormones:
- Progesterone
- Estrogen (estradiol is our main flavor of this hormone)
Progesterone starts to drop around age 40 and estrogen drops significantly during perimenopause (generally starting around age 46-47).
Here's the deal...estrogen can go a roller coaster ride as it enters a cat-and-mouse relationship with FSH (another key hormone).
Research is showing that about 25% of women will have a debilitating perimenopause.
That being said, roughly 50% will have very severe symptoms.
For those ladies, estrogen's wild ride into the sunset had a slew of effects across multiple pathways.
Think of all the perimenopause (or PMS) symptoms.
Estradiol is not just for making babies...it's a powerful hormone that governs your heartbeat, metabolism, and brain function!
One of those pathways is a major player in mood.
Let's go there now.
Estrogen and serotonin for irritability
Let's introduce serotonin.
It's commonly called our "feel good" hormone but that's a bit misleading.
This isn't a "pleasure" angle as much as a feeling grounded effect.
Basically, it's more a function of feeling bad when it's too high or too low.
We can look to SSRIs and serotonin syndrome for the crazy side effects of having levels too high.
Equally bad, the list when serotonin is too low.
Here's the fascinating piece.
Estrogen has a direct handle on the levels of serotonin!
Both its creation and removal:
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.
https://www.zrtlab.com/blog/archive/impact-hormones-serotonin-depression/
TRPH is tryptophan which is the raw material for serotonin.
Our body will actually starve it out during infection which why low mood generally accompanies the flu.
On the back end, MAO breaks it down.
The general effect of higher estrogen is higher serotonin. Even for males (converted from testerone in the brain).
Your body and serotonin pathway are used to this nudge for four decades (albeit with monthly fluctuations) and then it goes haywire before a plummet.
The knock-on effects of this are incredibly important (see CBD and BDNF as an example).
Check out CBD versus SSRI's for serotonin here.
Let's get to serotonin for irritability and anger.
Serotonin and irritability or anger during perimenopause
Serotonin has been described as our resilience neurotransmitter.
There are lots of studies that point to how serotonin "models" our stress response.
For example, one study depleted tryptophan (serotonin's raw material) and then placed participants under a stressful situation:
ATD influenced the HPA axis (associated with higher cortisol levels), apparently independent of CO(2) or air inhalation stressors.
https://www.ncbi.nlm.nih.gov/pubmed/16962720
To translate, the participants with less serotonin had a stronger stress response than the controls.
Another study looked at levels of tryptophan and found effects directly affecting irritability:
In healthy people with high trait irritability, tryptophan, relative to placebo, decreased quarrelsome behaviors, increased agreeable behaviors, and improved mood.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077351/
Just a head's up...eating foods with tryptophan do not increase its levels in the brain since it competes with other amino acids for entry across the blood-brain barrier. We have a whole review on tryptophan as a social stress buffer.
Then there's the question of emotional regulation and serotonin.
Of course, studies with SSRI's (which boost serotonin) for people with low irritability also offer a clue:
Furthermore, the magnitude of changes in assaultiveness, irritability, negative affect, and affiliation was correlated with plasma levels of SSRI.
https://neuro.psychiatryonline.org/doi/full/10.1176/jnp.15.3.294
You can think of serotonin as a support system for keeping our cool:
In many of the studies on serotonin function in aggression, various emotions, especially anger or irritability and difficulties with affect modulation were associated with serotonergic dysfunction.
https://neuro.psychiatryonline.org/doi/full/10.1176/jnp.15.3.294
Do you get irritable if you go too long without food?
Fluctuations of serotonin levels in the brain, which often occur when someone hasn't eaten or is stressed, affects brain regions that enable people to regulate anger, new research from the University of Cambridge has shown.
https://www.sciencedaily.com/releases/2011/09/110915102917.htm
And remember the sadness?
Reported levels of happiness were positively correlated and reported levels of sadness were negatively correlated with serotonin synthesis in the right anterior cingulate cortex.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077351/
So...maybe it is the "feel good" neurotransmitter after all.
The issue with SSRIs is that the brains work against them and drops your natural serotonin production (called normalization) and they are blunt instruments.
Check out the problem with ssris.
Are there other ways to support this pathway to take the edge off of perimenopause irritability and anger?
We're going to look at other ways to boost serotonin but first...CBD.
Can inflammation affect perimenopause irritability and anger?
Many mood issues are pointing back to inflammation in some way or another (see CBD and neuroinflammation for anxiety or even CBD for perimenopause).
What about outright irritability or anger?
Individuals who meet criteria for the intermittent explosive disorder have higher levels of plasma high-sensitivity c-reactive protein (CRP) and interleukin (IL)-6 than either normal control subjects or individuals with other psychiatric diagnoses.
https://www.psychcongress.com/blog/does-inflammation-cause-more-depression-or-aggression
CRP and IL6 are signatures of systemic inflammation.
Inflammation in our nervous system has been shown to manifest itself as anxiety, depression, and even...explosive anger!
But even for the average person, there's a correlation between anger and inflammation:
Within the population as a whole, measures of aggression were highly correlated with inflammation: the more aggressive people were, the higher their levels of CRP and IL-6 were likely to be.
The question is then this...can we add inflammation to a person's system and cause anger?
That would help with the arrow of cause and effect.
Look at what happens when people with hepatitis are treated with interferon, a known inflammatory agent:
In contrast to the untreated reference group, we found significantly increased scores for depression (p <.001) and anger/hostility (p <.001) during interferon alfa therapy in the treatment group.
https://www.ncbi.nlm.nih.gov/pubmed/12823087
It's not just anger of course:
These proportions rose to 35.0% (depression), 25.6% (anxiety), and 24.5% (anger/hostility).
Check out CBD and perimenopause anxiety or CBD and perimenopause depression.
Let's look at a study on typhoid vaccination which is known to create an inflammatory response:
Subjective reports of depressed mood, anhedonia, anxiety, irritability, memory, and attentional disturbance assessed with clinical depression scales usually develop later, between the first and third months of IFN-α therapy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885494/
Interestingly, it was a typhoid vaccine that sent me spiraling during perimenopause (story is here).
More importantly, the effects above occur a few months after so we're talking about chronic inflammation.
They even did brain scans to see where this effect was caused:
Furthermore, inflammation-associated mood change reduced connectivity of sACC to the amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6.
There's that inflammatory agent IL6 and look at the reduced activity across key areas of the brain we looked at for the mechanisms of anxiety here.
Fascinating!
Finally, when our body is faced with infection (or chronic stress - it can't tell the difference), it starves tryptophan which starves serotonin.
This is now established as a key pathway for depression, anxiety, and even anger.
Ancient protections that go awry if chronic.
Let's get to the other side...are there things we can do here.
We'll start with CBD.
Can CBD help with perimenopause irritability or anger?
We looked at key pathways tied to perimenopause irritability and anger.
The big one was serotonin function which is directly controlled by estrogen in women.
Let's start there since it has roots in many of the symptoms of perimenopause.
CBD has been shown to have powerful effects on serotonin function.
We'll start with the most recent finding:
Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
- Analgesia - reduction in pain (See CBD and perimenopause pain)
- Anxiety reduction - See CBD and perimenopause anxiety
And finally...5-HT (serotonin).
Pay attention to the language all the studies use.
They don't say increase or decrease.
We want to avoid this since serotonin is so powerful. Too high (serotonin syndrome) or too low (all the symptoms mentioned above and more) are potentially dangerous.
Throughout the studies, you'll see words like "modulate" or "normalize".
This is critical!
Balancing key systems is the de facto role of the endocannabinoid system that CBD supports.
Let's look at other studies.
Speaking of modulates:
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
https://www.ncbi.nlm.nih.gov/pubmed/30157131
Allodynia is central pain sensitivity. Various aches and pains is a known issue with perimenopause. And irritability!
Of course, we've covered the benefits of CBD for anxiety in-depth.
To round it out…
Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.
https://www.ncbi.nlm.nih.gov/pubmed/26711860
Here's the important piece.
CBD versus SSRI's for perimenopause anger
SSRIs directly increase the availability of serotonin.
This can have a slew of side-effects (which I personally experienced) and the brain pushes back by reducing normal levels of serotonin (called normalization).
We would expect higher doses of CBD to have this same effect if it worked the same way.
It doesn't show this!
They've tested CBD at very high doses (1500 mg up to 1 gram) with a very strong safety profile.
This speaks to a "constraint" action of CBD on serotonin function.
A feedback mechanism (too high?? lower it. Too low, boost it).
That's the only way we can avoid the signs of serotonin imbalance up or down.
Check out CBD versus SSRIs for more information.
What about the other piece..inflammation?
This may be CBD's second-biggest attribute behind the serotonin and neurotransmitter pathway.
Remember how IL6 kept popping up above with anger (or depression).
In a study on asthma, an inflammatory agent was given and followed by CBD.
The results:
The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458548/
What happened to IL10?
Oh...that's an anti-inflammatory cytokine which calms down our inflammatory response.
Goodness.
This has implications across a range of health and mental health issues.
Let's look at some other powerful tools we found along the way.
Supplements for perimenopause irritability
Here are additional tools during this period of time:
- Siberian Rhubarb (review is here). This is a safe and amazing substitute for the mood-related benefits of estradiol. Buy here.
- Pregnenolone - mother of all steroidal hormones including progesterone (review here). Buy here
- Fisetin - a powerful anti-inflammatory with longevity effects (review here) Buy here
- Berberine - critical for gut barrier and inflammation (review here) Buy here
- Curcumin - powerful anti-inflammatory Buy here
- L-Tryptophan - the raw material for serotonin for people with a poorly functioning conversion (review here). Buy here
- Magnesium Glycinate - powerful stress response booster. Buy here
Back to practical questions on CBD.
How much CBD to take for perimenopause anger
We don't have exact research on this but we can look to depression which appears to be the opposite side of the coin to anger in our body's response to inflammation/infection.
Very ancient survival mechanisms to threat.
A starting dose is generally accepted at about 25-30 mg to test on your body.
The fact that inflammation is involved points to a peak dose of about 300 mg.
That's the level where the maximum amount of neurogenesis (brain repair) occurs.
See CBD and neurogenesis here.
In one of the CBD studies on serotonin for depression, they used the equivalent of 360 mg for a 160-pound person.
Again, other studies showed peak neurogenesis at 300 mg so I actually take two doses at 150 mg twice a day.
CBD uses the same liver pathways as other medications so work with a doctor or naturopath and always take away from medication.
Test CBD levels based on how you feel.
Our estimate is between 50 - 100 mg with the 300 mg being the high end.
What about the type of CBD?
What's the best CBD for perimenopause irritability
We start with the basics:
- Organically grown in the US at an FDA certified farm
- 3rd party tested (we test both biomass and finished product separately)
- THC free (THC can actually cause psychosis)
- No pesticides
- No mold
- No heavy metals
- No bacteria
That's a baseline (which many brands don't meet).
We actually test twice (biomass and finished product) since our whole family uses our CBD.
There's another important aspect.
CBD full spectrum versus CBD isolate.
We focus on CBD Isolate because that's what the research is based on.
More importantly...histamine or allergy response!
There's a known tie between perimenopause and allergy issues.
Check out CBD and perimenopause allergies or histamines!
All the plant material in full-spectrum CBD is liable to trigger this response.
In fact, most of the side effects we see with clients from their prior full spectrum CBD goes away when they use our Isolate.
You'll see this consistently in the reviews and it's how we found isolate ourselves.
Think back to a strong allergic reaction….any irritability associated with it?
Look what researchers found when they triggered a strong histamine release:
The cognitive changes consisted of diminished attention and memory, and the effective changes of anger, irritability, and, to a lesser extent, depression.
https://www.ncbi.nlm.nih.gov/pubmed/3749421
Everyone out there is pushing full-spectrum (see CBD full spectrum versus Isolate) even though 40-60% of the population has histamine issues.
We've been there personally and that's why we started this whole thing, to begin with!
So...before someone else tells you to "relaaaaax", check out some of the tools mentioned above till estrogen is done with its wild ride.
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.
Related Research:
Why do some women have terrible perimenopauses
Understanding serotonin and inflammation for perimenopause
Your estrogen guide
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.