It's a common complaint.
Migraine headaches either arriving or worsening during perimenopause.
This is especially true for women who are already prone to migraines.
Women already have a 3 to 1 risk for migraines to begin with so hormones are clearly at play.
Once you see the connection with hormone fluctuation below, it will all make sense.
For anyone who's suffered from migraines, it can be debilitating.
I had migraines early in life which trailed off as I got older.
All of a sudden, they came back almost daily, especially with the visual aura.
I would wake up every morning with that telltale "fluttering" in the corner of my eye.
Never a good sign!
There is interesting new research on how to address aura migraines directly.
We'll also look at CBD for perimenopausal migraines.
These are the areas we'll cover:
- Why does perimenopause cause more migraines
- Estrogen and migraines during perimenopause
- HRT and migraines
- Magnesium and ocular perimenopause migraines
- Can CBD help with perimenopause migraines
- How much CBD to take for perimenopause migraines
- What's the best CBD for perimenopause migraines
Let's get started before the next one comes.
First, what's the connection between perimenopause and migraines?
Why does perimenopause cause more migraines
Most people (including doctors) think that perimenopause is this nice, gradual reduction in hormones as we slip, slide right into menopause.
Like a velvet glove.
Nothing could be further from the truth for a good percentage of us.
It's estimated that 25% of women will have a debilitating perimenopause and I'm one of those fortunate ones.
That story is here but there was nothing gradual about it.
Check our perimenopause versus menopause review.
Progesterone is dropping gradually but estradiol is doing flying kickflips.
There can be a very chaotic cat-and-mouse dance between estradiol and FSH.
The effect of this flux in estradiol directly impacts migraines:
If a woman is already a migraineur subject, the attacks often worsen during both the early and late phases of the menopausal transition, whereas an onset of a migraine is quite rare.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759136/
This is a clue since the early and late periods reflect the most flux in key hormones.
Let's really focus on estradiol since it's the main actor in this terrible play.
We'll cut to the chase:
Recent data support the historical view of an elevated risk of migraine with significant drops in estrogen levels.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102139/
How does this happen?
First, keep in mind that estrogen (we'll use interchangeably with estradiol -e2, our most prominent estrogen) has its hands in almost every pathway of the body.
Check out our full review for estradiol to understand just how important it is.
Interestingly, genetic studies have pinpointed an association with migraine and ESR1 gene.
https://www.ncbi.nlm.nih.gov/pubmed/23674830/
But what about men who get migraines?
Yes, men have estrogen as well.
In fact:
A study of 39 men found that those affected by migraine had higher levels of estradiol, an estrogen, than those without migraine.
https://www.ajmc.com/newsroom/increased-estrogen-levels-associated-with-migraine-in-men
Some men "aromatize" or turn typical male hormones into estrogen at a faster clip.
Remember it's the "drop" in estrogen that can cause migraines:
Analyses of within-woman rates of decline showed that E1c decline over the 2 days following the luteal peak was greater in migraineurs for both absolute rates of decline.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932235/
Let's look at estradiol's relationship with migraines to understand why.
Estrogen and migraines during perimenopause
If you've read any of our articles, you know we like to really dig deep into a subject.
Migraines for women are no different.
Here's the current state of research in a nutshell.
Estrogen has direct control over key levels and pathways of other powerful substances:
- Estradiol controls both the creation of serotonin (see Tryptophan and serotonin) and break-down (MAO)
- Estradiol controls CGRP levels (we'll explain below...it's critical to migraines)
- Estradiol controls mast cell release of histamine in the brain
Let's focus on just those three.
The current belief is that significant drops in estrogen (change is key...not level) causes an intense release of CGRP in the trigeminal nerve.
CGRP is a powerful vasodilator (expands arteries/veins in size). This points to the fact that researchers thought migraines were a vascular issue for decades.
Indeed, they were able to track and influence pain according to vascular dilation.
Turns out CGRP may be the cause of it.
In fact, the leading medications for migraines called triptans basically normalize CGRP.
They do this via the serotonin system:
Many effective anti-migraine drugs used currently are serotonin receptor agonists such as triptans.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117063/
The net effect of this serotonin activity on CGRP?:
Accordingly, triptans act on the trigeminovascular system and bring the elevated serum levels of CGRP to normal 13 to bring about migraine relief.
Make sure to check out the side-effects of Triptans before you rush out and get one.
I had a week-long migraine after taking a triptan...thought I was never going to come out!
What happens when researchers infused CGRP directly to people who get migraines?
Infusion of CGRP in migraine patients results in a delayed migraine-like headache, occurring around 1–5 h after treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088188/
So let's follow the trail:
- Estrogen controls serotonin levels
- Serotonin levels control GCRP levels
- CGRP causes expansion of the vascular system (among other effects) in the trigeminal nerve tied to migraine.
Nice and tidy.
By the way, you're miles ahead of most doctors on the actual mechanism now.
Perimenopause (or monthly cycle) can be characterized by sudden drops in estrogen.
It's like a big Jenga tower where you pull out one block at the bottom.
As for the other things a boost in CGRP levels causes:
Mast cell release in the dura mater (literally the lining of the brain and spinal cord)
This is histamine and it's incredibly inflammatory!
In the worst possible place (our brain sac of all places).
This is the pain part:
Histamine plays a crucial role in migraine pathogenesis: sustaining the neurogenic inflammation pathway. Interaction between mast cells (MC) and calcitonin gene-related protein (CGRP) results in sensitization of trigeminal afferents and trigeminal ganglia.
https://www.ncbi.nlm.nih.gov/pubmed/28862769
Basically, mast cells (where histamine, our allergy responder is released) interact via CGRP to inflame key nerves in your brain stem!
That becomes very important with the type of CBD we want to take which we'll discuss later.
The smoking gun:
During some migraine attacks, increased concentrations of CGRP can be found in both salivae and in plasma drawn from the external jugular vein.
https://en.wikipedia.org/wiki/Calcitonin_gene-related_peptide
So estrogen's a big deal.
Again, it's the change that matters as migraines tend to go down or away at menopause when hormone levels are relatively stable.
Another big question that comes up as a result of this.
HRT and migraines
Can replacing hormones, especially estradiol, cause or help with migraines?
Again, the point is a drop in estrogen.
Low or high levels are less of an issue compared to the rapid change between the two.
This is born out in research as well:
HRT should be administered continuously, without intervals, to avoid sudden estrogen deprivation and the consequent possible onset of a migraine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759136/
Just one more example of how the synthetic estrogens are not the same thing as bio-identical estradiol:
In contrast to contraceptive doses of ethinylestradiol, migraine aura does not contraindicate the use of physiological doses of natural estrogen.
https://www.ncbi.nlm.nih.gov/pubmed/28994639
Check out the summary of estradiol supplementation to really understand this.
Keep in mind that during perimenopause, estradiol and progesterone (or their equivalents, Siberian Rhubarb and Pregnenolone) provide a steady base but you may still have underlying fluctuation.
Let's look at an interesting tool that has been a lifesaver personally.
Magnesium and ocular perimenopause migraines
Many women get the "aura" with their migraines. It's like a two-fer!
I have tried almost everything for migraines.
- Triptans
- NSAID's
- Over the counter
Nothing worked.
Once that aura started and I had the weird numbness in my left hand and face...it was game on.
The only thing I could do was go sleep in a dark room and if I didn't give it enough time, it would come back.
Terrible terrible feeling. And the "hangover" for the next few days was brutal.
Literally like the flu. Brain flu.
Researching online (which takes up a lot of my time if you haven't noticed), I came across an interesting tidbit on magnesium glycinate and migraines.
Sure, I'll try it!
Goodness...if I can take magnesium even after the aura starts, it will stop the migraine cold.
NOTHING has ever done this. It really feels like magic if you've suffered for decades from migraines.
I now take 200mg of mag 3 times a day and I never get migraines (unless really really stressed).
I'll sometimes alternate with mag theorate or citrate. Any of the "ates".
It can't be the standard mag you find down at the grocery store.
What on Earth is going on there based on what we looked at above for the migraine pathway?
Just this:
However, treatment with MgSO4 infusion significantly decreased circulating CGRP in women with PRP only from median 15.5 (range 10-48) to 10 (range 10-110) pmol l-1) (P < 0.05).
https://www.ncbi.nlm.nih.gov/pubmed/7820978
MGSO4...That's magnesium sulfate.
The current theory is that under stress (lack of sleep, histamine response, perimenopause, etc), some brains use up magnesium more quickly.
There's a great review of how powerful magnesium is for hormone balancing here:
https://www.larabriden.com/8-ways-that-magnesium-rescues-hormones/
Magnesium is one of our body's first responders for stress.
Its direct effect on stress is many-fold such as:
Magnesium can suppress the ability of the hippocampus to stimulate the ultimate release of the stress hormone, it can reduce the release of ACTH (the hormone that tells your adrenal glands to get in gear and pump out that cortisol and adrenaline), and it can reduce the responsiveness of the adrenal glands to ACTH.
You really have to read that article...so interesting!
Most of us are running low of this key substance.
So, it's an easy try. Definitely worth checking out.
Finally, what about CBD for migraines from perimenopause?
Can CBD help with perimenopause migraines
So the question of the day (or article)....can CBD help with perimenopausal migraines.
First, we'll start with anandamide, our naturally occurring endocannabinoid in the brain.
It's called the "bliss" molecule and named after Anand, the goddess of bliss.
Good place to start.
It turns out that people with migraines have reduced levels of anandamide in general and especially when having a migraine:
Clinical observations, in particular, show that the levels of anandamide (AEA)-one of the two primary endocannabinoid lipids-are reduced in cerebrospinal fluid and plasma of patients with chronic migraine (CM), and that this reduction is associated with pain facilitation in the spinal cord.
https://www.ncbi.nlm.nih.gov/pubmed/29615860
They go on to say that a potential therapeutic approach is to reduce FAAH which breaks down anandamide (see the woman who can't feel pain, anxiety, or depression here).
What does CBD do there?
Studies on schizophrenia were telling:
The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
How did it do this…
Cannabidiol may enhance endogenous anandamide signaling indirectly, by inhibiting the intracellular degradation of anandamide catalyzed by the enzyme fatty acid amide hydrolase (FAAH).
That's exactly what we're looking for with migraines.
This effect on anandamide is very important for other reasons.
Remember how migraines are partially a vascular response especially in the dura mater (the sac that holds the brain and spine)?
Anandamide is a powerful anti-inflammatory and its effects are directly tied in here:
Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%.
https://www.ncbi.nlm.nih.gov/pubmed/14718591
Keep in mind that a key aspect of migraines are vascular dilation and the rebound constriction from our bodies.
Next up...serotonin and CBD.
Remember how serotonin is higher up on the chain of events above CGRP?
In fact, triptans are basically serotonin boosters.
And the wonderful estrogen effect (hint hint perimenopause):
It has been observed that varying levels of ovarian hormones especially estrogen influence serotonin neurotransmission system and CGRP levels making women more predisposed to migraine attacks.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117050/
In fact, when they boosted anandamide levels prior to a migraine, it reduced the attack!
The study confirms that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that pharmacological modulation of CB receptors can be useful for the treatment of migraine pain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072518/
What does CBD do there?
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
Allodynia is a fancy way to say an increased pain threshold.
Our favorite word there is "modulates". Not boosts or drops. Balances and supports.
Just look at the COMMON side effects of Aimovig which blocks CGRP:
Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site.
https://www.drugs.com/sfx/aimovig-side-effects.html
The actual triptans which boost serotonin can be even more brutal.
I experienced serotonin syndrome which is where your serotonin goes too high.
That story is here but it was the worst thing I've ever experienced in my life!
There's even a gene mutation tied to migraines and guess where it is?
CB1 Receptors (our endocannabinoid system receptor for anandamide).
https://www.ncbi.nlm.nih.gov/pubmed/19539700
There's also the see-saw effect in vascular expansion and compression accompanied by a tremendous amount of inflammation.
That's the pain side of things.
What can CBD do there?
CBD is showing powerful effects there to bring balance to this system.
CBD decreases the production of inflammatory cytokines, influences microglial cells to return to a ramified state, preserves cerebral circulation during ischemic events, and reduces vascular changes and neuroinflammation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/
Just a head's up...ischemic events means strokes and there's a clear connection between migraines and stroke risk.
Again, for pure pain, check out CBD versus Tylenol for an interesting study of the relationship between the two.
Let's look at actual migraines.
Of course, the Europeans are way ahead of us there.
79 chronic migraine sufferers were given amitryptiline (leading triptan migraine medication) or a combination of THC/CBD.
TCH-CBD combination yielded slightly better results than amitriptyline (40.1 percent) with a 40.4 percent reduction in attacks (better than the triptan which can have huge side effects)
Furthermore,
Cannabinoids reduced pain intensity among migraine patients by 43.5 percent.
Even better was the list of side effects from this study:
The incidence of stomach ache, colitis, and musculoskeletal pain – in female subjects – decreased.
That study included THC which we have some concerns about (See CBD versus THC here) but goodness...the question is why are we prescribing medication with very serious side effects.
Finally, the histamine piece.
There is interesting research on our histamine response (Dura mast cells) and migraines.
They either contribute the migraine processor to its inflammatory response.
Cannabinoids have been found to limit or manage our immune response via the histamine pathway.
For example:
This limits excessive activation and maturation of MCs from resident progenitors via "tonic" CB1 stimulation by locally synthesized endocannabinoids.
https://www.ncbi.nlm.nih.gov/pubmed/22226549/
MC is short for mast cells like those that go haywire in the dura mater during migraines.
Check out CBD and histamines here.
There's a great review of current research on endocannabinoids and migraines here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928495/#B15
For the wonderful tag-along with migraines, check out:
So...some practical questions.
How much CBD to take for perimenopause migraines
We don't have solid research on migraines specifically.
Let's look at the range to get better acquainted.
A starter dose is usually 25-30 mgs to see how your body responds.
- Sleep help is showing around 160 mg.
- Neurogenesis (brain repair) for anxiety, depression, and the like peak at 300 mg.
- 600 mg has been used for public speaking social anxiety episodes.
Here's what we do know.
Beyond 300 mg, CBD starts to boost a pathway called TRPV.
TRPV is actually tied to pain sensitization.
This is why the anti-pain effects of CBD appear to be on a bell-curve.
Up till about 300 mg and starting to trail off as we get closer to 600 mg.
This is an interesting effect that most websites don't really go into!
For that reason, migraines might respond best between 100-300 mg.
Again, test on yourself and for all that's good in the world, look at Magnesium Glycinate or Citrate (you can purchase here).
Again, I take 200 mg 3 times a day and as needed for extreme stress.
It's literally your stress mop in the nervous system and perimenopause is a flood!
Next, a very important piece I found out the hard way.
What's the best CBD for perimenopause migraines
First, the bare minimum requirements still apply:
- 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 takes it so…
There's another important piece for migraines specifically.
You may have noticed a powerful histamine angle to how migraines progress.
Histamine issues increase as we get older and hit women much more strongly.
Perimenopause is a known period of increased allergies and histamine issues.
Most of the CBD market is pushing full spectrum CBD which has a lot more plant material.
This could be a nightmare for anyone with histamine issues.
I tried 3-4 of the biggest brands when I started this journey and immediately had allergic responses.
CBD by itself is shown to reduce mast cell release so the allergy response must be due to all that plant material.
For that reason, we eventually found CBD Isolate.
Also, all the research is on CBD by itself and hopefully, it's obvious that we work based on research.
We'll leave marketing hype to those that don't know migraines the way we do.
Be well and take care of each other.
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.