The other symptoms are bad enough.
Mood swings, hot flashes, and weird pains aren't enough?
Now we add a wonderful layer of nausea to our perimenopausal journey.
The trip can last a few years so let's see if we can take that item off the menu.
We covered the mechanics of nausea quite a bit in our CBD and anxiety nausea.
That may be required reading since anxiety is one of the top symptoms for perimenopause.
It was definitely the focus of my experience as estradiol started to spike and drop.
That story is here.
Let's focus on nausea that can come with perimenopause and see what we can do about it whether from related anxiety or hormonal fluctuation itself.
Just a note... the pathways for nausea in general are the same as we drill down.
We'll then look at what can help there including CBD.
We'll cover these areas:
- Why does perimenopause cause nausea
- Serotonin and perimenopause nausea
- The endocannabinoid system and perimenopause nausea
- Can CBD help with perimenopause nausea
- How much CBD to take for perimenopause nausea
- What's the best CBD to take for perimenopause nausea
Let's get started! Before lunch, please.
Why does perimenopause cause nausea?
Everyone has experienced nausea at some point in their life.
Women may be more familiar with this from monthly cycles, pregnancy, and...perimenopause.
That's a big clue as to what is going on.
In fact, women who experience nausea due to their monthly cycle typically feel it right before or after their period.
There's an interesting study where they showed that nausea increased for all women in an experiment during their monthly cycle:
However, an inspection of Table 1 shows a trend toward higher scores during menses for all of the subjective measures of nausea.
That's not the interesting part.
When they looked at women who took birth control (a steady hormone release essentially), the trend was broken:
This same trend is not observed for women on oral contraceptives, which is not surprising given their attenuation of cyclic menstrual hormones.
So it's not the levels of hormones per se as the fluctuations in them.
There's no greater fluctuation than perimenopause (aside from pregnancy and maybe watching Love Actually).
With perimenopause, progesterone starts to decrease gradually...much earlier than you would expect.
That process actually starts in the late '30s and early '40s!
It's generally gradual and continues to very low levels by the time true perimenopause starts.
In fact, you may have no progesterone release during your final periods since an egg release is required for progesterone.
Check out our full review of progesterone
Estradiol (our primary estrogen - E2) is a very different story.
This bad girl is driving perimenopause in all its glory or terror!
It's so important to our health that we did a full review of estradiol and perimenopause here.
It's not just for reproduction!
Bones. Brains. Hearts. You name it.
Let's add stomachs to that list.
Actually, an intersection of gut and brain!
The body panics.
Estradiol production by the ovaries is dropping and the overseer of this process called FSH (another powerful hormone) tries to juice up the ovaries to make one...more...egg.
This can cause spikes in estradiol during perimenopause.
No slow decline like progesterone.
It's the spike and drops of estradiol that lead to the rollercoaster effect.
Ever get nausea on a roller coaster??
This is seen in pregnancy as well:
After adjusting for length of gestation, mean levels of total estradiol were 26% higher and mean levels of sex hormone-binding globulin binding capacity were 37% higher in patients with hyperemesis gravidarum than in control subjects.
Why would spikes in fluctuations in estradiol lead to nausea and even vomiting?
Serotonin and perimenopause nausea
It's a workhorse neurotransmitter.
Not only for the brain but for the gut (our second brain by the way).
In fact, over 90% of our serotonin is made in the gut.
That's why there are so many digestive issues listed on SSRI's side effect panels.
SSRIs boost serotonin which you can learn all about CBD versus SSRI for serotonin.
Anyway, fluctuations or increases in serotonin are tied to nausea directly.
In fact, back to pregnancy and extreme nausea and vomiting:
When the groups were compared with respect to serotonin levels, the group with hyperemesis gravidarum was found to have significantly higher serotonin levels
Hyperemesis just means vomiting.
Look, serotonin is a master regulator in the body so we're not surprised by this effect.
Drugs that block 5HT3 are very effective in controlling nausea and vomiting produced by cancer treatment and are considered the gold standard for this purpose
5HT3 is part of the serotonin pathways.
In fact, there's a whole class of anti-nausea drugs that work via the serotonin pathway.
So...what does serotonin have to do with estradiol?
Oh, just this…
Estrogen has been reported to have potent serotonin-modulating properties from the level of neurotransmitter synthesis via the regulation of tryptophan hydroxylase (Lu et al., 1999) and degradation of 5-HT to the density and binding of 5-HT receptors
To translate...estrogen controls both the production of serotonin (via tryptophan - see CBD, tryptophan, and serotonin here) and MAO, which breaks up serotonin.
It literally governs the available levels of serotonin on both the front and back end.
As for the specific 5ht3 pathway that anti-nausea meds use…
For example, the gonadal steroids 17β-estradiol and progesterone appear to act as non-competitive antagonists, with IC50 values similar to those observed for their inhibitory action on glycine and nACh receptors
Basically, estradiol and progesterone directly affect the 5ht3 receptors.
And the net effect of this…
fluctuation in gonadal steroids may underlie some behavioral disorders and nausea, for example during pregnancy, 5-HT3 receptors have been proposed to provide a potential target for new drugs to treat these problems.
Okay...so serotonin is a powerful balancer and estradiol governs its levels.
In fact, across a wide range of initiators of nausea and vomiting…
In most of these examples, the initial trigger for emesis (vomiting) is the release of serotonin (5-HT) from enterochromaffin cells that are distributed throughout the epithelium of the gastrointestinal tract
During perimenopause, the controller (estradiol) is asleep at the wheel (bouncing around the control room is a better analogy).
One more stop before we check out CBD and other helpers with perimenopause nausea.
The endocannabinoid system and perimenopause nausea
We all have this system naturally in our bodies and it's shared with every living animal (including sea urchins).
Research is showing that this system is tasked with balancing or finding "homeostasis" for other key systems from fluctuations (stress...essentially):
- Nervous system - including neurotransmitters such as serotonin, dopamine, and more
- Immune system - inflammatory agents and stress response
- Endocrine system - hormones such as estradiol, cortisol, and progesterone
Ummm...do any of those seem relevant to perimenopause (fluctuation in hormones) nausea (resulting fluctuation in serotonin)?
They discovered this effect with nausea resulting from cancer treatment...chemotherapy and radiation.
Most of the typical anti-nausea and vomiting medications were not effective.
Cannabis (the plant that CBD comes from as well as THC) would actually help in this case.
In clinical trials, cannabis-based medicines have been found to be effective anti-emetics and even surpass some modern treatments in their potential to alleviate nausea
But how is the endocannabinoid system involved at all in nausea?
We'll start with animal studies.
They found that CB1 receptors (the primary endocannabinoid system in the nervous system) were linked with vomiting and nausea:
Both rats (that do not vomit) and the house musk shrew (that does vomit) CB1 receptor agonists reduce intestinal 5-HT release, suggesting that enterochromaffin cells express functional CB1 receptors
5-HT is serotonin. So when CB1 receptors activity is boosted, serotonin activity is blocked.
That's the direction we want to go for nausea.
In fact, when they compared a synthetic endocannabinoid (dronabinol) versus the most popular anti-nausea drug ( ondansetron), the results were clear:
Rates of absence of nausea were 71% with dronabinol, 64% with ondansetron and 15% with placebo
THC directly fits into the CB1 "lock" but there's another way to get there without the negatives which we'll get into below.
It's called Anandamide...the endocannabinoid that THC plays the substitute teacher for with CB1 receptors.
Anandamide is called the "bliss" molecule and named after the Hindu goddess of bliss, Anand.
FAAH is another powerful endocannabinoid (it's in you right now!) that eats up anandamide.
In fact, check out FAAH's power with the woman who can't feel pain, anxiety, or depression (and we're betting nausea) here.
Why does it matter for perimenopause nausea?
Stay with us here...we'll explain after:
The anti-emetic effects of exogenous anandamide administration have been found to be reversed by the CB1 antagonist, AM251 (Van Sickle et al., 2005), and the suppression of nausea by the FAAH inhibitor URB597 was reversed by the CB1 antagonists AM251 and SR141716
That's a mouthful.
Basically, by boosting anandamide levels, there was a anti-nausea effect.
When they block FAAH, there was an anti-nausea effect.
So...reduce FAAH to block nausea.
How can we do this safely since THC has nasty side effects?
Can CBD help with perimenopause nausea
We'll look at studies on CBD and nausea studies but also how CBD affects what drives perimenopause nausea specifically.
Let's start with the components:
- Serotonin fluctuation from estradiol spikes during perimenopause
- Anandamide and FAAH levels
We saw how fluctuations in estradiol can make serotonin erratic.
What does CBD do for serotonin levels?
A lot of this research was born out of depression studies since serotonin is powerful there (See CBD and perimenopause depression).
Unlike SSRI's which just boost serotonin in one direction, CBD has a very different effect:
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain
"Modulates". Our favorite word!
Not increase. Not decrease. Balances!
This is so important with a powerful neurotransmitter like Serotonin.
Just check out CBD and Serotonin Syndrome to see why.
The other word you see in research is "normalize":
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
Another study found that CBD works on the same pathways as SSRI's but without the cumulative boosting that causes the side effects:
Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST.
FLX is fluoxetine, or Prozac, an SSRI.
In fact, when they combined ineffective levels of CBD with ineffective levels of the SSRI, there was a cumulative effect that then worked.
Again, the safety profile of CBD is much stronger.
Next component piece for perimenopause nausea...anandamide.
We saw above how anandamide directly blocks nausea and FAAH lowers anandamide.
THC fills in for anandamide but there are downsides there.
Is there another way to affect this pathway for nausea?
In as study looking at stroke prevention and CBD:
CBD increases circulating endocannabinoids through inhibition of fatty acid amide hydrolase (FAAH)34 and competition for intracellular lipid catabolism
That's exactly the direction we want to go for nausea!
The net effect of blocking FAAH:
CBD potentiates anandamide by reuptake inhibition of the anandamide membrane transporter (AMT) in vitro although this finding is controversial and needs to be replicated in vivo.
They also looked at CBD's effect on weight and arteriosclerosis as a result of this effect...two issues tied intimately to perimenopause!
Now...studies on CBD and perimenopause nausea directly.
Animal studies point first to the serotonin pathway (as we might expect):
These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT(1A) autoreceptors in the DRN.
This mirrors the pathway for the anti-anxiety drug which reduces nausea, buspirone (without the side effect profile).
Another study found CBD's effects from various cues:
On the other hand, Δ9- THC, URB597 and CBD all reduce these contextually-elicited conditioned nausea reactions
This is the so-called anticipatory nausea tied with a specific cue.
One note...studies are showing that estradiol lowers CB1 activity (which was key to keeping nausea at bay).
This indicates that it may be the spikes in estradiol that drive bouts of nausea:
Collectively, these findings are largely consistent with the fact that estradiol downregulates CB1 receptors in the rat hypothalamus
This brings up some practical questions.
How much CBD to take for perimenopause nausea
This is really going to be a trial and error approach, unfortunately.
Unlike perimenopause anxiety, where we have better guidance, there isn't a researched level of CBD for nausea.
It makes sense to start low at first...25-30 mg (about 1 dropper of the 1000 mg bottle).
You can go up from there as research showed a maximum neurogenesis effect at about 300 mg.
Neurogenesis is the process of repairing and replenishing brain tissue!
A full review here.
One note...if you hold the CBD under your tongue up to 60 seconds, it can speed the uptake and also allow more to be bioavailable.
This is important for nausea where you generally need immediate relief.
This also makes it easier to test what level works for you.
What's the best CBD to take for perimenopause nausea
Since we're dealing with perimenopausal nausea, we want the cleanest CBD available.
CBD Isolate in MCT oil is what we use for a reason.
It also needs the following requirements:
- Organically grown in the US at a registered FDA farm
- CO2 processed (cleanest option)
- 3rd party tested for:
- No THC (there are too many issues with THC for health uses - see CBD to protect against THC)
- No pesticides
- No heavy metals
- No bacteria
- No mold
Again, the last thing we need is to introduce some foreign entity that elicits...nausea!
That brings up histamines.
It's definitely involved in the motion sickness pathway which is a close cousin to nausea:
Antihistamines block emetic H1-receptors to prevent motion sickness.
Histamine issues go hand in hand with perimenopause (as I found out the hard way) so we don't want a bunch of plant material to set off that alarm.
Many people try full-spectrum CBD and have bad reactions (including nausea).
Around 30–40% of women who have asthma experienced worsening of their symptoms during the perimenstrual phase, the so-called perimenstrual asthma.
It's also the reason we only deal with CBD Isolate and not full-spectrum.
Be well and know that 12 months of no periods is our goal for perimenopause.
CBD is great to lessen the load during this time of stress but I would have been a mess without hormone support.
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.
Let's take care of each other!
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.