Research on CBD and Perimenopause Sleep Issues

cbd for perimenopause sleep


It's quite unsettling.

 

To go from really consistent sleep to suddenly not knowing what to expect before any given night during perimenopause is a huge draw on general wellbeing.

 

Perimenopause is stressful enough.  

 

Combine that with poor sleep and all other symptoms suffer.

 

Then, there's this little beauty: 

Despite the fact that sleep complaints are approximately twice as prevalent in women of all ages compared to men, most sleep research has been conducted with men while factors unique to women have been ignored. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185248/

 

We went through why perimenopause is so different from menopause here but a quick recap.

 

Dropping progesterone and erratic drops and increases in estradiol!

 

We'll get into the whole mechanics of it below.

 

These hormones are so much more important than just reproduction and that holds especially true for sleep.

 

Just look at the effect of their fluctuation and drop: 

The prevalence of sleep disturbance varies from 16% to 42% in premenopause, from 39% to 47% in perimenopause, and from 35% to 60% in postmenopause. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185248/

 

That's from the massive SWAN study of women's health.

 

Roughly half of women are suffering from sleep issues during this period of time!

 

That's millions of women and the knock-on effects from disrupted sleep is directly tied into related mental health and cardiovascular issues.

 

A study found that one night of bad sleep is indiscernible from high anxiety in brain scans!

Sleep loss triggers the same brain mechanisms that make us sensitive to anxiety to begin with—regions that support emotional processing and also regions that support emotion regulation 

https://www.popsci.com/sleep-deprivation-brain-activity/

 

In fact, sleep loss and anxiety can go hand and hand.

 

Check out CBD for perimenopause anxiety here.

 

So...what's causing the disruption in sleep?

 

More importantly, what can we do about it and does research show that CBD can help with that pathway?

 

All great questions!

 

We'll cover the following:  

  • Why does perimenopause disrupt sleep
  • Progesterone and sleep
  • Estradiol and sleep
  • GABA and sleep during perimenopause
  • Histamine and sleep during perimenopause
  • The endocannabinoid system and sleep
  • Can CBD help with perimenopause sleep
  • CBD versus Tylenol PM, Valium, and other sleep aids
  • How much CBD to take for perimenopause sleep issues
  • The best CBD for perimenopause sleep issues

 

Grab a cup of coffee (unless it's 2am) and let's get started.

 

We'll also cover other things we found along the way

Why does perimenopause disrupt sleep 

First, keep in mind that perimenopausal symptoms can begin years before you actually lose your period.

 

12 months without a period is generally assumed as the beginning of menopause.

 

Progesterone actually starts to go down late 30's and early 40's which is critical for sleep.

 

So during perimenopause, we have two things occuring:

  • Progesterone continues to decrease as ovarian production shuts down.
  • Estradiol (our main estrogen called E2) can go on a roller coaster ride in a last ditch efforts to make another egg

 

This fluctuation (as opposed to a straight drop) is what makes perimenopause very different from menopause.

 

It's an estradiol shit show (excuse our language but it almost crushed me...that story is here).

 

For 25% of women it can be debilitating and as we saw above, another 25% just have really bad sleep as a result.

 

Learn all about the perimenopause difference from menopause here.

 

At my lowest point, before progesterone supplementation, my sleep was a mess.

 

Some of this was due to racing heart and panic-like spates during the night.

 

I would literally wake up with a jolt and it felt like my whole body was vibrating.

 

I'm part of that 25% group where it went haywire.

 

That may be payback for relatively smooth periods all my life.

 

The effects of perimenopausal hormone fluctuation is different from that during normal cycles when younger.

 

They can actually see it on brain scans in studies like this one: 

The women also woke up more often and had more arousals -- brief interruptions in sleep lasting 3 to 15 seconds -- than they did in the days after their menstrual periods. In contrast, sleep tends to be stable throughout the menstrual cycle in younger women. 

https://www.sciencedaily.com/releases/2015/06/150616131534.htm

 

The key there is the comparison with younger women cycles.

 

Yes, age plays into this but hormone fluctuation is different in perimenopause even when we still have a cycle: 

Within any ovulatory menstrual cycle, follicular phase estradiol (E2) levels tend to be lower, luteal phase E2 levels tend to be higher, and luteal phase progesterone levels are lower than in reproductive-aged women 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810528/

 

More extreme gaps across the cycle!

 

Then, there's the lovely band of other perimenopause symptoms.

 

Hot flashes are a known culprit as are joint and muscle aches.

 

Interestingly, new research is pointing to a connection between hot flashes and sleep apnea (chronic breath catching which disrupts sleep).

 

We'll look at that below in more detail along with a fascinating way to address it.

 

So...at a summary level, drops in progesterone and fluctuations in estradiol.

 

Let's tackle those two first in terms of their effects on sleep.

 

We'll start in order of when we start to lose them.

Progesterone and sleep 

As we mentioned above, progesterone levels start to drop late 30's and early 40's for most women.

 

That's a shame since it has powerful effects across the entire brain and body.

 

At my worst point in perimenopause, my 4th doctor finally started me on bio-identical progesterone and it was night and day (literally).

 

The effect was almost immediate.

 

Why?  What does progesterone do for sleep?

 

Get ready to get blown away (and angry if your doctor says your levels are just fine).

 

In general, estrogen is pro-growth and excitatory.

 

Progesterone is the opposite.  Calming and anti-inflammatory.

 

In fact, it has its hand directly on the lever of GABA.

 

If you have sleep issues, GABA is your new best friend.

 

In fact, it's the direct lever that benzo's push like Valium, Xanax, Ativan, and Klonopin (which basically tranquilizes you).

 

Check out CBD and GABA here but we'll look at that below in the CBD section.

 

Here are the stages of GABA levels reflected by increasing benzo doses: 

  • Calm (anti-anxiety effect)
  • Drowsy (anti-insomnia)
  • Hypnotic
  • Anaesthetic
  • Dead

 

Of course, the downside of benzos is addiction, short-lived effect, brain offsets the other way, etc.

 

Check out CBD versus benzos for more info.

 

Nevertheless, GABA is our "sleep" chemical in the brain.

 

It's cycle with Glutamate (the "gas pedal"), cortisol, and histamine govern the wake/sleep cycle.

 

You'll never guess what progesterone does in that pathway: 

Progesterone stimulates benzodiazepine receptors, causing the release of gamma-aminobutyric acid (GABA), a sedating neurotransmitter that can potentially facilitate sleep 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607064/

 

Did you catch that...the "benzodiazepine receptor".

 

Yes, the very receptor that benzos attach to but without the nasty dopamine addiction add-on.

 

It's our natural valium and Progesterone boosts its signalling.

 

Progesterone has its hands all over sleep initiation, quality, and disruption as a result.

 

By the way, you've been losing progesterone for years now by the time you're reading this (hopefully not at 3am).

 

All those ladies having a glass of wine at night in their 40's and 50's….here's why.

 

Of these LGICs, γ-aminobutyric acid type A (GABAA) receptors appear to occupy a central role in mediating the effects of ethanol in the CNS. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC165791/

 

Yes, alcohol boosts GABA but it also creates a host of inflammation and oxidative stress.

 

It's self-medicating for loss of hormones and almost every woman I know in perimenopause is using this backdoor route to GABA.

 

You don't want to use up your glutathione which protects your brain, especially during times of inflammation and stress (such as perimenopause).

 

Check out CBD and oxidative stress or CBD and glutathione.

 

First, the GABA angle.

 

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. These results are consistent with the anxiolytic actions of the steroid. 

https://www.ncbi.nlm.nih.gov/pubmed/2880640

 

So, progesterone boosts GABA and suppresses glutamate (excitatory).

 

Anxiolytic just means anti-anxiety (the first calm stage).

 

Then there's quality of sleep.

 

First the headline: 

Progesterone prevents sleep disturbances and modulates GH, TSH, and melatonin secretion in postmenopausal women.

https://www.ncbi.nlm.nih.gov/pubmed/21289261

 

We could stop right there but details were interesting.

 

Basically, progesterone did not act as a depressant.  It did, however, reduce interruptions of sleep!

 

That's what we're after, right??

 

Mean duration of wake after sleep onset was 53% lower, slow-wave sleep duration almost 50% higher, and total slow-wave activity (reflecting duration and intensity of deep sleep) almost 45% higher under progesterone than under placebo (P ≤ 0.05). Nocturnal GH secretion was increased, and evening and nocturnal TSH levels were decreased under progesterone (P ≤ 0.05).

 

So… 

  • Longer durations of sleep
  • Deeper quality of sleep (slow-wave)

 

GH is growth hormone which only gets released at night is showing up all over the new age-reversal studies (see our review on Metformin).  

 

It's also a really good indicator of good sleep since sleep disruption interferes with its release.

 

Melatonin was also controlled by progesterone and it's key not only to sleep (which most of us have heard of) but as a master regulator downstream for age related pathways.

 

Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics, Autophagy and Circadian Rhythm Pathways

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200827/

 

The most telling studies are those when sleep get immediately disrupted from having ovaries removed.

 

If you need a wake-up call for the importance of progesterone and estradiol on the brain: 

Impaired cognition, impaired short-term memory, sleep disturbance and vasomotor instability reflect nervous system effects, including decreased brain blood flow and degenerative changes, pre-disposing to functional cognitive decline and dementia. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5248494/

 

It's not just for reproduction ladies!

 

As for progesterone and estradiol supplementation effect on perimenopause insomnia?

All doses of TX-001HR significantly improved the Sleep Problems Index I subscale at all time points. The sleep somnolence subscale significantly improved from baseline with 0.5 mg E2/100 mg P4 and 0.5 mg E2/50 mg P4 at month 12. The incidence of somnolence as a treatment-emergent adverse event ranged from 0.2% to 1.2% versus 0% with placebo. 

https://journals.lww.com/menopausejournal/Fulltext/2019/06000/Improvement_in_sleep_outcomes_with_a.9.aspx

 

P4 is progesterone.  That's a new bioidentical hormone combination of estradiol and progesterone.

 

Check out our review on pregnenolone which boosts not only progesterone but all steroidal hormones which drop as we get older.

 

The new studies on DHEA and allopregnenolone are very interesting.

 

Allopregnenolone is the basis for the new postpartum depression medication at $25K.

 

You can get it via pregnenolone for $10 here.

 

It's effects on GABA are pronounced: 

However, allopregnanolone significantly potentiated the inhibitory responses to GABA(A) receptor agonists.  

https://www.ncbi.nlm.nih.gov/pubmed/16574382

 

This is important...it facilitates GABA activity.

 

The net effect was to balance serotonin function which is in a dizzy during perimenopause: 

This effect on 5-HT neurotransmission may have relevance for mood disorders commonly associated with reproductive hormone events, such as premenstrual dysphoric disorder and postpartum depression.

 

5HT is the serotonin pathway and it's critical to just about everything that happens in your brain (including sleep).

 

Check out CBD for serotonin here.

 

So...progesterone is steadily dropping...starting around age 40.  

 

When eggs stop producing, it takes another deep dive down which can occur even before your periods end.

 

Next up, the culprit behind most severe perimenopause transitions.

Estradiol and sleep 

Oh...estradiol!

 

It's so important and fascinating that we did a full review here.

 

We'll use estradiol interchangeably with estrogen since it's our dominant estrogen.

 

As we mentioned above, in general, estradiol is pro-growth.  

 

Depending.

 

There are actually two receptors (alpha and beta) and the effects can be quite different depending on which one estradiol binds with.

 

So...to clarify further… 

  • ERa (estrogen receptor alpha) is pro-growth
  • ERb (estrogen receptor beta) is actually calming and anti-inflammatory

 

In fact, ERb binding protects from some of the cancerous effects of the ERa activity.

 

That's why we looked at Siberian Rhubarb in-depth here  (loves the ERb receptor and helps with symptoms of peri/menopause including….sleep!).

 

So...what does estradiol have to do with sleep?

 

Estradiol appears to be a master regulator of the wake-sleep cycle.

 

For example in animal studies: 

Estradiol promotes arousal in the active phase in sleep-satiated rats, but after sleep loss, both estradiol and progesterone selectively facilitate REMS rebound while reducing NREMS intensity.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27049por17/

 

This means it's boosting both the wake side (arousal) AND the sleep side (deeper REM sleep).

 

As for estradiol and perimenopause or menopause: 

Similarly, transdermal estradiol is also associated with increased sleep quality, reduced sleep latency and number of awakenings, and improvement in somatic, mood and vasomotor symptoms. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607064/

 

So...better quality, quick time to get to sleep, fewer awakenings and all the associated benefits of good sleep.

 

Speaking of which, anxiety and depression can be directly tied to sleep disturbances with hormone loss/fluctuation.

 

For example, one study compared estradiol versus a sedative, zolpidem: 

For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135198/

 

Basically, they found improvements in their depressive states solely from improving sleep!

 

This isn't surprising since brain repair mainly occurs during deep sleep.

 

Check out CBD and BDNF for neurogenesis here.

 

That's a fascinating result!

 

Is lack of sleep from hormone loss/fluctuation the core driver of many of these other issues?

 

Sleep is SOOO important.

 

The improvements in sleep from estradiol supplementation are widespread: 

In addition to performing better on subjective tests of memory, women using the estrogen patch experienced less cortical atrophy and were less likely to show amyloid on brain imaging. 

https://www.mdedge.com/clinicalneurologynews/article/204936/alzheimers-cognition/transdermal-estradiol-may-modulate

 

Less brain withering and fewer signs of dementia in brain scans.

 

Also improved cognitive functioning.

 

They went on to say...

We previously found that preservation of dorsolateral prefrontal cortex over 7 years was associated with lower cortical beta-amyloid deposition on PET only in the estradiol group, pointing out the potential role of estrogen receptors in modulating this relationship.

 

Just a head's up.  There's a window to look at hormone supplementation.

 

When women wait too long to start, it can significantly reduce the effects.

 

There's a caveat we'll get to below in the endocannabinoid section.

 

A silver lining.

 

A great way to see the effects directly are at our review of Siberian Rhubarb (an alternative to estradiol replacement).

 

The results here:

 Sleeping problems 

Siberian Rhubarb ERr 731 result:    -1.9 points (out of 4 total)
Placebo Result:  -0.1 points 

Scale 1-4 on MRS scale - https://www.ncbi.nlm.nih.gov/pubmed/16894335

 

That's one of the best results by category for an estrogen result!

 

As for estradiol and insomnia, this is the most interesting: 

Estrogen replacement therapy improved sleep quality, facilitated falling asleep, and decreased nocturnal restlessness and awakenings (p < 0.001). 

https://www.ncbi.nlm.nih.gov/pubmed/9609575/ 


The more severe the insomnia, the greater the benefit from estradiol replacement!

 

Estradiol affects so much in the brain and body.

 

How does it affect sleep so powerfully?

 

First, estradiol control serotonin both at the creation side (tryptophan processing) and at the breakdown side (MAO).

 

It's a master regulator for serotonin, our so-call "feel good" neurotransmitter.

 

But...it's only for reproduction (sarcasm).

 

With serotonin...balance is everything!

 

Too much and you have insomnia like I did for 3 nights with Lexapro (SSRI -see CBD versus SSRI's). 

 

Too little, and you have other sleep issues.

 

Balance.  The great balancer (estradiol) is in a bipolar state, spiking to unseen  levels and dropping repeatedly.  

 

To be succinct:

As the precursor for melatonin, it helps regulate the body's sleep-wake cycles and the internal clock.

https://www.medicalnewstoday.com/kc/serotonin-facts-232248


 
For now, just put a note next to serotonin balance for later in the CBD section.

 

Next up, an actor in the perimenopausal sleep play close to our heart.

Histamine and sleep during perimenopause 

Notice how antihistamines make you drowsy?

 

It's right on the box as a side effect.

 

There's probably a few million women taking Tylenol PM or Benadryl to sleep during perimenopause and menopause right now.

 

It's the anti-histamine effect!

 

Just a heads up, that same antihistamine taken regularly has been tied to dementia.

 

Common anticholinergic drugs like Benadryl linked to increased dementia risk 

https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667

 

Ladies, you don't want to lose your choline (which these meds interfere with) as we get older.

 

You can supplement with CDP-Choline here.

 

Back to histamine.

 

It's known that roughly 40-60% of people have histamine issues.

 

This number goes up for women and increases as we get older.

 

Just look at asthma, an obvious histamine related issued: 

 Around 30–40% of women who have asthma experienced worsening of their symptoms during the perimenstrual phase, the so-called perimenstrual asthma. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/

 

This obviously has to be hormone related.

 

It turns out that estrogen (pro-growth) can increase histamine response while progesterone reduces it!

Estrogens are a natural enhancer of humoral immune responses (antibody production) and promote autoimmunity; on the contrary, androgens and progesterone (as well as glucocorticoids) physiologically have an immunosuppressive effect 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746020/

 

There's a great walk through here: 

https://www.larabriden.com/the-curious-link-between-estrogen-and-histamine-intolerance/

 

Balance between the two is key.

 

As for progesterone and histamine directly?

Progesterone has an inhibitory effect on histamine secretion following mast cell binding. However this effect is likely tempered by the regulation of progesterone expression and activity at a genomic level by oestrogen 

https://www.fxmedicine.com.au/blog-post/relationship-between-histamine-oestrogen-progesterone-and-cortisol

 

The net net of this is…

 

Too much estrogen relative to progesterone levels can result in increased histamine issues.

 

I personally saw it.

 

Starting around age 44-45, I noticed I could no longer eat certain things.

 

Peppers.  Fermented foods. Tea - black or green.

 

Eventually, I was having issues with sun block and almost all makeup.

 

When I finally got a doctor to run my full hormone panel (Dutch test) it showed I had almost no progesterone.

 

No wonder I was a mess!

 

I can now start to eat peppers and things that would have send me spiraling before.

 

Why does this matter for sleep?

 

Leave it to a review on narcolepsy to tease out the relationship: 

Studies in animals and humans have shown that histamine neurons help promote and stabilize wakefulness by activating the cortex and wake-promoting neurons outside of the hypothalamus, and inhibiting non-REM sleep–promoting neurons and REM sleep–promoting neurons.2,5-7 

https://knownarcolepsy.com/hcp/histamine

 

Histamine is excitatory in the brain.  Just like cortisol.

 

It's the opposite of GABA we discussed up above.

  

Make a note next to that since it directly ties in with CBD's effects and the type of CBD to stay away from.

 

Check out CBD and histamines for women

 

I learned the hard way on that one.

 

Next up, let's look at some of the perimenopause darlings that conspire to rob us of sleep.

Perimenopause hot flashes and sleep 

My mother complained of hot flashes as her primary issue with perimenopause.

 

To be so lucky!

 

That being said, hot flashes have a definite effect on sleep quality.

 

A study looked specifically at women in perimenopause: 

Hot flash-associated wake time per night was, on average, 16.6 min (95%CI:10.8–22.4), which accounted for 27.2% (SD 27.1) of total wakefulness per night 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252627/

 

And at the root of all this is estradiol fluctuation: 

The strong overlap in timing between HF onset and awakenings that we and others have found suggests that these events may be driven by a common mechanism within the CNS in response to fluctuating estrogen levels, although sweating triggered by an HF may still contribute to or extend the interval of waking

 

Addressing hot flashes, night sweats, and other compounding issues is critical and hormones or Siberian Rhubarb can be essential.

 

Check out the review of Siberian Rhubarb or pregnenolone (for progesterone).

 

It has its biggest effect on hot flashes out of all the categories:

 

Siberian Rhubarb and Hot Flashes or periods of sweating

 

Siberian Rhubarb ERr 731 result:    -2.1 points (out of 4 total)
Placebo Result:  -0.2 points 

Scale 1-4 on MRS scale - https://www.ncbi.nlm.nih.gov/pubmed/16894335

 


Next up...sleep apnea.

 

Is there a tie there with hormones?

Perimenopause and sleep apnea 

Aside from weight gain and other issues driven by perimenopause that contribute to sleep apnea, hormones have a direct effect.

 

Remember...estradiol and progesterone have receptors throughout the body including muscles in the throat: 

These hormones act as stimulants and play a role in keeping airways open by maintaining muscle tone in the throat. As they decrease, the chances of obstructed breathing rise.  

https://www.sleepfoundation.org/articles/how-handle-obstructive-sleep-apnea-during-menopause

 

In fact, sleep apnea risks trends with perimenopause and menopause: 

Compared to participants in premenopause, apnea-hypopnea index was 21% higher among participants in perimenopause (95% Confidence Interval [-4, 54]), 31% higher among participants in postmenopause ([2, 68]), and 41% higher among participants whose menopausal stage could not be distinguished between peri- and postmenopause  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266663/ 


One study even separated out age and other body measurements (size of throat or weight) and still found that perimenopause had an increased risk of sleep apnea which continued into menopause: 

Our analysis found that the transition from premenopause to postmenopause is associated with increased severity of sleep-disordered breathing, and that these changes are not entirely explained by chronological aging, or by changes in body habitus.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266663/

 

It's really important to get a handle on this as the health effects of constantly interrupting sleep is just short of catastrophic.

 

The breathing process itself is governed by hormones we're covering here: 

According to animal studies, the influence may be immediate through androgen, progesterone and estradiol receptors present in the nervous system (carotid body, brainstem). 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507108/

 

If we need a silver bullet: 

In post-menopausal women on estrogen therapy the incidence of sleep-associated breathing disorders is lower than in treatment-naive women. The connection is even stronger in subjects on estrogen-progesterone therapy, indicating the synergistic effect of those hormones

 

Again, check out our reviews on estradiol or Siberian Rhubarb (estrogen alternative) or pregnenolone for progesterone.

 

Of course, you can also consider bio-identical hormones.

 

We're getting closer!

The endocannabinoid system and sleep 

We all have one.

 

It's about 650 million years old and we share it with all animals.  No insects.

 

This system is generally tasked with balancing other key systems: 

  • Nervous system including neurotransmitters like serotonin, GABA, and Glutamate
  • Endocrine system including hormones like histamine, cortisol, and others
  • Immune system including inflammatory agents

 

This is the system that CBD works within so does it have anything to do with sleep?

 

A series of studies looked at this system for sleep stability which is crucial for housekeeping activities, especially of the cardiovascular system: 

These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis. 

https://www.ncbi.nlm.nih.gov/pubmed/27031992

 

CB1 is the primary endocannabinoid receptor in the nervous system.

 

Other studies have drilled down to the component pieces such as FAAH and Anandamide (two natural endocannabinoids in you right now!): 

Among the modulatory properties of the endocannabinoid system, current data indicate that the sleep-wake cycle is under the influence of endocannabinoids since the blocking of the CB1 cannabinoid receptor or the pharmacological inhibition of FAAH activity promotes wakefulness, whereas the obstruction of AMT function enhances sleep.  

https://www.ncbi.nlm.nih.gov/pubmed/28240187

 

FAAH just blocks anandamide activity but anandamide is definitely an agent of interest for perimenopausal sleep.

 

It's something we can actually influence as we'll see below.

 

What does it do with sleep?

 

Speaking to perimenopausal sleep issues: 

Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study.

https://www.ncbi.nlm.nih.gov/pubmed/28240187

 

This speaks to the "getting to sleep" part.

 

Adenosine is very important for sleep: 

Adenosine operates as a neuromodulator in the brain, and has the effect of inhibiting many of the bodily processes associated with wakefulness, particularly those involving the neurotransmitters norepinephrine, acetylcholine and serotonin.

https://www.howsleepworks.com/how_homeostasis.html

 

Put a check mark next to both anandamide and adenosine.

 

Oh yes...progesterone boosts adenosine and you've lost most of that by the time perimenopause kicks around: 

Progesterone may have an antiseizure effect with the additional finding decreased levels of adenosine deaminase that would have resulted in increased adenosine levels that exerts anticonvulsant effect via GABA-A receptors.  

https://www.tandfonline.com/doi/abs/10.1080/00207450802055374

 

So finally...can CBD help with perimenopause sleep?

Can CBD help with perimenopause sleep 

Let's look at the pathways we discussed first.

 

We'll hit these areas: 

  • CBD and GABA
  • CBD and adenosine
  • CBD and anandamide
  • CBD and serotonin

 

Those are big players in the sleep process.

 

First, GABA, since it's literally the basis for most tranquilizers.

 

CBD and GABA for perimenopause sleep 

 

Piggybacking off its effects on anxiety, CBD directly boosts GABA signalling in the nervous system.

 

Across regions, CBD increased GABA+ in controls, 

https://www.ncbi.nlm.nih.gov/pubmed/30758329

 

This goes to the whole process of managing GABA and glutamate levels: 

Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels

 

GABA is our calming neurotransmitter and it's directly tied to anxiety and sleep.

 

Check out CBD and GABA here for more information.

 

Adenosine, however, is more directly involved in sleep itself. 


CBD and adenosine for perimenopause sleep

 

We'll jump right to it since adenosine builds up during the day and should trigger sleep induction and maintenance.

 

CBD increases brain adenosine levels by reducing adenosine reuptake. Increased adenosine is associated with neuroprotection and decreased inflammation after brain trauma 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/

 

Neuroprotection and reduced inflammation is great but we want the sleep, Thank you.

 

Remember how anandamide was a big player in that pathway?

 

It is called the "bliss" molecule after all. 

 

CBD and anandamide for perimenopause sleep 

 

An amazing study looking at the effects of CBD on schizophrenia dived into this piece: 

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia


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

 

How does it do this?

 

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)

 

Basically, it blocks anandamide from being broken down by FAAH.

 

FAAH is the key to the woman who can't feel pain, anxiety, or depression.

 

We imagine her sleep is pretty solid as well.

 

Finally, the master regulator to everything.


CBD and serotonin for perimenopause sleep

 

We saw how estradiol controls serotonin levels and serotonin is integral to sleep.

 

What about CBD and serotonin?

 

Looking at studies on pain (again, serotonin is everywhere): 

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/

 

The most important word in that entire study is "modulates".

 

CBD doesn't jack up serotonin.  It doesn't drop it.  It doesn't work in one direction.

 

That's critical with serotonin since it's all about balance.

 

You see this all over the studies for CBD and serotonin.

 

Check out CBD versus serotonin for more information here.

 


CBD and histamines for perimenopause sleep

 

One final stop.

 

Histamine is excitatory and we know from Tylenol PM and benadryl that this is a key pathway for perimenopause sleep issues.

 

So...what does CBD do for this pathway?

 

Let's look at a signature result from excessive histamine and mast cell activation…

 

Asthma!

 

Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma.

https://www.ncbi.nlm.nih.gov/pubmed/30481497

 

This system is complex but CBD's effect is partially due to its effect on the PPAR pathway.

 

It boosts signalling in this system.

 

The effects of this stimulation in animal studies for histamine effects: 

Administration of PPAR-gamma agonist significantly decreased the number of nasal rubs, nasal histamine responsiveness, serum IgE, IL-5 production from the spleen, and eosinophilic infiltration in the nasal mucosa. 

https://www.ncbi.nlm.nih.gov/pubmed/19307774

 

Check out CBD and histamines here.

 

This is great and all but what about results on….sleep!

 

So...a larger study on effects of CBD with sleep and anxiety: 

Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/

 

There are lots of animal studies as well.

 

For example: 

The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration. 

https://www.ncbi.nlm.nih.gov/pubmed/23343597

 

Just a head's up...THC, CBD's cousin, can increase sleep but impair the quality of sleep: 

Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term.  

https://www.ncbi.nlm.nih.gov/pubmed/28349316

 

Learn all about how THC is very different from CBD here along many pathways.

 

Remember...much of what interrupts sleep during perimenopause is from other factors such as sleep apnea, hot flashes, and even anxiety!

 

Maybe anxiety is the #1 culprit.  It sure was for me!

 

What about CBD's effect on anxiety as it relates to sleep?: 

Conclusively, CBD may block anxiety-induced REM sleep alteration via its anxiolytic effect, rather than via sleep regulation per se. 

https://www.ncbi.nlm.nih.gov/pubmed/21867717?dopt=Abstract

 

We've covered CBD's effects on perimenopause anxiety in detail.

 

Afterall, it's what wrecked me back in the day (that story is here).

 

Another study on Parkinson's and it's known sleep issues also reflects CBD's effect on calming neural activity: 

Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series.

https://www.ncbi.nlm.nih.gov/pubmed/24845114?dopt=Abstract 

 

Next up, let's look at CBD versus the standard go-to's.

CBD versus Tylenol PM, Valium, and other sleep aides 

There are really two very popular classes for sleep.

 

  • Benzos (Valium, Ativan, Xanax, Klonopin, etc)
  • Antihistamine agents - Tylenol PM, Benadryl, etc

 

We've covered the benzos in detail at our CBD versus benzos for GABA here

 

Basically, they boost GABA levels.

 

The issue is that they also boost dopamine which leads to addiction.  Quickly and Strongly.

 

This is the next up-to-bat crisis when we finally dig ourselves out from under opioids.

 

Check out how I used CBD to wean off of benzos.

 

Most doctors start there for women with perimenopause (usually due to anxiety at first).

 

It's a terrible option:   

  • Short lived
  • Addictive
  • Normalizes for see-saw effect
  • Does nothing for underlying issue...drop in hormones!

 

After you read the CBD versus anti-anxiety meds, it's hard to understand why they're still prescribed.

 

Research and be informed!

 

The common alternative over the counter generally relies on an anti-histamine which should tells you something!

 

Histamine is a huge deal.

 

We would love to know what percentage of Tylenol PM sales (or total pills used) are for women over the age of say….45. 

  • 50%?
  • 70%?

 

We personally know a slew of ladies who use Tylenol PM this way.

 

We covered CBD versus Tylenol in depth for the pain pathway.

 

Granted, pain can come along with perimenopause (check out CBD for perimenopausal pain) and this affects sleep, but sleep is the antihistamine effect.

 

Check out CBD and histamines or CBD and mast cell activation.

 

What about other things we have found during a blistering perimenopause (and we've tried everything)!

 

As for basic nutrition:  

  • High levels of Vitamin C would help with histamine response
  • Vitamin D is a given for better sleep
  • B vitamins (especially methylated).  I had a B shot which literally felt like a tranquilizer! 


Metformin and perimenopausal sleep


We recently started metformin after the ridiculous studies on reversing epigenetic aging (See full review here) and it had an immediate effect on sleep.

 

There's also interesting studies on metformin and sleep apnea.  Make sure to supplement B12 when taking metformin.

 

Low dose naltrexone and perimenopausal sleep

 

This speaks more to immune and inflammatory response but the "jolts" at night went away as a result

 

And finally, hormones.

 

Look...CBD and nutrition are great but you're trying to fill in a balloon with drops of water without hormones.

 

They are so critical to everything that makes you...YOU!

 

Bio-identical progesterone or pregnenolone as an alternative.

 

The progesterone pathway will have an immediate effect on sleep during perimenopause.

 

The sleep results for Siberian Rhubarb are pretty fantastic.  Again, check out that review since the Germans have studied it extensively.

 

Of course, exercise, meditation, and CBD (see review here).

 

Now, on to some practical questions.

How much CBD to take for perimenopausal sleep issues 

We actually have some better research here.

 

Studies on sleep showed help around 160 mgs.

 

It's best to start low at about 25-30 mgs to test your body's response.

 

You can take CBD before sleep.  If you need a quicker response, hold it under tongue up to 60 seconds.

 

Otherwise, about 1 hour before going to sleep is probably perfect.

 

Make it part of your nightly pre-sleep routine.

 

Interestingly, if you take CBD during the day, it can have a wake-promoting quality!

 

Again...this whole system (endocannabinoid) is about balance.

 

Now, a very important note we learned the hard way when we first started investigating CBD for perimenopause.

The best CBD for perimenopausal sleep issues 

Of course, the basic requirements apply: 

  • Organically grown in the US at a FDA registered farm
  • 3rd party tested for:
  • NO THC (THC impairs sleep quality even it if makes you sleepy)
  • No pesticides
  • No heavy metals
  • No bacteria
  • No mold

 

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

 

Afterall, our entire family is the biggest customer.

 

Now...specifically for perimenopausal sleep.

 

Everyone out there is pushing full spectrum CBD.

 

Here's the issue...I tried all those big brands and had terrible histamine responses.

 

The very plant material they're selling as beneficial can have opposite effects for women in perimenopause who have histamine issues!

 

Histamine response is directly tied to this period of time.

 

Histamine is excitatory...it actually eats up GABA, the very thing we're trying to boost.

 

Plus, all the research is on CBD isolate by itself.

 

Learn all about CBD isolate verus full spectrum here.

 

Hopefully it's obvious that we rely on research...not marketing.

 

CBD isolate, when I finally found it, was a game changer.

 

That's why we focus on CBD Isolate.  

 

Be well.  Be empowered.  And get some sleep!

 

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