Updated Research on CBD and PMS or PMDD

research on CBD and PMS or PMDD

 

We've spent quite a bit of time on hormones here.

 

After all, it was a brutal perimenopause that drove us to discover CBD to begin with.  That story is here.

 

As a result, we dove deep into progesterone, estrogen, and even how CBD affects those pathways.

 

After all, the endocannabinoid system that CBD works in has direct control over the hormonal balance.

 

Balance is the keyword there for PMS and PMDD.

 

As we'll see, in many ways, monthly cycles that cause all the pain and mood shifts with PMS and PMDD are like little mini perimenopauses.

 

We'll also look at the pathways of progesterone and estrogen for very powerful neurotransmitters and pain signallers which are directly tied to hormone shifts.

 

Here are the topics we'll cover: 

  • What causes PMS and PMDD
  • The power of progesterone and estrogen
  • How does the body control progesterone and estrogen shifts (the "why me" question)
  • The endocannabinoid system and PMS or PMDD
  • PMS and PMDD connection with pain
  • PMS and PMDD connection with mood shifts
  • Can CBD help with PMS and PMDD (plus other tools)
  • How much CBD for PMS and PMDD
  • What's the best CBD for PMS and PMDD

 

Let's get started!

What causes PMS and PMDD 

First, the difference between PMS and PMDD is not just one degree.

 

PMS generally displays about 4 days before the period which speaks to a drop in key hormones (estrogen and progesterone).

 

PMDD can occur a few weeks prior and stop abruptly when the period starts.

 

We'll see below what lies at the root of these two different effects.

 

The quick teaser: 

  • PMS is due to a drop in key hormones
  • PMDD is due to insensitivity in brain receptors to metabolites of those hormones

 

PMDD generally refers to the mood changes tied to hormone imbalances such as anxiety and depression.

 

PMS is a more generalized term for any symptoms tied to hormone fluctuations including pain and mood issues.

 

Either way, the key driver is a flux in progesterone and estrogen, our two primary steroidal hormones (for women).

 

Both hormones have monthly cycles but coordinate to drop right before the cycle.

 

Other fluxes confirm these effects such as puberty, pregnancy, perimenopause, and menopause.

 

Most people just think of progesterone and estrogen as chemicals tied to reproduction but that couldn't be further from the truth!

 

Let's dive into just how powerful they are!

The power of progesterone and estrogen 

Mother nature is very efficient.

 

If she has a toolset, she'll commonly multitask key pathways to carry out other functions.

 

We see this throughout every pathway we research and its main reason for side effects to medications.

 

Unintended consequences!

 

Progesterone and estrogen are probably two of the most powerful examples of this by far!

 

You have receptors for both hormones on practically every cell type in the body...and brain!

 

In fact, progesterone and estrogen literally shape the heartbeat (see CBD and perimenopause heart arrhythmia and blood pressure).

 

They manage gut integrity which is key to autoimmune which confidently, hits women at an 8 to 1 clip versus men.

 

Since men don't have the same levels of estrogen and progesterone, their bodies use other pathways to manage gut barrier integrity and mood.

 

Maybe most importantly these days is that progesterone and estrogen directly manage our immune response!

 

Estrogen is immune-enhancing (a general growth feel everywhere) while progesterone calms the immune response.

 

The reason why is fascinating!

 

The amniotic sac with a newborn is actually "constructed" by genes from the father.

 

It's a bit of a hostile takeover from a purely biological point of view.

 

The mother's immune system would immediately attack this foreign interloper but progesterone levels spike during pregnancy to calm this immune response.

 

New studies are pointing to reduced progesterone as a key driver of premature births!

 

A large 2003 study in which we participated showed that weekly progesterone (17-OHPC) injections given to pregnant women with a history of at least one prior preterm delivery reduced the risk of delivery before 37 weeks by 34%. 

https://utswmed.org/medblog/progesterone-and-premature-birth-what-new-study-means-pregnant-women/

 

Basically, with a progesterone deficiency, the immune system is winning (against the amniotic sac).

 

Here's the deal...progesterone drops by 50% at age 40 on average so we see all the risks creep up from that then on: 

  • Autoimmune
  • Histamine response (allergic reactions)
  • Mood disorders (we'll look at why below)
  • Gut issues

 

Estrogen drops more slowly but then falls off a cliff in the late '40s.

 

PMS and PMDD are mini versions of this drop but on a monthly cycle!

 

It follows an expected trajectory once you understand the roles of estrogen and progesterone for reproduction.

 

Estrogen is pro-growth and also increases sexual arousal.

 

The pro-growth is key to quickly making the uterine lining needed in case of conception.

 

It also sets the stage in terms of mood!

 

Progesterone also spikes in case there is a conception for the reasons listed above!

 

Otherwise, the immune system will quickly attack any new amniotic sac formation.

 

Once it's determined that there isn't conception, both drop significantly.

 

That's where PMS and PMDD strike and we'll compare it with other big changes such as postpartum later.

 

Maybe, more importantly, is the question of why?

 

Why do some women get hit so hard while others don't?

 

We actually have research on this now which is exciting!

How does the body control progesterone and estrogen shifts (the "why me" question) 

Steroidal hormones (like estrogen and progesterone) are very complicated cascades of powerful chemicals that all interact.

 

What could go wrong?

 

First, new studies are pointing to gene cluster which is tasked with managing the ebbs and flows of hormones and how 'sensitive" other pathways are to these changes.

 

First, you have genes themselves.  The input.

 

On the other side, you have pathways that are affected by hormones.

 

In between, you have control genes that manage how these two interact.

 

What research is finding is that this level (called epigenetics) is where there's a difference between women with PMS or PMDD and those without.

 

It's a sensitivity to the changes that matters!

 

More than half of the ESC/E(Z) genes were over-expressed in PMDD patients' cells, compared to cells from controls.But paradoxically, protein expression of four key genes was decreased in cells from women with PMDD. 

https://www.sciencedaily.com/releases/2017/01/170103084608.htm

 

So...genes were turned up but the output from these genes (proteins) was reduced.

 

That's the control mechanism between the two layers.

 

Interestingly, progesterone would boost these proteins while estrogen reduced them.

 

There's another wrinkle to this equation which deals with a powerful metabolite from progesterone call allopregnanolone.

 

This is the basis for the new blockbuster postpartum depression medication called Zulresso.

 

We've covered this in detail at our pregnenolone review which by the way, boosts allopregnanolone at about $10/bottle versus the $25K overnight hospital stay for Zulresso.  

 

This metabolite has a powerful effect on our GABA receptors which is the target for benzos.

 

Essentially, calm and sleep is the net result in terms of mood (we'll cover in-depth below).

 

For women with PMS and PMDD, there appears to be a lack of response at the GABA receptor to allopregnanolone.

 

This is the basis for tolerance we see with addictive drugs (see CBD and addiction or CBD and tolerance).

 

Essentially, if too much pushing of GABA activity is occurring from allo, the body will start to push back by reducing sensitivity!

 

It's classic tolerance.

 

here are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA-A receptor to high and continuous allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone may develop.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031054/

 

This is a hormonal imbalance!

 

In fact, in this case, giving this pathway a break can help to restore function.

 

The net effect: 

numerous studies finding that allopregnanolone levels typical of the luteal phase (top of an inverted U-shaped curve) trigger adverse symptoms in women with PMDD. 

https://www.zrtlab.com/blog/archive/your-guide-to-pmdd-causes-and-treatment/

 

Translation...too much of a good thing.

 

One of our favorites, Lara Briden, goes into this whole process here: 

https://www.larabriden.com/progesterone-mood-treat-pmdd/

 

This is such a perfect intro for the endocannabinoid system where CBD works.

The endocannabinoid system and PMS or PMDD 

We all have one and it dates back about 600 million years evolutionarily speaking.

 

This system is tasked with balancing other key systems: 

  • Nervous system - GABA, serotonin, and more
  • Immune system - inflammation response and cellular birth/death cycles
  • Endocrine system - Hormones!!!

 

Goodness...the cross-section of PMS and PMDD.

 

As researchers put it: 

There is a complex interplay between the ECS and the hypothalamic-pituitary-ovarian axis, and an intricate crosstalk between the ECS and steroid hormone production and secretion.  

https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-018-0478-9

 

The ECS is all over this process with a general role of balance.

 

Balance is exactly what we're missing with PMS and PMDD.

 

Remember how too much allopreg can overwhelm GABA function and cause desensitization?

 

Or how there's a mismatch between progesterone levels and cycle?

 

In fact, our review on endocannabinoid deficiency really begs the question..do many diseases if not all rely on a deficit in this key balancing agent?

 

Let's zero in on PMS and PMDD before moving on.

 

First...the system is highly integrated around all these players: 

Stimulation of PPAR-α by N-palmitoylethanolamide engages allopregnanolone biosynthesis to modulate emotional behavior 

https://www.researchgate.net/publication/331078884_Stimulation_of_PPAR-a_by_N-palmitoylethanolamine_engages_allopregnanolone_biosynthesis_to_modulate_emotional_behavior

 

That's a mouthful….let's translate!

 

PPAR is a powerful pathway triggered by endocannabinoids (and CBD)
PEA is a backup endocannabinoid which we cover in our review here.


Stimulation of this pathway is key to allopreg production!

 

Stay with us...it's about to get really interesting.

 

Why is there a known relationship between early trauma and stress with PMDD and PMS later in life?

 

Basically, trauma, beit all at once or chronic (as in chronic stress) can disrupt the endocannabinoid system so it's unable to carry out its balancing act.

 

Look at just one effect of this which is so important to our discussion: 

Furthermore, stress favors a GABAA receptor subunit composition with higher sensitivity for Allo 

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13843

 

Goodness...stress (acute or chronic) slowly changes the GABA receptors to be more sensitive to allo.

 

This makes sense...allo is there to calm things down (as in time of stress) but if hit too hard and too often, the receptors develop tolerance.

 

Remember from above that part of PMDD and PMS is a change in GABA receptor activity to allo?

 

Goodness.  We now know why...prior stress and trauma.

 

By the way, these results were teased out of PTSD studies (see CBD and PTSD).

 

We see this throughout the body especially with pain (also under the management of the endocannabinoid system).

 

In fact, the whole theory behind topical ketamine is that it gives the neurons a break from constant glutamate spiking.

 

So they can "normalize".

 

To wrap this up (because it's complicated).

 

Early stress/trauma combined with genetic difference leaves key pathways (such as GABA and pain signallers) susceptible to tolerance from hormones.

 

That's a mouthful.  Let's break out the two biggest pieces to understand what's going on at a 40,000-foot level.

 

We'll start with pain.

PMS and PMDD connection with pain 

In our review of CBD versus NSAIDs like Advil or Motrin, we looked a special class of pain signallers called prostaglandins.

 

These messengers basically initiate the pain signal but like we mentioned, mother nature gave them a side hustle.

 

They're instrumental in breaking down the uterine wall if there's no conception.

 

During your period, prostaglandins trigger muscles in your uterus to contract. These contractions help expel the uterus lining. Higher levels of prostaglandins can cause more severe menstrual cramps, and severe contractions may constrict the blood vessels around the uterus. 

https://www.everydayhealth.com/prostaglandins/guide

 

Goodness.  That's the pain, cramping, nausea, headaches, and bloating feeling.

 

Progesterone's effect on these pain signallers?  Just this: 

It also affects the regulation and synthesis of prostaglandins and leukocytes

 

Here's where it gets interesting for CBD and the endocannabinoid system.

 

Let's introduce anandamide, a primary endocannabinoid in your body right now which is named after the Hindu goddess of bliss, Anand.

 

That naming should give you a pretty good indication of its role.

 

It's a backup reserve to calm all types of pathways across the body including...pain!

 

Just look at the effect of NSAIDs which are commonly used for PMS and PMDD pain symptoms: 

R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.  

https://d1wqtxts1xzle7.cloudfront.net/48713813/j.neuropharm.2013.03.02120160909-1201-1oz0fvi.pdf

 

We've covered this in detail at our review of the woman who can't feel pain.

 

She has a version of a gene called FAAH which allows for lots of anandamide to freely flow.

 

FAAH is the pathway that readily breaks down anandamide, almost as quickly as its made.

 

This will play an important part in how CBD affects this pain pathway.

 

Upstream from prostaglandins, you have a master control switch called COX2 which is keyto how NSAIDs work (they block it).

 

The problem with NSAIDs (Motrin, Advil, ibuprofen, etc) is that they can block too much which has unintended consequences for heart and GI: 

Traditional NSAIDs inhibit both COX-1 and COX-2, and in so doing not only decrease inflammation and pain but also promote gastrointestinal tract damage and bleeding.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069032/

 

See CBD versus Ibuprofen and NSAIDs for more info.

 

Not a long-term solution.

 

We'll see how CBD affects pain below.

 

Let's turn to mood disorders tied to both PMS and PMDD.

PMS and PMDD connection with mood shifts 

There's a subtle difference in how mood shifts play out between PMS and PMDD.

 

First, understand that our hormones directly drive very powerful neurotransmitters: 

  • Progesterone boosts GABA, the brain "brake pedal" tied to anxiety and insomnia (too little)
  • Estrogen boosts serotonin, our master regulator of mood, and all human behavior really
  • GABA is key to calm, stress response, and being able to sleep
  • Serotonin is key for irritation, depression, and a slew of different effects

 

We've covered them in detail at CBD and GABA or CBD and serotonin.

 

Needless to say, the first course of treatment for women is usually benzos (boosts GABA) and SSRIs (boost serotonin) but those have major issues.

 

First, benzos (like valium, Ativan, and Xanax) are highly addictive and build tolerance brutally fast.

 

SSRIs (like Lexapro, Prozac, and Effexor)are not technically addictive (don't spike dopamine) but they build tolerance and with such a critical pathway, this can also be excruciating.

 

They're also not meant for on-off use tied to cycles.

 

Learn more at CBD versus benzos or CBD versus SSRIs.

 

We actually learned about CBD as a result of weaning off of these meds from a brutal perimenopause (that story is here).

 

Current research is really pointing to different causes of mood issues for PMS and PMDD.

 

PMS can be viewed as the rug being pulled out from under us in terms of estrogen and progesterone.

 

This is why it happens right before our period when those both plummet.

 

PMDD is different.  It's tied to the ramp-up of these hormones which occur a few weeks prior to the period starts!

 

This points to the mismatch of allopregnanolone to GABA receptors.

 

The boost in progesterone should feel good...calming even!  Better sleep, calm mood.

 

Remember from above though that the GABA receptors have been "primed" by too much allo (released due to trauma or stress) and are no longer sensitive to it.

 

This is trickier as it's now about allowing those receptors to "normalize" or get a break.

 

We've looked at this question with benzo addiction where the GABA receptors also change due to too much stimulation and actually reduce sensitivity.

 

See CBD wean off benzos for more detail.

 

We'll look at CBD's role therein "rescuing" this pathway based on the addiction studies.

 

We also covered a great deal of mood changes from our studies on perimenopause (our first love/hate) which originates from hormone flux: 

  • CBD and perimenopause anxiety
  • CBD and perimenopause depression
  • CBD and perimenopause irritability
  • CBD and perimenopause mood changes

 

Again, this is a drop in the hormones although, really bad perimenopause are generally characterized by a roller-coaster effect on estrogen (and therefore serotonin).

 

Let's finally turn to CBD, please.

Can CBD help with PMS and PMDD (plus other tools) 

First, it's important to understand CBD's role in the endocannabinoid system as this really is the key secret.

 

We don't want to push systems up or down in one direction (like NSAIDs with COX2) as this leads to nasty side effects over time.

 

CBD is technically called an allosteric negative modulator.

 

This is just fancy speak for...a feedback mechanism!

 

It's very different from how its cousin, THC, works which pushes anandamide-like activity in one direction.

 

The net effect of this is side effects and tolerance with long-term use.

 

We don't want to end up worse than when we started so avoiding tolerance is key.

 

CBD has shown not to be addictive or cause tolerance (see CBD and tolerance).

 

To give you just one example of the feedback approach, consider the following effects on inflammation (prostaglandins are inflammatory agents by the way): 

  • Healthy cells with low inflammation -  CBD has no effect
  • Healthy cells with high inflammation - CBD reduces inflammation
  • Cancerous or virally infected cells - CBD INCREASES inflammation

 

The last one makes sense once you realize that our body's natural way to get rid of broken cells is to boost inflammation.

 

Chemo and radiation are essentially massive doses of inflammation (in the form of oxidative stress).

 

Three different states - three different effects

 

This is very rare in the chemical world and speaks to the beauty of the endocannabinoid system (balance) and how CBD works in it.

 

Okay...let's now take this info and apply it to the pathways we've discussed above: 

  • CBD and hormones
  • CBD and prostaglandins
  • CBD and anandamide
  • CBD and GABA
  • CBD and serotonin
  • CBD and PMS
  • CBD and PMDD

CBD and hormones 

We don't have direct studies on CBD and the hormone imbalance but we know that the endocannabinoid system is partly to blame.

 

We can look at other issues tied to hormone imbalance such as PCOS or endometriosis.

 

First, endocannabinoids directly manage hormone balances and fluctuation: 

endogenous cannabinoids have been confirmed to participate in the regulation of food intake and energy homeostasis of the body, and have a significant impact on the endocrine system, including the activity of the pituitary gland, adrenal cortex, thyroid gland, pancreas, and gonads 

https://pubmed.ncbi.nlm.nih.gov/30618031/

 

So there's a there...there.  Meaning, imbalances of hormones may be driven by insufficient endocannabinoid "tone".

 

We look at this question in our Endocannabinoid deficiency review.

 

The important word above is "gonads" as that is where estrogen and progesterone are produced and "pituitary" as it functions as a control unit.

 

We actually see this across the hormone playing field including those tied to metabolism (energy, fat, appetite, etc).

 

It is well known that the ECS regulates energy balance by regulating appetite, food intake, and glucose metabolism 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332911/

 

PCOS is one example of a disease driven by hormone imbalance and the tie with the ECS?: 

Using real-time PCR, these authors demonstrated that CB1 transcripts from omental adipose tissue were lower in PCOS subjects vs. those without PCOS  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332911/

 

CB1 is the receptor for anandamide primarily.

 

CBD has been shown to support CB1 activity by blocking FAAH (which eats up anandamide).  We'll cover that more below.

 

THC also acts there but remember...THC works in one direction and it overshoots which causes tolerance.

 

See CBD versus THC to learn more on how they're so different.

 

We want to support anandamide when exhausted...but not indefinitely.  That's the feedback mechanism from above.

 

What about endometriosis which is an overproduction of tissue due to hormone imbalance?

 

As we mentioned above with ECS deficiency: 

The endocannabinoid system (ECS) has emerged recently as an important factor in endometriosis development, maintenance, and pain mechanisms 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436335/

 

Big shocker.

 

Don't take our word for it: 

Some of the studies that we reviewed described endometriosis as an “endocannabinoid deficiency” condition, thereby partially explaining its implication with pain 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436335/

 

Interestingly, the body appears to be using anandamide and a backup called PEA to counter the effects of endometriosis (including the pain): 

They also found elevated levels of AEA in women with moderate-to-severe dysmenorrhea (visual analog scale 51–100) and elevated PEA levels in women with moderate-to-severe dyspareunia (visual analog scale 51–100).

 

CBD has been found to directly "rescue" anandamide when exhausted from pain, trauma, and stress.

 

We'll cover that in the anandamide section.

 

We've looked at CBD's effect on estrogen and it doesn't directly drive changes there which is important.  THC acts like a wet blanket on steroidal hormones so we want to be careful there. 

 

Okay….we can quickly get lost in the hormone world...let's turn to CBD and pathways from above.

CBD and prostaglandins 

This is the pain piece of PMS and PMDD.

 

We really go through the pathways at our CBD versus Tylenol or CBD versus NSAIDs but some quick takeaways specific to PMS pain.

 

First, prostaglandins, the inflammatory agents at the heart of this process.

 

Remember that COX2 drives prostaglandin activity: 

There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol 

https://pubmed.ncbi.nlm.nih.gov/14963641/

 

We get a reduction in oxidative stress (the free radical piece) as well.

 

Interestingly, CBD does not have the side effects (even with long-term use) that NSAIDs have on heart and gut function.

 

In fact, CBD has powerful effects in the gut (see CBD and gut inflammation or CBD and leaky gut).

 

These effects on pain occur along multiple pathways: 

  • COX2 and prostaglandins - key for PMS and PMDD
  • Anandamide - powerful anti-pain pathway
  • PPAR - powerful anti-inflammatory pathway
  • TRPV - pain signaling pathway
  • Serotonin - master pain sensitivity regulator
  • GABA - key to neuropathic pain

 

Some studies directly tied to CBD for pain: 

Patients with non-cancer pain and mental-health symptoms achieved improvements to patient-reported pain and depression and anxiety symptoms (P<0.05). 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330185/

 

A look at CBD, chronic pain, and opioid use: 

Over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements.  

https://pubmed.ncbi.nlm.nih.gov/31711352/

 

We've looked at CBD and opioid addiction specifically here.

 

Another study across MS, spinal cord injury, and other serious sources of pain: 

Pain relief associated with both THC and CBD was significantly superior to placebo. 

https://pubmed.ncbi.nlm.nih.gov/12617376/

 

As we mentioned above, the issue with THC is that it causes tolerance with long-term use which means our basic levels of pain relief decrease over time.

 

CBD does not have this effect and in fact, counters THC's effect (see CBD and cannabis addiction).

 

CBD appears to have the most benefit with pain tied to inflammation.

 

Just a reminder, the pain of PMS is inherently inflammatory in nature! 

 

Prostaglandins are actually inflammatory agents that break down the uterine lining.

 

Pain is a great segue into anandamide.

CBD and anandamide 

We noted that anandamide is the backup guard for all types of stress in the body and brain.

 

Basically, when key systems are overwhelmed by outside factors (stress, pain, psycho-social stress, etc), anandamide is ramped up.

 

When it's exhausted, we're in trouble for both pain and mental health.

 

Let's look at two very powerful examples of how CBD is the back-up to the back-up!

 

First, mental health:

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/

 

This is profound as schizophrenia is a very complex disease resting on neurotransmitter imbalance (primarily dopamine).

 

We see this effect via anandamide throughout the mental health space (see CBD and mental health).

 

Essentially, CBD blocks FAAH which eats up anandamide.

 

We don't want too much anandamide as this has unintended consequences.

 

That's the issue with THC which basically imitates anandamide in the brain but for too long and at too high a level.

 

The brain pushes back!  (tolerance).

 

As for pain, the connection is even more powerful.

 

There are people who have variants of the FAAH gene where they don't really make any.

 

This means that anandamide freely flows un-checked.

 

The results?

 

They can't feel pain at ALL!

 

This is actually dangerous as their arm can be on fire and they won't know it till they smell something.

 

We did a big review on the woman who can't feel pain here.

 

CBD works as feedback and slows down FAAH but it doesn't get rid of it!

 

This is what we want...balanced effects.

 

Let's turn to the GABA question since it's so important for anxiety, sleep, mood and how PMS and PMDD actually cause issues.

CBD and GABA 

Three quick reminders: 

  • Progesterone directly boosts GABA function via its metabolite allopregnanolone
  • Progesterone drops right before the period
  • Women with PMDD have GABA receptors that become insensitive to allo

 

Let's look at the first two.

 

A drop in progesterone leads to a drop in GABA for PMS.

 

CBD is an allosteric negative modulator (feedback mechanism) for GABA.

 

This means it supports it when low!

 

We see this across a range of issues tied directly to GABA: 

 

Remember, GABA is the brake pedal in the brain.

 

One example which is very interesting for our discussion: 

Overall, these findings show that CBD can restore cannabinoid/GABAergic signaling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure. 

https://pubmed.ncbi.nlm.nih.gov/31202911/

 

Stay with us...this is interesting.

 

Remember how there's a connection with early trauma/stress and PMS/PMDD later in life?

 

A "priming" of systems if you will.

 

The same thing can happen with infection (even in utero) and later mental health issues.

 

In this study, mice were exposed to bacterial infection in utero (3rd trimester appears to be really important).

 

As a result, the mice later experience a higher risk for mental health equivalents to schizophrenia.

 

This involves an imbalance in GABA (too little) and endocannabinoids trying to calm things down like anandamide (too little).

 

CBD "restored signaling"!

 

We can't express how powerful this one example is of CBD's interaction in the body.

 

It doesn't boost GABA in one direction or you would have the nasty side effects of benzos (see CBD versus benzos).

 

It supports it when low!

 

Now...we know GABA is low with PMS due to the loss of progesterone.

 

What about PMDD which has a different driver?

 

This experiment is even more pressing there.

 

"Rescuing" the GABA insensitivity to allo is key there and it's very similar to the "priming" effect we see with immune response to early infection.

 

We have a whole review at CBD and GABA or CBD to wean off benzos (again, rescuing insensitivity in the GABA pathway).

 

Let's turn to the master regulator of mood and pain sensitivity. 

CBD and serotonin 

Researchers looked at CBD's effects after injury which included increased anxiety, hyperactive pain response, and a range of different issues.  Pain exhaustion basically.

 

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/

 

Goodness...let's translate.

 

  • Reduction in pain (analgesia) - there's that TRPV pathway
  • Reduction in anxiety (the body doesn't differentiate between physical and mental pain)
  • "Rescue" of serotonin function!

 

Serotonin is really a big player in pain.

 

Even a bigger player in mood such as anxiety, depression, irritability, etc.

 

In fact, we looked at whether serotonin is the linchpin for self-esteem here.

 

That one study above looks at both "rescue" of serotonin for pain (allodynia) AND mood (anxiety).

 

Check out CBD and serotonin to really dive in.

 

Let's recap the two main issues.

CBD and PMS 

A quick recap with the research above for backup.

 

PMS is driven by a sharp drop in progesterone and estrogen.

 

Progesterone drives GABA in the brain, our primary "brake" pedal tied to calm, sleep, and mood.

 

CBD supports GABA function when low (but not when high).

 

CBD does not directly affect progesterone levels.

 

Estrogen supports serotonin, our master mood regulator and pain threshold manager.

 

CBD "rescues" serotonin when low due to pain or stress.

 

CBD does not directly boost estrogen.

 

CBD calms the pain signaller response for prostaglandins upstream with COX2 but not in one direction.

 

This avoids the GI and heart side effects of NSAIDs

 

CBD supports anandamide, our natural backup when systems are overwhelmed due to pain, stress, and flux.

 

There are other inflammatory pathways such as PPAR, TRPV, etc that are tuned with CBD support.

 

Again, research for this in the above 4000+ words or across the site.

 

Also, see can you take CBD during PMS.

 

What about PMDD

CBD and PMDD 

PMDD is primarily driven by insensitivity in the GABA pathway (our brake pedal) to allopregnanolone.

 

This metabolite of progesterone actually increases 2 weeks prior to the period so PMDD is usually much worse during this luteal phase and stops when the period starts.

 

CBD has shown promise in "normalizing" GABA function in other situations such as with immune system priming (too much glutamate - the "gas pedal") and benzo withdrawal.

 

The latter is very telling since chronic benzo usage will actually cause GABA receptors to drop in number and sensitivity...a similar situation to what happens in PMDD from too much allopreg.

 

The excess allopreg may result as compensation from earlier exposure to stress or trauma.

 

After all, allo is a powerful wet blanket for stress/trauma in the brain.

 

Too much of it causes tolerance.

 

We know of no other chemical that has a multiphasic (different results) effect like CBD on GABA receptors.

 

Again, benzos push GABA in one direction so our natural GABA function just gets worse (the wrong direction).

 

SSRIs build tolerance so our natural serotonin levels get worse.

 

Adding progesterone (which would normally help) actually make things worse as well.

 

The goal is to give the GABA pathway a reprieve so it can come back online.

 

Studies show it takes about 30 days after benzo use for the DNA to actually turn back on for the 5 proteins that make GABA receptors.

 

That's a great segue into the next section.

How much CBD for PMS and PMDD 

We'll tackle this in two way: 

  • Short term symptom relief
  • Long term changes

 

Studies have tested CBD up to 600 mg daily for more acute (now!) and serious issues such as public speaking with social anxiety or opioid withdrawal or even high-risk psychosis.

 

The safety profile was very strong in all cases.

 

Most women will not need these levels so it's important to test what works for you.

 

Always take at least 4 hours away from other medications.

 

You can break up the dosage into 3 as peak CBD is usually about 4 hours after taking it

 

Holding it under your tongue up to 60 seconds will increase speed and bioavailability.

 

That's for the few days before the period with pain, anxiety, and sleep issues.

 

For PMDD and long term recovery, we can look at two key aspects around one dosage.

 

300mg daily is the best dosage for maximum neurogenesis (brain change/repair).

 

That effect starts to go down beyond 300 mg and this is the key piece for GABA receptor recovery.

 

After all, rewiring brain pathways relies on this pathway.

 

See CBD and brain repair.

 

We also see this level after the initial 10 days for drug withdrawal up to 30 days and beyond.

 

See CBD and BDNF to learn what's really at the heart of this!

 

On a side note, here are some interesting tools to look at: 

  • Magnesium glycinate - mag is a powerful supporter of GABA for sleep, anxiety, and even pain
  • PEA - THC without the high or side effects (see review here)
  • Berberine - powerful balancer of hormonal systems
  • NAC - powerful supporter of detox and mood
  • Vitamin D - master regulator of immune system and almost everything!

 


Mag and B6: 

After the intervention, the mean score of PMS significantly decreased in all the three groups (p < 0.05). The decrease was the greatest in the Mg plus vitamin B6 group, and was the least in the placebo group. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208934/

 

Check your MTHFR or MTRR gene status as methylated B vits may be key.

 

PEA (palmitoylethanolamide) and endometriosis pain: 

At the end of the treatment, all patients showed a significant improvement in chronic pelvic pain, deep dyspareunia, dysmenorrhea, dyschezia, as well as in quality of life and psychological well-being. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697671/

 

Berberine is fascinating in its support of the gut but with the side effect results on hormone balancing such as with PCOS: 

Our study found that administration of berberine alone may improve the menstrual pattern and ovulation rate in anovulatory Chinese women with polycystic ovary syndrome. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672885/

 

NAC and hormone balance for infertility: 

The number of follicles >18 mm was significantly higher in the letrozole + NAC group (P = 0.007). The ovulation and pregnancy rates were also significantly higher in the letrozole + NAC group (P = 0.045). No adverse side effects and no cases of ovarian hyperstimulation syndrome were observed in NAC group. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036781/

 

Its effects are pronounced for mood (see NAC and mental health).

 

The Vitamin D connection? 


Low serum levels of calcium and vitamin D during the luteal phase of the menstrual cycle were found to cause or exacerbate the symptoms of PMS. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422848/

 

Okay...these tools along with CBD are an impressive list.

 

One more really important and practical question.

What's the best CBD for PMS and PMDD 

First, the basics: 

  • Organically grown in the USA at FDA registered farm
  • CO2 processed
  • 3rd party testing
  • No THC - remember that THC only works in one direction and builds tolerance
  • No heavy metals
  • No solvents
  • No pesticides
  • No mold
  • No bacteria

 

Our 3rd party testing can be found at the top of any page.

 

Next up is probably the most important piece.

 

CBD isolate versus full spectrum.

 

The whole market is pushing full spectrum here's the secret they're not letting out.

 

40-60% of the population has histamine issues and this number goes up as we get older and for women

 

Why women?  Progesterone is dropping!

 


Remember that progesterone calms immune response and histamine or our allergic reaction is part of this response.

 

Many women have bad side effects on full spectrum CBD only to see those go away with CBD isolate.

 

We found isolate the same way after a brutal perimenopause (that story is here).

 

The last thing you want when progesterone is dropping is a bunch of plant material to set off allergic responses.

 

Remember that histamine is excitatory in the brain and it directly opposes GABA, the very thing we're trying to support with CBD.

 

Plus, the 1000's of studies on CBD are almost entirely on CBD isolate.  

 

We've covered the whole CBD isolate versus full-spectrum question here but this is really important for women with PMS or PMDD.

 

There's a great walkthrough of the tie between histamine and PMS/PMDD here: 

https://www.larabriden.com/histamine-intolerance-pms-pmdd/

 

Finally, there's cost.

 

The key metric is cost per mg of CBD.

 

We intentionally price our 6000 mg bottles at 2 - 3 cents per mg of CBD before discounts up to 50%.

 

Why?

 

We've been there and perimenopause is basically a 3-4 year version of PMS/PMDD.

 

If we can help reduce suffering, then all of this is worth it.

 

Be well. Take care of each other.  Take care of yourself!

 

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