Can CBD Help With Perimenopause Weight Gain, Bloating, and Obesity?

cbd for perimenopause weight bloating and obesity


 
If you read my brutal perimenopause story here, there's a mention of the ship putting on water (and weight).

 

That started early with the hectic requirements of raising two boys but perimenopause added a whole new dimension to this equation.

 

Aside from losing 30 pounds in one month (not advisable!!) from the side effects of SSRI's, the weight battle took on a new dimension during this time.

 

I'm not out of the ordinary in this respect.

 

Once you drill down into hormone's powerful effects on metabolism, fat creation, and weight...it's not surprising.

 

We'll get into all of it.

 

This isn't going to be your standard article on weight loss (exercise more, eat less, blah blah blah).

 

We're going to new, exciting realms of research like DNA-PK and metformin.

 

Why??

 

They found that a drug-like compound that blocked DNA-PK activity cut weight gain in the mice by a whopping 40 percent! 

https://directorsblog.nih.gov/2017/05/09/muscle-enzyme-explains-weight-gain-in-middle-age/

 

That's an NIH report from the director...not some salesy, cheesy pitch from Kardashians!

 

Most importantly, we'll look at whether CBD (and other things) can affect this pathway in the right direction.

 

We'll cover these topics: 

  • How does perimenopause affect weight 
  • Hormone changes and weight during perimenopause
  • Compensation of the body for loss of essential hormones
  • Estradiol and weight gain during perimenopause
  • Progesterone and weight gain during perimenopause
  • Perimenopause and bloating
  • The endocannabinoid and perimenopause weight gain
  • TRPV1 and weight gain
  • Can CBD help with perimenopausal weight gain
  • Other important tools for perimenopausal weight gain
  • How much CBD to take for perimenopausal weight gain
  • What's the best CBD for perimenopausal weight gain

 

Let's get into it.  Quick...before the Holidays!

How does perimenopause affect weight  

First, we need to separate out the weight gain associated with aging.

 

That's the fascinating effect of DNA-PK we mentioned above.

 

This is brand new research.

 

Essentially, DNA-PK increases as we get older and when researchers blocked its activity: 

They found that a drug-like compound that blocked DNA-PK activity cut weight gain in the mice by a whopping 40 percent! 

https://directorsblog.nih.gov/2017/05/09/muscle-enzyme-explains-weight-gain-in-middle-age/

 

They went onto to tie the effect to mitochondria, our cell's power sources.

 

The researchers found in these muscle cells that DNA-PK decreases the capacity of the mitochondria, the powerhouses that burn fat for energy. The enzyme also causes a decline in the number of mitochondria in these cells.

 

Later, we'll look at some tools we can use to reproduce this effect including vanillin and curcumin.

 

The net take-away for now thought… 

Recent evidence indicates that DNA-PK activity increases with age in skeletal muscle promoting mitochondrial loss and weight gain.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986591/

 

It turns out that this chemical in the body which increases as we get older directly interferes with a pathway for longevity and faster metabolism called AMPK.

 

You can learn all about the powerful effects of AMPK on age-related weight gain and longevity at our Metformin review here.

 

It might be THE miracle drug so far as we get older.

 

So...what about weight issues directly tied to perimenopause?

 

First, perimenopause is all about hormone fluctuation.

 

Primarily, estradiol (our main estrogen) and progesterone.

 

Progesterone starts dropping around age 40 and estradiol can go through a chaotic spasm of peaks and valleys during perimenopause.

 

It eventually settles into a steady dropping pattern going forward to menopause.

 

Learn all about how perimenopause is completely different than menopause!

 

So… 

 

First, you have to forget everything you (or your doctors) know about sex hormones.

 

They are NOT just for reproduction.

 

Progesterone and especially estradiol have their hands on almost every lever across every cell in the body.

 

Heart.  Brain.  Bone.  Fat!!

 

It's the last one we'll focus on here of course.

 

We're going to focus on two key effects that hormones have on the weight and obesity pathways

 

Direct effects of hormones on metabolism, fat creation, and weight
compensation of the body for loss of essential hormones.

 

These are what drive perimenopause and eventually, menopause weight gain.

 

This is more important than just from a vanity point of view (but yes, we're not immune to looking and feeling good!): 

The hormonal changes across the perimenopause substantially contribute to increased abdominal obesity which leads to additional physical and psychological morbidity. 

https://www.ncbi.nlm.nih.gov/pubmed/22978257

 

Let's look at those in more detail now.

Hormone changes, loss, and weight during perimenopause 

The first question is this...does weight gain occur from the fluctuation of hormones or decreasing levels of hormones?

 

There's a difference there!

 

A rather large study pinned it more on the loss of estradiol and progesterone as opposed to the flux we experience during perimenopause.

 

The SWAN study confirmed what was found in other studies: 

In a telephone survey of 16 000 study participants, no difference in self- reported BMI was found between premenopausal and postmenopausal women, adjusting for age and other covariants. 

https://www.tandfonline.com/doi/full/10.3109/13697137.2012.707385

 

That's total weight however.

 

What can change as a result of hormone flux is "distribution" of weight or fat.

 

There tends to be an accumulation of body fast around the abdomen as a result of estradiol.

 

We'll look at that more closely below.

 

In terms of perimenopause, the resulting weight gain appears to be more from loss of female hormones.

 

Keep in mind that both drop significantly as their production is primarily driven by the monthly egg-creation cycle (estradiol to make it...progesterone after release).

 

Perimenopause is literally the wind-down of this process!

 

Let's look at an abrupt change in these female hormones...removal of the ovaries.

 

Any effect on weight there?

 

Ovariectomy (OVX) produced hyperphagia and increased gain in both lean and fat mass. 

https://www.ncbi.nlm.nih.gov/pubmed/11158936

 

The researchers pinpointed downstream effects on a powerful obesity-linked hormone called leptin.

 

Leptin basically signals to your brain (your hypothalamus specifically) that you're hungry.

 

They found the following: 

Loss of ovarian function in human and rat is associated with increased fat mass gain and increased circulating leptin levels.

 

Since we know that estradiol and progesterone are the key losses, what's the connection there?

 

This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495667/

 

We're quickly losing that regulator during perimenopause.

 

But estradiol is just for baby-making!

 

We'll get into the each hormone specifically below but here's where it gets really interesting.

Compensation of the body for loss of essential hormones 

So up until around your mid-40's, ovarian production is the primary source for essential estradiol and progesterone.

 

All is well as these hormones are critical to every important system in your body and brain.

 

Just check out our review of estradiol to really understand the gravity of maintaining these hormones.

 

In fact, age-related loss of pregnenolone (the precursor to ALL our steroidal hormones) is a benchmark of aging.

 

They can tell your age roughly just by looking at these levels.

 

Check out full review of pregnenolone.

 

We bring preg up specifically for a reason.

 

A study found that they could lower cholesterol in people in their 50's simply by supplementing pregnenolone.

 

Wait, what?

 

Pregnenolone is made solely from cholesterol (yes, the boogeyman of our healthcare system).

 

As preg drops, the body increases cholesterol to make up for this loss.

 

That's how important our steroidal hormones are.

 

We see this across many different pathways in the body and brain.

 

Work-around options to keep critical rivers flowing.

 

What about estradiol and progesterone?

 

Yes!

 

In fact, as the ovaries shut down, in a panic, the body routes more production to the other options.

 

Primarily adrenal glands and….wait for it….Fat!!

 

This may be the key driver of accumulated fat during perimenopause and into menopause.

 

We'll let the researchers say it: 

However, there is substantial evidence that the perimenopause is associated with a more rapid increase in fat mass and redistribution of fat to the abdomen, resulting in a transition from a gynoid to an android pattern of fat distribution and an increase in total body fat. 

https://www.tandfonline.com/doi/full/10.3109/13697137.2012.707385

 

The body is trying desperately to pump up estrogen levels any way it can!

 

More fat = more back-up estrogen production!

 

Similarly to the pregnenolone and cholesterol effect, we would expect to see estrogen replacement have a similar effect there.

 

Does it?

 

Let's look at rats who have ovaries removed and then some of them get estrogen replacement treatment: 

After eight weeks, body weight, body mass index (BMI), visceral fat, apelin and lipid profiles (P < 0.01) were increased significantly in OVX rats compared to sham group. Treatment with estrogen leads to significant reduction in body weight and BMI (P < 0.05), 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770528/

 

So...following ovariectomy, all rats gained weight.

 

The rats that then got estrogen replacement lost it!

 

I think we can drop the mic there.

 

This is interesting because estradiol itself can actually increase weight gain as we'll see in the next section.

 

This speaks to the mechanism we spoke of...the body is losing a CRITICAL pathway (estrogen) and will do whatever it takes to try and make up for it.

 

Again, you have to read the review on estradiol or Siberian Rhubarb (estradiol substitute) to truly appreciate the power of estrogen in our bodies.

 

Just look at the extent the body will to replace this lost estrogen: 

Although food intake was similar, OVX mice gained 25% more weight than SHM mice.  

https://www.ncbi.nlm.nih.gov/pubmed/19179442?dopt=Abstract

 

25% increase in fat….but with the same calorie intake!!

 

Ladies, you've been fighting the tide with diets and exercise until that is corrected.

 

The knock-on effects from this increase fat (to get estrogen) is not good of course.

 

Increase fat also increases systemic inflammation which is the root of all medical evil these days (see CBD and inflammation here).

 

Did you know that 80% of autoimmune diagnosis are for women and that really hits around perimenopause?

 

OVX mice displayed evidence of immune infiltration and inflammation in adipose tissue, because perigonadal and inguinal adipose depots from OVX mice had increased expression of TNFalpha, iNOS, CD11c, and other hallmarks of adipose tissue inflammation.  

https://www.ncbi.nlm.nih.gov/pubmed/19179442?dopt=Abstract

 

To translate (please!!)..

 

Immune infiltration - bacteria crossing gut barrier which is the linchpin for autoimmune 

 

Check our article on CBD and neuroinflammation to see how this can translate into mood disorders such anxiety and depression which are staples of perimenopause.

 

In fact, it's hard to separate out mental health issues and weight gain for perimenopause and menopause.

 

One study found anxiety and depression to be a better correlation with weight gain: 

These findings suggest that screening for depression and anxiety may be important clinical assessments to identify women at increased risk of substantial weight gain. 

https://www.ncbi.nlm.nih.gov/pubmed/12876110

 

Check out CBD and perimenopause anxiety or CBD and perimenopause depression for more information.

 

Let's jump to the two key hormones to see how they impact weight gain.

 

We'll start with the star player...estradiol.

Estradiol and weight gain during perimenopause 

Estogen is all over appetite, food intake, how much of that is converted to fat, and even where the fat is concentrated.

 

As researchers stated: 

In female animals, the activational effects of estradiol acutely and chronically influence body weight homeostasis.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889220/

 

Let's break down some of these pieces.

 

First, the appetite piece of it.

 

Estrogen exerts a tonic inhibitory effect on meal size and daily food intake throughout the ovarian cycle and a cyclic inhibitory effect during the peri-ovulatory phase.

 

This basically means that estrogen governs how much you eat per meal and during the course of a day.

 

Changes in its level will cause changes in food intake!

 

Let's introduce NPY (neuropeptide Y).

 

It's the "I'M HUNGRY" chemical in the body.  Caps are intentional.

 

It's more forceful in its effect than ghrelin, the appetite hormone.
So what does estradiol do there?

 

Collectively, these results show that estrogen suppresses NPY levels and release selectively from the PVN. 

https://www.ncbi.nlm.nih.gov/pubmed/8194462/

 

The net effects of this reduction: 

The results show that uninterrupted physiological levels of E2 in ovariectomized rats suppressed daily food intake and body weight gain. 

 

In fact, researchers found that rats with ovaries removed (who subsequently gained weight) showed a marked increase of NPY in certain parts of the brain.

 

Back to our other appetite hormone, Ghrelin from above.

 

There's an interesting experiment where adding ghrelin (which makes us hungry among other things) has an impact on rats with ovaries removed and male rats versus rats with ovaries intact..

 

This points to estrogen's modulating effect on ghrelin.

These data suggest that estradiol inhibits the orexigenic action of ghrelin in females, that weight gain associated with OVX is ghrelin mediated, and that this endocrine interaction may account for an important sex differences in food intake and the regulation of body weight. 

https://www.ncbi.nlm.nih.gov/pubmed/17251274/

 

Estrogen is acting as a buffer from ghrelin's effects!

 

This offsetting effect of estrogen was also present for another appetite boosting hormone called melanin concentrating hormone (MCH).

 

We could go on and on.  

 

Check out the review below for all the different pathways (insulin, leptin, serotonin, CCK, etc) that estradiol manages for appetite. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889220/

 

As for fat accumulation and distribution, estradiol is front and center.

 

In fact, when researchers knock out receptors for estrogen in the body, there's a resulting increase in fat (adiposity) for both male AND female.

 

Some key takeaways.

 

Weight gain tied to estrogen appears to be tied more to how energy is used as opposed to caloric intake.

 

The effects appears mainly in the ERa receptor (there's an A or B version) which is pro-growth.

 

As researchers put it: 

Knockdown of VMH ERα results in obesity due to an anabolic process, with changes in energy expenditure primarily mediating the weight gain. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889220/

 

They've even found genetic variants in this pathway that can predispose people to obesity.

 

It also explains why removal of estrogen can cause significant weight gain EVEN if caloric intake remains the same.

 

This is at the heart of "metabolism".

 

Estrogen ramps up metabolism as it's pro-growth (via the ERa receptor at least).

 

Then, there's estrogen's powerful effect as anti-inflammatory.

 

Just look at this crazy connection: 

Symptoms of a metabolic syndrome increase when animals are maintained on a high-fat (HF) diet or when females have low ovarian hormone levels.

 

So...diabetes risk goes up if you eat lots of high fat food OR have lower estrogen.

 

As we discussed in our Metformin review, insulin and energy metabolism are at the heart of aging and age-related diseases (the AMPK pathway).

 

Goodness.  Loss of estradiol is literally a ramp up of aging.

 

This makes sense from an evolutionary point of view (no longer can make offspring) but that doesn't mean our medical community has to buy in!


As for fat distribution, this is very critical to health in general (cardiovascular, etc).

 

There is a contrast between: 

  • visceral fat - around the stomach and organs
  • subcutaneous fat - just under the skin

 

Visceral fat is not good for health and subcutaneous fat is what makes skin plump and healthy.

 

Estradiol has direct controls on this as well.

 

Look what happens when rats have their ovaries removed: 

Ovariectomized (OVX) rats gain fat, specifically visceral fat with no change of subcutaneous fat. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889220/

 

What happens when the supplement estradiol?

 

Peripheral or central administration of estradiol to OVX rats restores central leptin sensitivity and changes their body fat distribution to mirror that of intact females. 

 

This speaks to the transition to belly weight during perimenopause when estradiol really starts to drop.

 

On a side note, estrogen has a u-curve response for weight.

 

Too much estrogen can cause weight gain.

 

This may be in the form of water (bloating) and there can be spikes of estrogen during perimenopause.

 

This is very similar to the bloating that occurs during the cycle but more intense.

 

In the end, we're aiming for balance.

 

We could spend all day on estradiol and weight but you get the picture.

 

Let's check out progesterone.

Progesterone and weight gain during perimenopause 

Progesterone's role appears to be more nuanced.

 

It shows modulating if not offsetting effects to estradiol.

 

For example, estradiol has been shown to increase growth hormone release at night.

 

This is very important as growth hormone declines as we age and the new study on reversing epigenetic aging (see metformin review) focused on its pathway.

 

Progesterone has recently been shown to counter this effect: 

However, P4 diminished ghrelin-stimulated pulsatile GH release with or without E2. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889220/

 

This is mirrored across other metabolic pathways between estrogen and progesterone.

 

Here's the deal...we're swimming in estrogens: 

  • Plastics which mimic estrogen
  • Increased estrogen production from fat cells
  • Pesticides which interfere with endocrine production

 

On top of this, progesterone starts dropping way back in the early 40's so this can lead to an imbalance between estrogen and progesterone.

 

The net net is this…

 

If you already have normal progesterone levels (relative to estrogen), then more progesterone may lead to weight gain.

 

However, if you have lower levels (welcome to perimenopause) relative to estrogen, then progesterone can actually help with weight.

 

You have to get your hormone panels such as the Dutch test to find out where you are.

 

It's not just weight of course...this directly affects cancer risk since estradiol by itself is pro-growth.

 

Just look at the connection between BMI and the transition to menopause: 

Accordingly, postmenopausal obese women have >40% increases in both circulating estrone (E1) and estradiol (E2) as compared to postmenopausal women with a BMI in the normal range. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964851/

 

This causes the further break-down of testosterone to estrogen which just furthers the cycle.

 

And then progesterone's role in all this: 

In obese women, lack of progesterone due to anovulation, similar to that observed in polycystic ovarian syndrome (PCOS), can contribute to endometrial cancer risk.

 

There's a great walk through of this estrogen-progesterone interaction here: 

https://www.restartmed.com/does-progesterone-cause-weight-gain/

 

Also, we're only talking about bio-identical progesterone (or pregnenolone).

 

The synthetics like those found in birth control are a completely different animal.

 

Even the NIH references this even if your doctor says it's no big deal.

 

Kinda like how hydrogenated oil was no big deal for a few decades of cardiovascular destruction!

 

In fact, studies have shown that most women gain up to 5 pounds taking progestin-only birth control medications. 

https://www.restartmed.com/does-progesterone-cause-weight-gain/

 

We saw clearly how estradiol controls many levers of weight gain and obesity.

 

Progesterone is as a needed counterbalance since the two were designed to work together (and did) for decades in your body.

 

One direct effect of progesterone we do want to focus on for healthy weight is the thyroid.

 

Your thyroid is critical to proper weight maintenance: 

The thyroid hormones increase the basal metabolic rate and have effects on almost all body tissues.[25] Appetite, the absorption of substances, and gut motility are all influenced by thyroid hormones. 

https://en.wikipedia.org/wiki/Thyroid

 

"Basic metabolic rate".

 

Remember how the rats would put on more weight with the same caloric intake?

 

That's metabolic rate at its finest (or worst).

 

So...what's the relationship with progesterone and thyroid function?

 

Progesterone therapy increases free thyroxine levels--data from a randomized placebo-controlled 12-week hot flush trial.

https://www.ncbi.nlm.nih.gov/pubmed/23252963

 

The thyroid really requires a whole separate article.

 

Let's turn to a related question...bloating and perimenopause.

Perimenopause and bloating 

This is a very common complaint right alongside weight gain with perimenopause.

 

Of course, progesterone and estradiol are to blame: 

Estrogen and progesterone exposure have important effects on both body fluid regulation and cardiovascular function and both of these reproductive hormones impact blood pressure responses to sodium loads.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984489/

 

Let's introduce vasopressin.

 

You may not have heard of it but it's critical to perimenopausal bloating (as well as a host of other issues).

 

Basically, more vasopressin = more water retention.

 

As for the hormones, one more example of the yin-yang effects of estradiol and progesterone.

 

First, estradiol: 

Transdermal treatment with estradiol alone by means of patches in a dose of 100 ug/ 24 h for five days resulted in an elevation of the mean plasma concentration of this hormone from undetectable to 262 pmol/1 and increase in mean circulating levels of vasopressin from 0.82 to 1.22 pmol/1 and of oxytocin from 2.50 to 3.98 pmol/1. 

https://obgyn.onlinelibrary.wiley.com/doi/abs/10.3109/00016349509024387

 

And progesterone is the countering balance: 

Progesterone therapy caused an increase in plasma ANF and osmolality levels and the AVP threshold and a decrease in AVP levels and sensitivity and urinary cyclic nucleotide levels. 

 

So that's general bloat.  Water retention.

 

There's also the bloating feeling that comes from GI issues in the gut.  Bloating that comes from gas primarily from changes in our gut bacteria.

 

Is there a connection with perimenopause?

 

The increase in GI symptoms around the time of menses and early menopause occurs at times of declining or low ovarian hormones, suggesting that estrogen and progesterone withdrawal may contribute either directly or indirectly. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322543/

 

Look at what happens between before and after perimenopause: 

Thirty-eight percent of postmenopausal women reported altered bowel function, in contrast to 14% of premenopausal ones. 

https://www.ncbi.nlm.nih.gov/pubmed/9796084

 

Goodness that's a jump.

 

When are the symptoms worse?

 

The prevalence of IBS-type complaints peaked to 36% during the climacteric period (40-49 years). 

 

"Climacteric" is a fancy way to say perimenopause.

 

We can look at supplementation of hormones (OC = oral contraception) to see effects: 

Overall, the women with IBS who were taking OCs containing both estrogen and progestin appeared to have reduced levels of abdominal pain/discomfort compared with the women with IBS who were not taking OCs. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322543/

 

Look...we try to touch on our microbiome in every article because all the new research is pointing there.

 

Does estrogen (and its loss) affect our gut biome?

 

Of course it does!

 

There's a great review on both mouth and gut bacteria reactions with estrogen here but the net take-away: 

Interestingly, the presence or absence of estrogen may be able to alter the gut microbiota equilibrium and corresponding disease pathways. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625026/

 

Autoimmune really figures in here and that's important for women (who make up 80% of the diagnosis) and for perimenopause (a key period of diagnosis).

 

Obesity and weight gain are directly tied to changes in gut bacteria make-up.

 

This could literally be the most important synopsis of this article: 

The relationship between the gut microbiota and a lack of estrogen is likely responsible for weight gain and lipid deposition during menopause. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625026/

 

Taking in vegetable sources of estrogen can directly impact this obesity pathway: 

This suppression of Clostridiaceae, a family of Clostridia associated with obesity 1), likely explains why diets containing phytoestrogens have been shown to improve weight gain in menopausal women.

 

Organic tofu and soy as an example.  

 

You may become upset that you didn't know the impact on our gut bacteria earlier after reading this: 

When the distal gut microbiota from the normal mice was transplanted into the gnotobiotic mice, there was a 60% increase in body fat within 2 weeks without any increase in food consumption or obvious differences in energy expenditure. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082693/

 

60% increase in body fat just from switching out gut bacteria!

 

You could almost argue that obesity is a disease not of us but of our microbiome!

 

If we combine that 60% with the 40% we had from estrogen removal, we're getting somewhere and it has nothing to do with what we put in our mouths!

 

Check out CBD and probiotics or our metformin review for gut bacteria insight.

 

Really look at the link below.  It's a fascinating walk-through the interactions of sex hormones, gut bacteria and a host of health issues (bone loss, cancer, autoimmune, etc).

 

We're getting there...the endocannabinoid system.

The endocannabinoid and perimenopause weight gain 

The key to understanding CBD's effects in the body is to first look at the system it operates within.

 

The endocannabinoid system.

 

We all have one and it's placed at about 600 million years old (way before our favorite dinosaurs).

 

It's roughly tasked with balancing other key systems: 

  • Nervous system including neurotransmitters like serotonin, GABA, and more
  • Endocrine system including hormones like ghrelin, leptin, and vasopressin
  • Immune system including inflammatory agents like microglia and cytokines

 

The crux of perimenopausal weight gain lies at the intersection of these three system!

 

For that matter, almost any health-related issue does as well.

 

Let's look at some quick examples before we jump into CBD's direct effects.

 

We'll begin at the start….appetite.

 

Is there's an interaction there?

 

It is now confirmed that endocannabinoids, acting at brain CB1 cannabinoid receptors, stimulate appetite and ingestive behaviours, partly through interactions with more established orexigenic and anorexigenic signals. 

https://www.ncbi.nlm.nih.gov/pubmed/16787229

 

So...how does it work its magic.

 

Remember ghrelin from above?

 

It's the hormone that signals to the brain that we're hungry.  The appetite hormone (along with NPY).

 

Watch this..when researchers blocked CB1 (the primary receptor for the endocannabinoid system), additional ghrelin (the appetite hormone) did NOT increase appetite: 

Ghrelin did not induce an orexigenic effect in CB1-knockout mice. Correspondingly, both the genetic lack of CB1 and the pharmacological blockade of CB1 inhibited the effect of ghrelin on AMPK activity. 

https://www.ncbi.nlm.nih.gov/pubmed/18335063

 

Your desire for that chocolate croissant goes right through the endocannabinoid system.

 

On a side note, check out the crazy connection between chocolate and CBD here.

 

Just to add parity, what about the other side of the coin...feeling full?

 

Remember leptin, the hormone that signals that we're full?

These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin. 

https://www.ncbi.nlm.nih.gov/pubmed/18335063

 

Goodness.

 

Then there's the whole issue of food addiction.

 

The endocannabinoid system has powerful roles to play in the addiction pathway (check out CBD and addiction or how I used CBD to wean off benzos here.

 

That angle is here: 

The hedonic component of hypercaloric nutrition (24) could possibly be targeted by a CB1 antagonist, which might be able to diminish the possibly addictive aspect of food intake in some individuals, in combination with decreasing orexigenic drive and lipogenesis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166302/

 

Hedonic just means pleasurable...the addiction piece of food consumption.

 

A CB1 antagonist is a chemical that slows down processing for CB1 receptors.

 

CBD is called a negative allosteric modulator...essentially a break, when needed, or a constraint on CB1 activity.

 

We'll talk about that more below.

 

Let's end with this as a small example of the entire metabolism complex.

 

Brown fat!

 

Yes, it's a real thing and it's very important for weight loss/gain.

 

Essentially, brown fat burns calories!

 

It was thought that only babies could make brown fat but new research is throwing that notion on its head.

 

This is one element that the endocannabinoid system governs: 

Interestingly, the endocannabinoid system was recently shown to control several metabolic functions by acting on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. 

https://www.ncbi.nlm.nih.gov/pubmed/18601709

 

Adipocytes?  Fat cells.

 

Brown fat (as opposed to white) has that color because it's jammed packed with mitochondria, the little powerplants of our cells.

 

The more brown fat we have, the better!

 

In 2014, Chondronikola and coworkers reported that adult men with active BAT showed a significant increase of resting energy expenditure compared to BAT negative men.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163475/

 

We'll look at brown fat below.

 

The net take away is this: 

Cannabinoid receptors (CB) regulate thermogenesis, food intake and inflammation. CB1 ablation or inhibition helps reducing body weight and food intake. Stimulation of CB2 limits inflammation and promotes anti-obesity effects by reducing food intake and weight gain. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163475/

 

So….less CB1 activity = more appetite and weight
More CB2 activity = less appetite and weight

 

Guess where CBD operates?  Yes, CB2 primarily.

 

Let's finally (thanks for staying with us) look at CBD's effects on perimenopausal weight gain.

Can CBD help with perimenopausal weight gain 

We've looked at many different pathways.

 

How does CBD affect these?

 

Let's recount them: 

  • Ghrelin - creates appetite
  • Leptin - reduces appetite
  • Serotonin - sweet spot is good for weight loss
  • Brown fat - increases energy usage

 

Ghrelin and Leptin both share similar pathways.

 

CB1 activity increases ghrelin (feel hungry) and decreases leptin (feel full hormone).

 

This is why THC is a powerful booster of appetite!

 

THC fits nicely in the shoes of our main natural CB1 actor, anandamide.

 

Hence the munchies.

 

There's a great review of THC's effects on many hormones here.

 

In almost all respects, CBD counters the effects of THC (Check out CBD versus THC here).

 

CBD basically puts a constraint on CB1 activity.  It's a like a rubber band and when CB1 activity run too hot or too cold, it sends a signal to reign it in (either way).

 

This is why you don't see overdoses on CBD.  Technically, that would make it one of the best "adaptogenics" out there along with curcumin, etc.

 

In fact, "reduced appetite" is a noted side effect of CBD (we'll take it!).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043845/#B7

 

Let's look at the synthetic CBD, rimonabant since there's lots of research there.

Here's where it gets interesting.

 

Rimonabant was actually approved as an anti-obesity drug!

 

They pulled it due to side effects (which CBD does not have).

 

How does it work?

 

Rimonabant is an inverse agonist for the cannabinoid receptor CB1 and was the first drug approved in that class.[4][5]

 

It's literally a big Pharma workaround to get the benefits of CBD!

 

  • Rimonabant blocks CB1 activity
  • CBD blocks chemicals that boost CB1 activity

 

Six or half a dozen.

 

On average, patients lost 10 pounds MORE than the control group: 

Patients given rimonabant had a 4.7 kg (95% CI 4.1-5.3 kg; p<0.0001) greater weight reduction after 1 year than did those given placebo. 

https://www.ncbi.nlm.nih.gov/pubmed/18022033

 

One reason for this was rimonabant's effect on ghrelin (hunger hormone): 

Similarly, it was found that this injection significantly decreased ghrelin‐induced GH secretion without any effect on growth hormone‐releasing hormone (GHRH)‐induced GH discharge. 

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2826.2010.02065.x

 

It's sad that we need an expensive (translated patentable) drug to drive research but that's where we're at.

 

The synthetics never work as well as the real deal (look at progestins versus progesterone) but it does shed light on pathways with obesity.

 

Plus all the nasty side effects that CBD doesn't have.

 

You can't directly block CB1 activity because it's so crucial to proper functioning especially in the brain.

 

You can, however, keep it from going to high!

 

Downregulation of CB1 activity in rodents and humans has proven efficacious to reduce food intake, abdominal adiposity, fasting glucose levels, and cardiometabolic risk factors. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679742/

 

Hello CBD!

 

Let's look at specifics please.

 

First, the brown fat effect.

 

What does it do there?

 

These data suggest possible roles for CBD in browning of white adipocytes, augmentation of lipolysis, thermogenesis, and reduction of lipogenesis. 

https://www.ncbi.nlm.nih.gov/pubmed/27067870

 

To translate: 

  • Browning of fat - increases resting energy usage
  • Lipolysis - the breakdown of fats
  • Thermogenesis - making more heat which burns calories
  • Reduction of lipogenesis - making less fat to begin with

 

Goodness...we can drop the mic now.

 

First, let's bring it all back around to perimenopause weight gain.

 

Remember how estradiol is spiking and eventually dropping during this period?

 

Follow us on this because it's really cool.

 

Estradiol is a direct controller of serotonin, our feel good neurotransmitter.

 

It governs both the creation (from tryptophan) and the break-down (MAO).

 

Serotonin is incredibly important for appetite: 

Our studies with volunteers found that when people consumed a pre-meal carbohydrate drink that made more serotonin, they became less hungry and were able to control their calorie intake. Volunteers whose drinks contained protein—so that serotonin was not made—did not experience any decrease in their appetite. 

https://www.psychologytoday.com/us/blog/the-antidepressant-diet/201008/serotonin-what-it-is-and-why-its-important-weight-loss

 

Why?  Because it's a powerful signal to get more tryptophan.

 

Read that review...it's fascinating.

 

Tryptophan needs carbohydrates to get into the brain.  That's why you crave that dinner roll or starchy snack.

 

The net effect of this: 

Serotonin is nature's own appetite suppressant. This powerful brain chemical curbs cravings and shuts off appetite.

 

And estradiol's gone rogue at the helm of this critical neurotransmitter.

 

This may be CBD's greatest gift to us.

 

In studies on pain, anxiety, and nerve issues, CBD shows its effect on the serotonin pathway: 

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/

 

Remember how we said CBD acts as a constraint both on the low and high end?

 

You'll see words like "modulate" and "normalize".

 

Not boost or reduce (see CBD versus SSRI for serotonin).

 

Also, check out CBD, tryptophan and serotonin here.

 

As for bloating?

 

Remember how vasopressin is key to retaining water.  Most of the weight gain during monthly cycles is actually water retention.

 

We can look to blood pressure for CBD's effects since vasopressin directly affects blood pressure as well (literally more water in your cardiovascular system). 

CBD reduced resting systolic BP (-6 mmHg; P < 0.05) and stroke volume (-8 ml; P < 0.05), with increased heart rate (HR) and maintained cardiac output.  

https://www.researchgate.net/publication/317615325_A_single_dose_of_cannabidiol_reduces_blood_pressure_in_healthy_volunteers_in_a_randomized_crossover_study

 

Furthermore, it was found that anandamide (our primary endocannabinoid) may have an impact on fluid retention: 

Work from other laboratories suggests that both anandamide and 2-arachidonylglycerol, released from the hypothalamus, may modulate the release of hypophyseal hormones, including vasopressin. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533417/

 

We need more info but the effects of CBD on the microbiome is better established and balancing.

 

See CBD and probiotics or CBD and the microbiome.

 

On a side note, you really have to look at hormones since they drive this crazy  train.

 

Check out the following: 

 

Now, on to some practical questions.

How much CBD to take for perimenopausal weight gain 

There isn't good research on this yet and in case you haven't noticed, we're all about research.

 

Definitely start low to test on your system at about 25-30 mg.

 

Sleep help is showing around 100-160 mg.

 

Neurogenesis for anxiety, depression, and the like max out at 300 mg.

 

Weight issues probably shouldn't require very high needs as a longer term assistance of a very complex system.

 

This of course depends on how much stress your under (perimenopausal or other).

 

I was in a tailspin from perimenopause with weight being the least of my issues so I take 150 mg in the morning and night.

 

The goal is to take some of the swing out of weight (water) and also add some balancing to the hormones that drive it.

 

What about the best CBD for perimenopausal weight gain?

What's the best CBD for perimenopausal weight gain 

There are basic requirements for any CBD: 

  • Organically grown in the US by an FDA registered farm
  • CO2 processed for cleanest result
  • 3rd party tested free of:
  • NO THC (THC increases appetite)
  • No pesticides (directly affect hormones in charge of obesity)
  • No heavy metals
  • No bacteria
  • No processing agents

 

These are basics and we requires this for IndigoNaturals.

 

Afterall, our entire family uses the product so we actually test twice.

 

Then, there's the question of full spectrum versus CBD isolate.

 

This is especially important for ladies in perimenopause.

 

Histamine issues start to increase for women and really kick up during perimenopause.

 

40-60% of people have histamine issues and we guarantee it...women in perimenopause round out the high side of that.

 

Why does this matter?

 

All that plant material in full spectrum CBD that everyone's pushing is going the wrong way!

 

We learned the hard way with 3-4 major brands when we first started our CBD journey.

 

SIde effects were in full histamine effect.

 

That's how we eventually found CBD isolate and why we eventually crafted Indigo Naturals.

 

The full story is here but be well.  Take care of yourself and you'll get to the other side as well.

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