CBD and the Pathways of Fibromyalgia

cbd and fibromyalgia

 

 

We're doing a deep dive here.

 

There's lots to unpack with Fibromyalgia...important clues that point to key pathways.

 

The big one is gender with women being hit at twice the rate of men.

 

We'll dig into that along with the common onset (35-45) which offers yet another clue.

 

Then there's the newer data on infection, trauma, and immune response as a result of early stress.

 

Even early trauma in childhood or infection in utero.

 

Wait till you see the systems impacted by this early immune system hyperactivity (cough cough...pain sensitivity threshold manager serotonin).

 

The newest research is landing squarely on the immune system which is true for most mental illnesses these days (see CBD and mental health or CBD and trauma).

 

Of course, the gut and its microbiome are key inflammatory thermometers for the rest of the body so we'll go there as well.

 

Steroidal hormones are front and center with an emphasis on progesterone and testosterone.

 

Let's get started!

 

compare cbd isolate options 

 

These are the topics we'll cover: 

  • A quick look at fibromyalgia and its risk factors
  • How the immune system is charged up with fibromyalgia
  • The gut and microbiome with fibromyalgia
  • Steroidal hormones and fibromyalgia
  • The serotonin pathways and fibromyalgia
  • The TRPV pathway
  • Research on CBD and the pathways of fibromyalgia
  • How much CBD to take for fibromyalgia
  • What's the best CBD for fibromyalgia

 

Let's get started!

A quick look at fibromyalgia and its risk factors 

There are plenty of sites to get the general lay of the land including symptoms of fibromyalgia so we'll skip this part.

 

A quick description: 

Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.  

https://www.mayoclinic.org/diseases-conditions/fibromyalgia/symptoms-causes/syc-20354780

 

These issues alone point to a powerful clue which we'll cover below.

 

First, what are primarily associated risks we can zero in on?

 

The main list: 

  • Sex. Women are twice as likely to have fibromyalgia as men.
  • Stressful or traumatic events, such as car accidents, post-traumatic stress disorder (PTSD)
  • Repetitive injuries. ...
  • Illness (such as viral infections)
  • Family history.
  • Obesity. 

https://www.cdc.gov/arthritis/basics/fibromyalgia.htm

 

For the gender piece, we'll go through steroidal hormones below.  It's so pivotal!

 

There's stress, trauma, and infection.  That's the lynchpin we want to focus on based on newer research.

 

Repetitive injury speaks to exhaustion of certain pathways (hint hint...serotonin).

 

Family history...hmmm.  Genetics.  What' genetics are at play?

 

Genome-wide association studies investigated genes potentially involved in fibromyalgia pathogenesis highlighting that genetic factors are possibly responsible for up to 50% of the disease susceptibility. Potential candidate genes found associated to fibromyalgia are SLC64A4, TRPV2, MYT1L, and NRXN3 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322092/

 

SLC64A4 is a...serotonin transporter gene.  Go figure.

 

TRPV is interesting in that it's tied into sensory neurons in the spinal cord and brain.

 

There's a known connection between fibromyalgia and spinal cord sensory processing.

 

Obesity is yet another clue since serotonin directly manages appetite.

 

Let's start to tie all these pieces together...one step at a time.

 

First, the trigger.

How the immune system is charged up with fibromyalgia 

We now know that inflammation is front and center with fibromyalgia: 

Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

https://pubmed.ncbi.nlm.nih.gov/28424559/

 

What's scary is that if you google fibromyalgia and inflammation, some of the top pages says no.

 

Goodness...outdated and wrong information.

 

Inflammation in the nervous system is of special import to our discussion: 

There is increasing evidence of neurogenically derived inflammatory mechanisms occurring in the peripheral tissues, spinal cord and brain in fibromyalgia. These involve a variety of neuropeptides, chemokines and cytokines with activation of both the innate and adaptive immune systems.  

https://pubmed.ncbi.nlm.nih.gov/29556959/

 

We can actually drill down into cytokines, the little chemical messengers of inflammation to be exact (and close the case): 

Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P = 0.0034; I2 = 71%, Q2P = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P = 0.045; I2 = 39%, Q2P = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P = 0.01; I2 = 61%, Q2P = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P < 0.001; I2 = 10%, Q2P = 0.34) in fibromyalgia patients compared with HC. 

https://academic.oup.com/rheumatology/article/60/6/2602/6134095

 

2021 study.  TNFa, IL6, IL8, IL10.  The first three are inflammatory while the last one is actually anti-inflammatory as the body is trying to calm the cytokine storm.

 

There's also a robust elevation of a specific chemokine (inflammatory agent) called eotaxin.

 

Interestingly, eotaxin target a part of the immune system (called eosinophils) and their job?

 

Fight parasites, bacteria, and viruses.

 

One in particular is fascinating...Lyme disease.

 

Our immune system is incredibly complicated (see CBD and dementia or CBD and neuroinflammation) but clearly, the immune system is front and center with fibromyalgia.

 

Interestingly, the immune system can get primed for hyperactivation by a slew of onslaughts...chronic stress, trauma, and even infection.  Especially at key periods of brain development like the 3rd trimester.

 

We go deep into this at our CBD and trauma review some key takeaways: 

Childhood traumatic experiences, not only in general, but also with all subtypes, were also reported to be significantly more in FMS patients.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657761/

 

This also figures into mental health co-morbidities.  Brain inflammation is the enemy of healthy brains.

 

Interestingly, our immune system does a bad job of differentiating between psychological stress and bacteria strains.

 

It's a one-trick (albeit with many moving pieces) pony.

 

So why would early exposure to stress, infection, or trauma lead to fibromyalgia decades later?

 

There's a whole cascade of "settings" that are affected by early trauma.

 

The three we'll focus on: 

  • Serotonin
  • GABA
  • Inflammation

 

Reported childhood abuse is associated with low serotonin transporter binding in vivo in major depressive disorder

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858631/

 

Look at what happens when they introduce flu virus to mice in the 3rd trimester: 

When compared to controls, there was a significant decrease in serotonin levels in the cerebella of offspring of virally exposed mice at P14 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714699/

 

P14 is later in life (for a mouse!).

 

So...a downregulation of serotonin function following trauma, infection, or chronic stress.

 

Interestingly, there's a whole series of literature on how Fibromyalgia starts after some traumatic event...even injury (we'll get to that later).

 

Downregulation of exhaustion (the injury and chronic stress piece) of serotonin is a clear lever in this disease.  One we can actually affect!

 

Then there's GABA.

 

GABA's our nervous system's primary "brake pedal". 

 

We covered it in detail at our GABA review since it's so intimately tied to anxiety, depression, and just about every mental health issue.

 

It also plays a critical role in pain!  Both nervous system transmission and even peripheral pain.

 

In fact, the research on Ketamine looks at blunting glutamate (the opposing force to GABA) at the nerve endings...especially the pain-sensing aspects… so they can normalize.

 

Essentially, it's an overload of the nerves both in the body and via transmission to the brain.

 

And with fibromyalgia?

 

Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM).  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374930/

 

Specifically...

 

GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls

 

Why does that area matter?

 

Right anterior insula is associated with pain generalization in patients with fibromyalgia. 

https://journals.lww.com/pain/abstract/9000/right_anterior_insula_is_associated_with_pain.97955.aspx

 

Let's drill down because it's too interesting...what does the right insula do?

 

The right anterior insula is engaged in interoceptive awareness of homeostatic emotions such as thirst, pain and fatigue, and the ability to time one's own heartbeat. 

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

 

Just your internal feeling of pain and fatigue.  Can we drop the mic now?

 

Finally, early trauma and inflammation.

 

Basically, trauma (including infection) can prime the immune system to hyperactivate.

 

a number of blood biomarker studies have reported that compared to healthy controls, individuals with PTSD exhibit significantly elevated levels of proinflammatory markers, such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein.  

https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12820

 

That's PTSD but the same holds true for early infection/trauma.  Even later infection/trauma.

 

Basically, an unbalancing of the immune system.

 

Let's keep moving on...to the gut!

The gut and microbiome with fibromyalgia 

All inflammatory roads lead to the gut these days (in research).

 

This makes sense since the first handshake with the outside world to our internal space is the gut via trillions of bacteria, viruses, and more that hitchhike on our food.

 

Skin being the second one.

 

The gut is really the trojan horse so our gut and the microbiome...the trillions of beneficial bacteria that line it, act like a thermostat for inflammation across the body and brain (via the vagus nerve).

 

So...what do we see with fibromyalgia?

 

First...the gut bacteria: 

The composition of the gut bacterial community is altered in individuals with FM, with an altered abundance of a small subset of bacterial species.  

https://pubmed.ncbi.nlm.nih.gov/32116215/

 

More importantly, the species that flourish with fibromyalgia have specific metabolism that directly affect symptoms.

 

You also see tell-tale signs of gut imbalance such as inflammatory diseases: 

Some reports say approximately 60 percent of people with fibromyalgia have IBS, and conversely, 60 or 70 percent of people with IBS also have fibromyalgia. 

https://www.everydayhealth.com/fibromyalgia/gut-health/

 

Check out CBD and IBS or CBD and gut inflammation.

 

Most of your serotonin is made in the gut.  And GABA/glutamate balance?

 

Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia 

https://www.sciencedirect.com/science/article/pii/S2352396419304736

 

There's a whole question of whether fibromyalgia is auto-immune.

 

If the gut barrier is broken down by inflammation (such as with IBS), bacteria/viruses can escape into the body and auto-immune may just be a resulting symptom. 

 

See CBD and autoimmune to learn more.

 

Speaking of which: 

Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome 

https://pubmed.ncbi.nlm.nih.gov/18540025/

 

Okay okay...the gut's in play.

 

Let's turn to hormones.

Steroidal hormones and fibromyalgia 

Women are hit twice as hard.

 

Let's look at other clues.

 

What about when ovaries (and thus progesterone and estrogen) are removed?

 

A study on mice found that a mouse model of fibromyalgia resulted in severe sleep issues in addition to pain, fatigue: 

Our results demonstrated that RES induced pain-related behavior (50-70%) in OVX rats and altered sleep architecture by the increase of total wake time (38%), diminution of the no-REM stage (SWS-I 33% and SWS-II 76%), and abolition of the REM sleep 

https://pubmed.ncbi.nlm.nih.gov/29326058/

 

Sleep issues are the #3 symptom for fibromyalgia along with pain and fatigue.

 

Interestingly, support of the serotonin system helped with these issues.

 

And women?

 

Total FIQ scores from women who had had a hysterectomy were higher (worse symptoms) than those who had not  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191932/

 

FIQ is a standard fibromyalgia symptom severity test.

 

What's going on here?

 

We're not surprised even if most of the medical community is behind the times on steroidal hormones.

 

Estrogen directly promotes serotonin!  Serotonin supports BDNF, our brain's fertilizer.

 

See Estrogen and mental health to learn more.

 

Progesterone directly supports GABA and calms the immune system.

 

Progesterone drops by 50% by age 40 and continues down while estrogen goes through a roller-coast spasm mid to late 40s and then plummets.

 

You really have to address these powerful players first as we've found out.

 

Everything else is fiddling while Rome burns.  Progesterone review here.

 

Testosterone is the male equivalent to estrogen in supporting serotonin and general replenishment for every structure in your body and brain.

 

To that end… 

Assessment of the typical symptoms of fibromyalgia by patient questionnaire and tender point exam demonstrated significant change in: decreased muscle pain, stiffness, and fatigue, and increased libido during study treatment.  

https://www.sciencedirect.com/science/article/pii/S1567576915002453

 

One note...in women, most libido is driven by Estrogen.

 

The timing of these drops also mirrors the key windows of fibromyalgia onset (outside of trauma/injury and even then!).

 

The whole "your numbers are fine for your age" is the biggest tragedy in today's medical world. 

 

Work with a naturopath or doctor who's up on research.  We looked at estrogen safety and the newest study on bioidenticals here.

 

Finally, let's start to zero in on the key pathways we can affect.

The serotonin pathways and fibromyalgia 

Serotonin is a master regulator of all human behavior.

 

This includes pain sensitivity, sleep, and mood.

 

The tie-in with fibromyalgia?

 

Newly diagnosed FM women have significantly low-serum serotonin levels 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116663/

 

Maybe most importantly, serotonin manages our stress response.  In fact, it's a stress response buffer that can exhaust.

 

Needless to say, this is important for fibromyalgia: 

In addition, all transmitter systems found to be altered in fibromyalgia influence the body's stress systems. 

https://www.hindawi.com/journals/prt/2012/741746/

 

Let's zero into the common symptoms of fibromyalgia.

 

First, pain and serotonin.

 

Let's look at increased (or hyperactive) somatic awareness.

 

Simply put, this means feeling too much of what you're feeling inside your body.

 

Sound pertinent to fibromyalgia?

 

Serotonin is the barometer for this "threshold": 

Low levels of the chemical have already been linked to psychological issues, such as depression, and physical problems, involving fatigue, nausea, and digestion. There is now a case for associating the deficiency with heightened somatic awareness. 

https://www.medicalnewstoday.com/articles/325576#Treating-somatic-symptoms

 

Pain is the extreme of this.  

 

As we mentioned above, estrogen directly drives serotonin and women make up the vast majority of cases!

 

Those reviews actually tracked genetic differences which matched variants in serotonin processing genes and this state of heightened somatic awareness.

 

We also just linked fatigue, nausea, depression, and gut issues.

 

Let's dive into those quickly.

 

Interestingly, serotonin is a direct modulator (manager) of dopamine.

 

Dopamine is our ambition and reward pathway.

 

Do you know those days when you just feel like getting everything done?  

 

Hello dopamine (with a little acetylcholine and adrenaline for a kicker).

 

The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357260/

 

Too much or too little dopamine can result in fatigue.

 

As for the gut, fibromyalgia is starting to be viewed as a metabolic disease (isn't everything these days).

 

Sugar (fructose) blocks the absorption of tryptophan in the gut which is the only source of serotonin.

 

Reduction of sugar and carbs can directly impact this loop.

 

Studies with rats found that a keto diet (reduced carbs/sugar) directly reduced pain sensitivity: 

Feeding with a ketogenic diet increased the latency to show behavioral indications of pain, i.e. it produced hypoalgesia to thermal pain. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124736/

 

Hypoalgesia is a reduced feeling of pain.

 

Check out CBD and pain.

 

As for depression and mood in general, serotonin is a master player there.

 

We'll leave the heavy lifting to our CBD and depression review but the star of the show is actually BDNF.

 

BDNF is our brain's fertilizer and it's tasked with replenishing, rebuilding, and repairing the brain material and networks.

 

Finally, remember that early trauma can downregulate serotonin later in life: 

following LH/MS, 5-HT-deficient animals had significantly less mRNA expression of the mineralocorticoid receptor in the amygdala than wild-type animals.  

https://pubmed.ncbi.nlm.nih.gov/25602134/

 

LH is learned helplessness and MS is maternal separation. Both early in life.

 

The result of this early trauma was reduced serotonin especially in key areas of the brain that govern mood and stress response.

 

The issue with SSRIs (which boost serotonin) is that they build tolerance which leaves you worse off than when you started.  See CBD versus SSRIs or how SSRIs actually work.

 

Another result of early stress is reduced GABA.

 

Let's go there now.

The GABA pathway and fibromyalgia 

GABA deficiency is intimately tied to issues around sleep, anxiety/depression, and pain.

 

What about fibromyalgia?

 

GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374930/

 

Remember the tie-in with stress and fibromyalgia onset or symptoms?

 

Stress eats up GABA through its primary player, cortisol (see CBD and stress).

 

Same thing with serotonin by the way.

 

That part of the brain mentioned above is interesting: 

Within the right posterior insula, higher levels of GABA were positively correlated with pressure–pain thresholds in the FM patients 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374930/

 

GABA is basically a backstop for pain threshold both systemically (brain/spinal cord) and peripherally (individual nerves that sense pain in the body).

 

It's also the primary supporter of sleep (see CBD versus benzos or CBD and GABA).

 

There's a slew of research on calming glutamate (the opposite of GABA) for pain including regional pain syndromes.

 

This is the whole premise behind ketamine (which builds tolerance)...give a break to glutamate activity so nerves can recuperate.

 

Serotonin and GABA are master regulators...let's drill one level down.

The TRPV pathway 

Spicy peppers.

 

The "pain" associated with these hot edibles is from a substance called capsaicin.  It directly stimulates TRPV receptors which creates the feeling of pain.

 

Inflammation can also trip this wire and the pathway coming into focus with fibromyalgia: 

Transient receptor potential V1 (TRPV1), which is reported as a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of fibromyalgia pain. 

https://cmjournal.biomedcentral.com/articles/10.1186/s13020-021-00451-0

 

Electroacupuncture partially benefits people with fibromyalgia by reducing activity via TRPV.

 

In fact, removal of the TPRV gene and/or acupuncture both reduced pain sensitivity in the same manner.

 

EA and Trpv1 deletion reduced the cold stress-induced increase in inflammatory mediators and TRPV1-related molecules in the hypothalamus, periaqueductal gray (PAG), and cerebellum of mice. 

https://cmjournal.biomedcentral.com/articles/10.1186/s13020-021-00451-0

 

This breaks the immune system's pain loop.

 

Okay...so why go into all this?

 

Because these are pathways we can directly affect without tolerance or addiction.

 

Let's finally go there.

Research on CBD and the pathways of fibromyalgia 

CBD is a substance that directly supports our endocannabinoid system.

 

That system is about 600 million years old and we share it with all animals.

 

Heavily conserved so very important.

 

It basically balances other key systems: 

  • Immune system - inflammation and cellular birth/death cycles
  • Nervous system -including neurotransmitters like GABA and serotonin
  • Endocrine system - hormones including cortisol (stress) and steroidal hormones

 

Interestingly, TRPV is thought to be an endocannabinoid pathway more directly.

 

Clearly, this system is outgunned with fibromyalgia so what's going on there?

 

shop and compare isolate cbd online

 

Before jumping into CBD, let's introduce its cousin that does a lot of heavy lifting in your body right now.

 

Anandamide- one of the 2 primary players named after the Hindu goddess of bliss, Anand.

 

A study looked at pain after exercise between people with fibromyalgia and a control group.

 

A strong positive correlation existed between anandamide and glutamate in the control group post exercise but not in the chronic pain group. Moreover, the glutamate/anandamide ratio increased significantly in the control group and differed significantly with the chronic pain group post exercise.  

https://journals.sagepub.com/doi/full/10.1177/1744806919898360

 

Essentially, in people with fibromyalgia, after stress, glutamate shot up (remember...this hammers GABA) and anandamide increased to try to right the ship.

 

This points to reduced GABA function as we mentioned above.

 

Check out our review on endocannabinoid deficiency and migraines, IBS, and fibromyalgia all share this trait.

 

statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder 

https://www.liebertpub.com/doi/pdfplus/10.1089/can.2016.0009

 

Too little (or exhausted) anandamide function.

 

Notice the PTSD effect.  This makes sense...anandamide has to try to make up for lost serotonin and GABA function.

 

Okay...let's finally get to CBD.

 

We'll break it up into these categories: 

  • CBD and inflammation
  • CBD and pain
  • CBD and serotonin
  • CBD and GABA
  • CBD and TRPV
  • CBD and anandamide
  • CBD and fibromyalgia studies

 

Let's get started.  We have giant reviews on each topic so we'll hit the highlights here.

 


CBD and inflammation

 

Remember that there's a chronic inflammatory state tied to fibromyalgia.

 

The immune system can get complicated so let's zero in on a few key players: 

The most studied inflammatory markers in FM patients are IL-6, IL-8, IL-1β, TNF-α. 

https://www.sciencedirect.com/science/article/abs/pii/S0165572817302849

 

CBD is a powerful anti-inflammatory depending on the state of the system.

 

A study of asthma (increased inflammatory state) points to CBD's effects: 

The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458548/

 

That's IL6, TNF-A.  What about IL8?

 

Let's look at a study on rheumatoid arthritis: 

CBD increases intracellular calcium levels, reduces cell viability, and IL-6/IL-8/MMP-3 production of RASF by activating TRPA1 and mitochondrial targets 

https://www.nature.com/articles/s41419-020-02892-1

 

See CBD and autoimmune or CBD and rheumatoid arthritis.

 

Okay...and IL-1B?

 

From a study on dementia: 

Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression 

https://pubmed.ncbi.nlm.nih.gov/17592514/

 

See CBD and dementia.

 

All hyperinflammatory states.  

 

Here's where it gets interesting.

 

We don't want to just suppress inflammation in one direction (hence the long list of nasty side effects from autoimmune medications).

 

That's the beauty of CBD (the endocannabinoid system really).

 

The effect depends on the state of the system!

 

For example, the immune governs cancer cell removal: 

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

 

Read that back over.  3 different responses from the 3 different states.

 

The last one makes sense once you understand that our immune system's natural way to weed out bad cells is to kill them off with inflammation.

 

Oxidative stress technically.  Chemo and radiation are massive doses of oxidative stress.

 

Okay...what about pain?

CBD and pain 

We have a huge review on CBD and pain.

 

Also, check out CBD versus Tylenol to learn more.

 

For fibromyalgia pain directly: 

many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. 

https://pubmed.ncbi.nlm.nih.gov/33004171/

 

Some of the studies look at CBD while others look at cannabis.

 

One note...THC mimics anandamide but it causes tolerance which leaves you worse off than when you started with repeated use.  See CBD versus THC.

 

CBD supports anandamide when low!  More on that below.

 

As an example with CBD: 

It is thought to have significant analgesic, anti-inflammatory, anti-convulsant and anxiolytic activities without the psychoactive effect of THC 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277878/

 

Analgesic is pain-reducing.

 

The key there is "without the psychoactive effect" which speaks to how THC hits the anandamide receptor (CB1) too hard and thus causes tolerance.

 

In fact: 

The U-M team found that more than 70% of people with fibromyalgia who used CBD substituted CBD for opioids or other pain medications. Of these participants, many reported that they either decreased use or stopped taking opioids and other pain medications as a result. 

https://labblog.uofmhealth.org/body-work/people-fibromyalgia-substituting-cbd-for-opioids-to-manage-pain

 

Goodness.  CBD also supports the opioid system in our body without building tolerance or causing addiction (see CBD for opioid addiction).

 

In terms of NSAIDs (Motrin, Celebrex, etc), there are huge differences in the risk profile between CBD and this class of drugs around gut and heart health longer term.  See CBD versus NSAIDs.

 

Let's go upstream to see what's partially driving this effect on pain.

CBD and serotonin 

As we mentioned many times above, serotonin is a key player with fibromyalgia.

 

It directly touches on all the major symptoms of the illness.

 

Serotonin is also very tricky to work with since it's tied into every system of our behavior and too little is just as bad as too much (see serotonin syndrome).

 

SSRIs are a common recommendation but SSRIs also build tolerance because the body doesn't like when serotonin is boosted in one direction.

 

It's technically called serotonin withdrawal syndrome - not classical addiction but it doesn't feel much better (we can attest).

 

Reminds you of the special label given to Perdue pharma for oxycontin.

 

Anyway, that's the beauty of CBD.

 

CBD is an allosteric positive modulator for serotonin.

 

This means that it works like a feedback mechanism when serotonin is running low.

 

We don't see serotonin syndrome even at very high doses up to 1500mg!

 

It supports serotonin when low and no study explains this better especially in light of fibromyalgia.

 

Rats were given a severe, chronic injury that depleted their serotonin and as a result, caused anxiety and inflammation.

 

Remember that serotonin is our pain threshold so chronic or acute pain can exhaust it.

 

CBD's effect: 

Overall, 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/

 

  • CBD reduced pain threshold (analgesia)
  • CBD reduced anxiety
  • CBD "rescued" serotonin (5-HT)

 

This was under neuropathic pain...systemwide (brain/spinal cord) pain elevation.

 

Any of this sound familiar?

 

There's that TRPV pathways we noted above.  We have a whole review on CBD and serotonin here.

 

Let's turn to GABA.

CBD and GABA 

GABA is critical to calm our nervous system (stress, inflammation, pain, etc) with fibromyalgia.

 

CBD also works as an allosteric positive modulator for this pathway!

 

Supports when low.

 

This is key to CBD's effect on sleep, anxiety, and a host of mental health issues.

 

See CBD and GABA for more.

 

For fibromyalgia, you see a class of GABA boosting meds being replaced by CBD successfully: 

The majority (n = 632, 72.0%) reported substituting CBD products for medications, most commonly NSAIDs (59.0%), opioids (53.3%), gabapentanoids (35.0%), and benzodiazepines (23.1%). Most substituting participants reported decreasing or stopping use of these pain medications. 

https://pubmed.ncbi.nlm.nih.gov/33992787/

 

Gabapentanoids are synthetic versions of GABA (side effects and tolerances - see CBD versus gabapentin).

 

Benzos - directly boosts GABA which huge risk of addiction and tolerance.  (see CBD versus benzos).  These are Xanax, Valium, Ativan, etc.

 

Don't get us started on these...the research is pretty conclusive on their risks.

 

So about 1/3rd of the patients are some class that boosts GABA.

 

Again, this is the whole premise behind Ketamine (which can be toxic to nerves longer term).

 

So...what about CBD and GABA?

 

First, CB1 and CB2 (our endocannabinoid receptors) are all over GABA and glutamate pathways: 

The analgesic effects of cannabinoids and their ligands are primarily mediated by the CB1 receptor via inhibition of presynaptic gamma-aminobutyric acid (GABA) and glutamatergic transmission, which suppresses neuronal excitability 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451533/

 

Essentially, the pain effects of CBD are partially about calming activity in nerves which are hyperactive in situations of pain.

 

The balance between GABA and glutamate.

 

Since CBD doesn't directly drive GABA in one direction like benzos or barbituates (or alcohol), we don't see the slippery slow of system slow down: 

  • Calm
  • Sedated
  • Hypnotic
  • Amnesiatic
  • Dead!

 

CBD stops somewhere between calm and sedated depending on the sleep/wake cycle (see - can I take CBD in the middle of the day).

 

Neuropathic pain - pain that resides in the transmission lines rather than at a specific area is even more suited to this approach.

 

Let's turn to that TRPV pain pathway.

CBD and TRPV 

We mentioned the TRPV pathway as a key one with links to fibromyalgia...primarily as a result of inflammatory states.

 

Let's cut to the chase: 

Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1575333/

 

To translate (please!!!), CBD's effect on TRPV is key to calming a hyper-pain scenario in the body following inflammation.

 

Goodness.  We can drop the mic there.

 

In a study of Parkinson's, CBD had this same effect: 

The CBD treatment decreases hyperalgesia and allodynia in experimental parkinsonism. 

https://www.sciencedirect.com/science/article/abs/pii/S0028390819303703

 

Hyperalgesia is a heightened pain response (hmmm).
And allodynia??

 

Allodynia is a type of neuropathic pain (nerve pain). People with allodynia are extremely sensitive to touch. Things that don't usually cause pain can be very painful. 

https://my.clevelandclinic.org/health/symptoms/21570-allodynia

 

Again, right up our fibromyalgia alley!

 

CBD calms this pathway directly.

 

A note from that study leads us to our next section: 

FAAH inhibitor or TRPV1 antagonist potentiates the CBD antinociceptive effect.

 

Ahhh...FAAH.  

 

Let's go there now!

CBD and anandamide 

Along many pathways, anandamide is the backup reserve.

 

Stress.  Inflammation.  Pain.  All signs that many key pathways are out of balance.

 

This is fine for short periods of time but chronic imbalance leads to disease and damage.

 

The endocannabinoid system is tasked with righting the ship and anandamide is one of the key players there.

 

Check out our review on endocannabinoid deficiency. Endo just means our own internal cannabinoids...not the ones from the cannabis plant.

 

THC directly mimics anandamide but it stays too long and too strong which leads to tolerance among its other "effects".

 

Can we get the benefits of supporting anandamide (which is outgunned with fibromyalgia) without the tolerance and side effects?

 

Hello CBD!

 

FAAH (from above with fibromyalgia) can be slowed down so more anandamide can flow.

 

In fact, we did a big study on a woman who has no FAAH and therefore, no pain, anxiety, depression, etc.

 

Zero.  It's a rare mutation since you need pain for survival (touching a hot pan, etc).

 

But...we can slow down FAAH so there's more anandamide reserve.

 

This is where CBD comes in.  Check out one of many studies (since anandamide plays in so many different pathways) on schizophrenia: 

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

https://www.nature.com/articles/tp201215

 

And how did it do this?

 

We confirmed this result showing that cannabidiol inhibits FAAH in rat brain membranes with a median effective concentration of 8.6±0.2 μM (n=12). We further found that cannabidiol, at a concentration that reduces FAAH activity by ∼50%

 

Okay!  Let more anandamide balance...in this case, dopamine levels in different parts of the brain (too low in the prefrontal cortex and too high in the striatum).

 

We did a huge review of CBD and schizophrenia or CBD and mental health since anandamide is tied into all of every issue.

 

Let's look at direct studies.

CBD and fibromyalgia studies 

After everything you just read, you would think we would have major trials on CBD for fibromyalgia...especially with the study showing the percentage of people with FB drop their opioids after using CBD.

 

Unfortunately, trials cost many millions and there's no big pharma company to can profit from CBD, a natural substance.

 

There's a large placebo, the double-blind trial is finally underway (started 2020) so we'll have to wait for those results.

 

There's more research on cannabis: 

many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. 

https://pubmed.ncbi.nlm.nih.gov/33004171/

 

Cannabis has two major elements: THC and CBD.

 

THC mimics anandamide but too much. CBD supports anandamide when low (hence, no tolerance).

 

We can extrapolate from those cannabis studies a positive result for CBD by itself, especially in light of the studies on specific attributes/symptoms (pain, sleep, inflammation, etc).

 

As for these studies and FB pain: 

Pain intensity (scale 0–10) reduced from a median of 9.0 at baseline to 5.0 (p < 0.001), and 194 patients (81.1%) achieved treatment response. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616435/

 

There is a large-scale phone study on CBD itself and fibromyalgia. The results: 

Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. 

https://pubmed.ncbi.nlm.nih.gov/33400996/

 

One note...there's a great deal of mis or poor information on dosage with CBD.

 

Studies point to 300 mg as peak levels for neurogenesis (brain/nerve repair). Many products on the market might have 300 mg in the full bottle!

 

We'll get into that below as well as the type of CBD (very important).

 

Another cannabis study: 

However, after the intervention, the cannabis group presented a significant decrease in FIQ score in comparison with the placebo group (P = 0.005) and in comparison with cannabis group baseline score 

https://pubmed.ncbi.nlm.nih.gov/33118602/

 

FIQ is a standard fibromyalgia test.

 

We can't stress this enough...THC will build tolerance with longer-term use.

 

The body will literally reduce the number and sensitivity of CB1 receptors (where THC and anandamide plug into) over time.

 

This means LESS anandamide function….the opposite direction we want to go.

 

CBD does not build tolerance, is not habit-forming, and not psychoactive.

 

We do not see the side effect profile with CBD that THC (or other meds like SSRIs have).

 

Even at higher doses (600-800mg).

 

Speaking of doses.

How much CBD to take for fibromyalgia 

We don't have specific research (yet) on dosages for fibromyalgia.

 

So let's walk through the range first.

 

A test or wellness dose is generally 30-50 mg daily.  That's a full dropper at 1000 mg bottle level roughly.

 

Sleep studies came in around 160mg daily.

 

Neurogenesis peaks at 300mg daily.  This is critical to brain and nerve function/repair.  See CBD and brain repair here.

 

Remember, part of fibromyalgia is a nervous system inflammatory state.

 

More serious issues (opioid withdrawal, schizophrenia, public speaking anxiety, etc) all were from 600-800mg daily.

 

That's a high dose.

 

What we've seen for people who are weaning off of benzos (very difficult withdrawals) is an initial period of 600mg daily for 10 days and then 300mg from day 10-30 while adjusting afterwards as needed.

 

Always go slow and adjust according to how you feel.  Everyone's system is different.

 

The impact on serotonin generally takes about 14 days to kick in (just like SSRIs).

 

GABA and inflammation will be more immediate.

 

Other tools to investigate: 

  • Magnesium glycinate
  • Vitamin D
  • PEA
  • Steroidal hormones

 

Mag is a fantastic supporter of GABA and calming agent across multiple pathways.  Remember how migraines are comorbid (tends to jointly affect) with fibromyalgia.

 

30% shared overlap.

 

Magnesium glycinate is a powerhouse for migraines...especially with aura (see mag and migraines).

 

The net net: 

Magnesium deficiency has been largely associated with muscle pain along with fatigue, sleep difficulties, and anxiety; all of which are common symptoms of fibromyalgia.  

https://journals.sagepub.com/doi/full/10.1177/21501327211038433

 

Vitamin D is a major player in the immune system, sleep, and more.

 

A large meta-study: 

Our meta-analysis showed that vitamin D serum levels of patients with fibromyalgia was significantly lower than that of control group. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665736/

 

All the pieces fit when you look at what Vitamin D deficiency does.

 

Get tested...and try to get levels up to 70-80 ng/ml (based on what endocrinologists say).

 

So...what's PEA?

 

It's actually a backup, backup endocannabinoid.

 

It supports anandamide!

 

So...what about studies with PEA and fibromyalgia: 

Regarding efficacy, in the 359 analyzed patients, the change over time in Visual Analogue Scale pain score was statistically significant, ranging from 75.84 (±15.15) to 52.49 (±16.73) (p<0.001). Regarding quality of life, the change over time in Fibromyalgia Impact Questionnaire score was statistically significant, ranging from 68.4 (±14.1) to 49.1 (±19.6) (p<0.001). 

https://www.ingentaconnect.com/content/ben/cnsnddt/2019/00000018/00000004/art00009;jsessionid=7nf3vqiu65o04.x-ic-live-01

 

That's a large drop for pain and general symptom scores.

 

We highlighted these three with CBD because they're all very safe and don't build tolerance which is such an issue with many current options (SSRIs, NSAIDs, synthetic GABAs, benzos, etc).

 

You need to test your Vitamin D but so many people are deficient in the general population, not to mention the population with fibromyalgia.

 

Finally, the gender risk factor that compounds with age.

 

Progesterone is front and center.  It drops by 50% by age 40 and continues down from there.

 

Get your levels checked.  Progesterone is a master regulator of sleep (via GABA) and the immune system.  It calms it down...hence the concurrent increase in auto-immune for women starting in their 40's.

 

Estrogen is also involved in the repair, replenishment, and growth needed throughout every pathway of a woman's body.

 

It's also a direct booster of serotonin!   A key player with fibromyalgia.

 

Perimenopause (the transition to menopause) is all about estrogen leaving the scene (see why some women are hit so hard by perimenopause).

 

The clue with fibromyalgia??:

 

FM women with early age-of-onset of menopause displayed greater pain and non-pain sensitivity than FM women with late age-of-onset of menopause, whereas no differences were observed in healthy women due to age-of-onset of menopause.  

http://www.chialvo.net/chialvo.net/Publications_files/FribroMercedes2013.pdf

 

Estrogen!!   

 

Bioidentical progesterone and estradiol only according to newer research (see Bijuva studies or my estrogen journey).

 

Alright...what type of CBD? 

What's the best CBD for fibromyalgia 

First, there are basic requirements: 

  • From organically grown US hemp at an FDA registered farm
  • CO2 cold-processed
  • 3rd party tested
  • No THC (builds tolerance)
  • No Pesticides
  • No Heavy Metals
  • No Mold
  • No Bacteria

 

Our testing is available at the top of every page.

 

The next big question of which there is so much misinformation revolves around full spectrum versus CBD isolate.

 

All the research above (except for the cannabis piece) is based on CBD by itself.

 

Isolate.  

 

The issue with full-spectrum aside from the small levels of THC is that of histamine.

 

Many people have bad reactions to CBD and this is down to either bad product (above requirements) or histamine response to the plant material and full-spectrum mix.

 

40-60% of the population has histamine issues and those numbers go up for women (hint hint) and as we get older (thanks for leaving progesterone).

 

Histamine (key to allergic response) is part of the immune system.  It's a type of inflammation.

 

For example, it's known that patients with fibromyalgia have more difficulty controlling asthma than those without FB.

 

The last thing we want to do is introduce a substance that triggers this response.

 

Histamine is also excitatory in the nervous system...the opposite direction we're trying to go (we want more GABA, not less).

 

Histamine also figures into the sleep architecture (on the wake side) as well.

 

In fact, histamine may directly tie into ramping up the pain-sensing area in the brain: 

As a result, inhibiting mast cell stimulation could be used as a novel approach for reducing pain and the symptoms of FMS. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687840/

 

Mast cells are where histamine comes from.  CBD isolates calms mast cell release (see CBD and mast cells).

 

CBD isolate matches the research.  Full-spectrum doesn't and you're likely to notice a very different response between the two.  Don't take our word (or research) for it….test like we originally did.

 

Finally, there's cost.

 

The key metric is the cost per mg of CBD.  Our 6000 mg bottles are priced at 2-3 cents per mg of CBD before discounts up to 50% (referral, subscriptions, etc).

 

The other big issue is product levels not matching what research is showing.  A bottle with 250mg total is basically really expensive oil.

 

Our 6000 mg bottle is 200mg per dropper (30 droppers).  This is matching the test level (50mg) to the more serious intervention (600mg) with 300 mg for neurogenesis right in the middle.

 

Thanks for staying with us.  We did this deep dive for a person who enquired directly but CBD could be a powerful tool that doesn't build tolerance or addiction and hits multiple pathways tied to fibromyalgia so it's worth it.

 

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

 

shop cbd isolate oil online 

 

Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

 

 

 

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