CBD Research - How CBD Works
HOW DOES CBD WORK FOR BIPOLAR?
It's not a small deal.
Just under 6 million people in the US alone will experience a bipolar episode.
That's almost 3% of the total population.
Just one person matters if it's you or a loved one.
Before we get into the endocannabinoid system and CBD, let's look at all the new and different research on what is going on.
Yes, we know that neurotransmitters are lurking there.
But bodies and brains are complicated.
- Why are people with bipolar 3 1/2 times more likely to have migraines?
- Why do inflammatory markers spike during episodes?
- How can the level of certain hormones predict episodes 3 days prior?
- Why are women 22 times more likely to be diagnosed after pregnancy?
We'll get into it.
What about the role for bipolar with:
- Hormones
- Inflammation
- Genetics
- Preservatives and Chemicals
- Gut bacteria
- Histamine response
- Neurogenesis
As we said, this isn't your father's bipolar article.
If you've studied 100's of NIH articles for various different issues (some correlated with bipolar), the same suspects keep coming up.
We'll get an overview of where the research is and then we'll dive into CBD and its stage, the endocannabinoid system.
You can jump right to the best CBD for bipolar here:
Otherwise, feel free to jump to any of these sections:
- A quick overview of modern research on bipolar
- Neurotransmitters and bipolar
- Hormones and bipolar
- Inflammation and bipolar
- The Gut, probiotics, and bipolar
- Methylation and bipolar
- Preservatives and chemical's effect on bipolar
- Histamine response and bipolar
- Mitochondria, Neurogenesis and bipolar
- The endocannabinoid system and bipolar
- How does CBD work with bipolar
- The best CBD for bipolar support
- How much CBD to take for bipolar
Let's jump into it!
A Quick Overview Of Modern Research On Bipolar
The top 10 sites with a google search for bipolar give a pretty good and traditional overview of the symptoms, mechanics, and triggers for bipolar.
Consequently, they tend to be a bit staid in their treatment of it.
There's lots of new research especially on the triggers, genetics, and unique correlations with bi-polar.
We're in a unique period where illnesses that didn't change much for 50 years are seeing updates weekly.
Big and unexpected ones!
The first thing you start to notice after reading 100's of these studies is this...
The body and brain are complicated webs of interconnected pathways.
Hormones. Neurotransmitter. Immune response (the new kid on the block). Genetics. Environment.
They all interplay!
Let's look at how this works with bi-polar.
We'll follow the researcher's understanding of the disease from early on to recent.
Neurotransmitters Were The First Targets
Researchers found rather early on the dysregulation of neurotransmitters (serotonin, norepinephrine, dopamine, glutamate, and others).
Rather than get bogged down in the chemistry, these pathways (among others) govern:
- Appetite
- Mood
- Libido
- Energy
- Sleep
- Emotion
All are hallmarks of bi-polar symptoms (swings too high and too low).
So neurotransmitters are the levers at work in the swings!
Many of the suspected genes are pointing to the sensitivity and function of these different neurotransmitters.
Of course, these chemicals don't operate in a vacuum and that's where the new research gets interesting.
Rather than using a hammer on a given neurotransmitter (SSRIs, lithium), let's look at the downstream causes and triggers before we look at the endocannabinoid system and CBD specifically (exciting research there).
We'll start with the common dance partners for neurotransmitters (if not the music itself)...hormones.
Hormones And Bipolar
Look at the possible areas that can swing above.
- Appetite. Governed by hormones
- Libido. Hormones
- Sleep. Hormones partially
- Mood. Heavily influenced by hormones
- Energy. Hormone
Okay, we get the point.
For a subset of people (especially women), bi-polar might just be a case of really drastic hormonal swings.
This is a smaller subset for men but some men's body aggressively turns testosterone into estrogen!
More detail here:
To rule either out, go get a Dutch test or the equivalent.
Dutch is the gold standard to see how your body actually metabolizes hormones.
This is mandatory for women age 40 and older!
View Dre's Story on Perimenopause here to see how that can go badly.
Men also need this test to make sure testosterone is adequate and is metabolizing the right way.
Just a head's up...your general doctor and even many OBGyn's will have no idea what you're talking about.
That could be a sign!
Get the Dutch test (or equivalent) and rule out hormones first.
This is especially true for rapidly cycling bipolar episodes.
That's a clue!
They even found that blood levels of certain hormones could predict mania and depressive periods 3 days prior to the event!
A further feather in the hormone imbalance as culprit cap is the curious tie with traditional periods of hormone imbalance.
Such as pregnancy:
women diagnosed with bipolar disorder are more than 23 times more likely to be admitted for reasons related to their bipolar disorder (e.g. depression, mania, etc.) during the first month after childbirth than during their actual pregnancy.
The above article is an awesome resource to try and tease out whether hormones are significant in a given case!
There is also the link between PMS, monthly cycle, and worsening bipolar symptoms:
22 to 77 percent of women with bipolar disorder met the criteria for premenstrual dysphoria, and 15 to 27 percent met the criteria for premenstrual dysphoric disorder (PMDD).
Think of three levels of orchestration:
- The neurotransmitters are at the bottom and they cause the immediate effect (the foot soldier)
- The hormones reside above and help to govern their balance and interaction (the commander)
- The endocannabinoid sits above both and tries to balance them (the general)
We'll look at that later but the keyword for bipolar is....balance!!
Now, on to the new rising star in bipolar potential!
Inflammation And Bipolar
Mark our words.
All roads in the future of medical leads to Rome.
Rome is the Immune system.
It's popping up in the most unpredicted places:
- Blood pressure
- Dementia
- Diabetes
- Autoimmune diseases
And Bipolar.
First, go get the book The Inflamed Brain by Edward Buller.
Must read for bi-polar (and really anyone with a brain...literally).
The first clue was when inflammatory markers were shown to be elevated in people with Bipolar.
Just read the list of triggers here:
What do they all have in common?
Acute or chronic STRESS.
What's our body's reaction to stress?
Inflammation and immune response.
If your skin is stressed (by infection, injury, allergies, etc) the effects are obvious.
Redness. Inflamed. Swelling. Etc.
But what if your nervous system or the brain itself is stressed?
What's the symptom?
The new theory is that many of our psychiatric issues are inflammation of the brain and central nervous system PLUS the immunes response to said inflammation!
Take one of the most common triggers for bipolar...disruption in sleep.
A recent study showed that lack of sleep looks just like acute anxiety in the brain under scans.
The inflammatory response raises significantly in the brain as a result.
Studies show that inflammatory agents in the brain cross the blood-brain barriers:
Inflammation has also been found to play a major role in glutamatergic neurotransmission involved in mood regulation in depression and bipolar disorder.4-6
This triggers an imbalance that goes to the heart of both manic and depressive episodes:
Imbalances in the metabolites of kynurenine which serve as either N-methyl-D aspartate agonists or antagonists and decreased serotonin production, in turn, may contribute to the onset of manic and depressive symptoms.
This is very intriguing since both swings are affected!
The balancing system itself rather than just one neurotransmitter.
New research is pointing to the systems that the brain and central nervous system use to remove toxins from cells:
correlations representative for the activity of cytotoxic pathways in monoamine metabolism were more pronounced in patients.
This just means that the immune response in the brain affected neurotransmitters (like serotonin) directly.
You can learn all about CBD and Inflammation here.
As we mentioned...all roads lead to the immune system and that's located smack in the gut!
That's our next logical stop from inflammation.
Gut Bacteria, Probiotics, And Bipolar
The most exciting and surprising studies these days deal not with our bodies but the trillions of bacteria that live in and on them.
The gut bacteria are the most intriguing.
80% of your serotonin is made in the gut, not the brain!
Serotonin is a key component of bipolar disease.
Furthermore, there's a complex communication system between the brain and gut (often referred to as the second brain).
For example, the presence H Pylori (often suspected for ulcers) increases mood disorders including depression:
We found that H pylori seropositivity was associated with 2.5 times higher odds of dysthymia among women
Dysthymia is a fancy word for a depressive episode.
The quantity and type of bacteria in the gut can have a direct effect on bipolar disease (initialed as BP):
Decreased diversity of certain gut bacteria have been linked to ASD, BPD, depression, and chronic fatigue syndrome.
The real intrigue started when researchers looked at the results of antibiotics on bipolar symptoms.
In the study population, 7.7% of the patients with acute mania were found to be prescribed antibiotics.
That was 7 times the level of people who did not display bipolar symptoms!
There's the other side of the coin.
Probiotics (supplement healthy strains of gut bacteria) were found to affect symptoms of bipolar:
During that time, 50% of the patients required rehospitalization, but the rate was lower �by a factor of 3 in the probiotic group. A similar reduction was seen in the duration of hospital stays for patients who were given the probiotic.
The microbiome really is one of the new frontiers in medicine.
You can check out your own inner-world at viome now.
It's very exciting now on this front.
They are even studies now on gut bacteria transplants.
Stayed tuned on that front.
Methylation, MTHFR, MTRR, And Bipolar
Most people have never heard of methylation.
Sounds a little above our pay grade.
It shouldn't be!
It's estimated that roughly 40% of the US population has a mutation in MTHFR or MTRR where they properly use Vitamin B12 and Folate (not folic acid).
Your local Whole Foods or Pharmaca will have many brands of "methylated" B vitamins now.
There's a direct tie between MTHFR and bipolar:
evidence for diagnostic moderation indicating a significant association with BPD
MTRR is for folate:
Bipolar subjects and relatives with TT and/or AA and AC genotypes had elevated homocysteine, reduced folate and B12 levels
This is a simple fix.
Just supplement with methylated B12 and Folate!
It's very common now as people start to realize how important it is!
Remember the whole gut biome connection with bipolar above?
Let's find out how we're wrecking that whole system.
Preservatives And Chemical Affect Of Bipolar
We'll jump right into it.
Nitrates used to process meats and other foods have been linked to manic episodes:
people hospitalized for an episode of mania had more than three times the odds of having ever eaten nitrate-cured meats than people without a history of a serious psychiatric disorder.
Okay, but can they show that nitrates cause the mania episode?
Experiments in rats by the same researchers showed mania-like hyperactivity after just a few weeks on diets with added nitrates.
Additives, preservatives, and pesticides affect change via the gut biome primarily.
It shows you just how powerful that ecosystem is to your wellbeing!
Check out CBD and the gut more intriguing stories.
To see just how new this line of research is, look at this brand new study:
Two types of bacteria, Coprococcus and Dialister, are depleted in people with depression
We are finally getting good research on all these chemicals and how they affect our health.
Histamine Response And Bipolar
We've covered histamines extensively since they are popping up in research on many issues.
Simply put, histamines are tasked with removing unwanted entities from the body.
The problem is that we're swimming in unwanted chemicals in our modern world.
This system is overworked, over-stressed, and over-responding.
Histamine is also the hormone responsible for arousal, energy, and alertness in the brain!
It controls the wake/sleep cycle which is a major issue for bipolar.
New research is pointing to the histamine pathway in bipolar disease:
the histamine system is likely to be involved in the pathophysiology of several psychiatric diseases such as BD
The article looks at fatty acid ratios in the brain as a potential pathway to this histamine connection.
There's a good analysis of the different "types" of bipolar here including histamine related types:
Finally, let's look at common medications for bipolar disorder like Seroquel.
Guess what their effect is on the histamine system...
They're anti-histamines!
You can learn all about CBD and Histamines here.
Mitochondria And Bipolar
If you don't know the term mitochondria, you may want to get up to speed.
Not only might they be the key to longevity but they're being targeted as a ROOT cause for bipolar and other neuropathic diseases.
for about 80% of the bipolar patients, hippocampal mitochondria were smaller than even the smallest of the control subjects mitochondria
We'll see below that the hippocampus is key to the bipolar progression so a powered down cell in that region could have a key role in the disease.
Okay...we've covered a lot. Let's finally get into why we're here.
Before we jump off to CBD's system, here's a great summary of different aspects of bipolar (must read):
We'll leave you with an overarching framework in which to view all this:
- Loss of neurons in key areas of the brain as a result of inflammation, stress, or genetics
- The resulting imbalance in neurotransmitters in these key areas
- Poor functioning of mitochondria (power your cells) may partially be a driver to all this
One more stop (we promise).
The Endocannabinoid System And Bipolar
The endocannabinoid system spans all animals and dates to about 600 million years old.
We all have one!
Research is showing it's tasked with balancing other key systems:
- Nervous system – neurotransmitters such as dopamine, serotonin, glutamate, and more
- Endocrine system – hormones such as estrogen
- Immune system – inflammation and immune agents such as histamine!
Okay, we just outlined all the key players in the bipolar disorder.
Here's a quick visual.
Let's now look at research...is there any relationship between bipolar and the endocannabinoid system at all?
First, there's an association between bipolar disease and specific gene variation:
That gene happens to be a CB receptor gene. CB stands for cannabinoid.
Their conclusion:
results suggest that the CB2 cannabinoid receptor may play a role in BD.
There are other genes that come into focus:
We want to get to CBD so we'll leave these links below for key systems tied to bipolar that are intimately linked to the endocannabinoid system.
- CBD and inflammation
- CBD and the gut biome
- CBD perimenopause (for hormone balancing)
- CBD and migraines (significant tie with bipolar)
- CBD and depression (1/2 the equation)
Here's the key point.
Very similar to migraines, bipolar appears to be a crescendo of imbalance that then radiates across other pathways.
Consequently, there is an exhaustion of the accelerated neurotransmitters, hormones, and the pendulum swings the other way.
This is very common in the brain (think of the crash after a sugar high).
The endocannabinoid system is tasked with balancing or homeostasis.
Since we took up so much time with the different aspects of bipolar disorder, we'll leave the additional reading above to you.
Let's look at CBD specifically!
How Does CBD Work With Bipolar
There are lots of anecdotal stories of CBD helping people with bipolar but the big studies that we like to see are in the process now.
Comprehensive studies on CBD and bipolar specifically are in the works.
They're due to be completed in 2020 at NIH and then we'll report on them.
While we're waiting, let's take a different tact.
Let's look at the current medications for bipolar and see how CBD mirrors their effects in the body (without the nasty side effects).
The common approach (with lots of side effects) for bipolar involves the following:
- Mood stabilizers like lithium
- Anti-psychotic medications
- Anti-convulsants
- Anti-depressants
Usually, it's a mix of the above and there is no one silver bullet.
Let's look at CBD's effect on each of these pathways since they are intimately tied to the progression of bipolar.
Mood Stabilizers Like Lithium Versus CBD
Mood stabilizers aim to balance neurotransmitters and/or hormones.
After all, they govern mood!
Common meds like lithium tend to hammer all mood so that the peaks are less pronounced.
Interestingly, most of the lithium's benefits appear to come from neurogenesis...the creation of new nerve growth.
Cellular stress and neuron death are long researched hallmarks of bipolar.
CBD has been shown to have a powerful effect on all these pathways including neurogenesis!
Let's take a quick detour to the hippocampus where this neurogenesis and cell protection occurs with CBD:
The loss or damage of brain cells in the hippocampus can contribute to mood disorders. The hippocampus is the part of the brain associated with memory. It also indirectly affects mood and impulses.
Umm...mood and impulses? Check!
Why is this specifically important for bipolar?
A new study found that a volume decrease in certain parts of the hippocampus, a brain region known for mood and memory processing, is linked to bipolar disorder.
It went on to say...
non-psychoactive cannabidiol (CBD), may also affect adult hippocampal neurogenesis. Repeated treatment with CBD for 15-days prevented amyloid-induced neurotoxicity via activation of the proliferator-activated receptor, suggesting a mechanism for CBD neuroprotective effects
In fact, CBD's calming effects on anxiety appear to be a result of anti-inflammation and neurogenesis:
anxiolytic effect of chronic CBD administration (14 days) in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signaling
Two birds with one stone!
You can learn all about neurogenesis and CBD here.
Remember, its likely stress and toxins that are causing the destruction of the neurons to begin with.
CBD is a powerful neuroprotective agent:
The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders.
Get the full story at our CBD and inflammation page here.
Anti-Psychotic Medications Versus CBD
This may be our favorite aspect of CBD.
It is showing powerful anti-psychotic effects on the brain with very little safety issues.
Common meds like Zyprexa and Seroquel are used to balance serotonin and dopamine.
Basically, the goal is to reduce the tendency for mania in the brain.
CBD has powerful effects on these symptoms.
Our favorite study deals with a study that showed CBD "reset" the brain and normalized activity (on scans) for people who were pre-psychotic:
the study's authors found that patients at high risk of psychosis had abnormally elevated activity in these regions compared to the control subjects. But one large dose of CBD 600 milligrams � quickly and significantly reduced the brain activity in those brain regions down to normal levels.
The three areas...hippocampus (mentioned above), the striatum (reward center), and mid temporal lobe.
That striatum piece is important for bi-polar:
Our finding of a link between bipolar disorder and the striatum at the molecular level complements studies that implicate the same brain region in bipolar disorder at the anatomical level, including functional imaging studies that show altered activity in the striatum of bipolar subjects during tasks that involve balancing reward and risk
CBD was shown to normalize levels in both the hippocampus and striatum which are directly tied to bi-polar!
This may single-handedly be the reason for all the anecdotal stories on CBD.
You can learn all about CBD and psychosis here or CBD neurogenesis here.
There's also the tie in for mitochondria (power plants in our cells) with more detail for CBD and mitochondria here.
Next up...
Anti-Convulsants Versus CBD
Anti-convulsants seem like a strange choice for bi-polar but they work to control hyperactivity in the brain and thus convey an anti-psychotic effect.
By the way, psychotic just means an imbalance in the neurotransmitters or activity of the brain.
CBD's potential was originally found AS an anti-convulsant.
In fact, it was originally discovered as a last resort for people with epilepsy.
The first FDA approved drug based on CBD is actually an anti-convulsant!
This goes to the heart of CBD's effect on our endocannabinoid system.
To strengthen it's balancing effect!
A study here shows it to not only be anti-convulsant but neuroprotective in children:
Inhibition of surviving PV+ and CB1+ interneurons may be facilitated by CBD implying a protective role in regulating hippocampal seizures and neurotoxicity at juvenile ages.:
This has huge potential for ADHD and Autism as well.
Finally...the depressive episodes.
Anti-Dipressants Versus CBD
This is a common course of treatment for bipolar disease.
The anti-depressant effect of CBD are well established and you can read up further at CBD and depression here.
The key takeaway is that CBD appears to balance serotonin levels in the brain:
Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).
Again, learn all about it (many examples and pathways) at the link above.
- We've looked at the different elements and pathways of bipolar.
- We've covered the main classes of bipolar treatments and how CBD works within the same pathways.
There are lots of studies on CBD directly with bipolar going on now.
Primarily because the side effects for all the medications listed above can be quite severe (as anyone with bipolar can attest).
One keynote...many medications use the same pathway as CBD in the liver so it's best to take CBD at least 2 hours away from other meds.
Preferably, after a fatty meal.
Always work with a doctor who will work WITH you of course.
We want to hear your results and story.
How much CBD should we look at for bipolar and what's the best type?
The Best CBD For Bipolar Support
A few important notes.
First, the general requirements we have for CBD:
- Grown in the US organically
- 3rd part tested
- Free of solvents, pesticides, bacteria, mold, heavy metals
- THC free
Secondly, we want CBD Isolate (just CBD with a base oil) as opposed to full spectrum.
For a few reasons.
- We want ZERO THC which can actually have negative effects on bipolar symptoms.
- We want to avoid allergy/histamine issues to the plant material
The research is all on CBD – we don't know how the other materials affect bipolar
- We want affordable CBD per mg of CBD so that we can actually use this approach.
- We want verifiable levels of CBD per bottle (some brands can be confusing on this matter)
The two brands that meet these requirements with the lowest cost per mg of CBD are:
We'll explain why the cost is so important below!
How Much CBD To Take For Bipolar
This is why the cost is important.
For the different aspects of bipolar that we went through above (mood-stabilizing, anti-psychotic, anti-depressant, etc), the research is looking at 300-600 mg of CBD doses.
Many of the big brands on the market with good CBD are charging way too much to get there!
If a 2000 mg bottle of CBD is $120, who can afford going through a bottle every 4 days!
Obviously, start low at about 25-30 mg of CBD to see how your body responds.
Make sure to check out the safety page and CBD dosage information for more detail.
Especially make sure to take at least 2 hours away from medications and work with your doctor with any supplement like CBD.
Most importantly, let us know your results. We'll publish so that people can share what works!
You can also find the best priced CBD oils for Bipolar here:
Let us know what works, at what dosage, and with what results.
Let's help others learn from your experience!