Research on How CBD Helps with Long Term Anxiety

cbd for long term anxiety


Yes, the studies showing immediate effects of CBD on anxiety symptoms are nice.

 

What about long term?

 

The goal is to not have symptoms at all?

 

Is there a benefit to CBD for the longer term picture?

 

Yes!

 

There's very interesting research on the mechanics behind long term anxiety.

 

It's also called "trait anxiety" and we've covered a great deal of the mechanism in our General Anxiety Disorder and CBD article.

 

We're not talking about the one-off feeling of anxiousness from speaking in front of a group of people or fear of taking a test.

 

We're going to dive deep into brain areas!

 

Don't worry, we'll explain along the way but long term anxiety is ingrained in the brain itself.

 

It's either the result of:

  • Injury, infection, or inflammation chronically or at specific times in development
  • Genetic variations that affect development and balance
  • Gut dysbiosis which creates a hostile workplace for the brain to be in

 

There are particular areas that are much more vulnerable to these effects and guess what...they are at the heart of the anxiety pathway.

 

You're going to get reacquainted with your hippocampus shortly.

 

We'll cover these various topics:

  • Where is long term anxiety in the brain?
  • What research shows as the drivers of long term anxiety
  • The vulnerable hippocampus and long term anxiety
  • Age's effect on long term anxiety
  • Genes and long term anxiety
  • How to repair brain areas tied to long term anxiety
  • CBD's benefits for dealing with long term anxiety
  • Best CBD for long term anxiety
  • How much CBD to take for long term anxiety

 

Lots to cover.  After-all, this is long term anxiety….not a one-night stand!

Where is long term anxiety in the brain?

Everyone feels anxiety at some point in their life.

 

Everyone aside for the few exceptions like the woman who can't feel pain or anxiety (see article here...fascinating).

 

Of course, those people are rare... mainly because it's so dangerous not to ever be able to feel pain or anxiety.

 

Survival becomes very difficult.

 

You need anxiety sometimes like when a threatening person approaches or a bus is careening towards you.

 

The issue we're looking at called "trait anxiety".

 

Anxiety that continues regardless of situation for days, months, years, and even lifetimes.

 

This is more an imbalance in our natural pathway of fear.

 

We've covered this pathway quite a bit in our CBD benefits for anxiety here but let's get a quick lay of the land.

 

At the brain area level, you have really have two different brains.

 

Yes, almost opposing voices.

 

The old "reptilian" brain areas tied to anxiety are generally comprised of the:

  • Amygdala - our fear and emotional processing center
  • Hippocampus - key to determining threats and initiating fear and stress responses

 

This is the very old part of our brain evolutionarily speaking and it reacts first and fast!

 

You wouldn't be around if this wasn't the case.

 

There's no time to rationally determine if that flutter in the bush is really a tiger.

 

You jump!

 

After this signal, the slow poke (and lazy) prefrontal cortex then gets the information.

 

This is your rational brain behind your forehead and is the new kid on the block.

 

Is that REALLY a tiger?  Turns out, it's a rabbit.

 

Stand down brain and body.  Drop the heart rate.  Relax the muscles.  

 

All clear here.

 

To say these are two separate brains in your head is not a leap of imagination.

 

Check out the book, Think Fast and Think Slow to get a better sense of it.

 

Between these two brain areas are relays and processors (like the Anterior Cingulate Cortex) which hope to bridge the gap between two very different operators.

 

A translator and communicator of sorts.

 

Now, long term anxiety can result: 

 

Now, we all have variation naturally here.

 

You could argue that a much more anxious person would fare better in a very dangerous environment (taking less risk, etc).

 

The bravest person in battle is also most likely to die first.

 

Secondarily in long term anxiety, you have neurotransmitters, the worker bees of the brain, that can be out of balance.

 

The main culprits (from a growing list) are: 

  • GABA - our brain's "brake"  and the target of benzodiazepines like Xanax, Valium, and Ativan (See CBD versus benzos here)
  • Serotonin - the workhorse of the brain and target of SSRI's (See CBD versus SSRI here)

 

There's a slew of other important players:  Dopamine, NPY, Glutamate, Histamine, hormones, etc.

 

In long term anxiety, these different worker bees can be working incorrectly.

 

Finally, there's the gut!

 

Yes, your stomach and its inhabitants have huge impacts on long term mood and anxiety.

 

Just a course of antibiotics at a critical period in life can have long term ramifications.

 

Check out CBD and probiotics for more understanding of this process. 

 

That's a great place to jump into the drivers of long term anxiety before we look at how to reverse any damage.

 

What does research shows as the drivers of long term anxiety

 

Why do some people get anxiety long term while others do not?

 

That's the key question.

 

Research is showing that it is generally relates to one of the following:

  • Injury, infection, or inflammation chronically or at specific times in development
  • Genetic variations that affect development and balance
  • Gut dysbiosis which creates a hostile workplace for the brain to be in

 

We'll look at each.

 

Yes, there are many lifestyle changes that can directly affect the anxiety circuit: 

  • Exercise
  • Diet
  • Sleep
  • Social interaction
  • Trauma
  • Artificial preservatives and pesticides
  • Drug use and withdrawal
  • Prescription medications
  • Meditation
  • Chronic stress
  • Age and related reductions in hormones and activity

 

We could go on and on.

 

New research is pointing to a host of assaults that conspire towards long term anxiety.

 

Ultimately, the damage (or benefits) from our activities will show their marks on brain activity, neurotransmitters, and gut health.

 

Let's focus there for long term anxiety!

 

First, brain area activity and long term anxiety.

 

We've covered quite a bit of this in our CBD and general anxiety disorder article and for good reason.

 

That's so-called "trait" anxiety.

 

A state of anxiety tied to systemic causes rather than reactions to episodes.

 

Feeling anxious for no good reason.

 

All the new research is on stress and anxiety.  Chronic stress.

 

Let's think of stress as a wide net of outside effects that negatively impact brain activity in the anxiety circuit. 

  • It could be in the form of inflammation from infection.
  • It could the stress of dealing with social situations if a person has autism.
  • It could be stress from harmful chemicals that hurt brain activity (nicotine and THC are two good examples).
  • It could be intense and overwhelming stress from trauma (such as PTSD).

 

It could even be stress that your ancestors dealt with!

 

Previous studies showed that genetic switches turned on up to 10 generations ago affect your current "mix".

 

It's called epigenetics.

 

 Your genetic blueprint is just a master record keeper of all your genes.

 

What genes are turned on and off depends on outside influences.

 

In fact, there was a study of the children of Holocaust survivors:

Descendants of Holocaust Survivors Have Altered Stress Hormones 

https://www.scientificamerican.com/article/descendants-of-holocaust-survivors-have-altered-stress-hormones/

 

A more recent and much more sophisticated update on this actually found reduced amount of grey matter in those descendents (the relay lines between brain areas). 

https://medicalxpress.com/news/2019-07-reveals-biological-toll-brain-function.html

 

The effects were even found in brain area connectivity: 

Survivors showed a significantly decreased volume of grey matter in the brain compared with controls of a similar age who had not been directly exposed via personal or family history to the Holocaust.

 

Maybe more intriguing, the people who were young at the time of the war, had much more reduction in downline descendents then those who were older:

reduction in grey matter was significantly more expressed in younger survivors, which may be attributed to the higher vulnerability to a stressful environment of the developing brain in childhood.

 

Think about that.  This means that stress at the time of key brain development windows can affect that person's life and even their descendents.

 

Don't get too depressed (as you think back to your parents and grandparents!).

 

We'll spend the last half of this article on what research is showing for actually repairing this damage.

 

Genes can turn on as well as off (and vice versa) based on what we do!

 

Infection exerts another form of stress on the brain (developing and developed).

 

Our immune system can over-react to infections and actually go after our own brain tissue!

 

This is really the new frontier in mental health...so called immunopsychiatry.

 

We'll start with animal studies with a focus on anxiety but really, every mental health issue has similar ties:

Anxiety-like behavior and blunted stress responses have been reported in rodents after in utero exposure to lipopolysaccharide (LPS) which mimics exposure to an infective agent 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458064/

 

LPS is the outer shell of bacteria that our immune system is trained to find.

 

Then there's the effect of high at diets or the mother: 

High-fat diets fed to pregnant rodent mothers led to offspring who, as adults, showed anxiety behavior, increased stress responses associated with increased corticosterone receptors in the amygdala, and changes in inflammatory gene expression in both the hippocampus and the amygdala

 

Why would this be?

 

A high-fat diet appears to expose the neonate to increased inflammatory cytokines that adversely affect neural development 

 

Cytokines are important inflammatory agents in our immune system.

 

Basically, the foot soldiers of inflammation.

 

It's not all your mother's fault!

 

Early life infection can also exact a toll:

Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9), social phobia (OR = 5.8), overanxious disorder (OR = 6.1), panic disorder (OR = 12.1), and oppositional defiant disorder (OR = 3.7). 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248872/

 

Then, there's the whole antibiotic effect which is a nice transition over to the gut. 

Treatment with a single antibiotic course was associated with higher risk for depression with all antibiotic groups, with an adjusted OR (AOR) of 1.23 for penicillins (95% CI, 1.18-1.29) and 1.25 (95% CI, 1.15-1.35) for quinolones. 

https://www.ncbi.nlm.nih.gov/pubmed/26580313

 

Check out our article on CBD, tryptophan and anxiety to understand how our serotonin levels respond to inflammation.

 

The gut is a whole separate deal.

 

Most of the new research is on how our gut bacteria have incredible impacts on our well-being.

 

This is equally true for mental health issues such as anxiety.

 

Check out CBD and gut bacteria for anxiety here.

 

We focused on two strains of gut bacteria that research is showing for anxiety: 

  • B Infantis
  • B Rhamnosus

 

You can buy these to supplement existing gut biome many places now.

 

Finally, don't underestimate the effects of chemicals and hormone disrupters (especially for women).

 

Since we're talking about long term anxiety, let's focus on brain region activity.

 

In recent studies, THC (CBD's cousin in cannabis) has been shown to reduce grey matter brain mass.

 

Yes, the same grey matter discussed above as a link between different brain areas which is directly tied to the anxiety circuit.

 

This has been know for a while with chronic use but a recent study showed that even 1-2 uses in adolescents during critical brain development periods can affect this communication system: 

GMV in the temporal regions was associated with contemporaneous performance on the Perceptual Reasoning Index and with future generalized anxiety symptoms in the cannabis users.  

https://www.jneurosci.org/content/39/10/1817

 

Did you catch that last part?

 

"Future generalized anxiety symptoms".

 

General anxiety is technical speak for long term anxiety.

 

Changes in brain structure and communication that result if an anxious state.

 

Check out THC or weed versus CBD for anxiety to get much more research.

 

THC pumps up the levels of anandamide (our naturally occuring endocannabinoid) and pregnenolone.

 

If a person is self-medicating (as opposed to occasional recreational use), they be trying to make up for reduced levels there!

 

Those are much easier to supplement directly without the loss of grey matter.

 

Speaking of pregnenolone, the interaction between hormones and anxiety are complex and interwoven.

 

Check out CBD, pregnenolone and anxiety for a thorough walk-through (especially for women and everyone as we get older).

 

The net effect of these various insults can be long term changes in brain structure.

 

Check out our CBD and general anxiety disorder or CBD and teenage anxiety to see the research on the actual brain areas affected.

 

One particular area is very vulnerable by nature of what it does.

 

Let's check out the hippocampus.

The vulnerable hippocampus and long term anxiety 

If you read a few 100 NIH studies on anxiety, CBD, and brain function, you'll see this player come up over and over again.

 

The hippocampus.

 

It's part of our ancient "reptilian" brain along with Amygdala (which figures dominantly into the anxiety circuit).

 

Think of the hippocampus as a manager that sits above the two competing brain areas.

 

It's takes in the initial signals and decides whether to respond with anxiety.

 

It's also the seat of memory, especially long term memory.

 

That's why it's so vulnerable to change!

 

It's in a constant state of change by sheer value of its ability to dynamically create, access, and destroy memories. 

The hippocampal formation is at the same time a very plastic brain region and a very vulnerable one to insults such as head trauma, ischemia, seizures and severe stress. 

https://www.sciencedirect.com/science/article/pii/S1044576584710311

 

It's especially susceptible to stress...long term or very intense stress.

 

The results of stress can be profound: 

Structurally, human and animal studies have shown that stress changes neuronal morphology, suppresses neuronal proliferation, and reduces hippocampal volume.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561403/

 

Keep in mind that mild stress is actually good for the hippocampus.

 

Hence the benefits of exercise and learning something new.

 

Check out this diagram for a good look at the effect of stress based on intensity: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561403/figure/KIMLM037291F1/

 

This is where it gets interesting.

 

Remember how we discussed how stress (whether from a situation, an infection, a chemical contact, etc) in childhood or even in the womb can cause future anxiety?

 

In particular left hippocampal white matter was smaller in patients, who had emotional childhood neglect, compared to those without neglect.  

https://www.sciencedirect.com/science/article/abs/pii/S0022395610000154

 

So that's the tie between early stress and hippocampus brain volume.

 

What about the resulting effects? 

Both emotional neglect and brain structural abnormalities predicted cumulative illness duration and there was a significant interaction between emotional neglect and prefrontal volumes as well as hippocampal white matter on the illness course. 

 

There, they were looking at depression but anxiety follows similar tracks in terms of hippocampus function.

 

Again, this may sound depressing but we will show that the hippocampus (and other brain area) loss can be reversed based on real research!

 

Check out:

CBD for hippocampus repair and anxiety
CBD, stress, and anxiety

 

Next up…

Age's effect on long term anxiety 

Two things happen as we get older which directly impacts the anxiety circuit on a long term basis: 

  • The hippocampus shrinks
  • Our hormone levels drop

 

Check out our article on CBD, mindful meditation, and exercise to repair the hippocampus article.

 

Researchers looked at hippocampus volume and various metabolites (key chemicals from hippocampus function) for HEALTHY individuals: 

in 24 healthy adults from 36 to 85 years of age. NAA/Cho decreased by 24% (r = 0.53, p = 0.01) and NAA/Cr by 26% (r = 0.61, p < 0.005) over the age range studied, whereas Cho/Cr remained stable, implying diminished NAA levels. 

https://www.ncbi.nlm.nih.gov/pubmed/10588575

 

More telling:

Hippocampal volume shrank by 20% (r = 0.64, p < 0.05).

 

We've seen studies which point to about 1.5% loss per year from age 20-70.

 

Exercise was shown to reverse this effect and actually cause an increase in hippocampus volume!

 

Again, check out that article on the three items that are shown to repair hippocampus loss.

 

Then there's hormones.

 

Goodness, they are underappreciated.

 

This is really the train that lead us to IndigoNaturals and 1000's of hours of NIH research.

 

You can read that story here but essentially, hormones levels drop as we get older.

 

Most people (including our entire medical community and tradition) view hormones strictly as useful for reproduction.

 

Nothing could be further from the truth!

 

Bone health.  Heart health.  Immune function.  Brain health.

 

Almost every type of tissue in your body has a progesterone receptor. 

(progesterone) plays an important role in non-reproductive tissues such as the cardiovascular system, bone and the central nervous system, highlighting the widespread role of this hormone in normal physiology  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807635/#r37

 

As for anxiety, hormone receptors are written all over the anxiety circuit: 

The classical estrogen receptors (ERα/β) (Gundlah et al., 2001; Mitra et al., 2003) and progesterone receptors (PRA/B) (Brinton et al., 2008) are highly expressed in brain areas involved in emotion and cognition, such as amygdala and hippocampus. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335177/

 

Again, learn about the Amygdala at our CBD and anxiety here or the Hippocampus on how CBD helps to repair the hippocampus for anxiety.

 

Obviously, there will be differences in "sex" hormones between the genders but that's not the case for pregnenolone.

 

The levels by gender are the same throughout life (clue #1) and the levels drop by about 70% from age 18 to 70 (clue #2).

 

Pregnenolone is actually three things: 

  • The precursor or "raw material" for all hormones
  • The precursor for all neurosteroids (used to repair nerves and brain tissue)
  • An endocannabinoid!!!   (interacts with our natural cannabinoid system to balance neurotransmitters)

 

Perimenopause knocked me off my feet.

 

The hormone drop sent me spiraling into 24/7 rolling anxiety and panic attacks.

 

The benzos and SSRI's prescribed (see CBD versus anxiety medications) almost finished me.

 

Bioidentical (synthetics have many issues), CBD, and pregnenolone addressed 95% of the issue.

 

Check out the review on Pregnenolone here.

Genes and long term anxiety

Yes, we have to talk about genes.

 

Of course, we're all bringing a different gene mix to the party.

 

This used to look like a life-long sentence but that's no longer the case after CRISPR.

 

CRSPR is the handy trick we "borrowed" from bacteria that allows us to seamlessly (accuracy and safety improves by month) switch out genes.

 

It's the biggest thing since antibiotics (with less damage to our gut bacteria!).

 

Don't listen to the naysayers who say that's years (or even decades) in the future.

 

It's happening now.

 

Very recent examples:

  • Scientist used CRISPR to wipe out HIV in living animals (here)
  • FDA approved first drug based on CRSPR for fatal blood disease (here)
  • Deaf parents line up for CRSPR treatment for children to prevent deafness (here)

 

This is all brand new and just picking up steam!

     

    It will totally revolutionize medicine.

     

    Let's look at anxiety as an example.

     

    We discussed just one gene called FAAH in our CBD and woman who doesn't feel pain or anxiety article.

     

    She has a variant of the FAAH gene which makes it impossible to EVER feel pain, anxiety, or depression.

     

    FAAH just happens to be an endocannabinoid which eats up anandamide (our "bliss" endocannabinoid in the brain).

     

    Now, we need to be able to feel pain or be anxious some times to keep us alive.

     

    But, there are different levels of FAAH activity we all have based on gene variants.

     

    Imagine if you could CRSPR out a percentage of FAAH genes to lower pain and anxiety threshold (which is what nature did over the course of a few million years).

     

    That's not the only gene!

     

    Check our CBD and the Genes of Anxiety for more detail and also what we can do to "up-regulate" the good genes and "down-regulate" the bad genes.

     

    The point is this...the section will be temporary with CRSPR technology on the horizon. 

     

    Long-term may not be so long after all.

     

    Till then, what can we do to repair long term anxiety pathways NOW? 

    How to repair brain areas tied to long term anxiety with CBD

    Just five minutes ago, i was having a discussion with a parent we knew from our child's elementary school.

     

    We got on the topic of how CBD, mindful meditation, and exercise have all been shown in NIH research to reverse the loss of hippocampus volume and function.  

     

    He looked at me and said something rather profound.

     

    "Yea, but all those things also reduce stress and maybe that's why they work".

     

    Lightbulb!!

     

    Yes, we know that stress is a major assault on the hippocampus and all brain areas really.

     

    Chronic stress can even enlarge the Amygdala (our fear center) and make it more prone to respond and respond more strongly over time.

     

    Don't take our word for it:

    We found a mechanism for the effects of chronic stress on amygdala activity, specifically that chronic stress increased excitability of LAT pyramidal neurons recorded in vivo. This hyperexcitability was caused by a reduction of a regulatory influence during action potential firing, facilitating LAT neuronal activity. 

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882519/

     

    To translate, chronic stress caused too much activity in the Amygdala (fear center...see CBD and anxiety here) which basically took the brake off longer term and made it more active!

     

    So...chicken or egg.

     

    Does exercise, CBD, and mindful medication slow down the assault of chronic stress so the brain can repair naturally (dependent on serotonin and other powerful chemicals)...

     

    Or...

     

    Do the three boost the pathways that actively repair brain tissue?

     

    Turns out it's both!

     

    Check out our CBD, mindful meditation, and exercise article for lots of research on how these three exert their effect.

     

    For stress response (slow or stop the damage):

     

    For brain repair (turn the dial the other way):

     

    Let's give two powerful examples (of dozens) for each.

       

      First, stress response.

       

      In our CBD and performance anxiety study, we came across NPY.

       

      Think of it as our "resilience" chemical.

       

      In fact, a study looked at soldiers that came back from war and had PTSD versus those that did not.

       

      One chemical difference came up in their blood panels.

       

      NPY.  

       

      We discussed Anandamide above...what's its effect on NPY?:

      The cannabinoid agonists anandamide (AEA) and CP55,940 both significantly augmented resting and KCl-evoked NPY release.

      https://www.semanticscholar.org/paper/Cannabinoids-augment-the-release-of-neuropeptide-Y-Gamber-Macarthur/632b4534e1ac9e07f40f16bf207afc1b0158c226

       

      Okay, so does CBD affect levels of anandamide in any way?

       

      Glad you asked…

      Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

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

       


      In fact, CBD's boosting of anandamide is thought to provide a great deal of it's antianxiety and antidepressant effects.

       

      For long term anxiety though, we really have to get at the heart of what's going wrong.

       

      We looked at how chronic stress was a constant barrage on the anxiety circuit.

       

      One of the main messengers of stress is cortisol (our most potent and present corticosteroid as it's called).

       

      Can CBD blunt its level or effect in the nervous system?

      Another crossover study showed that plasma cortisol levels decreased more significantly when given oral CBD, 300 to 600 mg, but these patients experienced a sedative effec

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

       

      See CBD, cortisol and anxiety here.

       

      Then, there's the instigator of our stress response...corticotropin releasing factor or CRF.

      Recent findings have shown that CRF exists in extrahypothalamic areas in the brain as well as in the hypothalamus, and extrahypothalamic CRF is also deeply involved in stress responses.

      https://www.ncbi.nlm.nih.gov/pubmed/19811447

       

      Think of CRF as the switch for fight or flight.

       

      What's the effect of CBD on CRF (too many letters...we apologize)?

      Interestingly, cannabidiol at low (5 mg/kg) and intermediate doses (15 mg/kg) successfully blocked the effects induced by acute stress on corticotropin-releasing factor, pro-opiomelanocortin and glucocorticoid receptor gene expression. 

      https://journals.sagepub.com/doi/abs/10.1177/0269881118805495?journalCode=jopa

       

      Did you catch that last part?

       

      Remember that our prior insults (even back generations such as the holocaust descendents) are coded in "epigenetics".

       

      What genes are turned on and off and at what rate.

       

      The above study pinpoints how things we do now can change our long term "state".

       

      Basically, CBD offset the gene expression for a heightened stress response!

       

      So does exercise and mindful meditation.

       

      It's a work-around till we have CRSPR.  Boost the good genes with behavior and dampen the bad genes with behavior.  Power!

       

      Check out the CBD, CRF, and anxiety article for an interesting exploration of how this all works! 

       

      Remember all the insults from infection, stress, and inflammation?

       

      What about turning back existing damage.

       

      We're talking about actual brain area volume and connectivity.

       

      Can CBD help there?

       

      Yes!

       

      In fact, new research is showing that CBD's primary effect (like SSRI's) is on repairing brain areas through neurogenesis.

       

      Aside from NPY, there are two powerful players on this front.

      • Serotonin
      • BDNF

       

      Serotonin is the target of SSRI's for depression and anxiety and it's the reason that they usually take 2 weeks to start working (see CBD versus SSRI's for anxiety).

       

      Serotonin is critical to replenishing and repairing brain areas:

      One of the most important factors regulating proliferation in the DG is serotonin. Brezun and Daszuta (1999) 192 R.L. Djavadian found, that depletion of serotonin in the brains of adult rats decreased the numbers of the BrdU-labeled (newly generated) neurons in both SVZ and DG.

      https://pdfs.semanticscholar.org/195e/f2c59104aed40b466b26b4866307454ce021.pdf

       

      The DG is an important part of the hippocampus (from above) where new neurons are created and then spread throughout the brain.  

      Several factors may decrease the rate of generation of these new cells in the adult DG. Some of the better known factors are glucocorticoids

      https://pdfs.semanticscholar.org/195e/f2c59104aed40b466b26b4866307454ce021.pdf

       

      Guess what our most prevalent glucosteroid is…

       

      Cortisol (discussed above).

       

      Learn more about CBD and serotonin here.

       

      Then there's BDNF.

       

      It's basically a workhorse in repair and rebuilding of our nervous system.

       

      We discussed it's impact on anxiety in our CBD, Genes, and anxiety article.

       

      The net net...reduced BDNF is implicated in anxiety and depression which we should expect for neurogenesis.

       

      What does CBD do there?

      Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.

      https://www.ncbi.nlm.nih.gov/pubmed/29869197

       

      Synaptogenesis is a technical way to say building new brain pathways!

       

      If we had to take all this info and sum it up:

      In a chronic study, systemic CBD prevented increased anxiety produced by chronic unpredictable stress, in addition to increasing hippocampal AEA; these anxiolytic effects depended upon CB1R activation and hippocampal neurogenesis, as demonstrated by genetic ablation techniques 

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/

       

      • Chronic stress.  Check.
      • AEA or Anandamide. Check.
      • Hippocampus neurogenesis.  Check.

       

      See the connections there?

       

      This is the heart of long term anxiety depending on a person's stress response.  

       

      What does all this mean?

       

      It's best to think of anxiety and depression as a brain that is slowly becoming less integrated over time...less connected due to various insults (infection, immune response, chronic stress, chemicals, etc).

       

      That sounds like a bold leap but let's go way out on a tangent here.

       

      What about the new studies on psilocybin (so-called magic mushrooms or psychedelics) and anxiety or depression.

       

      The New York Times best seller, How to To Change Your Mind by Michael Pollan is a fascinating introduction.

       

      The studies have been nothing short of amazing for anxiety and depression.

       

      Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

      https://journals.sagepub.com/doi/pdf/10.1177/0269881116675513

       

      There's a great NIH review of psilocybin and mental health here:

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007659/

       

      See its effects for OCD (which may be a coping mechanism for anxiety anyway), addiction, PTSD, and depression.

       

      Why do we even bring this up?

       

      It's now known that the root of psilocybin's effect is via the serotonin 2a pathway.

       

      In fact, recent studies show that psilocybin causes an explosion in brain neurogenesis and plasticity:

      New images of dentrites (picture the branches coming off a tree but in this case, the tree is a neuron) exploding outward after a single use of psilocybin are intriguing.

      https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30755-1

       

      Remember the key part of the brain that is supposed to be the voice of reason to our Amygdala or fear center?

       

      The prefrontal cortex.

       

      A preponderance of evidence from a combination of human imaging, postmortem studies, and animal models suggests that atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders and is precipitated and/or exacerbated by stress

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082376/

       

      There's that stress effect (let's include immune response to infection, chemical exposure, etc).

       

      Why are we even bringing this up?

       

      It's one more totally separate example of how research is showing brain connectivity and function loss as a key driver of long term anxiety (and a host of other mental health issues).

       

      That matches with the studies we showed on mindful meditation, CBD, and exercise (all decidedly different) for neurogenesis and anxiety depression (that review here).

       

      They ALL share one pathway in common.

       

      Neurogenesis or brain growth and interconnectivity (primarily via serotonin pathway).

       

      So...we can exercise.  We can practice mindful meditation.  Colorado and Oakland just legalized use of psilocybin and there's now a ton of studies looking at it.

       

      As for the CBD, what's the best way to go for long term anxiety.

      The Best CBD to buy 

      A few caveats are important here.

       

      First, the most basic requirements: 

      • Organically grown in the US
      • CO2 processed (cleanest approach)
      • 3rd party tested
      • No pesticides
      • No heavy metals
      • No THC (see THC versus CBD for anxiety)
      • No solvents
      • No bacteria
      • No mold

       

      We designed IndigoNaturals based on all these requirements (we actually 3rd party test twice).

       

      Beyond that, research does provide some guidance.

       

      All the studies are based on CBD isolate.  CBD by itself.

       

      Unfortunately, 90% of the market is selling full spectrum.

       

      Check out CBD isolate versus full spectrum for anxiety here to get the low down.

       

      Here's the issue.

       

      Roughly 40-60% of the population has histamine (allergy) issues and they're likely to have a bad response to all that plant material.

       

      A good 70% of those people also have bad reactions to THC!

       

      Check out CBD, histamines, and anxiety here to see why this is so important.

       

      More importantly, there's no research to back up their claims and we based everything on research.

       

      That brings up another key point since we're talking about "long term" anxiety.

       

      The studies show that 300 mg of CBD shows the highest amount of neurogenesis.

       

      It actually starts to go down from there as another channel is triggered (TRPV).

       

      For this reason, we generally don't want to go higher than that level and it always makes sense to start low and test your body's response.

       

      Check out how many mg of CBD for anxiety for more detail.

       

      We've been in the throes of anxiety and CBD was a critical tool to get out.

       

      At 70 mg per dropper, the 2000 mg bottle is a good middle ground.

       

      Be well!  Long term that is.

       

       

       

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