What does Research Show for CBD and OCD

can cbd help with ocd
 
There's exciting new research on OCD which we'll get into below.  

 

I can speak personally to its effect after perimenopause sent me reeling.

 

Combine OCD with health anxiety and it was a recipe for disaster.

 

The lowest point is when I bruised my arm from taking my blood pressure over and over.

 

Repetitive thoughts, ruminating, the whole OCD sandbox was mine to play in.

 

We've covered CBD and negative thoughts in detail here but we want  to dive deep in OCD to find out what's going on.

 

  • What's the connection with sudden OCD (so-called PANDA) for children and inflammation?
  • Why is OCD gender-neutral (unlike other types of anxiety)?
  • Why in the world would benadryl help with OCD symptoms?
  • What do new gene discoveries say about OCD pathways?
  • Why is CBD more common in the developed world? 

 

We'll also touch base on CBD's effect as well as other researched options.

 

These are the topics we'll look at with tons of NIH research: 

  • What is OCD in the brain
  • OCD and neurotransmitters
  • Brain inflammation and OCD
  • Genes tied to OCD
  • Hormones and OCD
  • Histamine, MTHFR, and OCD
  • The endocannabinoid system and OCD
  • Can CBD help with OCD
  • CBD versus OCD medications
  • How much CBD for OCD
  • What's the best CBD for OCD

 

Roll up your sleeves...we're going to get our hands dirty….towards the goal of not feeling the need to clean them!

What is OCD in the brain 

It's fascinating.

 

Within the last few years, we actually have better research on what's happening in the brain with OCD.

 

It used to be grouped under a general anxiety umbrella, but researchers are starting to think it's a separate thing altogether.

 

Roughly 2.5% of the world's population will experience OCD during their lives.

 

The new research revolves around three key factors coming out of newer brain scans: 

  • Irregular activity between impulse area of the brain and rational oversight 
  • Irregular activity between cingulo-opercular (error detection) area of the brain and the cortex
  • Irregular activity in the striatum (reward processing)

 

Let's look at these in detail to unglaze your eyes.

 

First, there's a very old (evolutionarily speaking) part of the brain that process primitive impulses like cleanliness, sexuality, and aggression.

 

It's a circuit running from your prefrontal cortex (just behind your eyes) to the thalamus in our "reptilian" older brain.

 

It's old world (animal instinct) meets new world (humanity!).

 

The caudate nucleus sits between these two players acting as a relay and interpreter.

 

Basically, the primitive impulse arises and the rational brain decides what to do about it.

 

Erupt in rage or calmly walk away.

 

By the way, the prefrontal cortex (calmly walk away) is partially shut down for remodeling in our teenage years (see CBD and teenage anxiety).

 

Go figure.

 

For example, after you use the restroom, there's an impulse (hopefully) to clean your hands.

 

This impulse gets approved by the prefrontal cortex as being a sound approach.

 

For OCD, the impulse can continue beyond the behavior:

For example, your brain may have trouble turning off thoughts of contamination after leaving the restroom, leading you to wash your hands again and again. 

https://www.verywellmind.com/causes-of-ocd-2510476

 

Recent improvement in scans have shown this in actual brain activity: 

Scans of those with OCD show abnormal activity in different parts of this circuit including the orbital frontal cortex, cingulate cortex, p-0 and caudate nucleus of the basal ganglia.

 

This circuit in the brain is in charge of motivating you to do certain things (over and over again with OCD).

 

More recent studies have looked at error detection areas of the brain which seem to be on hyperdrive.

 

This involves the cingulo-operative networks which is on the lookout for errors.

 

Usually, one part of the brain looks for errors while another area calls off the dogs and "resolves" the error signal.

 

In OCD, this circuit is not working correctly: 

Compared with people who did not have OCD, those with the condition displayed significantly more activity in brain areas associated with recognizing an error, but less activity in the brain regions that could stop an action. 

https://www.medicalnewstoday.com/articles/323905.php

 

Think of a watchdog that never truly believes (or hears) the signal that everything is okay.

 

Interestingly, the anxiety that results is now seen as a secondary response to not being able to act knowing that the response is incorrect:

The anxiety that many OCD patients experience is now thought to be a secondary effect of their condition, brought on by recognizing that their repetitive behaviors are not needed but being unable to control the drive to do them. 

https://www.sciencedaily.com/releases/2018/11/181129084703.htm

 

This is all well and good but we want to look at ways to actually impact OCD.  

 

We'll touch on inflammation and repair molecules that can actually change some of the brain areas and connections mentioned above.

 

Let's start to look at some of those now.

OCD and neurotransmitters 

There are key neurotransmitters tied OCD which we'll dive into now.

 

Above we talked about too much or too little activity for different brain areas and circuits.

 

Neurotransmitters do the heavy lifting in these circuits so let's dive in.

 

We'll look at these players: 

  • GABA/Glutamate
  • Serotonin
  • BDND

 

GABA and Glutamate lie at the heart of OCD.

 

Basically, GABA is our "brake" pedal in the brain while glutamate is our "gas" pedal.

 

Not only can GABA make us feel calm (see CBD versus benzos for anxiety), but it actually slows down activity within and between neurons.

 

Some of the clues between these players and OCD came from gene discovery (more on that below).

 

Looking at GABA: 

These results support that GABA concentration in the OFC area of patients with OCD is significantly decreased and the concentration in the ACC has a trend of decreasing.  

https://www.ncbi.nlm.nih.gov/pubmed/28638200

 

What's the OFC, you ask?

 

Oh, it's just the orbitofrontal cortex we discussed above.

 

The ACC is a key hub between the old and new brain.

 

Keep in mind that GABA is the check on glutamate (they are diametrically opposed).

 

This is very important since too much glutamate is actually toxic to neurons and can cause them to die.

 

Enough of this for longer periods can result in...reduced brain volume and activity.

 

A potential tie to the brain area deficits we saw above.

 

We would expect to see too much glutamate if GABA is reduced in OCD.

 

So… 

They found that individuals with OCD had higher levels of glutamate in the CSF than psychiatrically healthy controls. 

https://iocdf.org/expert-opinions/expert-opinion-glutamate/

 

A few studies have born this out now and there's even an autoimmune angle which we'll cover below: 

CSF glutamate (mmol/l) level was found to be significantly higher [F(1,31) ¼ 6.846, p ¼ 0.014] in OCD patients (47.1274.25) compared to control subjects (41.3673.63) on analysis of covariance. 

http://img2.timg.co.il/forums/1_143264754.pdf

 

CSF is cerebrospinal fluid.  It's the conduit between brain and body we'll look at further.

 

In fact, some people with OCD find benefits with low glutamate diets in terms of symptom severity: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859338/

 


Next us Serotonin.

 

Serotonin is a workhorse neurotransmitter in the brain.

 

It's the primary lever for the most common medication used for OCD, SSRI's.

 

See CBD versus SSRI for serotonin here.

 

It has its finger in so many pies across the brain and gut which speaks to the wide range and severity of side effects.

 

Many studies have looked at SSRI's effectiveness on OCD and it's a mixed bag.

 

The bar is set pretty low: 

Generally 40% to 60% of patients with OCD will experience at least a partial reduction in symptoms after treatment with an SSRI. However, many continue to have residual symptoms. 

https://www.health.harvard.edu/mind-and-mood/treating-obsessive-compulsive-disorder

 

Partial is a very wide range.

 

Looking another study of various SSRI's including the most prescribed and supposedly effective one (clomipramine): 

These findings demonstrate that pharmacological blockade of serotonin reuptake alone is not sufficient for an antiobsessional response. 

https://www.sciencedirect.com/science/article/pii/0006322385901763

 

We'll look at the meds below but back to serotonin,

 

What we found with heavy investigation of SSRI's for anxiety is that the real mechanism was neurogenesis (making new brain connections) as a function of repair!

 

Our brain is constantly under assault from: 

  • Inflammation
  • Infection
  • Over-reaction from immune system
  • Too much glutamate and histamine
  • Stress (chronic or acute such as with PTSD)

 

We also have entire systems to find and repair damage.

 

Serotonin and BDNF are big players in this process.

 

The interesting part was this...the neurogenesis effect of SSRI's pumping up serotonin occurred through CB1 receptors.

 

Ummmm...those are our endocannabinoid receptors in the brain that CBD interacts with.

 

More on that below but check out CBD and neurogenesis for anxiety here.

 

So, serotonin's role with OCD may not be so much about processing messages but repairing circuits!

 

Speaking of.....,next up,  BDNF.

 

Where serotonin wears many hats, BDNF's hat is a construction one.

 

It's in the business of repair and remodel of brain networks and neurons.

 

BDNF acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses 

https://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor

 

If OCD is tied to brain inflammation and loss as we described above, then repair is a key component.

 

The first clue came from new gene studies:

Sequence Variants of the Brain-Derived Neurotrophic Factor (BDNF) Gene Are Strongly Associated with Obsessive-Compulsive Disorder 

https://www.sciencedirect.com/science/article/pii/S0002929707619247

 

Interestingly, poor BDNF function affects serotonin function so maybe we're establishing cause effect.

 

Looking at mice with genetic variants, the effect starts early but has effects on adult serotonin process: 

a partial impairment in BDNF expression causes physiological disturbances in central serotonergic (5-HT) neurons in early adulthood and eventually leads to a structural deterioration of these neurons in advanced age

 

The effects on anxiety and depression are well-established: 

Moreover, BDNF deletion mutants are more vulnerable to stress, as shown by hypothalamo-pituitary axis hyperactivity, impaired working memory and increased depressive-like and anxiety-like behavior  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399209/

 

In fact, BDNF is required for SSRI's to actually work!

 

Finally, mice lacking BDNF have impaired antidepressant responses (Monteggia et al., 2004), and BDNF also seems to be required for the antidepressant actions of fluoxetine on synaptic transmission,

 

So...what about OCD?

 

When they looked at levels of BDNF across different anxiety disorders (although technically, OCD is now removed from that umbrella), guess which one was most closely correlated with BDNF levels!

 

OCD!

 

Although BDNF levels appear to be reduced in individuals with an anxiety disorder, this is not consistent across the various anxiety disorders and may largely be explained by the significantly lowered BDNF levels found in OCD. 

https://www.ncbi.nlm.nih.gov/pubmed/23908608/

 

Interestingly, the levels of BDNF appears to be how medications have a primary effect: 

Brain-derived neurotrophic factor (BDNF) plasma levels in drug-naïve OCD patients are lower than those in healthy people, but are not lower than those in drug-treated OCD patients 

https://www.sciencedirect.com/science/article/abs/pii/S0165032711001546

 

We have a big write up on BDNF and the neurotrophins coming soon in light of groundbreaking new research.

 

Another study found that interaction with the MAPK pathway is key to OCD.

 

This gets a little into the weeds but BDNF has a primary role in this pathway.  

https://www.nature.com/articles/mp2016232

 

All of this is about neuroplasticity...repair and remodelling of brain networks.  

 

Interestingly, one of the last-ditch efforts for OCD is deep brain stimulation either through the skull or via surgery.

 

Yes, this is for debilitating OCD where nothing else is helping.

 

What is the mechanism by which this works? 

Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737469/

 

Okay...we have to move on or we'll never get to ways to increase BDNF.

 

Check out CBD for neurogenesis and anxiety to get more detail.

 

Neurogenesis just means repair and building after various insults damage brain areas tied to OCD.

 

Remember that the prefrontal cortex was key to controlling or offsetting OCD tendencies.

 

Go figure with the following: 

For example, a high level of brain-derived neurotrophic factor (BDNF) in the PFC has been found to prevent or reverse stress-related mental illness by enhancing stress resilience 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803248/

 

Let's look at those insults now.

Brain inflammation and OCD 

So...what's doing all this damage to brain areas in the OCD circuit?

 

We're going to focus on two primary culprits: 

  • Infection and immune system over-response
  • Stress either chronic or acute (PTSD)

 

The two may be the same in terms of brain response.

 

In our CBD and neuroinflammation for anxiety, we looked at may components of this response.

 

We also covered the "enemy" in detail here: 

 

How does all this figure into OCD?

 

Are there signs we can actually measure?

 

Yes!

 

First, a signal of microglia (our immune responder in the brain) activity and OCD: 

In this case-control study, translocator protein distribution volume was significantly elevated in the CSTC of participants with OCD compared with healthy control individuals. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710556/

 

Translocator protein is a signature of microglia activation and brain inflammation.

 

In fact, the severity of symptoms was tied to the microglia activity in a part of the brain that might be familiar to you now:

The Yale-Brown Obsessive Compulsive Scale measure of distress associated with preventing compulsive behaviors was positively correlated with translocator protein distribution volume in the orbitofrontal cortex.

 

There's that orbitofrontal cortex we discussed up above in detail.

 

A key player in the OCD circuit.

 

This points to back to overactive immune response and OCD.

 

This brings up the most curious aspect of OCD...PANDA's.

 

It's short for pediatric autoimmune disorders associated with streptococcal infections

 

What in the world is that?

 

Basically, exposure to strep can cause the sudden onset of OCD: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780272/

 


This is very strange in mental health field (or is it???   Lots of new research on everything from Parkinson's to Schizophrenia).

 

In a subset of the population, the strep bacteria is able to cross the blood brain barrier.

 

The brain's immune system (microglia we mentioned above) panics and responds with a scorched earth approach.

 

After all, an infection in your skin can be uncomfortable.  

 

An infection in your brain may be a deal breaker.

 

The potential to over-react causes a tremendous of collateral damage to normal brain cells.

 

 

It's not just OCD though! 

Sixty-seven studies were included, involving 3,952 youth. Evidence for a proinflammatory state is strongest for autism spectrum disorders (ASD). PIMs are elevated in children and adolescents with major depressive disorder (MDD), bipolar disorder (BD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), Tourette's disorder (TD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SZ). 

https://www.sciencedirect.com/science/article/abs/pii/S0890856713008794

 

OCD is right there and newer research is backing this cause/effect: 

The results were clear: in the brain regions associated with OCD, individuals with the disorder had 32 percent more inflammation when compared with people without the condition.

"This finding represents one of the biggest breakthroughs in understanding the biology of OCD, and may lead to the development of new treatments."


https://www.medicalnewstoday.com/articles/318036.php

 

We're even seeing genetic roots to this.

 

For example: 

An early study reported that knockout of the Hoxb8 gene produces compulsive grooming, progressing to hair removal and ultimately to skin lesions [19]. Hoxb8 expression in the brain is restricted to microglia (identified in these experiments by their expression of the cell-surface marker CD11b+ 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174185/

 

They even took bone marrow (where this gene is produced) from OCD type mice and implanted them in non-OCD mice.

 

The net effect??

 

Conversely, excessive grooming is produced by transplantation of bone marrow from Hoxb8 KO mice into wild-type animals 

 

That's a microglia gene that could directly cause OCD symptoms in mice.

 

There's a range of studies on different inflammatory markers in people with OCD.

 

Everything from neuroprotection to synaptic "pruning".  

 

There's even a tie between microglia and glutamate levels (the excitatory chemical which can be toxic if not controlled by GABA) - see CBD for GABA and anxiety).

 

MECP-null microglia release dramatically higher levels of glutamate, and microglia-derived glutamate has neurotoxic effects on dendrites and synapses  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174185/

 

Glutamate is a weapon of choice from the microglia to attack enemies (such as the stray strep bacteria that sneaks across the blood/brain barrier).

 

Unfortunately, it can also turn on our own cells.

 

Remember how certain brain areas showed reduced activity and volume with OCD?

 

Then there's stress response.

 

One study found that levels of cortisol, our primary stress hormone (see CBD, cortisol, and anxiety) is tied to the obsessive component of OCD but not the compulsive one:

The present data reveals that cortisol levels and the stress scores in the PSS-10 were significantly higher in OCD patients that in controls. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613755/

 

Cortisol is a great measure of stress in our bodies.

 

Look...chronic and acute stress (PTSD) can result in actual loss of brain matter and activity (sounds a lot like immune response and infection above): 

Specifically, stress can lead to neuronal atrophy in frontal cortices (particularly the medial prefrontal cortex), the dorsomedial striatum (caudate), and the hippocampus. Stress can also result in neuronal hypertrophy in the dorsolateral striatum (putamen) and amygdala.  

https://www.ncbi.nlm.nih.gov/pubmed/29527593

 

Why does this matter in case it's been a while since your last biology class?

 

These neurobiological effects mirror reported neural abnormalities in OCD and may contribute to an imbalance between goal-directed and habitual behavior, an imbalance that is implicated in the pathogenesis and expression of OCD symptomatology. 

 

To translate...the brain activity loss from stress mirrors that found in OCD!

 

We can't talk about OCD (or any mental health issue touched by inflammation) without looking at the gut.

 

Our immune response is partially governed by the trillions of bacteria in the gut.

 

OCD is no different.

 

Researchers were able to affect OCD symptoms and progression with probiotics: 

there is preclinical evidence that OCD-like behavior in rodents (frequently measured using the marble burying test, which aims to assess repetitive, compulsive behaviors, one of the core symptoms of OCD) can be modified by microbial treatments, including germ-free environments and probiotic treatments 

https://academic.oup.com/ijnp/article/22/1/37/5067516

 

Check out CBD and probiotics.

 


We mentioned chronic stress, but what about acute stress?

 

The relationship between PTSD and OCD is well established (as are both to anxiety): 

Research shows that the likelihood of a person diagnosed with PTSD developing OCD within a year is about 30 percent. 

 

There's a great review here: 

https://www.verywellmind.com/trauma-ptsd-and-ocd-2797516

 

Check out CBD and PTSD here to learn all about that pathway. 

 

Next, the genes tied to OCD.  These will make sense after what we've discussed so far.

Genes tied to OCD 

There's a clear genetic tie with OCD.

 

We know you’re four times more likely to develop OCD if you have a first-degree relative with the disorder 

https://www.newscientist.com/article/2150565-four-brain-genes-help-explain-obsessive-compulsive-disorder/#ixzz5x3u0opU5

 

Furthermore: 

Family studies report prevalence rates of 7% to 15% in first-degree relatives of child and adolescent probands with OCD 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824902/

 

There are some interesting candidates for OCD in genes and this will only get clearer as we move forward.

 

Some pathways are coming to light: 

  • Repair genes - Serotonin transporters - 5-ht genes; BDNF
  • Excitability genes - GABA function - GABBR1
  • Neurotransmitter degraders -COMT and MAO
  • Immune genes - OLIG2 and MOG

 

We're going to try not to get too deep in the weeds.

 

What's interesting is where these genes do a great deal of their work: 

  • Stratium (where the caudate nucleus resides...the relay between other two areas)
  • Thalamus (ancient part of the brain mentioned above)
  • Cortex (that area behind our eyes)

 

This "circuit" appears to be malfunctioning in people with OCD.

 

Until we get CRSPR technology to catch up where we can sub genes out, there are ways to boost certain pathways.

 

For example, the tie between methylated B vitamins and OCD is interesting.

 

B12 and folate are critical supporters of many if not most genetic pathways in the body.

 

40% of the population has a type of MTHFR gene that results in poorer processing of 

 

It's effect on OCD? :

It was found that vitamin B12 levels were decreased and homocysteine levels were increased in some OCD patients.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164291/

 

This is easy and cheap to address!  Just look at methylated b vitamins.  MTHR is the same fix.

 

We're going to see how CBD directly impacts many of these pathways, especially the repair, stress response, and excitability pathways below.

 

We'll also look at other ways to support these genetic pathways below.

 

One more stop before we get into CBD's world.

 

Hormones

Hormones and OCD

OCD is one of the few mental health issues (especially with an anxiety bent) that is gender neutral.

 

We can eliminate estrogen and testosterone from our equation with that effect.

 

Diagnosis are equal between the genders but severity of symptoms can definitely differ:

Exacerbation of OCD could be related to reproductive events in a considerable number of patients, especially the premenstrum. 

https://www.ncbi.nlm.nih.gov/pubmed/16528139

 

Whenever key hormones fluctuate, this effect can be seen: 

In a substantial number of patients, the onset or worsening of OCD was related to reproductive cycle events, especially at menarche and postpartum 

https://www.ncbi.nlm.nih.gov/pubmed/15816784

 

There is almost no more severe a fluctuation of hormones than right after delivery (hence postpartum depression).

 

Is there an effect for OCD there? 

There’s also clinical evidence that the perinatal period is a time of high risk for OCD onset, given that OCD affects 2.07 percent of pregnant women, compared to 1.08 percent of non-pregnant people. 

https://www.thecut.com/2018/02/pregnancy-put-my-ocd-into-overdrive.html

 

Roughly double!

 

That's onset...not severity of symptoms for existing OCD sufferers.

 

Why would this happen?

 

Hormones have powerful effects on neurotransmitters.

 

That's how we found CBD to begin with when perimenopause sent our founder into 24/7 anxiety and even OCD.  That story is here.

 

In fact, estrogen and progesterone have significant control over serotonin and GABA.

 

Do those sound familiar??

 

Read up on just the serotonin effect here: 

Estrogen and progesterone have powerful effects on serotonin levels and signaling. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253022/

 

As we discussed in our review of pregnenolone (must read), there's a cascade of different hormones and effects beyond just the obvious ones.

 

Some of the metabolites (resulting chemicals) such as oxytocin and vasopressin may be at play with OCD. 

 

In fact, this may be the mechanism by which common OCD medications have their effect: 

 Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities.

https://www.ncbi.nlm.nih.gov/pubmed/9829022

 

An interesting study looked at brain scans during the cycle with fascinating results: 

progesterone can change the shape of receptors present in the cerebellum, which forms connections with the limbic and prefrontal cortices, which are responsible for controlling emotion and behaviour. Changes to the receptors make them less receptive to a chemical called GABA. 

https://www.newscientist.com/article/dn20122-why-women-get-anxious-at-that-time-of-the-month/#ixzz5x49viWvy

 

This is the brave new world of understanding how powerful hormones are across the brain!

 

And yes, GABA is a primary lever for OCD relief!

 

Let's turn our attention to a very interesting connection between OCD and histamine (better known as allergies).

OCD, Histamine and MTHFR 

Most of us know histamine from its effect on allergies.

 

It's a powerful immune responder to get things out of our bodies!

 


Check out CBD, histamine, and anxiety.

 

It has a dual function in the brain which is as an excitatory neurotransmitter.

 

In fact, it directly controls wakefulness, alertness, and focus!

 

Yes, it's an opposing force to GABA which we mentioned above as the "brake" in the brain and key to calming OCD symptoms.

 

In fact, that's why antihistamines make you feel drowsy.

 

This brings up an interesting thing...benadryl can help with OCD!

 

A study compared an SSRI (clomipramine), a benzo (clonzepam or klonipin) and also hydrophenadine (Benadryl - an antihistamine)

 

Both the SSRI and benzo were effective in a percentage of the sufferers.

 

That's a checkmark for serotonin and GABA (see CBD versus anti anxiety medications).

 

What about the anti-histamine?

 

The control medication, diphenhydramine, itself produced a significant decrement in symptoms

https://www.ncbi.nlm.nih.gov/pubmed/1474179

 

Now all three have significant negatives which we'll get into but what's going on with histamine and OCD?

 

Let's introduce MTHFR again from above.

 

This is the gene where people don't process B12 well.

 

Roughly 40% of the population has this variant (I do).  

 

People with this gene are not able to "methylate" well.

 

This is a primary way that our body and brain turns various chemicals and genes "on" and "off" system-wide.

 

It's really important for neurotransmitters (such as serotonin, GABA, dopamine, etc).

 

People with the faulty MTHFR do not break down histamine effectively.

 

This causes it to build up and as we mentioned, it's excitatory in the brain.

 

That's the first aspect and more info here: 

https://www.psychologytoday.com/us/blog/holistic-psychiatry/201711/mthfr-methylation-and-histamine-in-psychiatric-conditions

 


The first clue came from studies on histamine and Tourette's, an illness with shared mechanisms and risk to OCD: 

recent observation of strong histaminergic control of this network of lateral feedback inhibitory connections between MSNs (Ellender et al., 2011) and observations of altered striatal histaminergic tone in Tourette's syndrome 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917894/

 


Let's decipher that a bit please.

 

First MSN are neurons that control GABA and make up 95% of the...striatum!

 

That's the part of the brain directly tied to the OCD circuit.

 

Irregular function due to histamine of this area were tied to Tourette's, a close cousin of OCD.

 

Maybe our favorite study involves histamine and microglia, the immune responders we looked at above.

 

Remember that histamine is also an immune responder and it's intimately tied with microglia.

 

There's a fascinating summary of different studies where researchers knock out specific microglia genes and resulting OCD behaviors occur: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC575850.

 


Think about that...they can knock out a gene tied microglia activity and OCD occurs.

 

They unblock it and OCD goes away!

 

So what dictates microglia activity?

 

Histamine!

 

results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson’s disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia-induced neuroinflammation.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893260/ 

 
This histamine effect becomes really important for the type of CBD we choose...more on that below.

 

Finally, to the playground of CBD...the endocannabinoid system.

The endocannabinoid system and OCD 

We all have an endocannabinoid system and it dates back about 600 million years.

 

In fact, we share it with all animals down to sea urchins.

 

Research is showing it's tasked with balancing other key systems from "stress": 

  • Nervous system - neurotransmitters including serotonin, GABA, glutamate and more
  • Endocrine system -hormones including progesterone, cortisol, histamine, and more
  • Immune system - response to inflammation/stress including microglia, cytokines, etc

 

So...basically the cross-section of everything we discussed above.

 


First, are there even endocannabinoid receptors (called CB1 or CB2) in brain areas tied to OCD?:

Cannabinoid receptors are significantly expressed in most parts of the main circuitry related to OCD, the cortico-striatal-thalamic circuitry, being able to modulate the release of key neurotransmitters such as glutamate, dopamine, GABA, and serotonin

https://www.researchgate.net/publication/282595499_Cannabinoids_and_obsessive-compulsive_disorder

 

New studies are really interesting as they tease out the mechanism of OCD.

 


For example, one study found that CB1 receptor activation in the OFC (brain area tied ot OCD) was the key to switching from goal-oriented behavior to habitual behavior.

When Dr. Lovinger and his colleagues selectively deleted a particular endocannabinoid receptor, called cannabinoid type 1 (CB1), from OFC neurons, they found that mice that lacked these receptors did not form habits, but used goal-directed responses to receive the food reward.  

https://www.nih.gov/news-events/news-releases/study-reveals-central-role-endocannabinoids-habit-formation

 

The OFC figures heavily into the OCD circuit.

 

To put a fine point on it… 

 An inability to shift between habitual and non-habitual behaviors has been implicated in obsessive-compulsive disorder (OCD), addiction, and other disorders characterized by impaired decision-making.  

https://www.nih.gov/news-events/news-releases/study-reveals-central-role-endocannabinoids-habit-formation

 


CB1 receptors are where endocannabinoids, naturally occuring chemicals in our brains, do their work.

 

CBD also interacts with the body and brain at these receptors (CB1 and CB2 types).

 

They then tested whether they could increase CB1 receptor activity to reduce OCD behavior in mice.

 

It worked!

 

Mice receiving the CB1 agonist buried fewer marbles than did the control with no deterioration of effect over ten days.  

https://www.ncbi.nlm.nih.gov/pubmed/21111767

 

They did this by increasing anandamide and/or blocking FAAH.

 

Anandamide is our "bliss" molecule named after the Hindu goddess of biss, Anand.

 

FAAH breaks up anandamide.

 

We've covered them in detail including our look at the woman who can't feel anxiety or pain here.

 

Wait till you see what CBD does here.

 

What about the serotonin pathway?

 

Almost all the current medications rely on boosting serotonin levels available to neurons.

 

The problem is that this carries pretty significant side effects and eventually loses its effect.

 

A new study points to focusing on the CB (endocannabinoid receptors) instead: 

Not only did WIN 55,212-2 have an anti-compulsive effect, but the effect was overwhelmingly apparent with a 50% reduction in measured compulsive behavior  

https://impulse.appstate.edu/sites/impulse.appstate.edu/files/Kirschner%20and%20Stavnezer%20final.pdf

 

There was also an antianxiety effect but we have an entire article on CBD and anxiety here.

 

Maybe more importantly and telling:  

In addition to WIN 55,212-2’s success as an anti-compulsive drug, its efficacy persisted in this longer-term treatment. 

 

Then there's the GABA/Glutamate (brake and gas pedal) imbalance with OCD...

 

The endocannabinoid system is the great balancer of gas/brake pedal: 

The first conclusive evidence supporting retrograde endocannabinoid signaling came from the observation of depolarization-induced suppression of inhibition (DSI)/excitation (DSE)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/

 

This just means that the ECS (endocannabinoid system) is able to both increase or decrease activity across almost all pathways.

 

Look...new research is pointing to GABA as the KEY, immediate lever for OCD.

 

Enough already...let's finally look at CBD and other options.

Can CBD help with OCD (plus other things to consider) 

We'll first look at the pathways described above and then look at actual studies.

 

The pathways for CBD and OCD: 

  • GABA and Glutamate (calming the brain activity)
  • Serotonin and BDNF (brain repair)
  • Microglia and neuroinflammation (calming immune response)

 

This is really a blend of both preventing damage and repairing it.  

 

There are many studies on the effects of CBD on OCD and related issues (anxiety, PTSD, Tourette's, ect).

 

We'll start with animal studies of course.

 

First, they studied a proxy for OCD in animal models (called marble burying): 

 CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile.

Research is here

 

The interesting thing there is that they studied many cannabinoids and only CBD had that effect.

 

THC did not have that effect (see CBD versus THC for anxiety).

 

This same study aimed to piece together what pathways resulted in this effect: 

Acute systemic CBD reduced marble-burying behavior for up to 7 days, with no attenuation in effect up to high (120 mg/kg) doses, and effect shown to depend on CB1Rs but not 5-HT1ARs 


There's that CB1 receptor that appears to lie at the heart of OCD.

 

Let's expand our reach a bit.

 

We'll take a detour to Tourette's which has shared pathways with OCD.

 

Interestingly, one study looked at THC and CBD.

 

There were improved results on tics but other negatives (that's the THC).

 

When they then looked at  a much higher level of CBD to THC, the improvement was striking … 

Following administration of a daily dosage of 10 mg delta-9-tetrahydrocannabinol combined with 20 mg cannabidiol (CBD), the patient showed a rapid and highly significant improvement in the Yale Global Tic Severity Scale. 

https://www.ncbi.nlm.nih.gov/pubmed/30058466

 

So much for the tired question, do you need THC to activate CBD.

 

As we've seen in countless studies, the two are diametrically opposed.

 

What about fear extinction...the ability to forget bad memories and bad habits.

 

It's great to teach you not to touch an electric socket but not so good in holding on to trauma.

 

This is especially relevant to PTSD and OCD (the two have a close affiliation).

 

Past trauma is a known cause of OCD.

 

Check out CBD and PTSD for lots of information on this front.

 

What's CBD's effect on fear extinction (which requires the brain builders by the way)... 

CBD, a non-psychoactive phytocannabinoid could be an interesting pharmacological approach to reduce the anxiogenic effects of stress and promote the extinction of fear memories. 

https://www.ncbi.nlm.nih.gov/pubmed/18706790

 

Speaking of affiliations..it's estimated that 11% of people with OCD also have social anxiety disorder.

 

This isn't surprising when your read some of the shared pathways at CBD and social anxiety disorder.

 

We can add OCD to the list of anxiety-related disorders: 

Overall, preclinical evidence supports systemic CBD as an acute treatment of GAD, SAD, PD, OCD, and PTSD, and suggests that CBD has the advantage of not producing anxiogenic effects at higher dose, as distinct from other agents that enhance CB1R activation. 

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

 

This is a great place to jump into the share pathways we mentioned above: 

  • Serotonin and BDNF
  • GABA and glutamate
  • Microglia and neuroinflammation
  • CB1 receptor activity
  • So let's dig deeper into how CBD is having these effects for OCD.

 

First, we'll start with the damage.

 

Serotonin and especially BDNF are key to repair in the brain following trauma, stress, infection, and other insults (when young, now, or even in the womb!).

 

Most of CBD's effect for anxiety is along this repair pathway.

 

We'll start with one of our favorite studies: 

Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.

https://www.ncbi.nlm.nih.gov/pubmed/30157131

 

This study was able to block the anti-anxiety effect of CBD by countering its effect on serotonin.

 

Another amazing study showed how the most common medication for OCD, SSRI's, have their effect via this same serotonin pathway.

 

The problem is that they boost serotonin levels in one direction.

 

The key word up above is "modulates".  Not boosts but balances.

 

See CBD versus SSRI's for serotonin to get more detail on why this is so important.

 

What about BDNF?

 

Maybe our second favorite study on this repair pathway: 

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

 

  • Increased BDNF.  Check.
  • Brain repair (synaptogenesis).  Check
  • Prefrontal cortex.  Check!

 

That prefrontal cortex is the part of the OCD circuit that's not "checking" the constant impulse for specific behavior.

 

Check our CBD and negative or unwanted thoughts to drill down further.

 

Those are key players for brain repair.

 

Let's look at the immediate lever of OCD...GABA and Glutamate.

 

Remember that GABA is being used up to offset the gas pedal of the brain, glutamate (and also histamine).

 

What can CBD do there?

 

Is asking for balance too much from CBD?

 

There's an interesting study where CBD was shown to actually balance the GABA and Glutamate levels.

 

They were studying the difference between people with autism and those without: 

Thus, CBD modulates glutamate-GABA systems, but prefrontal-GABA systems respond differently in ASD.  

https://www.ncbi.nlm.nih.gov/pubmed/30758329

 

There's that word again….modulate.

 

Not boost like benzos to the point that a person's passes out and eventually overdoses.

 

Modulate.

 

Then, there's the immune connection to OCD.

 

How does CBD affect our inflammatory pathway?

 

First, microglia, the immune responders which can go haywire and actually damage our brain tissue.

 

A study on Alzheimer's looked at CBD's effect on this hyperactivation of microglia: 

Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer's disease.

https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=21350020

 

Check out CBD, inflammation, and anxiety or CBD and oxidative stress for anxiety.

 

Finally, remember that the CB1 receptors were key to OCD symptoms.

 

CBD does not directly boost CB1 receptors the way THC does.

 

This is good news as it also lacks the issues that come with such boosting.

 

Research is pointing to CBD as a reverse communicator.  Where most neurotransmitters send a signal from a sending neuron to a receiving neuron, CBD communicates the other way.

 

It sends back from the receiving neuron.

 

This helps to explain it's role in "modulating" not boosting or decreasing indiscriminately.

 

For example, with the neurogenesis effect (brain repair), scientist were able to block CBD's positive effect by removing CB1 receptors: 

We found that the increase in BrdU cell survival induced by CBD was abolished in CB1-/- mice (Fig. 3; WT/CBD vs. CB1-/-/CBD: 716 ± 83 vs.152 ± 28; n = 5; p = 0.001). CB1-/- mice showed a decrease in the number of BrdU cells. 

https://biosignaling.biomedcentral.com/articles/10.1186/1478-811X-8-12

 

The fact that CBD has a positive effect on compulsive behavior in animal studies and we know this behavior is directly tied to CB1 receptors is our clue.

 

Let's finish with Anandamide, THE primary key to CB1 receptor's lock.

 

Remember the marble burying test above (animal equivalent to OCD behavior)?

 

It was Anandamide (our naturally occuring cannabinoid) that brought down excessive glutamate:

Cannabinoids inhibit glutamate release in the central nervous system 

https://www.ncbi.nlm.nih.gov/pubmed/21111767

 

What's the connection with CBD and Anandamide (so called the "bliss" molecule)... 

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/

 

Thanks were staying with us there.  It is brain science after all!

 

Goodness.

 

In addition to CBD, here are some other supplements showing effectiveness: 

 

Are you seeing a trend there??

 

Preventing damage to brain (antioxidants, minerals, vitamins, probiotics) and repairing damage (exerices, meditation, CBD)

 

It's the same story across mental illness if only our healthcare system will catch up.

 

What's causing all this damage and why do we find OCD more prevalent in the developed world?

 

Remember how we discussed the power of hormones for serotonin and GABA function up above?

 

The pesticide glyphosate and the non-stick chemical PFOA (actually, it's metabolite PFOS) both interfere with the beginning of this cascade...pregnenolone.

 

We all have this in our blood right now unfortunately.  

 

To understand how powerful this effect is, read the review on pregnenolone.  

 

Thanks for sticking with us...if you or a loved one suffers from OCD, it's worth the read to get to the bottom of it.

 

On to practical questions.

How much CBD for OCD 

We don't have exact research on CBD levels for OCD.

 

Anxiety is different and we can draw some guidance from there.

 

A study showed that the neurogenesis (repairing brain circuits) effect maxes out at 300 mg of CBD and then starts to go down from there.

 

Even though the anxiety effects kept increasing, we want to maximise brain repair.

 

Based on that 300 mg is a good max level.

 

In terms of minimum level, it's best to start slow (25 - 30 mg) as a test and work your way up.

 

OCD has the benefit that we can see when we're starting to get relief.

 

Some of the pathways are longer term (fear extinction, neurogenesis, etc) while others are immediate (GABA/Glutamate, social anxiety).

 

I personally take 160 mg in the morning and 160 mg before bed.

 

160 was shown for aiding in sleep but each person's "state" is different.

 

Again, the effects are cumulative for what's driving OCD.

 

For very acute situations, studies used 600 mg (such as the public speaking study here).

 

The peak level was 1-2 hours after taking it and generally lasted 4-6 hours in terms of half-life.

 

Let's look at some key considerations on the type of CBD.

What's the best CBD for OCD 

The basic requirements are present as always: 

  • Organically grown in the US
  • CO2 extraction (cleanest option)
  • 3rd party tested (we test twice actually)
  • No THC (see THC versus CBD for anxiety to see why - THC actually increases brain inflammation)
  • No Heavy metals
  • No Pesticides
  • No Bacteria
  • No Mold

 

Now, a look at CBD isolate versus full spectrum.

 

After all, everyone on the market is pushing full spectrum CBD as being "better".

 

According to what research?

 

There is none!

 

All the research above and throughout the site (100's of studies) are on CBD isolate.

 

Remember the strange effect Benadryl had on calming OCD symptoms?

 

Benadryl is an antihistamine.

 

Histamine is excitatory in the brain (eats up GABA) just like Glutamate.

 

That's absolutely the wrong way to go for OCD!

 

We want more GABA...not less!

 

CBD Isolate.

 

We basically designed IndigoNaturals based on research and many failed attempts at CBD with very large brands primarily due to this full spectrum issue.

 

Hopefully, all this research and work can help you or a loved one feel better like it did for us.

 

 

1000 mg cbd isolate for anxiety2000 mg of cbd isolate for anxiety

6000 mg of cbd isolate for anxiety

 

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