CBD and the Pathways of Tourette's
CBD was originally discovered due to its effects on seizures.
The first FDA-approved version of CBD (synthetic) is actually prescribed for certain types of seizures.
Interestingly, when you dig deep into the mechanics of Tourettes, you find shared pathways there.
That's where we're going...the key systems at play with Tourettes and how CBD directly affects those pathways.
There's exciting new research on the immune system and Tourettes which we'll dive into as well.
The immune system is becoming a hotbed of research for all things mental health as we'll see below.
Here are the topics we'll cover:
- Current view of what drives Tourettes
- The brain excitability balance (GABA and glutamate) and Tourettes
- Hyperactive immune response and Tourettes including Histamine
- Serotonin and Dopamine function with Tourettes
- The endocannabinoid system and Tourettes
- How CBD affects the pathways of Tourettes
- How much CBD to take for Tourettes
- What's the best CBD for Tourettes
Let's get started!
Current view of what drives Tourettes
Aspects of Tourette's mechanics share overlap with OCD, seizures, and even ADHD.
This alone sheds some light on underlying pathways at play.
There are three critical and overlapping areas to investigate
- The brain excitability balancing system which features GABA and glutamate
- The serotonin/dopamine motion and behavioral management system
- The immune system and inflammatory response
You can think of this as three separate levels.
- Glutamate/GABA (excitability) is the "right now" effect
- Serotonin and dopamine are the up-river drivers
- Immune response is the initial (and continuing) trigger that sets everything else in motion
We'll explain as we go through each level below with detail, research, and context.
Before we do that, let's look at important correlations.
Apart from the tics, most of the patients with Tourette syndrome have associated neuropsychiatric comorbidities consisting of attention deficit hyperactivity disorder, obsessive compulsive disorder, rage attacks, sleep issues, depression, and migraine.
We can really gleam a lot about a condition from shared issues which we know more about.
- OCD, anxiety, sleep, and migraines all point to excitability imbalance
- ADD is a combination of excitability and acetylcholine issues
- Rage, impulse control, etc point to serotonin issues
The immune system is involved in all of this as we'll see later!
Let's jump into each subsection.
The brain excitability balance (GABA and glutamate) and Tourettes
A quick introduction to the excitability circuit of your brain and Tourettes.
GABA is our brain's "brake" pedal - the primary inhibitory neurotransmitter.
It's tasked with keeping the "engine" from running too hot.
Its opposing force is glutamate, the brain's "gas" pedal and it's the largest neurotransmitter by volume in the brain.
The balance between these two sides is very important and every mental health issue shows some connection with this system.
The tell-tale signals on Tourettes lie in the nature of the symptoms and the comorbidities.
Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks.
We have a full dive on CBD and migraines here. Magnesium glycinate is a big player here which we'll look at below.
OCD is another clue.
Studies are pointing to excess glutamate in spontaneous compulsive issues:
The occurrence of spontaneous OCD-like behaviors that responded to glutamatergic agents suggests an underlying glutamatergic dysfunction in these animals.
As for people:
The first35 described measurements of glutamate in the CSF of 21 unmedicated adult patients and 18 controls and found statistically significantly higher glutamate levels in patients when compared with controls.
We see this play out across the spectrum of "anxiety" disorders including panic attacks, anxiety, performance anxiety, repetitive thoughts, etc.
Benzos have been effect by Tourettes but only in the short term since they're highly addictive and build tolerance quickly. See CBD versus benzos.
Benzos directly boost GABA so that's one more clue on this pathway.
We'll look at what may drive excess glutamate but first, let's turn our attention to GABA...the dam holding back the glutamate tide.
It's clearly not keeping up with Tourettes:
For example, studies involving brain scans of people with TS have shown that GABA levels are reduced by up to 50%.
Goodness. We can drop the mic right there.
We'll look at CBD (and other tools) to support this GABA pathway but let's turn to the person behind the curtain.
The immune system!
Hyperactive immune response and Tourettes including Histamine
You may be asking…"What does fighting colds and infections have to do with uncontrollable tics??"
Stay with us...it's about to get interesting (and much more current in terms of research).
Let's start with PANDA...not the cute bear but the curious connection between early infection and OCD or Tourette's later acquisition.
PANDA is short for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections
Essentially, interaction with the Strep bacteria infection can set off an autoimmune response that attacks the nervous system:
Streptococcus is suspected because there have been reports of the acute onset of Tourette's syndrome following streptococcal infections and worsening of tics in patients with Tourette's who have concurrent streptococcal infections.
Look at the connection with other autoimmune diseases:
A population-based investigation using the Swedish National Patient Register that assessed the association between TS and 40 autoimmune diseases (36) observed increased risk for comorbidity with Hashimoto's thyroiditis, celiac disease, scarlet fever, type 1 diabetes mellitus, and psoriasis
Psoriasis is interesting since it has a huge connection with strep infection in the back of the throat (see CBD and psoriasis).
It's not just Strep though as other viruses/bacteria are suspect as well.
Even more interesting (and connected to immune response) is the interplay with trauma...especially in utero.
Seventeen factors associated with an increase in Tourette symptoms included events causing anxiety, emotional trauma, and social gatherings.
An in utero?
With respect to in utero medication exposure, this was associated with global tic severity and a borderline higher risk for obsessive compulsive symptoms but a lower risk for symptoms of ADHD in individuals with TS
Prenatal maternal smoking was strongly correlated with increased tic severity and with the presence of comorbid OCD in these Tourette's syndrome subjects.
And during pregnancy/delivery:
Pregnancy complications: HT, DM, infections, (pre)eclampsia, psychosocial stress; (3) Delivery complications: meconium-stained amniotic fluid, premature rupture of the membranes, nuchal cord, fetal bradycardia, placenta previa, artificial delivery;V
Okay...stress during key periods of development.
What does this have to do with the immune system?
The immune system in the brain is very integral to managing architecture, build-out, and remodeling of the brain.
Early trauma and infection are so important to all mental health that we did a deep dive here.
When the immune system ramps up as a result of infection or chronic/acute stress, important things shift later in life.
See if you can spot a connection:
This study found that juvenile traumatic stress-induced chronic anxiety and spatial memory loss and reduced expression of GABAAR subunits in the adult rat brains
So early trauma caused a reduction later in life for GABA function (and therefore, anxiety).
Reported childhood abuse is associated with low serotonin transporter binding in vivo in major depressive disorder
Where serotonin goes, dopamine is soon to follow since the first manages the latter!
And then there's good old fashion inflammation...brain inflammation.
There's an interesting connection between our brain's immune sentinels called microglia and glutamate.
Glial cells have been proposed as potential candidate targets for both glutamatergic-and inflammatory-mediated alterations underlying MDD and suicidal behavior
MDD is short for major depressive disorder. See CBD and depression.
If microglia are "primed" to be hyperactive, there's a flood of glutamate which is highly destructive to the brain. Excess glutamate is toxic to the brain.
Early trauma and infection can ramp up inflammation and glutamate activity!
This all flows from the immune system as the microglia manage glutamate activity in the brain.
The immune system lies just below the surface.
Studies show that cytokines, inflammation markers, in the brain are significantly raised in children with Tourette's, especially in conjunction with OCD.
Let's turn to the repair side of the coin...starting with serotonin.
Serotonin and Dopamine function with Tourettes
Serotonin is a master regulator of all human behavior. We're not being excessive with that description.
Remember the connection with trauma (stress, infection, etc) before?
Look at what happens with serotonin as a result later in life:
Furthermore, there was a significant decrease in hippocampal serotonin content in offspring by postnatal day 50 following poly I:C administration by high-performance liquid chromatography.
Studies have shown that stress (chronic or acute) also downregulates serotonin later in life:
An aversive stimulus, foot shock (FS), during the early postnatal period (2-3 weeks after birth) produced behavioral, neuroanatomical and electrophysiological changes accompanied by serotonergic dysfunction, especially functional impairment of the serotonin (5-hydroxytryptamine; 5-HT)1A receptor in the cortico-limbic area.
5-HT is short for serotonin. Just know that early stress can impair future serotonin function which we'll address later.
Why does this matter for Tourette's?
Serotonin manages dopamine, our reward and motion neurotransmitter.
PET scans have shown the direct results for Tourette's:
The finding of decreased SERT BP, and the possible elevation in 5-HT2aR in individuals with TS who had increased DArel, suggest a condition of increased phasic DArel modulated by low 5-HT in concomitant OCD.
Let's translate, please!
Basically, low serotonin levels is leading to increased dopamine in certain brain areas.
Dopamine is the "action" chemical that drives the motion. For example, Parkinson's is reflected by a loss of dopamine and the inability to control body movements.
To show just how powerful dopamine is, look at schizophrenia where excess dopamine in a particular brain area can drive hallucinations, paranoia, and more.
As opposed to tics, these are manufactured thoughts, sounds, and visions.
We have a whole review on CBD and schizophrenia here.
Dopamine needs to be tightly regulated and serotonin has that job...but it's drawn down!
The PET scans show it.
We'll look at CBD's effects on both serotonin and dopamine below so let's take a step closer to that point.
The endocannabinoid system and Tourettes
We all have this system...it dates back about 600 million years. It's shared with all animals.
It's tasked with balancing our key systems including:
- Nervous system - including neurotransmitters like GABA, serotonin, and dopamine
- Immune system - inflammatory processes and birth/death cycles
- Endocrine system - hormones including stress and more
Okay...so right in our wheelhouse.
This is where CBD works.
So...what's the connection between the endocannabinoid system and Tourette's?
The clues are piling up.
The intragenic CNR1 polymorphism 1359(G/A) should be useful for association studies in neuro psychiatric disorders which may be related to anandamide metabolism disturbances.
Anandamide is the primary chemical in your body and brain that interacts with this receptor.
It's a major stress response buffer when all else fails. The backup crew.
Anandamide is named after the Hindu goddess of "bliss" so that's a pretty good indication.
THC mimics anandamide and fits into the CB1 receptor but it builds tolerance and lingers too long (hence, the psychoactive effects).
Researchers looked at our primary endocannabinoids (including anandamide) to see if there's a connection with Tourette's.
CSF levels of AEA (p = 0.0018), 2-AG (p = 0.0003), PEA (p = 0.02), and AA (p < 0.0001) were significantly increased in TS compared with controls
The backup has been called in but they're stretched!
Keep in mind that this system addresses imbalance across multiple pathways.
- Imbalance in neurotransmitters (GABA/glutamate or serotonin/dopamine)
- Imbalance in inflammation (microglia hyperactivation, cytokines, etc)
So...let's turn our attention to CBD….finally!
How CBD affects the pathways of Tourettes
So let's get into it!
First, a lay of the land...how does CBD work.
CBD works within the endocannabinoid system up above.
How it works is what makes it so different.
Technically, it's called an allosteric modulator for key pathways.
That basically means it works like a feedback mechanism!
This is very important since we don't want to push powerful pathways (like serotonin) up or down in one direction.
That leads to tolerance, addiction, and more...all of which are missing with CBD.
Let's get into the pathways directly tied to Tourettes that we've investigated above.
- CBD and GABA/glutamate for Tourette's
- CBD and serotonin/dopamine for Tourette's
- CBD and immune hyperactivation in the brain
- CBD and anandamide
- CBD and Tourette's research
First, the excitability piece.
CBD and GABA/glutamate for Tourette's
CBD is a positive allosteric modulator of GABA and glycine (a secondary inhibitory neurotransmitter in the brain).
This means that it supports it when low.
We see effects across a range of issues from anxiety to OCD to seizures.
Remember the tie-in with early infection (PANDA, in utero, etc)?
There are similar ties with many neurodevelopmental diseases including schizophrenia.
A study exposed mice in utero to infection which is known to dysregulate everything we've talked about above.
Look at CBD's effect:
Overall, these findings show that CBD can restore cannabinoid/GABAergic signaling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure.
Goodness...we could drop the mic there.
GABA. Anandamide. Specific brain areas.
By the way, schizophrenia is characterized by excessive dopamine in the striatum which causes "positive" effects like hallucination/paranoia and lowered dopamine in the prefrontal cortex which is tied to low effect, depression, and the like.
An interesting study looked at CBD's effect on GABA/glutamate balance with autism (another developmental disease linked with early trauma/infection).
Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant.
This is interesting because people with autism have reduced activity in the prefrontal cortex so we actually want more activity (less GABA) there with autism.
The effects of CBD were different depending on the state of the specific brain area!
This is so fascinating….you can't get these results with benzos (which pump up GABA everywhere...albeit with addiction and tolerance).
Again, the endocannabinoid system is about balance and CBD is a supportive feedback mechanism.
Check out CBD and GABA to learn more.
Let's turn to the heavy hitters.
CBD and serotonin/dopamine for Tourette's
We'll focus on serotonin since it manages dopamine in many respects.
CBD is also an allosteric modulator for serotonin...a feedback mechanism.
This is important since too much serotonin is just as bad as too little (see CBD and serotonin syndrome).
Infection, stress (chronic and acute), early abuse, etc can downregulate serotonin later in life.
Serotonin simply gets exhausted.
There's a perfect example of this with pain and injury (serotonin controls pain thresholds):
Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
Okay...we need to unpack this...it's too cool.
Basically, after chronic pain, serotonin was depleted leading to anxiety and pain.
- CBD supported pain thresholds
- CBD reduced anxiety
- CBD "rescued" serotonin (5-HT) function
Rescued. Not boosted. Rescued.
That's the feedback mechanism we've been talking about!
Check out CBD and serotonin to learn more.
As for dopamine, it's equally tricky.
Again, schizophrenia is characterized by too much dopamine in one brain area (striatum) and too little in another (prefrontal cortex).
The current meds are antipsychotics (the most common med for Tourette's by the way) which are basically hammers on dopamine (to suppress the "positive" side effects of too much dopamine).
This is where it gets interesting for Tourette's (specific brain areas flooded with dopamine).
First...the "too much" dopamine part:
After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=−1.4, 95% CI=−2.5, −0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=−0.5, 95% CI=−0.8, −0.1) and as not severely unwell (CGI-S: treatment difference=−0.3, 95% CI=−0.5, 0.0) by the treating clinician.
"Positive" symptoms originate from too much.
But what about the prefrontal cortex with too little dopamine?
Patients who received CBD also showed a trend-level improvement in their cognitive functioning, and a significant improvement of their motor speed compared with controls.
Improvement meaning...it didn't slam cognitive function the way that anti-psychotic do.
That's the trade-off with those meds...the hallucinations may drop but your cognitive selves suffer.
So...different effects in different parts of the brain...how?
We see this all the time with CBD research and cancer is a perfect example.
- Healthy cells or neurons with low inflammation - CBD has no effect
- Healthy cells or neurons with high inflammation - CBD reduces inflammation
- Cancerous or virally infected cell - CBD INCREASES inflammation
That last one is a doozy. Until you understand that our immune system's natural way to kill off wayward cells is to jack up inflammation (oxidative stress technically).
Chemo and radiation are giant doses of oxidative stress!
So CBD's effects differ depending on the state of the specific system.
In fact, CBD would support killing off cancerous cells while leaving healthy, adjoining cells alone.
This same effect is bearing out with serotonin and dopamine!
Let's turn to the root of maybe all of this dysregulation.
CBD and immune hyperactivation in the brain
We've talked quite a bit about how early infection (PANDA, etc) or trauma can ramp up the immune system.
Can this be calmed down?
Let's focus on these three elements:
First, the brain's immune sentinels.
CBD and microglia hyperactivation
We've covered this in detail at our CBD and neuroinflammation review.
First, from a study on Alzheimer's:
In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD.
Another study looked at a separate pathway that CBD triggers:
The TRPV-dependent phagocytosis-enhancing effect of CBD suggests that pharmacological modification of TRPV channel activity could be a rational approach to treating neuroinflammatory disorders involving changes in microglial function
Again, check out the review above.
Let's drill down into the little soldiers of the immune system.
CBD and cytokines (inflammatory agents)
First...the specific inflammatory markers tied to Tourette's.
IL2 and IL12 show a connection:
Findings suggest a role for IL-12 and IL-2 in TD, and that the TD+OCD subgroup may involve different neuroimmunological functions than the TD−OCD subgroup
First, IL2 which boosts T-cell, natural killer cells, etc.
CBD either enhanced or suppressed cytokine production (IL-2 and IFN-γ) in response to relatively low or high degree of immune stimulation, respectively.
Interesting! So it depends on the state of the system (too high or too low).
Same thing with IL-12. In diabetes, it would lower IL-12 (diabetes may in fact be partially auto-immune tied with much inflammation).
Same with EAE (mouse auto-immune disease) and autoimmune hepatitis.
However, it could also boost IL-12 when immune function is lower.
The link above has detailed info on both effects.
There's even research saying that Tourette's may be autoimmune (from the strep infection among others).
See CBD and autoimmune but the net-net is this...CBD appears to help the immune system re-balance which makes sense based on our endocannabinoid system.
Let's go to the heart of our inflammation control center.
CBD and gut inflammation
The gut and its microbiome are finally getting recognition.
This is our main inflammatory hub which makes sense since it's literally the daily entry point for trillions of bacteria, viruses, etc via our food.
There are anecdotal studies of how fecal transplant leads to pretty fascinating improvements in Tourette's symptoms...basically a replacement of the gut bacteria such as this one:
The restoration of B.coprocola was correlated with the improvement in tic symptoms (Spearman R = −0.900, P = 0.037).
YOu have to understand that a great deal of brain chemistry occurs in the gut.
A deep analysis of gut bacteria from people with Tourette's found distinct changes and the net effect:
Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway).
Okay...CBD's effect on gut inflammation.
A key to autoimmune is to slow or repair the breakdown in our gut barrier which keeps bacteria from entering the rest of the body.
CBD's effects after the introduction of c difficile (the nasty antibiotic-resistant bacteria in hospitals:
Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells
We'll look at other tools on this front below.
CBD and anandamide
We looked at how anandamide is a safety net for other key systems when out of balance.
THC directly imitates this chemical but does it too hard and for too long which causes tolerance (reduction in baseline natural function).
What about CBD?
CBD supports anandamide but in a feedback mechanism (as expected).
Remember how schizophrenia is characterized by imbalances in dopamine (similar to Tourette's)?
Look at how this intersects with anandamide and CBD:
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
Interestingly, in both Tourettes and schizophrenia, anandamide appears to be depleted.
How does CBD do this?
CBD reduces FAAH, an enzyme that breaks down anandamide.
We looked at how powerful this is with the woman who can't feel pain, anxiety, or depression (and probably never has Tourette's) due to a gene variant in FAAH here.
Interestingly, CBD doesn't keep pushing anandamide (really the CB1 receptor) activity in one direction or we would have the high associated with too much activity.
Let's look at specific research which dovetails from anandamide.
CBD and Tourette's research
Right now, most of the research is on cannabis.
We know that the two main constituents of cannabis are THC and CBD.
THC boosts CB1 activity like anandamide but with tolerance over time.
CBD supports CB1 activity when low.
From this, we can look at the research on cannabis such as:
Subsequently, a survey of TS patients found that 17 out of 64 consecutive respondents had used cannabis, and the majority of these (82%) reported that cannabis was effective in reducing tics, premonitory urges, and comorbidities
In another randomized double-blind, parallel-group placebo-controlled study over 6 weeks with 24 adult patients, a significant difference was found in the TSSL between the THC and placebo groups after 10 treatment days
See the power of anandamide when other systems are out of balance?!?!
We need to separate out the synthetics cannabinoids which have a slew of side effects not found in CBD isolate.
A few more tools to look at:
- Magnesium glycinate - supports GABA function and calms immune response
- PEA - THC without the high; supports the endocannabinoid system
- Vitamin D - master immune response regulator
- Berberine - supports healthy gut barrier and inflammatory state
Magnesium and OCD:
In another study, 48 patients with OCD were compared with 48 healthy controls and found that serum zinc, iron and magnesium levels decreased in patients with OCD;
The combined administration of oral THC (dronabinol) and the endogenous compound PEA (palmitoylethanolamide) is associated with symptomatic improvements in patients with treatment-resistant Tourette’s syndrome (TS), according to observational trial data published in the Journal of Neuropsychiatry
Again...THC has issues with tolerance (going the wrong direction) but PEA doesn't.
If you needed confirmation that the immune system is involved, look at Vitamin D:
Those children with CTDs exhibited significantly lower 25(OH)D levels than did healthy controls, and these reduced 25(OH)D levels were linked to increasing severity of tic symptoms. After treatment with supplemental vitamin D3, serum 25(OH)D level and scores of YGTSS total, motor tics, phonic tics, total tic, impairment, and CGI-SI improved significantly in children with CTDs without any adverse reactions.
Many people are deficient but make sure to get your levels tested.
Finally, the gut.
That's where berberine is strong:
In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency
Again, remember how most of our neurotransmitters rely on production (or pre-production) in the gut.
What about levels for Tourette's of CBD.
How much CBD to take for Tourettes
Okay...let's get practical.
There's interesting research showing some genetic risk due to poor BDNF function.
BDNF is our brain's fertilizer. It's a powerful player in all things mental health.
Think of it this way...early infection causes the immune system to over-react which creates tremendous collateral damage and even autoimmune responses.
BDNF is the opposing force to replenish, rebuild, and rewire.
As for Tourettes?:
The G196A polymorphism of the BNDF gene was genotyped in 88 GTS trios.
GTS is short for Guilles de la Tourettes Syndrome. There's a tie with downregulated BDNF function!
This brings us back to CBD.
Studies show that peak neurogenesis (boosting BDNF via serotonin) is at 300mg daily.
Learn more about our CBD and brain repair.
This can be broken up (3 x 100mg after meals) but that's the ideal level.
It takes at least 2 weeks for neurogenesis effects to kick in.
Make sure to take at least 4 hours away from any medications and work with your doctor of course.
What about the type of CBD?
What's the best CBD for Tourettes
First, some basic requirements:
- Organically grown in the US at FDA registered farms
- 3rd party tested
- CO2 processed
- No THC (builds tolerance - reduces anandamide function over time)
- No pesticides
- No solvents
- No heavy metals
- No bacteria
- No mold
Our 3rd party testing is available at the top of each page.
Then there's full spectrum versus CBD isolate.
We have 1 million+ words of reviews on NIH research and it's all on isolate.
Full-spectrum is more of a marketing ploy until we have research.
More importantly, roughly 40-60% of the population has histamine issues and the full spectrum can cause a range of side effects that go away with CBD isolate.
This is especially important with Tourette's since histamine is part of the immune response and we know that's an issue (hyperactivity).
Recent evidence for a contribution of histamine dysregulation to Tourette syndrome and tic disorders is particularly strong;
CBD isolate has actually been shown to calm histamine response in asthma and other studies.
Finally, there's cost.
To get to the 300mg daily for neurogenesis, affordability becomes an issue.
We price our 6000 mg bottles at 2-3 cents per mg before discounts up to 50%.
Originally, we discovered CBD isolate due to trauma from a brutal perimenopause. We've been there.
A visitor asked for more detail on Tourette's specifically so we went deep with the goal of reducing suffering.
Be well. Take care of each other. Take care of yourself.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.