Does CBD Help With Autism Anxiety

by Indigo Naturals June 06, 2019

Anxiety is the most common associated mental health issue tied to autism.

It can take many forms from panic attacks to OCD.



We've investigated the general circuit of anxiety in our CBD and anxiety article but we want to focus on autism-specific anxiety here.

Many doctors anecdotally claim that the common medication for anxiety (SSRIs) are not as effective for people with autism.

This is interesting since they're not terribly effective (roughly 30% experience benefit) for anxiety in people without autism (see CBD versus SSRI for anxiety).

This is our approach here.

We're going to look at the known players in the anxiety circuit and then see how they are different in people with autism.

We'll then look at whether CBD can positively affect these pathways when compared to the standard anxiety medications.

We'll cover these areas below:

  • The anxiety circuit and autism
  • The amygdala and autism anxiety
  • Neurotransmitters and autism anxiety
  • Gut biome and autism anxiety
  • Autism and the endocannabinoid system
  • Can CBD help with autism anxiety
  • How much CBD for autism anxiety
  • Best type of CBD for autism anxiety

Let's get started.

The anxiety circuit and autism

We've covered the anxiety circuit in detail with our CBD benefits for anxiety article.

We dive even deeper in our panic attacks and general anxiety disorder articles.

Let's hit the highlights in terms of how the circuit works.

The main players are:

  • The amygdala - fear center can be overactive
  • Prefrontal cortex- rational center which should dampen the amygdala
  • ACC - anterior cingulate cortex connector and key to empathy and social interaction
  • Uncinate Fasciculus - connector between brain areas tied to anxiety
  • GABA, Glutamate, Serotonin, and Histamine for autism anxiety

Let's get started. Lots to cover.

We'll start at the heart of it...the Amygdala.

The amygdala and autism anxiety

All anxiety roads run through the amygdala. It's Rome of this circuit!

The amygdala is an evolutionarily ancient part of our brain.

Part of the old "reptilian" brain (yes, reptiles also have one and it does about the same thing), it's our fear and emotional processing center.

Abnormal activity in the amygdala is almost always present in any form of anxiety.

What about autism anxiety and the Amygdala?

There are distinct differences in the Amygdala for people on the spectrum.

The original studies showed that the number of neurons in AS (autism spectrum) Amygdala's were larger in children and then pared down over time.

This is contrary to non-AS Amygdala's which grow over time.

What was striking in this study was that the number of neurons in the amygdala from individuals with autism was higher in young children, but lower in adults.

https://iancommunity.org/anxiety-amygdala-autism

In fact, amygdala development in AS children was the size of an adult's fully grown early in adolescents.

It then begins to pare down from there.

One theory is that increased amygdala results in increased anxiety which ultimately causes long-term tissue damage as a result of stress (See CBD and stress for anxiety or CBD and cortisol for anxiety).

As put here by researchers:

the greater the output from the amygdala, the larger the stress response. Interestingly, the amygdala in children with an anxiety disorder is both larger (De Bellis et al., 2000) and more active (Thomas et al., 2001) than that of age-matched controls

https://pdfs.semanticscholar.org/0b8e/f6f5ec5dfc3eded5241fd3d636a596b94d26.pdf

Here's where it gets interesting for our discussion.

Different studies have shown different "trajectories" and ending results of Amygdala processing for AS.

The researchers may have been generalizing results when there are distinct differences between AS and AS + Anxiety.


There's a difference in the amygdala process between people with Autism and people with Autism AND Anxiety.

A brain region that processes emotions, including fear, tends to be smaller in children who have both autism and anxiety than in those who have autism alone, according to a new study.

https://www.spectrumnews.org/news/anxiety-may-alter-processing-emotions-people-autism/

This new look at "allostatic" load fits many other aspects of both anxiety and autism.

Allostatic is a fancy way to say chronic stress.

Stress is extremely destructive to brain tissue (especially in the hippocampus) if left unchecked.

So research is showing distinct groupings:

  • AS with low anxiety - low amygdala activity which speaks to low social motivation
  • AS with anxiety - higher amygdala activity which speaks to higher anxiety/fear response

Put simply:

individual differences in social behavior and in anxiety have independent, opposite relationships with amygdala activity among individuals with ASD.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884314/

So...for AS with anxiety, we're seeing heightened amygdala activity and long term brain mass reduction likely due to stress-induced damage.

See CBD, stress, and anxiety here.

Interestingly, the hippocampus is larger for people with AS:

The Amygdala Is Enlarged in Children But Not Adolescents with Autism; the Hippocampus Is Enlarged at All Ages

https://pdfs.semanticscholar.org/9358/6eb2c9139d4a766a6f54d4da9e543b8b082b.pdf

Don't worry, we'll come around to all this later on.

Let's now shift focus to another key brain area showing up in research for AS.

The ACC.

This connector between the amygdala and the prefrontal cortex is a key player in the anxiety circuit.

A description of its function makes it equally important for AS:

The researchers were aware that activity in this part of the brain is coupled with the “theory of mind”, which makes it possible for most people to understand others because they can imagine themselves in their place. Empathy, the emotional counterpart to the “theory of mind”, is also based in this region of the brain.

https://neurosciencenews.com/acc-autism-6325/

This goes to the root of social interaction and understanding social rules.

What did the researchers find with AS individuals?

(they) used functional MRI images (fMRI) from autistic adolescents to discover unusual activity in a particular region of the brain, the anterior cingulate cortex (ACC).

The result of this was very interesting.

Essentially, people with AS are not able to update their social models as a result of experience:

“People with autism, however, cannot update the model in their head in such cases because the response in the cingulate cortex is too weak,”

Think about how stressful that would be.

The myriad rules of social interaction that we take for granted are extremely hard.

No wonder stress levels are elevated.

We've written extensively on CBD and social anxiety here and teenage anxiety here.

Both of these are applicable to "trait" states (long term as opposed to anxiety from a situation) with AS for anxiety due to social rules.

Again, the study with detail is here:

https://neurosciencenews.com/acc-autism-6325/

One more brain stop that shows up for both autism and anxiety.

The fasciculus!

You don't hear that word every day.

We covered it extensively in our CBD and general anxiety disorder...and for good reason.

Reduced activity in that white matter connector is directly tied to "trait" anxiety.

What about autism?

Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults compared with TD peers.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105348/

We could spend all day with the brain and autism anxiety.

Let's move on to another key facet before we jump into CBD's effects.

Gut biome and autism anxiety

New research is pointing to an intersection between the gut microbiome, inflammation, and autism anxiety.

The gut biome is comprised of trillions of bacteria and other simple life forms that populate our guts.

Their "handwriting" is written across activities both in the body and brain.


First on the autism front with the gut:

It is becoming more and more likely to be one of the major interfaces between environmental and genetic risk factors that are associated with autism

https://peripheralmindsofautism.com/2018/04/17/is-autism-a-stress-adaptation/

By the way, that article is a treasure trove of stress-related info for autism.

Impressive work!

We're going to leave the heavy lifting of gut bacteria research to this article, how CBD works for autism but some key takeaways:

Accumulating evidence demonstrates that gastrointestinal (GI) symptoms, such as abdominal pain, gaseousness, diarrhea, constipation, and flatulence, are a common comorbidity in patients with ASD

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408485/

So we know there's a gut issue associated with many AS cases.

Maybe more importantly...

Furthermore, the observed GI symptoms are associated with the severity of ASD

It gets more interesting from there:

A population-based cohort study revealed the use of various antibiotics during pregnancy as a potential risk factor for ASD/infantile autism

We have an article on the works on gut bacteria and anxiety but an interesting note from researchers:

The early feeding pattern also influences the gut microbiota of infants and is associated with ASD. Formula-fed infants present an increased species richness accompanied by an overrepresentation of Clostridium difficile compared with breast-fed infants

Now, let's zero in on the gut bacteria specific to autism AND anxiety.

Let's start with Clostridium D as ONE example.

The reduction of Clostridium yields significant improvements in children with ASD

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408485/

Furthermore, there are some really bad strains of gut bacteria that have a much higher prevalence in people with autism:

Stool analysis on 13 patients with regressive autism showed a dramatic increase in titers of the abnormal and potentially toxic Clostridia.

https://www.ageofautism.com/2017/09/hormones-from-the-microbiome-implications-in-autism.html


That's the bad side.

What about good bacteria.

Introduce L Reuteri and L Infantis

First L Reuteri (which you can supplement).

Single species of gut bacteria can reverse autism-related social behavior in mice

The researchers went on to say:

By adding this bacterial species back to the guts of affected mice, the researchers were able to reverse some of the mice’s behavioral deficits, which are reminiscent of symptoms of autism spectrum disorders (ASDs) in humans.

https://www.bcm.edu/news/neuroscience/species-gut-bacteria-autism-related-behavior

This is pointing to a general intersection of autism, anxiety, and inflammation (the domain of gut bacteria).

In fact, when the raised mice with no gut bacteria:

GF mice display lower expression of postsynaptic density protein 95 (PSD-95) and synaptophysin in the striatum, increased monoamine neurotransmission and motor activity and reduced anxiety compared with SPF mice

This was a result of reduced better neurotransmitter signaling such as serotonin!

We could spend all day here.

For more research:

Let's now look at the stage that CBD operates in as it pertains to autism anxiety.

Autism and the endocannabinoid system

Everyone shares this system.

It's naturally occurring with receptors throughout our body and brain.

Research is showing that it acts as a balancer for other key systems:

  • Nervous system - neurotransmitters and brain signaling
  • Endocrine system - hormones (such as oxytocin which is key to social interaction)
  • Immune system - inflammatory responders

Anxiety and even Autism are at the intersection of these three systems.

Some of the research on autism and endocannabinoids are cutting edge.

Such as this one.

Lower circulating endocannabinoid levels in children with autism spectrum disorder

https://molecularautism.biomedcentral.com/articles/10.1186/s13229-019-0256-6


Maybe more interestingly…


In some of these models, activating the ECS rescued the social deficits.

Specifically…

We found lower serum levels of AEA, PEA, and OEA in children with ASD.

AEA is interesting.

It's short for Anandamide, the so-called "bliss molecule".

There's a direct correlation between lower anandamide levels and increased anxiety:

Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.

https://cloudfront.escholarship.org/dist/prd/content/qt9vp7s85t/qt9vp7s85t.pdf

Basically, reduce levels of FAAH which breaks down anandamide and there's an anti-anxiety effect.

This alone may speak partially to why autism and anxiety tend to go hand and hand.

In fact, a group of researchers blocked FAAH in mice that were given a drug to induce autism-like behavior in utero:

Systemic administration of the FAAH inhibitor PF3845 (10mg/kg) attenuated the deficit in social behavior observed in VPA exposed male animals without altering nociceptive, repetitive or exploratory behavior.

https://www.ncbi.nlm.nih.gov/pubmed/27592249

Another study looked at fragile x mice:

Remarkably, we found that FAAH blockade completely reversed the social impairment in both mouse models. CB1 receptor blockade prevented the prosocial action of FAAH inhibition in BTBR mice

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549436/

As for FAAH and anxiety, look no further than the woman who is unable to feel pain or anxiety here.

Her experience is a result of a FAAH gene mutation where she has very low levels naturally.

So, Anandamide (the bliss molecule) can run rampant!

Differences in pain and anxiety thresholds may partially depend on this one tug-of-war between FAAH and Anandamide!

One of the other endocannabinoids listed is PEA.

It's a powerful anti-inflammatory and mediator of the gut-brain axis.

That's a mouthful and beyond the scope of this article but we discussed gut microbiome effects above on both anxiety and autism.

Put simply:

In conclusion, our results demonstrated a therapeutic potential of PEA in limiting ASD symptoms, through its pleiotropic mechanism of action, supporting neuroprotection, anti-inflammatory effects, and the modulation of the gut-brain axis.

https://www.ncbi.nlm.nih.gov/pubmed/30193877

There's a whole new tranche of research on whether anxiety, depression, (and even autism) are partially a result of brain inflammation.

PEA is a powerful manager of our brain's inflammatory agents including the all-powerful microglial cells.


For the first time, we demonstrated that PEA+luteolin compound exerts a significant antidepressant effect on a low dose and may be considered as a novel therapeutic strategy in depression.

It's also involved in the neurogenesis of new brain tissue we discussed above:

https://www.ncbi.nlm.nih.gov/pubmed/30193877

This is just a small sampling of the endocannabinoid cross-section between anxiety and autism.

We could go on for pages.

There's an extensive review of endocannabinoids and autism here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618565/

You can read more about CBD inflammation and anxiety here or how CBD works for autism here.

What about CBD?

How does it work within this system according to research?

Can CBD help with autism anxiety?

We're going to hit the highlights of how CBD works at the cross-sections of autism and anxiety we discussed above.

Then we'll look at actual studies which are finally starting to come in.

First, neuroplasticity.

Remember way up above where we talked about shrinking volume in certain key areas of the anxiety circuit and "connectors" between brain areas?

This is critical for both anxiety and autism.

We'll start with the hippocampus where cells were found that literally "originated" the switch for anxiety states (see CBD and the Hippocampus for anxiety).

What did researchers find for CBD and hippocampus neurogenesis:

CBD induced a substantial increase in net neurogenesis by a CB1 receptor-dependent mechanism

This has now been shown in many studies.

Maybe more importantly…

These data are supported by evidence that repeated administration of CBD to wild-type mice increases hippocampal NPC proliferation via CB1 receptors, which may underlie the anxiolytic effect of CBD in chronically stressed animals

Did you catch that last part?

Anti-anxiety (anxiolytic) effects in "chronically stressed" animals.

Remember that a prominent theory for anxiety and autism is that chronic stress of the challenges navigating social situations not to mention a general state of inflammation (gut bacteria and allostatic load) are reducing brain activity and neurons themselves!

That's chronic stress.

It's not just the hippocampus though.

When given CBD in mouse models of depression:

The acute antidepressant effects (30 min) were associated with increased expression of synaptophysin and PSD95 in the medial prefrontal cortex (mPFC) and elevated BDNF levels in both mPFC and hippocampus

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

The prefrontal cortex is our rational brain from up above and is the counterbalance to our fear center.

It's the part that hopefully takes control after puberty (see CBD and teenage anxiety).

There's that BDNF we discussed above. It's key to the brain's ability to reorganize!

Just to show how integral the endocannabinoid system is (which CBD supports), let's break out one example.

The PSD95 above. What the heck is that?

we describe the role of PSD-95 as an essential scaffolding protein during synaptogenesis and neurodevelopment.

https://www.ncbi.nlm.nih.gov/pubmed/29169997

Why does that matter for autism?


Recently, there has been overwhelming evidence that associates PSD-95 disruption with cognitive and learning deficits observed in SCZ and autism.

Okay...the point is this.

The systems that govern both anxiety and especially autism are incredibly complicated and interactive.

The power of CBD and the endocannabinoid system is not to push on just one lever.

We're talking about brain remodeling, neurotransmitters, inflammatory and immune agents...even hormones!

Finding balance among these systems is the core role of the endocannabinoid system.

CBD supports that system when it's low on fuel.

We digress (sorry but it's really fascinating!)

Let's look at the FAAH and Anandamide which are shown to have direct effects on both anxiety and autism.

As we discussed, FAAH breaks down anandamide in our bodies.

Reduced anandamide levels are tied to both higher anxiety and autism.

What does CBD do there?

While studying the impressive results of CBD on schizophrenia (which has some overlap with autism):

We further found that cannabidiol, at a concentration that reduces FAAH activity by ∼50% (10 μ), does not significantly interact with a broad panel of neurotransmitter receptors that are relevant to schizophrenia, including dopamine, glutamate, and serotonin.

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

50% reduction in FAAH!

This lead to their finding:


Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.


Let's look at some actual studies.


First, a study of CBD for "co-morbid" or associated issues with autism:

Results: 53 children at a median age of 11 (4–22) year received cannabidiol for a median duration of 66 days (30–588). Self-injury and rage attacks (n = 34) improved in 67.6% and worsened by 8.8%. Hyperactivity symptoms (n = 38) improved in 68.4%, did not change in 28.9% and worsened in 2.6%. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5%. Adverse effects, mostly somnolence and change in appetite were mild.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333745/


Unfortunately, they used a 20:1 CBD to THC ratio.


There's a known anxiety effect for THC (see CBD versus THC for anxiety here).


The studies we have seen for CBD and anxiety (see here) never show an increase in anxiety unless there's THC or full-spectrum (due to histamine response...see CBD and histamine for anxiety).


Another study looked at CBD's effect on Dravet Syndrome with autistic-like social symptoms:

We demonstrate here that treatment with CBD is beneficial for seizure frequency, duration, and severity and for autistic-like social deficits in a mouse model of DS.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651774/


Interestingly, its effect was partially due to GPR55 activation.


Okay, before you throw your hands up at GPR55, just know this:

information suggests that alterations in GPR55 expression may sub-serve some cognitive pathology as autism and anxiety.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771053/


I just made a note to learn everything about GPR55. Thanks a lot.


To sum it up:

CBD appears to stimulate synaptic plasticity and facilitates neurogenesis that may explain its positive effects on attenuating psychotic, anxiety, and depressive behaviors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/

Translation Please!

CBD spurs the system that allows the brain to repair, replenish, and change!


To add to that laundry list of benefits:

The mechanisms underlying these effects involve multiple cellular targets to elevate brain-derived neurotropic factor (BDNF) levels, reduce microglia activation, and decrease levels of proinflammatory mediators


Each of those requires a separate deep dive for autism anxiety but they are interesting.

  • BDNF is brain growth and "plasticity" supporter.
  • Microglia is immune attack agent key to inflammation
  • Proinflammatory mediators are attack agents that can ravage the brain

See why we're so excited!

How much CBD for autism anxiety

We don't have specific dosage research for autism itself.

Anxiety is a little clearer.

We can also look at the neurogenesis piece which is critical to both.

First, a general starting dosage is around 20-30 mg.

Since we only focus on CBD Isolate, the side effect profile is much better than full -spectrum (see below for that).

There are many studies on anxiety with dosages from 300 mg to 600 mg as the basis.

Interestingly, the neurogenesis effect goes down as we increase from 300 to 600 mg.

It peaks around 300 mg per day.

For that reason, 300 mg would probably be our upper threshold so we can get longer-term effects.

Also, see our article on CBD, mindful meditation, and exercise which all exhibit powerful effects on neurogenesis and brain plasticity.

More guidance is available at our how many mg of CBD for anxiety here.

Best type of CBD for autism anxiety

First, do no harm.

Look...all the research above is based on CBD by itself or CBD isolate.

There's almost no research for "full-spectrum" CBD that everyone's pushing on the market.

In fact, the original meaning behind the much purported "entourage effect" was research showing that CBD offset the negatives of THC!

Check out CBD versus THC for anxiety article to really get into that.

We crafted IndigoNaturals based on research (hopefully obvious from this and dozens of articles).

There's also the whole histamine issue!

Roughly 40-60% of the population has histamine issues.

Think allergies.

All that plant material in full-spectrum is actually excitatory and inflammatory in the brain with histamine release.

That's going the wrong direction for both anxiety and autism.

This is critical.

New research is pointing to mast cell release and histamine issues as a core cause for a subset of autism.

https://healinghistamine.com/autism-spectrum-disorders-linked-to-mast-cell-activation/

We want the cleanest CBD available and absolutely no THC.

Again, we designed IndigoNaturals after trying the biggest brands of full spectrums and had side effects that went away with CBD Isolate.

Our whole family takes this so it has to be just right.

We have clients (and friends) who use our CBD for autism anxiety. Let us know your results.

We love to hear how it works for you.

Check out:

Always work with a doctor or naturopath with any supplement!

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

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