Children with Autism Have Lower Levels of Endocannabinoids

Is there a link between autism and the endocannabinoid system? The research points to yes, but the supporting data in humans is scant.

A new study published in the journal Molecular Autism provides more evidence for the theory that the endocannabinoid system plays a causal role in autism spectrum disorder.

The Social Effects of Cannabinoids

Cannabis has a clear effect on how we act socially. Research dating back to the 1970s demonstrates that cannabis can improve communication and make people less hostile towards one another.

But how does cannabis affect your behavior?

In your brain, Tetrahydrocannabinol (THC) and cannabidiol (CBD), the most abundant cannabinoids in cannabis, target cannabinoid receptors, like CB1. Interestingly, CB1 receptors are enriched in the areas of the brain associated with social functioning.

The Endocannabinoid System

Your brain also makes its own cannabinoids (endocannabinoids) that can bind CB1 receptors and change your social behavior. Together, endocannabinoids and their receptors make up the endocannabinoid system (ECS).

The ECS is present throughout many systems in your body, not just the brain, and helps regulate appetite, pain, mood, and memory.

The Endocannabinoid System and Autism: An Intriguing Link

A growing body of evidence shows that the ECS also regulates our social behavior. The CB1 receptor together with the endocannabinoids anandamide and 2-arachidonoyl-glycerol (2-AG) play a role in anxiety and social cues in both mice and humans. Feelings of social reward are also regulated by the ECS in mice.

People living with autism spectrum disorder have a hard time communicating and interacting with others. This makes it difficult for those with autism to function and be successful in social situations like school and work.

Because social behavior relies on the ECS, researchers began testing whether there could be a connection between the function of the ECS and autism.

Data from Animal and Human Studies

Quite a few studies using animal models for autism have shown that activating the ECS can improve the symptoms of autism and autism-related behaviors. These can include repetitive behaviors and deficits in social reciprocity and communication.

But in humans, the evidence is more limited. Some studies suggest that mutations in the gene that encodes the CB1 receptor can affect how we process social cues. And post-mortem analysis of the brains of individuals with autism show lowered levels of the CB1 receptor.

The Search for More Evidence in Humans: A New Study

A new study published in the journal Molecular Autism takes a closer look at the relationship between the ECS and autism.

Researchers from the Neuropediatric Unit at the Shaare Zedek Medical Center in Israel took blood samples from children and adolescents (11 years of age on average) diagnosed with autism. The researchers also collected blood samples from a control group of non-autistic children.

They analyzed the blood samples for endocannabinoid content and compared the two groups.

The Study’s Results

The researchers found that the autistic group, on average, had significantly lower levels of several endocannabinoids in their blood samples.

Levels of anandamide and its structurally related compounds, N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), were lower in the autistic group. These differences held up even when controlling for other factors like age, gender, BMI, and diagnosis with attention deficit hyperactivity disorder (ADHD).

But blood levels of 2-AG and its metabolic byproduct arachidonic acid (AA) were not significantly different between the two groups.

Important Takeaways

The results of this study are simple but they have quite a few interesting implications.

Clinical Relevance

Unlike most other signaling molecules in the brain, endocannabinoids are not stored in cellular compartments where they await release after being made.

Instead, they are made on demand. This means that even small changes in blood levels could have large impacts on brain function, making endocannabinoids and the ECS a good target for drug therapy.

A Possible Mechanism for CBD

A previous study demonstrated that CBD could help to improve the symptoms of children with autism. The results of this new study point to a clear mechanism for this effect—CBD activates the ECS through CB1 which helps regulate social behavior. Additionally, CBD can also act to increase levels of the relevant endocannabinoids, anandamide, PEA, and OEA.

As an aside, researchers originally recruited the children that participated in this study as part of a separate clinical trial looking at the effect of CBD on autism. It will be interesting to see whether this model holds up in clinical trials.

Preventative Diagnosis

These results also offer the potential for a new autism biomarker.

Blood levels of endocannabinoids could be used as a diagnostic tool or to predict the risk of developing autism in predisposed children who may not be showing symptoms.

With earlier diagnosis, children can begin behavioral interventions sooner which leads to better symptom management as they grow older.


Children and adolescents with autism have lower circulating levels of endocannabinoids in their blood.

What’s the cause? Do they make less of these molecules or do their bodies degrade them faster? One study suggests it might be the former. But of course, future studies will need to address this in more detail.

Regardless, these results add to the growing body of evidence that links the function of the ECS to the development of autism and have some important implications for how we can better treat and diagnose autism in the future.


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