CBD in autism spectrum disorder: An update

We have written before on the theoretical application of cannabidiol (CBD) to the problem of autism spectrum disorder (ASD). Preclinical data is not encouraging. Still, because CBD shows itself to be active in cognitive function in ever-more-surprising ways, much curiosity about its eventual utility in this disorder remains among researchers. 

Part of the problem in autism research is that the neurological definition of the syndrome itself remains elusive. In a way, administration of CBD, much of whose mechanism of action is known, could conceivably shed light on what ‘autism’ is, however. 

One of the things that CBD appears able to to is modulate excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels in the brain, and that includes brain regions linked to ASD, like the basal ganglia and the dorsomedial prefrontal cortex. Because differences are known to exist in glutamate and GABA pathways in ASD, people’s response to CBD may differ, depending on whether or not they have ASD. 

To test this putative differential shift in glutamate and GABA levels, a team within King’s College London, the London and Maudsley NHS Foundation, and Johns Hopkins University have measured, against magnetic resonance spectroscopy, glutamate (Glx = glutamate + glutamine) and GABA+ (GABA + macromolecules) levels in 34 healthy men, 17 of them diagnosed with ASD, after a single oral dose of 600 mg CBD or placebo.* 

Across groups, CBD increased subcortical Glx, but decreased it in the cortex. CBD increased GABA+ across regions in controls, but decreased it significantly in the dorsomedial prefrontal cortex in the ASD cohort. CBD does modulate glutamate-GABA systems, and prefrontal-GABA systems do respond differently in ASD. 

The next steps would be to examine long-term administration of CBD, on brain and on behavior, and to evaluate whether acute brain changes predict durable response.

*Pretzsch CM, et al. Neuropsychopharmacology. 2019 Jul;44(8):1398-1405. doi: 10.1038/s41386-019-0333-8

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