CBD shifted glutamate and GABA levels in the brain, but differently in people with autism | Research

The takeaway

A single dose of CBD increased subcortical glutamate and decreased cortical glutamate across all participants. CBD increased GABA in neurotypical controls but decreased it in people with ASD.

Neuroscience researchers, autism specialists, and anyone interested in CBD's brain-level effects.

CBD increased GABA in controls but decreased it in ASD

What the researchers found

Across groups, CBD increased subcortical glutamate (Glx) but decreased cortical Glx. For GABA, CBD increased levels in controls but decreased them in ASD participants, with a significant group difference in the dorsomedial prefrontal cortex. This suggests the excitation-inhibition balance responds differently to CBD in ASD.

Why it matters

Excitation-inhibition imbalance is a leading theory in ASD neuroscience. This study provides the first direct evidence that CBD modulates glutamate and GABA differently in autistic versus neurotypical brains.

The numbers in context

34 men (17 ASD, 17 controls). 600 mg CBD. Subcortical Glx increased, cortical Glx decreased (both groups). GABA+ increased in controls, decreased in ASD. Group difference in DMPFC GABA+ was significant.

How the study worked

Double-blind, placebo-controlled, crossover design. 34 men (17 ASD, 17 neurotypical) received 600 mg oral CBD or placebo. Magnetic resonance spectroscopy (MRS) measured glutamate (Glx) and GABA+ levels in basal ganglia and dorsomedial prefrontal cortex at peak plasma levels (2 hours post-dose).

What this study cannot tell us

Small sample size (17 per group). Single dose. All male participants. MRS measures cannot distinguish between intracellular and extracellular neurotransmitter pools. No behavioral outcomes measured.

How to read the evidence

Moderate: double-blind, placebo-controlled crossover design using objective neuroimaging measures, but small sample.

When this study was published

Published in 2019.

The bigger picture

If CBD shifts the excitation-inhibition balance in ASD brains, this could explain both potential benefits and risks. The direction of the shift (decreasing GABA in ASD) was unexpected and needs further investigation.

Questions still open

Is the CBD-induced GABA decrease in ASD beneficial or harmful? Would chronic dosing produce different neurochemical changes? Does this mean CBD might worsen excitation-inhibition imbalance in some ASD individuals?

Common questions

What are glutamate and GABA?

Glutamate is the brain's main excitatory neurotransmitter (speeds up neural activity) and GABA is the main inhibitory one (slows it down). Their balance is critical for normal brain function and is thought to be disrupted in ASD.

Is it bad that CBD decreased GABA in people with autism?

It is unclear. The excitation-inhibition theory of ASD predicts that increasing inhibition (GABA) would be therapeutic. CBD doing the opposite in ASD raises questions that need to be addressed before clinical recommendations can be made.

Read the original research

Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(8), 1398-1405

View on PubMed ↗Publisher’s paper ↗

Citation

Pretzsch, Charlotte Marie; Freyberg, Jan; Voinescu, Bogdan; Lythgoe, David; Horder, Jamie; Mendez, Maria Andreina; Wichers, Robert; Ajram, Laura; Ivin, Glynis; Heasman, Martin; Edden, Richard A E; Williams, Steven; Murphy, Declan G M; Daly, Eileen; McAlonan, Gráinne M. (2019). Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(8), 1398-1405. https://doi.org/10.1038/s41386-019-0333-8