CBD shifted glutamate and GABA levels in the brain, but differently in people with autism
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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).
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- CBD increased GABA in controls but decreased it in ASD
- Evidence Grade:
- Moderate: double-blind, placebo-controlled crossover design using objective neuroimaging measures, but small sample.
- Study Age:
- Published in 2019.
- Original Title:
- 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.
- Published In:
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(8), 1398-1405 (2019)
- Authors:
- Pretzsch, Charlotte Marie, Freyberg, Jan, Voinescu, Bogdan(2), 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
- Database ID:
- RTHC-02242
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked 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.
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Cite This Study
https://rethinkthc.com/research/RTHC-02242APA
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
MLA
Pretzsch, Charlotte Marie, et al. "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, 2019. https://doi.org/10.1038/s41386-019-0333-8
RethinkTHC
RethinkTHC Research Database. "Effects of cannabidiol on brain excitation and inhibition sy..." RTHC-02242. Retrieved from https://rethinkthc.com/research/pretzsch-2019-effects-of-cannabidiol-on
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.