Research output: Contribution to journal › Article › peer-review
Charlotte Marie Pretzsch, Jan Freyberg, Bogdan Ioan Voinescu, David John Lythgoe, Jamie Horder, M Andreina Mendez, Robert Hendrik Wichers, Laura Ann Ajram, Glynis Ivin, Martin Heasman, Richard AE Edden, Steven Charles Rees Williams, Declan G Murphy, Eileen Daly, Grainne Mary McAlonan
Original language | English |
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Pages (from-to) | 1398-1405 |
Number of pages | 8 |
Journal | Neuropsychopharmacology |
Volume | 44 |
Issue number | 8 |
DOIs | |
Published | 1 Jul 2019 |
Additional links |
s41386_019_0333_8_reference.pdf, 1.5 MB, application/pdf
Uploaded date:15 Feb 2019
Version:Accepted author manuscript
There is increasing interest in the use of cannabis and its major non-intoxicating component cannabidiol (CBD) as a treatment for mental health and neurodevelopmental disorders, such as autism spectrum disorder (ASD). However, before launching large-scale clinical trials, a better understanding of the effects of CBD on brain would be desirable. Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels, including in brain regions linked to ASD, such as the basal ganglia (BG) and the dorsomedial prefrontal cortex (DMPFC). However, differences in glutamate and GABA pathways in ASD mean that the response to CBD in people with and without ASD may be not be the same. To test whether CBD ‘shifts’ glutamate and GABA levels; and to examine potential differences in this response in ASD, we used magnetic resonance spectroscopy (MRS) to measure glutamate (Glx = glutamate + glutamine) and GABA+ (GABA + macromolecules) levels in 34 healthy men (17 neurotypicals, 17 ASD). Data acquisition commenced 2 h (peak plasma levels) after a single oral dose of 600 mg CBD or placebo. Test sessions were at least 13 days apart. Across groups, CBD increased subcortical, but decreased cortical, Glx. Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant. Thus, CBD modulates glutamate-GABA systems, but prefrontal-GABA systems respond differently in ASD. Our results do not speak to the efficacy of CBD. Future studies should examine the effects of chronic administration on brain and behaviour, and whether acute brain changes predict longer-term response.
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