29468
Cannabidiol Modulates Brain Excitation and Inhibition Systems in the Human Brain; But Differently in Adults with Autism Spectrum Disorder.
Poster Presentation
Saturday, May 4, 2019: 11:30 AM-1:30 PM
Room: 710 (Palais des congres de Montreal)
C. M. Pretzsch1, J. Freyberg2, B. Voinescu2, D. J. Lythgoe3, J. Horder4, M. A. Mendez5, R. H. Wichers6, L. Ajram7, G. Ivin8, M. Heasman8, R. A. Edden9, S. C. Williams10, D. G. Murphy11, E. Daly6 and G. M. McAlonan12, (1)IoPPN King's College London, London, United Kingdom, (2)King's College London, London, United Kingdom, (3)Department of Neuroimaging, King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom, (4)Institute of Psychiatry, King's College London, London, United Kingdom, (5)Forensic and Neurodevelopmental Sciences, King's College London, London, United Kingdom, (6)Department of Forensic and Neurodevelopmental Sciences, and the Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom, (7)Institute of Psychiatry, London, United Kingdom, (8)South London and Maudsley NHS Foundation Trust Pharmacy, UK, London, United Kingdom, (9)Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, (10)Centre for Neuroimaging Sciences, King's College London, London, United Kingdom, (11)Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom, (12)Behavioural Genetics Clinic, Adult Autism Service, Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley Foundation NHS Trust, London, United Kingdom
Background: 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, e.g. autism spectrum disorder (ASD). ASD is a common but complex condition, which shortens life. Currently there are no effective pharmacological treatments for its core symptoms. Therefore alternative options, such as CBD, are beginning to be explored. However, before embarking on large-scale clinical trials, it is necessary to better understand how CBD acts on human brain, and in ASD specifically. Among CBD’s multiple actions there is preclinical evidence that it may directly or indirectly modulate brain excitatory glutamate (E) and inhibitory γ-aminobutyric acid (GABA) (I) systems, including in brain regions linked to ASD, such as the basal ganglia (BG) and the dorsomedial prefrontal cortex (DMPFC). Also, abnormalities in glutamate and GABA pathways are consistently associated with ASD.
Objectives: Therefore, for the first time, we tested whether CBD ‘shifts’ glutamate and GABA in the BG and DMPFC in adults with and without ASD in vivo.
Methods: We used a placebo-controlled, cross-over, double-blind design and magnetic resonance spectroscopy (MRS) to investigate the impact of CBD on measures of glutamate (Glx = glutamate + glutamine) and GABA in 34 healthy men (neurotypicals n=17, ASD n=17). Data acquisition from the left BG (including the caudate and putamen) and bilateral DMPFC (including the anterior cingulate cortex) was timed to commence (at peak plasma levels) 2 hours after a single oral dose of 600 mg CBD or placebo.
Results: There were no baseline group differences in Glx or GABA concentration. Also, the response of Glx to CBD challenge was similar. In both groups CBD increased Glx in the BG but decreased it in the DMPFC (F(1,21)=5.235, p=.033). In contrast, there were significant group differences in GABA response. In both regions CBD increased GABA in the neurotypicals, but decreased it in ASD (F(1,22)=13.506, p=.001).
Conclusions: Our results provide the first direct evidence that CBD can modulate the glutamate and GABA system in neurotypicals and in ASD. However, prefrontal-subcortical GABA systems respond differently in ASD. Our results do not speak to the efficacy of CBD; therefore the next steps will be to examine the effects of more chronic administration on brain and behaviour; and to determine if acute brain changes predict longer-term response.
