Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder

Shifting Brain Excitation-Inhibition Balance Through the Endocannabinoid System in Men With Autism Spectrum Disorder (ASD) and in Healthy Controls

This study investigates brain response to single acute dose of cannabidiol, cannabidivarin, and placebo in healthy men with and without autism spectrum disorder

Previous research suggests that cannabidiol (CBD) and cannabidivarin (CBDV) could have the potential to shift brain excitation and inhibition (E-I) in the healthy brain and in neurodevelopmental psychiatric conditions, where this balance is disrupted, such as autism spectrum disorder (ASD). However, no study to date has investigated this. Therefore, in this study, we invited 20 healthy men with and without ASD. Each participant received each drug once (600mg CBD/CBDV, or matched placebo) and magnetic resonance imaging was used to obtain measures of brain biochemistry, activity, and connectivity. We further obtained questionnaires, task data, saliva, urine and blood samples, and conducted visual tasks using eye tracking, electroencephalography, and retinal imaging.

Inclusion Criteria:

• men
• pass diagnostic threshold for ASD on the ADI-R (if informant is available)
• currently symptomatic on ADOS
• age 18-50 years
• can give informed consent
• IQ>70 (on a standard instrument such as WASI)
• medication-free in the month preceding participation (but regular medication with drug, which does not affect glutamate or GABA directly may be permitted)
• willing to provide urine samples to screen for use of illicit substances prior to each scan

Exclusion Criteria:

• IQ<70
• history of psychosis, co-morbid major mental illness, significant physical illness (heart disease, high blood pressure, seizures)
• habitual substance misuse (including alcohol)
• known allergy to cannabis
• ASD caused by a known genetic syndrome e.g. Fragile X or 22q11 deletion syndrome,
• past/present treatment for epilepsy
• Women will be excluded from this pilot study to reduce heterogeneity in a small sample; avoid the issues around exposing women of reproductive age to a drug; and because pregnancy is a routine exclusion criteria for research MRI. Lastly, ASD is more common in men.