Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder
- Registration Number
- NCT03537950
- Lead Sponsor
- King's College London
- Brief Summary
This study investigates brain response to single acute dose of cannabidiol, cannabidivarin, and placebo in healthy men with and without autism spectrum disorder
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 38
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description PLC, CBDV, CBD PLC Dose order: PL, CBDV, CBD CBD, PLC, CBDV PLC Dose order: CBD, PLC, CBDV CBDV, PLC, CBD CBD Dose order: CBDV, PLC, CBD CBDV, PLC, CBD CBDV Dose order: CBDV, PLC, CBD PLC, CBD, CBDV CBD Dose order: PLC, CBD, CBDV PLC, CBD, CBDV CBDV Dose order: PLC, CBD, CBDV PLC, CBD, CBDV PLC Dose order: PLC, CBD, CBDV CBD, PLC, CBDV CBD Dose order: CBD, PLC, CBDV CBD, PLC, CBDV CBDV Dose order: CBD, PLC, CBDV CBD, CBDV, PLC PLC Dose order: CBD, CBDV, PLC CBD, CBDV, PLC CBD Dose order: CBD, CBDV, PLC CBD, CBDV, PLC CBDV Dose order: CBD, CBDV, PLC CBDV, PLC, CBD PLC Dose order: CBDV, PLC, CBD CBDV, CBD, PLC PLC Dose order: CBDV, CBD, PLC PLC, CBDV, CBD CBD Dose order: PL, CBDV, CBD CBDV, CBD, PLC CBD Dose order: CBDV, CBD, PLC CBDV, CBD, PLC CBDV Dose order: CBDV, CBD, PLC PLC, CBDV, CBD CBDV Dose order: PL, CBDV, CBD
- Primary Outcome Measures
Name Time Method Brain biochemistry response to pharmacological stimulation In the months 1-2 following the last day of scanning. The measure of brain biochemistry response to PLC, CBD, and CBDV includes the following:
Assessment of the ratio of brain excitation and inhibition (measured as the balance of excitatory and inhibitory neurotransmitters) using using proton magnetic resonance spectroscopy \[1H\]MRS.
- Secondary Outcome Measures
Name Time Method Measurement of low frequency brain activity using resting state fMRI In the months 3-4 following the last day of scanning In the third and fourth month following the day of the last scan, we will measure whole brain low frequency brain activity using resting state functional magnetic resonance imaging. Measure of activity: fractional amplitude of low frequency fluctuations.
Measurement of brain functional connectivity using resting state fMRI In the months 5-6 following the last day of scanning In the fifth and sixth month following the day of the last scan, we will measure whole brain resting state functional connectivity using resting state functional magnetic resonance imaging. Measure of connectivity: correlation between pairs of regions.
Trial Locations
- Locations (1)
King's College London
🇬🇧London, United Kingdom