Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder

Autism Spectrum Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03537950
• Other study ID #: HR15-162744
• Status: Completed
• Phase: N/A
• Start date: August 22, 2016
• Est. completion date: March 1, 2017

Study information

• Verified date: March 2024
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: March 1, 2017
• Est. primary completion date: February 16, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive

Intervention

Drug:
• PLC
Single oral dose of PLC.
• CBD
Single oral dose of cannabidiol (CBD) - 600mg.
• CBDV
Single oral dose of cannabidivarin (CBDV) - 600mg.

Locations

Country	Name	City	State
United Kingdom	King's College London	London

Sponsors (1)

Lead Sponsor	Collaborator
King's College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain biochemistry response to pharmacological stimulation	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.	In the months 1-2 following the last day of scanning.
Secondary	Measurement of low frequency brain activity using resting state fMRI	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.	In the months 3-4 following the last day of scanning
Secondary	Measurement of brain functional connectivity using resting state fMRI	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.	In the months 5-6 following the last day of scanning