Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder
March 4, 2024 updated by: Dr Grainne McAlonan, King's College London
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
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
38
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
London, United Kingdom, SE5 8AF
- King's College London
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
14 years to 46 years (Adult)
Accepts Healthy Volunteers
Yes
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: PLC, CBD, CBDV
Dose order: PLC, CBD, CBDV
|
Single oral dose of PLC.
Other Names:
Single oral dose of cannabidiol (CBD) - 600mg.
Other Names:
Single oral dose of cannabidivarin (CBDV) - 600mg.
Other Names:
|
|
Experimental: PLC, CBDV, CBD
Dose order: PL, CBDV, CBD
|
Single oral dose of PLC.
Other Names:
Single oral dose of cannabidiol (CBD) - 600mg.
Other Names:
Single oral dose of cannabidivarin (CBDV) - 600mg.
Other Names:
|
|
Experimental: CBD, PLC, CBDV
Dose order: CBD, PLC, CBDV
|
Single oral dose of PLC.
Other Names:
Single oral dose of cannabidiol (CBD) - 600mg.
Other Names:
Single oral dose of cannabidivarin (CBDV) - 600mg.
Other Names:
|
|
Experimental: CBD, CBDV, PLC
Dose order: CBD, CBDV, PLC
|
Single oral dose of PLC.
Other Names:
Single oral dose of cannabidiol (CBD) - 600mg.
Other Names:
Single oral dose of cannabidivarin (CBDV) - 600mg.
Other Names:
|
|
Experimental: CBDV, PLC, CBD
Dose order: CBDV, PLC, CBD
|
Single oral dose of PLC.
Other Names:
Single oral dose of cannabidiol (CBD) - 600mg.
Other Names:
Single oral dose of cannabidivarin (CBDV) - 600mg.
Other Names:
|
|
Experimental: CBDV, CBD, PLC
Dose order: CBDV, CBD, PLC
|
Single oral dose of PLC.
Other Names:
Single oral dose of cannabidiol (CBD) - 600mg.
Other Names:
Single oral dose of cannabidivarin (CBDV) - 600mg.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Brain biochemistry response to pharmacological stimulation
Time Frame: 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. |
In the months 1-2 following the last day of scanning.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Measurement of low frequency brain activity using resting state fMRI
Time Frame: 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.
|
In the months 3-4 following the last day of scanning
|
|
Measurement of brain functional connectivity using resting state fMRI
Time Frame: 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.
|
In the months 5-6 following the last day of scanning
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Grainne McAlonan, PhD, King's College London
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 22, 2016
Primary Completion (Actual)
February 16, 2017
Study Completion (Actual)
March 1, 2017
Study Registration Dates
First Submitted
April 17, 2018
First Submitted That Met QC Criteria
May 15, 2018
First Posted (Actual)
May 25, 2018
Study Record Updates
Last Update Posted (Estimated)
March 5, 2024
Last Update Submitted That Met QC Criteria
March 4, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HR15-162744
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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