Back to resultsShifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder
Primary Purpose
Autism Spectrum Disorder
Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
PLC
CBD
CBDV
Sponsored by
About this trial
This is an interventional basic science trial for Autism Spectrum Disorder focused on measuring Cannabidiol, Cannabidivarin, E-I balance, pharmacological imaging
Eligibility Criteria
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.
Sites / Locations
- King's College London
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
PLC, CBD, CBDV
PLC, CBDV, CBD
CBD, PLC, CBDV
CBD, CBDV, PLC
CBDV, PLC, CBD
CBDV, CBD, PLC
Arm Description
Dose order: PLC, CBD, CBDV
Dose order: PL, CBDV, CBD
Dose order: CBD, PLC, CBDV
Dose order: CBD, CBDV, PLC
Dose order: CBDV, PLC, CBD
Dose order: CBDV, CBD, PLC
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03537950
Brief Title
Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder
Official Title
Shifting Brain Excitation-Inhibition Balance Through the Endocannabinoid System in Men With Autism Spectrum Disorder (ASD) and in Healthy Controls
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 22, 2016 (Actual)
Primary Completion Date
February 16, 2017 (Actual)
Study Completion Date
April 27, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
King's College London
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder
Keywords
Cannabidiol, Cannabidivarin, E-I balance, pharmacological imaging
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Repeated-measures cross-over study, where each subject received each of three pharmacological probes once (order of drug administration was pseudorandomised)
Masking
ParticipantInvestigator
Masking Description
Participants and investigators were blinded to the drug condition.
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PLC, CBD, CBDV
Arm Type
Experimental
Arm Description
Dose order: PLC, CBD, CBDV
Arm Title
PLC, CBDV, CBD
Arm Type
Experimental
Arm Description
Dose order: PL, CBDV, CBD
Arm Title
CBD, PLC, CBDV
Arm Type
Experimental
Arm Description
Dose order: CBD, PLC, CBDV
Arm Title
CBD, CBDV, PLC
Arm Type
Experimental
Arm Description
Dose order: CBD, CBDV, PLC
Arm Title
CBDV, PLC, CBD
Arm Type
Experimental
Arm Description
Dose order: CBDV, PLC, CBD
Arm Title
CBDV, CBD, PLC
Arm Type
Experimental
Arm Description
Dose order: CBDV, CBD, PLC
Intervention Type
Drug
Intervention Name(s)
PLC
Other Intervention Name(s)
Placebo
Intervention Description
Single oral dose of PLC.
Intervention Type
Drug
Intervention Name(s)
CBD
Other Intervention Name(s)
Cannabidiol
Intervention Description
Single oral dose of cannabidiol (CBD) - 600mg.
Intervention Type
Drug
Intervention Name(s)
CBDV
Other Intervention Name(s)
Cannabidivarin
Intervention Description
Single oral dose of cannabidivarin (CBDV) - 600mg.
Primary Outcome Measure Information:
Title
Brain biochemistry response to pharmacological stimulation
Description
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.
Time Frame
In the months 1-2 following the last day of scanning.
Secondary Outcome Measure Information:
Title
Measurement of low frequency brain activity using resting state fMRI
Description
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.
Time Frame
In the months 3-4 following the last day of scanning
Title
Measurement of brain functional connectivity using resting state fMRI
Description
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.
Time Frame
In the months 5-6 following the last day of scanning
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grainne McAlonan, PhD
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
King's College London
City
London
ZIP/Postal Code
SE5 8AF
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34210360
Citation
Pretzsch CM, Floris DL, Voinescu B, Elsahib M, Mendez MA, Wichers R, Ajram L, Ivin G, Heasman M, Pretzsch E, Williams S, Murphy DGM, Daly E, McAlonan GM. Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin. Mol Autism. 2021 Jul 1;12(1):49. doi: 10.1186/s13229-021-00454-6.
Results Reference
derived
Learn more about this trial
Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder
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