Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder

Sponsor
King's College London (Other)
Overall Status
Unknown status
CT.gov ID
NCT03537950
Collaborator
(none)
38
1
6
32.1
1.2

Study Details

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

Condition or Disease Intervention/Treatment Phase
N/A

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 Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Repeated-measures cross-over study, where each subject received each of three pharmacological probes once (order of drug administration was pseudorandomised)Repeated-measures cross-over study, where each subject received each of three pharmacological probes once (order of drug administration was pseudorandomised)
Masking:
Double (Participant, Investigator)
Masking Description:
Participants and investigators were blinded to the drug condition.
Primary Purpose:
Basic Science
Official Title:
Shifting Brain Excitation-Inhibition Balance Through the Endocannabinoid System in Men With Autism Spectrum Disorder (ASD) and in Healthy Controls
Actual Study Start Date :
Aug 22, 2016
Actual Primary Completion Date :
Feb 16, 2017
Anticipated Study Completion Date :
Apr 27, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: PLC, CBD, CBDV

Dose order: PLC, CBD, CBDV

Drug: PLC
Single oral dose of PLC.
Other Names:
  • Placebo
  • Drug: CBD
    Single oral dose of cannabidiol (CBD) - 600mg.
    Other Names:
  • Cannabidiol
  • Drug: CBDV
    Single oral dose of cannabidivarin (CBDV) - 600mg.
    Other Names:
  • Cannabidivarin
  • Experimental: PLC, CBDV, CBD

    Dose order: PL, CBDV, CBD

    Drug: PLC
    Single oral dose of PLC.
    Other Names:
  • Placebo
  • Drug: CBD
    Single oral dose of cannabidiol (CBD) - 600mg.
    Other Names:
  • Cannabidiol
  • Drug: CBDV
    Single oral dose of cannabidivarin (CBDV) - 600mg.
    Other Names:
  • Cannabidivarin
  • Experimental: CBD, PLC, CBDV

    Dose order: CBD, PLC, CBDV

    Drug: PLC
    Single oral dose of PLC.
    Other Names:
  • Placebo
  • Drug: CBD
    Single oral dose of cannabidiol (CBD) - 600mg.
    Other Names:
  • Cannabidiol
  • Drug: CBDV
    Single oral dose of cannabidivarin (CBDV) - 600mg.
    Other Names:
  • Cannabidivarin
  • Experimental: CBD, CBDV, PLC

    Dose order: CBD, CBDV, PLC

    Drug: PLC
    Single oral dose of PLC.
    Other Names:
  • Placebo
  • Drug: CBD
    Single oral dose of cannabidiol (CBD) - 600mg.
    Other Names:
  • Cannabidiol
  • Drug: CBDV
    Single oral dose of cannabidivarin (CBDV) - 600mg.
    Other Names:
  • Cannabidivarin
  • Experimental: CBDV, PLC, CBD

    Dose order: CBDV, PLC, CBD

    Drug: PLC
    Single oral dose of PLC.
    Other Names:
  • Placebo
  • Drug: CBD
    Single oral dose of cannabidiol (CBD) - 600mg.
    Other Names:
  • Cannabidiol
  • Drug: CBDV
    Single oral dose of cannabidivarin (CBDV) - 600mg.
    Other Names:
  • Cannabidivarin
  • Experimental: CBDV, CBD, PLC

    Dose order: CBDV, CBD, PLC

    Drug: PLC
    Single oral dose of PLC.
    Other Names:
  • Placebo
  • Drug: CBD
    Single oral dose of cannabidiol (CBD) - 600mg.
    Other Names:
  • Cannabidiol
  • Drug: CBDV
    Single oral dose of cannabidivarin (CBDV) - 600mg.
    Other Names:
  • Cannabidivarin
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 King's College London London United Kingdom SE5 8AF

    Sponsors and Collaborators

    • King's College London

    Investigators

    • Principal Investigator: Grainne McAlonan, PhD, King's College London

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Dr Grainne McAlonan, Deputy head of department, King's College London
    ClinicalTrials.gov Identifier:
    NCT03537950
    Other Study ID Numbers:
    • HR15-162744
    First Posted:
    May 25, 2018
    Last Update Posted:
    May 25, 2018
    Last Verified:
    May 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Dr Grainne McAlonan, Deputy head of department, King's College London
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 25, 2018