Autism Spectrum Disorder
Conditions
Keywords
Cannabidiol, Cannabidivarin, E-I balance, pharmacological imaging
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.
Interventions
DRUGPLC
Single oral dose of PLC.
DRUGCBD
Single oral dose of cannabidiol (CBD) - 600mg.
DRUGCBDV
Single oral dose of cannabidivarin (CBDV) - 600mg.
Sponsors
King's College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and investigators were blinded to the drug condition.
Intervention model description
Repeated-measures cross-over study, where each subject received each of three pharmacological probes once (order of drug administration was pseudorandomised)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United Kingdom
Outcome results
None listed