Clinical trial NCT03537950: 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
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: Cannabidiol
Cannabidivarin
E-I balance
pharmacological imaging
Lead sponsor: King's College London
Sponsor class: OTHER
First posted: 2018-05-25
Enrollment: 38
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Repeated-measures cross-over study, where each subject received each of three pharmacological probes once (order of drug administration was pseudorandomised)
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Brain biochemistry response to pharmacological stimulation
timeFrame: In the months 1-2 following the last day of scanning.
Secondary outcomes:
measure: Measurement of low frequency brain activity using resting state fMRI
timeFrame: In the months 3-4 following the last day of scanning
measure: Measurement of brain functional connectivity using resting state fMRI
timeFrame: In the months 5-6 following the last day of scanning
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College London
Study officials:
affiliation: King's College London
name: Grainne McAlonan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.