Shifting Brain Excitation-Inhibition Balance Through the Endocannabinoid System in Men With Autism Spectrum Disorder (ASD) and in Healthy Controls
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Brain biochemistry response to pharmacological stimulation
研究概览
简要总结
This study investigates brain response to single acute dose of cannabidiol, cannabidivarin, and placebo in healthy men with and without autism spectrum disorder
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants and investigators were blinded to the drug condition.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
PLC, CBDV, CBD
Dose order: PL, CBDV, CBD
干预措施: CBDV (Drug)
PLC, CBD, CBDV
Dose order: PLC, CBD, CBDV
干预措施: PLC (Drug)
PLC, CBD, CBDV
Dose order: PLC, CBD, CBDV
干预措施: CBD (Drug)
PLC, CBD, CBDV
Dose order: PLC, CBD, CBDV
干预措施: CBDV (Drug)
PLC, CBDV, CBD
Dose order: PL, CBDV, CBD
干预措施: PLC (Drug)
PLC, CBDV, CBD
Dose order: PL, CBDV, CBD
干预措施: CBD (Drug)
CBD, PLC, CBDV
Dose order: CBD, PLC, CBDV
干预措施: PLC (Drug)
CBD, PLC, CBDV
Dose order: CBD, PLC, CBDV
干预措施: CBD (Drug)
CBD, PLC, CBDV
Dose order: CBD, PLC, CBDV
干预措施: CBDV (Drug)
CBD, CBDV, PLC
Dose order: CBD, CBDV, PLC
干预措施: PLC (Drug)
CBD, CBDV, PLC
Dose order: CBD, CBDV, PLC
干预措施: CBD (Drug)
CBD, CBDV, PLC
Dose order: CBD, CBDV, PLC
干预措施: CBDV (Drug)
CBDV, PLC, CBD
Dose order: CBDV, PLC, CBD
干预措施: PLC (Drug)
CBDV, PLC, CBD
Dose order: CBDV, PLC, CBD
干预措施: CBD (Drug)
CBDV, PLC, CBD
Dose order: CBDV, PLC, CBD
干预措施: CBDV (Drug)
CBDV, CBD, PLC
Dose order: CBDV, CBD, PLC
干预措施: PLC (Drug)
CBDV, CBD, PLC
Dose order: CBDV, CBD, PLC
干预措施: CBD (Drug)
CBDV, CBD, PLC
Dose order: CBDV, CBD, PLC
干预措施: CBDV (Drug)
结局指标
主要结局
Brain biochemistry response to pharmacological stimulation
时间窗: 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.
次要结局
- Measurement of low frequency brain activity using resting state fMRI(In the months 3-4 following the last day of scanning)
- Measurement of brain functional connectivity using resting state fMRI(In the months 5-6 following the last day of scanning)
研究者
Dr Grainne McAlonan
Deputy head of department
King's College London