The Efficacy and Neurobehavioural Mechanism of Cannabidiol (CBD) for Alcohol Dependence: An Exploratory Pilot Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Changes in High Frequency Heart Rate Variability
研究概览
简要总结
The study will explore the psychophysiological and neurobiological and mechanisms of CBD in participants with alcohol use disorder
详细描述
New treatment strategies for treating symptoms of alcohol dependence are urgently needed. Although alcohol related disorders are a leading cause of preventable death in Australia, their treatment is generally not evidence based. Cannabidiol (CBD) may serve as a novel pharmacotherapeutic due to its anxiolytic, anti-epileptic, neuro-protective, antioxidant and neuroprotective properties as well as a particularly safe side effect profile. Further, CBD has been shown to modulate drug craving and seeking behaviours.
This project will examine whether CBD exerts an effect on cue-induced craving by reducing activation in areas of the brain responsive to alcohol cues in comparison to a placebo. This study will use functional magnetic resonance imaging (fMRI) to examine activity in the brain while participants are exposed alcohol related cues and magnetic resonance spectroscopy (MRS) to determine levels of neurotransmitters that may be responsible for craving. In addition, we aim to investigate the effects of CBD on autonomic nervous system parameters associated with alcohol withdrawal symptoms and anxiety, such as heart rate variability and skin conductance. Additionally, clinical outcome measures will be taken to investigate CBDs influence on drinking, sleep
This project uses a randomised, double blind, crossover design with 800mg CBD vs matched placebo. The dosing paradigm will consist of one dose per day for three days per arm with a 18 days washout period in-between arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients between ages of 18 and 65 meeting DSM-5 criteria for current alcohol use disorder
- •Adequate cognition and English language skills to give valid consent and complete research interviews;
- •A BrAC reading of 0.00
- •Must have a stable residence and be able to identify an individual who could locate subject if needed
- •Provision of informed consent
排除标准
- •Active major psychological disorder associated with psychosis, significant suicide risk
- •Pregnancy or lactation - women shall be advised to use reliable contraception for the duration of drug therapy and a urine pregnancy test will be performed where necessary;
- •Dependence on any substance other than nicotine (eg methadone)
- •Diagnosis of epilepsy, and/or current use of anti-epileptic drugs (AED)
- •Liver failure with jaundice or prolonged INR above 1.3
- •Medical complications such as liver failure, cardiac ischemia or conduction abnormalities, renal impairment or unstable elevated vital signs (systolic blood pressure > 180, diastolic blood pressure > 120 or heart rate > 150)
- •Severe cognitive impairment or insufficient English or literacy to complete study processes
- •Concurrent use of drugs potentially exacerbated by CBD via CYP3A5 including cardiac medication (e.g. betablockers, calcium channel blockers and statins), macrolides and recent antihistamine use.
- •Claustrophobia;
- •Extreme obesity;
- •Previous brain surgery;
- •Ever employed as a machinist, a welder or a metal worker;
- •Metal items such as pacemakers; aneurysm clips in the brain; metal dental implants; metallic fragments in the eye or anywhere else; insulin pump; metal implants; hearing aid or a prosthetic device.
研究组 & 干预措施
Cannabidiol (CBD)
For a total of three days, so that both study participants and staff are blind to treatment condition
干预措施: Cannabidiol (CBD) (Drug)
Placebo
For a total of three days, so that both study participants and staff are blind to treatment condition
干预措施: Placebo (Drug)
结局指标
主要结局
Changes in High Frequency Heart Rate Variability
时间窗: 22 days
To assess whether acute ingestion of CBD can modulate heart rate variability when responding to alcohol cues compared to neutral cues
Changes in Skin Conductance Levels
时间窗: 22 days
To assess whether acute ingestion of CBD modulates skin conductance levels when responding to alcohol cues compared to neutral cues
Changes in Brain Activation
时间窗: 22 days
To assess whether acute ingestion of CBD can attenuate brain activation via blood oxygen level dependent (BOLD) in areas associated with alcohol cue-elicited craving measured by an fMRI machine
Changes in Neurotransmitter levels in the Brain
时间窗: 22 days
To assess whether CBD treatment leads to changes in brain levels of the neurotransmitters: glutamate, gamma-aminobutyric acid (GABA), N-acetylaspartate (NAA) and glutathione (GSH)
Heavy Drinking Days
时间窗: Up to 43 days
Reduction in Heavy Drinking Days (HDD; defined as 4 or more drinks in a day for women and five or more drinks in a day for men). This will be measured by the Timeline Follow Back.
Absence of any Heavy Drinking Day
时间窗: Up to 43 days
Measured by Timeline Follow Back
Mean Alcohol Consumption per Drinking Day
时间窗: Up to 43 days
Measured by Timeline Follow Back
Alcohol Dependence Severity
时间窗: Baseline
Measured by the Alcohol Dependence Scale. The minimum score is 0 and the maximum score is 47. A higher score indicates more severe dependence.
Alcohol Craving
时间窗: Up to 43 days
As measured by the Penn Alcohol Craving Scale (PACS), which measures the amount of time spent thinking and craving for alcohol, difficulty in resisting consumption of alcohol if present and hypothetical pleasure associated with consumption of alcohol. This scale has a minimum score of 0 and a maximum score of 6. A higher score indicates greater levels of craving.
次要结局
- Changes in Alcohol Craving(22 days)
- Sleep Disturbances(22 days)
- Changes in Alcohol Craving in response to alcohol cues(22 days)
- Changes in Positive and Negative Mood States(22 days)
- Changes in Anxiety(Up to 43 days)
- Changes in Depression(Up to 43 days)
- Changes in Stress(Up to 43 days)
- Changes in Tension Reduction Alcohol Expectancies(Up to 43 days)
- Lifetime Consequences related to Drinking(Baseline)
- Recent Consequences related to Drinking(Baseline)
- Behavioural Inhibition/Avoidance Scales(22 days)
- Obsessive Compulsive Drinking(22 days)
- Self-Confidence to Remain Abstinent(22 days)
- Intolerance of Uncertainty(22 days)
- Impulsivity(22 days)
- Alcohol Withdrawal(22 days)
- Approach and Avoidance towards Alcohol(Up to 43 days)
- Response Time and Visuospatial Skills(Up to 43 days)
- Set-shifting Flexibility, Attention, and Inhibition(Up to 43 days)
- Risk/Reward Taking Behaviour(Up to 43 days)
- Decision Making(Up to 43 days)
- Response Inhibition(Up to 43 days)
- Working Memory Capacity to Update Information(Up to 43 days)
- Working Memory Capacity to Shift Information(Up to 43 days)
- Markers of neuroinflammation(Up to 43 days)
- Markers of Stress(Up to 43 days)
研究者
Kirsten Morley BPsych MPH PhD
Associate Professor Kirsten Morley
University of Sydney