Clinical trial NCT05387148: The Efficacy and Neurobehavioural Mechanism of Cannabidiol (CBD) for Alcohol Dependence
Official title: The Efficacy and Neurobehavioural Mechanism of Cannabidiol (CBD) for Alcohol Dependence: An Exploratory Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alcohol Use Disorder (AUD)
Keywords: Alcohol Withdrawal
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Lead sponsor: South West Sydney Local Health District
Sponsor class: OTHER
Collaborators: name: University of Sydney
name: Lambert Initiative for Cannabinoid Therapeutics
First posted: 2022-05-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The study will explore the psychophysiological and neurobiological and mechanisms of CBD in participants with alcohol use disorder

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Changes in High Frequency Heart Rate Variability
timeFrame: 22 days
measure: Changes in Skin Conductance Levels
timeFrame: 22 days
measure: Changes in Brain Activation
timeFrame: 22 days
measure: Changes in Neurotransmitter levels in the Brain
timeFrame: 22 days
measure: Heavy Drinking Days
timeFrame: Up to 43 days
measure: Absence of any Heavy Drinking Day
timeFrame: Up to 43 days
measure: Mean Alcohol Consumption per Drinking Day
timeFrame: Up to 43 days
measure: Alcohol Dependence Severity
timeFrame: Baseline
measure: Alcohol Craving
timeFrame: Up to 43 days
Secondary outcomes:
measure: Changes in Alcohol Craving
timeFrame: 22 days
measure: Changes in Alcohol Craving in response to alcohol cues
timeFrame: 22 days
measure: Changes in Positive and Negative Mood States
timeFrame: 22 days
measure: Changes in Anxiety
timeFrame: Up to 43 days
measure: Changes in Depression
timeFrame: Up to 43 days
measure: Changes in Stress
timeFrame: Up to 43 days
measure: Sleep Disturbances
timeFrame: Up to 43 days
measure: Sleep Disturbances
timeFrame: 22 days
measure: Changes in Tension Reduction Alcohol Expectancies
timeFrame: Up to 43 days
measure: Lifetime Consequences related to Drinking
timeFrame: Baseline
measure: Recent Consequences related to Drinking
timeFrame: Baseline
measure: Behavioural Inhibition/Avoidance Scales
timeFrame: 22 days
measure: Obsessive Compulsive Drinking
timeFrame: 22 days
measure: Self-Confidence to Remain Abstinent
timeFrame: 22 days
measure: Intolerance of Uncertainty
timeFrame: 22 days
measure: Impulsivity
timeFrame: 22 days
measure: Alcohol Withdrawal
timeFrame: 22 days
measure: Approach and Avoidance towards Alcohol
timeFrame: Up to 43 days
measure: Response Time and Visuospatial Skills
timeFrame: Up to 43 days
measure: Set-shifting Flexibility, Attention, and Inhibition
timeFrame: Up to 43 days
measure: Risk/Reward Taking Behaviour
timeFrame: Up to 43 days
measure: Decision Making
timeFrame: Up to 43 days
measure: Response Inhibition
timeFrame: Up to 43 days
measure: Working Memory Capacity to Update Information
timeFrame: Up to 43 days
measure: Working Memory Capacity to Shift Information
timeFrame: Up to 43 days
measure: Markers of neuroinflammation
timeFrame: Up to 43 days
measure: Markers of Stress
timeFrame: Up to 43 days
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Drug Health Services, Royal Prince Alfred Hospital
state: New South Wales
Study officials:
References: