Exploring the Effects of Cannabinoids on Alcohol Consumption and the Microbiota-Gut-Brain Axis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 2
- 主要终点
- Impulsivity Cognition: Stop Signal Task
研究概览
简要总结
This observational study aims to improve our understanding of how legal market cannabis use impacts acute and long-term alcohol use, the microbiota-gut-brain-axis (MGBA), and neurobehavioral alcohol use phenotypes such as impulsivity, impaired cognitive functioning, and craving, among individuals who regularly use both alcohol and cannabis. Over a period of one month, subjects will participate in this three-visit study. Blood samples will be collected to allow for the assessment of inflammatory markers and cannabinoids, a fecal sample will be collected to allow for the analysis of the gut microbiome, and participants will complete cognitive and impulsivity tasks and provide craving ratings during the course of an alcohol self-administration procedure. Subjects will also participate in two 14-day daily diary data collection periods between lab sessions. Daily diary data collection will be used to assess the effects of cannabis use on alcohol use and craving longitudinally.
详细描述
At present, the consumption of alcohol and alcohol use disorder (AUD) constitute a public health crisis. Due to the neurobiological complexity of AUD, the development of new treatments requires a deeper understanding of the molecular mechanisms underlying etiology and course of AUD. This includes the degree to which cannabis use may reduce or enhance harms of alcohol consumption through cannabinoid influence on gut and immune functions. One potential mechanism through which cannabinoids may exert beneficial effects in heavy drinkers is through their role in modulating the gut microbiome and immune system, which have been found to be disrupted by alcohol. However, it is also possible that cannabinoids, specifically delta-9-Tetrahydrocannabinol (THC), may confer harms in heavy drinkers by enhancing the intoxicating effects of alcohol. The current study will be the first to explore the acute and long-term effects of cannabis on alcohol use and neurobehavioral phenotypes, including alcohol craving, impulsivity, and impaired cognition, as well as the impact of cannabinoids on the microbiota-gut-brain-axis (MGBA) in human non-treatment-seeking, regular-cannabis-using heavy drinkers.
This study examines the effects of legal market cannabis on acute and long-term alcohol use, (specifically the effects of alcohol and cannabis use on gut microbiome and inflammatory markers in the blood) in a 4-week, observational design using both traditional and mobile lab settings, as well as self-report, daily diary methodology. Participants will complete two Phases (A and B) following by two visits to our mobile laboratory (Visits A and B), the order of which will be counterbalanced across participants so that half of participants will complete phase A/visit A first, and the other half will complete Phase B/Visit B first. Phase A involves 2 weeks of no cannabis use followed by a mobile lab session (Visit A), involving biological sample collection, neurobehavioral testing and an alcohol self-administration task. Phase B involves 2 weeks of ad lib use of participant preferred cannabis product, followed by a session in the mobile lab session (Visit B) in which participants will complete the same neurobehavioral tasks, biological sample collection, and alcohol self-administration task immediately following acute ingestion of preferred cannabis strain in participant homes.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •21-60 years of age
- •Able to provide consent
- •Heavy drinker, defined as: for men, consuming more than 4 drinks on any day or more than 14 drinks per week OR, for women, consuming more than 3 drinks on any day or more than 7 drinks per week over the last 3 months.
- •Regular legal-market cannabis smoker, defined as using smoked flower cannabis obtained from a dispensary at least 3 days per/week over the past 3 months
- •Willing to abstain from cannabis use for 14 days
- •We are prioritizing the recruitment of participants in the Fort Collins/Loveland area
排除标准
- •Daily tobacco use*** (Vape and Hooka included)
- •Actively seeking treatment for alcohol use disorder or other substance use disorder
- •Females cannot be pregnant, breastfeeding or trying to become pregnant
- •Meet criteria for psychotic, bipolar or major depressive disorder with suicidal ideation, or history of these disorders
- •Immune-relevant disease (e.g., osteoarthritis, HIV, cancer, recent infection, other autoimmune disorder) or currently taking an immune-modulating medication***
- •Current use of psychotropic medications (except anti-depressants )
- •Report illicit drug use in past 60-days or fail drug screen
- •Major medical condition that contraindicates the consumption of alcohol or cannabis.
- •Use of an antibiotic medication in the past 3 months
- •Current GI disorder including: inflammatory bowel disease, irritable bowel disease, diverticular disease, peptic ulcer/gastritis and gastroesophageal reflux disease.
- •Use of probiotic or supplement drinks at least once per week over the last 3 months
结局指标
主要结局
Impulsivity Cognition: Stop Signal Task
时间窗: Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart: Pre-alcohol/cannabis consumption, Post-alcohol/cannabis consumption
This task requires responding quickly to "go" signals, and occasionally inhibiting those responses when a "stop" signal is displayed.
Gut microbiota
时间窗: Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart.
Outcomes of interest include gut bacterial diversity and composition. Gut microbiome data from Session A will be compared with gut microbiome data from Session B.
Acute alcohol consumption
时间窗: Change over two time points: Session A (alcohol administration only) and Session B (alcohol administration + ad-libitum cannabis administration). Sessions A and B are 2 weeks apart.
Total number of drinks consumed (out of 4) in a one-hour period.
Inflammation
时间窗: Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart
Test levels of inflammation (panel of inflammatory cytokines) at Session A (following 2 weeks of no cannabis use) and Session B (following 2 weeks of ad lib cannabis use).
Daily alcohol consumption
时间窗: Change over two consecutive 14-day daily time periods
Two 14-day daily data collection periods using self-report of alcohol craving and amount of alcohol consumed
次要结局
- Change in Alcohol Craving (Visual-Analog Scale(Change over two time points: Session A (alcohol administration only) and Session B (alcohol administration + ad-libitum cannabis administration). Sessions A and B are 2 weeks apart)
- NIH Toolbox Flanker Test(Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart: Pre-alcohol/cannabis consumption, Post-alcohol/cannabis consumption)
- Intestinal permeability(Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart)
- The Alcohol Purchase Task (APT)(Change between reward value of alcohol when cannabis is on board (session B) compared to when it is not (session A). This task will also be administered at baseline (when not intoxicated) to compare sober state-level alcohol reward)
- Change in Alcohol Craving (Visual-Analog Scale(Change over two time points: Session A (alcohol administration only) and Session B (alcohol administration + ad-libitum cannabis administration). Sessions A and B are 2 weeks apart)
- NIH Toolbox Flanker Test(Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart: Pre-alcohol/cannabis consumption, Post-alcohol/cannabis consumption)
- Intestinal permeability(Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart)
- The Alcohol Purchase Task (APT)(Change between reward value of alcohol when cannabis is on board (session B) compared to when it is not (session A). This task will also be administered at baseline (when not intoxicated) to compare sober state-level alcohol reward)
研究者
Hollis Karoly
Associate Professor
University of Colorado, Denver