R01AA031664

EFFECTS OF FULL-SPECTRUM CANNABIDIOL ON ALCOHOL CONSUMPTION AND ALCOHOL USE DISORDER PHENOTYPES: IMPLICATIONS FOR PRECISION MEDICINE - PROJECT SUMMARY ALCOHOL USE DISORDERS (AUD) ARE A LEADING CAUSE OF MORBIDITY AND MORTALITY IN THE US, BUT EXISTING TREATMENTS SHOW ONLY MODEST EFFICACY, AND SOME HAVE MEDICAL CONTRAINDICATIONS WHICH LIMIT THEIR UTILITY. IDENTIFICATION OF SAFE, NOVEL AUD MEDICATIONS IS A HIGH RESEARCH PRIORITY. CANNABIDIOL (CBD) HAS GENERATED INTEREST AS A TREATMENT TARGET DUE TO PRECLINICAL STUDIES SHOWING THAT IT REDUCES ALCOHOL INTAKE AND DATA SUGGESTING IT IS SAFE AND WELL- TOLERATED IN HUMANS. HUMAN RESEARCH HAS MAINLY TESTED PURE CBD (WHICH DOES NOT CONTAIN OTHER COMPONENTS OF THE CANNABIS PLANT). HOWEVER, EMERGING DATA, INCLUDING OUR OWN PRELIMINARY WORK, INDICATE THAT WHEN CBD IS COMBINED WITH A SMALL (<1%) AMOUNT OF DELTA-9-TETRAHYDROCANNABINOL (THC), ITS EFFECTS—INCLUDING ITS ABILITY TO REDUCE DRINKING—ARE ENHANCED. THUS, A COMPELLING, LARGELY UNEXPLORED POTENTIAL TREATMENT IS FULL SPECTRUM CBD (FS-CBD, WHICH CONTAINS MOSTLY CBD, PLUS A SMALL [<.3%] AMOUNT OF THC AND OTHER CANNABIS PLANT COMPONENTS). NOTABLY, FS-CBD IS ALREADY WIDELY AVAILABLE COMMERCIALLY IN THE US AND IS THE MOST POPULAR CBD PRODUCT ON THE MARKET. THUS, IF IT SHOWS PROMISING EFFECTS, IT COULD BE RAPIDLY INTEGRATED INTO CLINICAL CARE. THE OVERARCHING GOAL OF THIS PROPOSAL IS TO CONDUCT A RANDOMIZED, PLACEBO-CONTROLLED TRIAL COMPARING THE EFFECTS OF FS-CBD RELATIVE TO BROAD-SPECTRUM CBD (BS-CBD, WHICH IS THE SAME AS FS-CBD EXCEPT THAT IT DOES NOT CONTAIN THC) AND PLACEBO, ON ALCOHOL CONSUMPTION (IN THE LAB AND IN THE REAL WORLD [AIM 1]) AND ON SEVERAL CLINICALLY RELEVANT AUD PHENO- TYPES (AIMS 2 AND 3), AMONG ADULTS WITH AUD. SPECIFICALLY, WE WILL TEST EFFECTS OF FS-CBD (VS. BS-CBD AND PLA- CEBO) ON A BATTERY OF AUD PHENOTYPING MEASURES (CORRESPONDING TO THE ADDICTIONS NEUROCLINICAL ASSESSMENT [ANA] DOMAINS) THAT COULD AID IN IDENTIFYING INDIVIDUALS FOR WHOM FS-CBD IS LIKELY TO BE AN EFFECTIVE TREATMENT (AIM 2) AND ON THE GUT MICROBIOME (EXPLORATORY AIM 3), WHICH HAS BEEN SHOWN TO PLAY AN IMPORTANT ROLE IN THE ETIOLOGY AND MAINTENANCE OF AUD. NO PRIOR STUDY HAS EVALUATED EFFECTS OF FS-CBD ON ALCOHOL CONSUMPTION IN THE LAB OR EXPLORED POTENTIAL MEDIATORS OF ITS EFFECTS. WE WILL RECRUIT ADULTS WITH AUD TO BE RANDOMLY ASSIGNED TO TAKE FS-CBD, BS-CBD OR PLACEBO DAILY FOR 4 WEEKS, DURING WHICH THEY WILL REPORT ON THEIR ALCOHOL USE VIA DAILY SURVEYS. THEY WILL COMPLETE A LAB SESSION AT THE END OF THE 4 WEEKS INVOLVING AN ALCOHOL SELF-ADMINISTRATION (BAR LAB) TASK, ANA ASSESSMENTS, AND A BLOOD DRAW (TO MEASURE AN ALCOHOL BIOMARKER AND CIRCULATING GUT MARKERS). PARTICIPANTS WILL PROVIDE FECAL SAMPLES FOR ASSAYING THE GUT MICROBIOME. THE ANA BATTERY AND BLOOD AND FECAL SAMPLES WILL ALSO BE COLLECTED AT BASELINE, SO THAT POST-INTERVENTION CHANGE IN THE PROPOSED MEDIATORS CAN BE MEASURED. GIVEN THAT FS-CBD IS ALREADY WIDELY USED, RESULTS WOULD HAVE IMMEDIATE PUBLIC HEALTH AND CLINICAL IMPACT. FIND- INGS COULD ALSO INFORM A PRECISION-MEDICINE APPROACH (USING ANA PHENOTYPING OR PHENOTYPING BASED ON GUT CHARACTERISTICS) TO IDENTIFY AUD PATIENTS LIKELY TO RESPOND TO CBD TREATMENTS. FINALLY, RESULTS WILL SHED LIGHT ON THE INTERACTION BETWEEN CBD AND THC IN THE CONTEXT OF AUD AND COULD DEEPEN OUR UNDERSTANDING OF THE LINK BETWEEN THE ENDOGENOUS CANNABINOID SYSTEM AND AUD, TO PROVIDE FOUNDATIONAL DATA FOR FUTURE RESEARCH.

The Regents Of The Univ. Of Colorado

TO DEVELOP A SOUND FUNDAMENTAL KNOWLEDGE BASE WHICH CAN BE APPLIED TO THE DEVELOPMENT OF IMPROVED METHODS OF TREATMENT AND MORE EFFECTIVE STRATEGIES FOR PREVENTING ALCOHOLISM AND ALCOHOL-RELATED PROBLEMS. THE NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM (NIAAA) SUPPORTS RESEARCH IN A BROAD RANGE OF DISCIPLINES AND SUBJECT AREAS RELATED TO BIOMEDICAL AND GENETIC FACTORS, PSYCHOLOGICAL AND ENVIRONMENTAL FACTORS, ALCOHOL-RELATED PROBLEMS AND MEDICAL DISORDERS, HEALTH SERVICES RESEARCH, AND PREVENTION AND TREATMENT RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION AND TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.273 - Alcohol Research Programs

National Institute on Alcohol Abuse and Alcoholism (NIAAA) [HHS - NIH]

Aurora, Colorado 80045 United States

Single Zip Code

Alcohol Treatment, Pharmacotherapy, and Recovery Research (R01 Clinical Trial Required) (PAR-23-250)