Cannabis is the most commonly used illicit drug in the United States. Although cannabis use is widespread and basic science research on cannabinoids is well-developed, advancements in medication development for cannabis use disorder (CUD) have been limited. Varenicline, a selective nicotinic nACH receptor partial agonist of the ?4?2 subtype and a full agonist of the ?7 subtype, is arguably the most effective pharmacotherapy for promoting tobacco abstinence, and has also shown promise for the treatment of alcohol use disorder. Varenicline may improve cannabis use outcomes through multiple mechanisms, including interaction with the mesolimbic dopamine system, enhancement of cognitive functioning, and restoration of inhibitory control. To date, however, varenicline has not been evaluated in individuals specifically seeking treatment for CUD. In this UG3/UH3 application, we propose to rapidly yet thoroughly assess the utility of varenicline for CUD to potentially advance varenicline through the FDA's drug development approval pipeline. In the UG3 component, we will conduct a six-week, placebo-controlled proof-of-concept clinical trial of varenicline for CUD, paired with pre- and post- evaluations of cognitive functioning and neural circuitry involved in cannabis cue reactivity and inhibitory control to elucidate the pharmacodynamics of varenicline as a treatment for CUD. If milestones of the UG3 component are met, the UH3 project will be an adequately powered 12-week clinical trial with follow-up to fully assess the efficacy of varenicline in this population.

Public Health Relevance

Cannabis is the most commonly used illicit drug, yet an efficacious pharmacotherapy for cannabis use disorder (CUD) has yet to be identified. This study will initially evaluate the efficacy of varenicline for CUD in a proof-of- concept clinical trial, paired with pre- and post-evaluations of cognitive functioning and neural circuitry involved in cannabis cue reactivity and inhibitory control. If milestones are successfully completed, a larger, 12-week trial of varenicline for CUD is proposed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
Project #
4UH3DA043231-03
Application #
9667836
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Hampson, Aidan
Project Start
2016-09-15
Project End
2022-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Psychiatry
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29407