Effects of Repeated CBD Administration on Cannabis Abuse-Liability and Analgesia: A Human Laboratory Study

Project Summary Over 50 million Americans suffer from chronic pain, and many use cannabis and cannabidiol (CBD), a constituent of cannabis, to treat their pain. Despite state-wide cannabis legalization and mainstream promotion of the medical benefits of these products, there are few carefully controlled empirical studies assessing the effects of cannabis and CBD when used repeatedly or used in combination. Pre-clinical studies show CBD enhances the analgesic efficacy of cannabis while attenuating its abuse-related properties, but the effect of repeated CBD use on cannabis-induced analgesia and abuse liability in humans is not known. In the proposed randomized, counterbalanced, human laboratory study, healthy adult cannabis smokers (N=72; 36M, 36F) will be randomized to receive one of four CBD doses (0, 50, 100, 300 mg/day) for 15 days. On days 1, 8, and 15, they will participate in a laboratory session, where they will smoke 75% of a cannabis cigarette (7% THC) and we will measure the time-course of abuse-related subjective effects (good drug effect, high) and experimental pain using two mechanistically distinct paradigms (Cold Pressor Test, Quantitative Sensory Testing) over 3 hours. We will then assess whether CBD alters cannabis’s reinforcing effects by providing participants the opportunity to self-administer up to 4 additional puffs of cannabis (7% THC). This study will answer two critical questions: Does daily oral CBD administration alter: 1) the abuse-related and reinforcing effects of smoked cannabis; 2) the analgesic effects of smoked cannabis. In addition to contributing novel data regarding the interaction between CBD and cannabis, this proposal will provide critical training needed to achieve my goal of becoming an independently funded researcher. Specifically, this mentored research scientist development application will advance my career by providing essential: (1) experience in human laboratory model study design and methodology, specifically to evaluate cannabinoids on abuse-and pain-related endpoints, and (2) training in statistics and grantsmanship. My past pre-clinical research experience combined with the goals I have set forth within this application will allow me to gain the skills and experiences to become an independent research scientist translating findings from pre-clinical animal models into human laboratory studies.