Clinical Trial Network, Ohio Valley Node

2.1 Study Objectives The objective of this within-subject study is to assess the effect of oral cannabidiol (CBD; 0, 200, 400, 800 mg) on smoked marijuana’s (0, 5.6% THC) subjective, reinforcing, cognitive, and cardiovascular effects. This experiment is expected to reveal CBD’s intrinsic effects when combined with placebo marijuana, as well as its ability to modulate the behavioral effects of active marijuana. 2.2 Study Design At each site, 12 non-treatment-seeking marijuana smokers will complete 8 outpatient clinic test sessions over the course of 8 weeks. Three sites will participate (and will complete a total of 36 participants across sites). 2.3 Treatment Participants will be administered oral cannabidiol (0, 200, 400, 800 mg) 90 min prior to smoking 50% of a marijuana cigarette (0, 5.6% THC). The order of administration of CBD and marijuana dose conditions will be counter-balanced. At select time points, participants will complete mood scales and performance tasks, and their heart rate and blood pressure will be measured. Participants will also have the opportunity to self-administer up to 3 additional puffs of marijuana to assess cannabidiol’s influence on marijuana reinforcement. 2.4 Safety Assessments Vital signs (heart rate and blood pressure) will be monitored during each session. 2.5 Efficacy Assessments Efficacy will be assessed by measuring the effect of oral cannabidiol (0, 200, 400, 800 mg) on smoked marijuana’s (0, 5.6% THC) reinforcing, subjective, cognitive, and physiological effects. 2.6 Analyses A between and within-subject repeated measures analysis of variance (ANOVA) with planned comparisons will be implemented to determine the effects of cannabidiol on marijuana’s reinforcing, subjective, cognitive, and physiological effects for each marijuana strength (active vs inactive).