The Effects of Cannabidiol and Analgesic Expectancies on Experimental Pain Reactivity in Healthy Adults: A Balanced Placebo Design Trial

Despite its frequent use for pain relief, no experimental pain research has tested the analgesic effects of cannabidiol (CBD) in humans. The goal of this study was to experimentally test the effects of CBD and expectancies for receiving CBD on human pain reactivity. Using a crossover, 2 × 2 factorial balanced placebo design, drug administration (given inactive substance or given active CBD) and verbal instruction sets (told inactive substance or told active CBD) were experimentally manipulated. Fifteen healthy adults each completed four separate experimental sessions. Participants were randomly assigned to different counterbalanced manipulation conditions at each session: control (told inactive-given inactive); expectancy (told active CBD-given inactive); drug (told inactive-given active CBD); and expectancy + drug (told active CBD-given active CBD). Primary outcomes were pain threshold, tolerance, intensity, unpleasantness, conditioned pain modulation (CPM), and offset analgesia (OA). There was a significant main effect of instructions on OA, such that the OA response was significantly larger when participants were told that they received CBD, regardless of drug content. Pain unpleasantness was significantly reduced in the drug, expectancy, and expectancy + drug conditions, relative to the control condition. The drug and expectancy conditions separately improved CPM, whereas the expectancy + drug and control conditions produced the lowest CPM change scores. We did not detect significant effects for pain threshold, tolerance, or intensity. Our results indicated that separate pain outcomes can be differentially affected by CBD and/or expectancies for receiving CBD. Future investigations of the psychological and pharmacological mechanisms underlying CBD analgesia are warranted. Public Health Significance Despite its frequent use for pain relief, no experimental pain research has tested the analgesic effects of cannabidiol (CBD) in humans. We experimentally tested the effects of CBD and expectancies for receiving CBD on human pain reactivity. This study found that CBD analgesia was driven by both psychological expectancies and pharmacological action.