The Power of Placebo: Evaluating cannabinoid-related beliefs and the role of cannabidiol (CBD) expectancy on acute stress and anxiety

Abstract

Cannabis is associated with several therapeutic and non-therapeutic effects, which may partly be related to varying ratios of cannabinoids like Δ-9-tetrahydrocannabidol (THC) and cannabidiol (CBD), each with unique effects, uses, and mechanisms of action. Expectations or beliefs about substances influence substance-related outcomes and are central to the “placebo effect”. While various reports indicate that CBD is utilized and perceived as beneficial for stress- and anxiety-related processes, findings from experimental and clinical investigations are equivocal. The extent to which CBD-related expectancy factors contribute to these purported stress and anxiety dampening effects is unclear. My dissertation aims to gain insight into the expectancy-related influences of well-recognized cannabinoids (THC, CBD), broadly, and as they relate to placebo CBD. Study 1 evaluated the extent to which a community sample of Canadian adults (n=345) endorsed various beliefs about THC and CBD using a cross-sectional survey. Participants tended to endorse beliefs that CBD-containing products (vs. THC) possessed more therapeutic effects (e.g., anxiolysis), and those with prior cannabis use experience (vs. no prior experience) endorsed higher positive beliefs regarding cannabinoid effects. Utilizing a community recruited sample of healthy adults (n=43), Study 2a and 2b evaluated the extent to which CBD-related expectation (i.e., the placebo effect) influenced various subjective-emotional and psychophysiological indices of acute stress and anxiety using an experimental crossover half-balanced-placebo design. Study 2a findings indicated that those with the strongest beliefs about CBD’s anxiety-dampening effects self-reported less anxiety when they thought they received CBD (vs. CBD-free oil). Heart rate variability (HRV) also appeared to be influenced by CBD expectancy within the context of a stressor. Study 2b revealed that CBD expectancy blunted cortisol reactivity; however, this was specific to the anticipation of stress and was predominantly observed among males. Taken together, my research suggests that people tend to have different expectancies regarding the effects of THC and CBD. Further, a placebo effect was identified for CBD in the context of stress and anxiety. This was pronounced among those who endorse strong beliefs about its helpfulness and occurs during the anticipation of a stressor, which could reflect the mechanism through which CBD influences future-oriented cognitive processes related to anxiety.