Abstract
RationaleCannabidiol (CBD) has been reported to attenuate stress and anxiety, but little is known about the extent to which such effects result from pharmacological versus expectancy factors.ObjectivesWe evaluated whether CBD expectancy alone could influence stress, anxiety, and mood, and the extent to which beliefs regarding CBD effects predicted these responses.MethodsIn this randomized crossover study, 43 health adults (23 women) attended two experimental laboratory sessions, where they self-administered CBD-free hempseed oil sublingually. During one session, they were (incorrectly) informed that the oil contained CBD and in the other session, that the oil was CBD-free. Following administration, participants engaged in the Maastricht Acute Stress Test (MAST). Heart rate variability (HRV) was assessed continuously, and subjective state was assessed at baseline, 90-min following oil administration, immediately following the MAST, and after a 10-min recovery period.ResultsThe CBD expectancy condition was associated with increased sedation as well as with changes in HRV that were consistent with heightened anticipatory stress regulation. Overall, there were no systematic changes in subjective stress, or anxiety, according to expectancy condition. However, participants who endorsed strong a priori beliefs that CBD has anxiolytic properties reported significantly diminished anxiety in the CBD expectancy condition.ConclusionsCBD expectancy alone impacted several subjective and physiological responses. Additionally, expectancy-related factors were implicated in anxiolytic effects of CBD for those who believed it was helpful for such purposes, emphasizing the need to measure and control for CBD-related expectancies in clinical research that involves the administration of CBD.
Highlights
In the past decade, there have been notable increases in cannabidiol (CBD) use globally for therapeutic purposes (World Health Organization (World Health Organization (WHO) 2018)
If a placebo effect is observed for CBD, it would bolster the case for future evaluation of whether CBD pharmacology interacts with expectancy to dampen stress- and anxiety-related responses using a full balanced placebo design (Rohsenow and Marlatt 1981)
We examined whether a priori beliefs about CBD influenced corresponding stress, anxiety, and mood responses according to expectancy condition
Summary
There have been notable increases in cannabidiol (CBD) use globally for therapeutic purposes (World Health Organization (World Health Organization (WHO) 2018). CBD has been shown to diminish several anxiety- and stress-related. Drug effects in humans are believed to be comprised of both direct pharmacological effects related to the drug itself and a placebo response (Kirsch 1985). Psychopharmacology (2021) 238:1965–1977 regarding the content and effects of a substance Such expectations can be formed by verbal information about the content and supposed effects of a substance, prior experience, and observational learning (Kirsch 2018). Given the current state of research to our knowledge, CBD-related placebo responses have never been systematically examined. If a placebo effect is observed for CBD, it would bolster the case for future evaluation of whether CBD pharmacology interacts with expectancy to dampen stress- and anxiety-related responses using a full balanced placebo design (Rohsenow and Marlatt 1981)
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