Evaluating cannabidiol (CBD) expectancy effects on acute stress and anxiety in healthy adults: a randomized crossover study

Abstract

Rationale Cannabidiol (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. Objectives We evaluated whether CBD expectancy alone could influence stress, anxiety, and mood, and the extent to which beliefs regarding CBD effects predicted these responses. Methods In 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. Results The 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. Conclusions CBD 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.

The safety and relative effectiveness of non-psychoactive cannabinoid formulations for the improvement of sleep: a double-blinded, randomized controlled trial

“…In previous clinical research, melatonin has been shown to have modest effects on sleep relative to placebo, 48 though clinical evidence of CBD's effect relative to placebo remains limited, albeit promising. [23][24][25] Notably, previous clinical research suggests that placebo response could play a major role in the effect of CBD on stress and anxiety, 49 though the impact of this response has yet to be explored for CBD and sleep. Further placebo-controlled studies are needed to determine the therapeutic effects of CBD for sleep.…”

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia

“…This was observed more frequently in male patients. Human laboratory experiments suggest that patient's expectations play a major role in both the analgesic and anxiolytic effects of CBD ( 34 , 35 ). Therefore, overemphasizing the analgesic potential of CBD could result into negative treatment outcomes when such expectations are not met ( 36 ).…”

Development and initial psychometric properties of the Cannabidiol Outcome Expectancies Questionnaire (CBD-OEQ).

“…The CBD-OEQ may also be useful for clinical trial or administration research, as emerging research suggests that preexisting CBD-related outcome expectancies influence subjective effects (e.g., anxiety reduction) of CBD regardless of actual pharmacology (Spinella et al, 2021). The CBD-OEQ could be used to expand upon the Spinella et al (2021) administration study by testing whether CBD-OEQ subscales moderate the relationship between administration condition and other outcomes of interest. For example, researchers could test whether the CBD-related pain expectancy subscale (collected prior to administration of CBD) moderates the relationship between condition and subjective reports of pain.…”

“…However, the study is somewhat limited by using single items to assess expectancies and not assessing desirability ratings of the expectancies, which is problematic because isolating expectancy from value ratings and their interaction is important for understanding outcome expectancies. It may also be important to assess and understand other expectancies (e.g., sleep, pain) that are beyond the scope of the Spinella et al (2021) study. Yet, no known CBD-specific outcome expectancy measure exists.…”

“…In the only known study of CBD-related expectancies, Spinella et al (2021) conducted a randomized two-session cross-over study assessing whether expecting to receive CBD influenced self-reported stress, anxiety, and mood during a laboratory-based stress test and whether beliefs about CBD products (assessed prior to the administration session) moderated the relationship between expectancy condition and self-report outcomes. Beliefs about CBD were assessed via three items that asked participants to rate the extent to which they believed CBD “improves mood,” “reduces anxiety,” and “reduces stress” from 1 ( not at all ) to 10 ( completely ).…”