CBD vs response expectancy and placebo effect

Written by Sabina Pulone

In which extent our expectations can modulate beneficial CBD effects on anxiety and stress? Is there a correlation between our beliefs and the actual pharmacological effect of this cannabis phytochemical?

Answering these questions is at the basis of the recent scientific research of Spinella et al. (2021) [1], in which for the first time CBD-linked placebo responses on stressful states of mind are systematically analysed. A randomized crossover trial on healthy adults was carried out to test weather CBD expectancy alone could positively influence acute stress and anxiety. Heart rate (HR) and heart rate variability (HRV) are the physiological parameters to be measured in order to evaluate the stress response. The root mean square of successive differences (RMSSD) reflects the beat-to-beat variance in HR [2] and a lower value of it indicates a larger stress response.

During the initial orientation meeting, Cannabis use frequency and  a priori CBD expectancies and beliefs of each participant were collected through single item research questions. Two experimental sessions followed: the participants were subjected to the Maastricht Acute Stress Tests (MAAST) in order to elicit subjective and physiological reactions linked to stress and anxiety. MAAST involves 5 minutes of explanations of procedures and 10 minutes of cold pressure trials [3] : participants were alternating between putting their hand into ice-cold water and counting backwards in steps of 17 or 13 starting at a random four-digit number while they were put under pressure by negative social evaluation feedbacks. [1] CBD-hemp free oil was administered during both experimental sessions, but participants were incorrectly informed about the presence of CBD into the oil in one of the two experiments. Spinella et al. [1] found that strong baseline expectancies regarding CBD-reducing anxiety are linked with decreased subjective anxiety. For those without strong a priori beliefs on CBD effects, expectancy-related changes in their mood were not identified. This study is an additional confirmation of the expectancy theory proposed by Kirsch in 1985, stating that expecting a specific response to occur would enhance the likelihood of said response to actually occur. [4]

A better understanding of the correlation between active response and non-pharmacological CBD influence on anxiety conditions could help improving the design of clinical research experiments thus the setting of specific therapeutic treatments.


[1] Spinella T.C. et al. Evaluating cannabidiol (CBD) expectancy effects on acute stress and anxiety in healthy adults: a randomized crossover study. Psychopharmacology. (2021) [Journal Impact Factor = 3.424]


[2] Minarini, G. Root Mean Square of the Successive Differences as Marker of the Parasympathetic System and Difference in the Outcome after ANS Stimulation. Autonomic Nervous System Monitoring – Heart Rate Variability. (2020) doi:10.5772/intechopen.89827


[3] Smeets T. et al. Introducing the Maastricht Acute Stress Test (MAST): A quick and non-invasive approach to elicit robust autonomic and glucocorticoid stress responses. Psychoneuroendocrinology, 37(12),1998-2008. (2012) doi:10.1016/j.psyneuen.2012.04.012
[Times cited = 186 ] [Journal Impact Factor = 4.732]


[4] Kirsch, I. (1985). Response expectancy as a determinant of experience and behavior. American Psychologist, 40(11), 1189–1202. [Times cited = 1200] [Journal Impact Factor = 6.54]



About the author

Sabina Pulone