Cannabidiol presents an inverted U-shaped dose-response curve in the simulated public speaking test

Abstract

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. Method: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. Results: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. Conclusion: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential

“…Unfortunately, these studies have very small sample sizes. [36][37][38][39][40][41][42][43][44][45][46][47][48] This means exaggerated responses or lack of significant effects could be due to a lack of statistical power. All of the studies use singledose CBD, so the chronic impact of the drug cannot be determined.…”

“…Responses from normal volunteers to a stressor might be less severe than people with anxiety disorders, diminishing the extent of benefit that could result from effective treatment. [36][37][38][39][40][41][42][43][44][45][46][47][48] The first category of studies assessed the impact of single-dose CBD to attenuate the anxiety-promoting effects of single-dose delta-9-THC. [36][37][38][39] These trials suggest that CBD reduces higher-dose delta-9-THCinduced anxiety as assessed by subjective ratings or the validated Visual Analog Mood Scale or State-Trait Anxiety Inventory.…”

“…[36][37][38][39] Prophylaxis with CBD a couple of hours before public speaking (the anxiety stressor) might provide relieve from anxiety during or shortly after the speech ( Table 2). [40][41][42] The studies comparing multiple CBD doses were likely underpowered to assess all doses adequately, but the 300-mg dose might provide greater benefits than smaller or larger doses. This U-shaped relationship between CBD dose and efficacy could suggest a single effective dose for all patients or might be misleading because the patients were generally similar in size and general health.…”

Cannabidiol: A budding industry!

“…These studies involved the acute administration of CBD doses, ranging from 100 to 900 mg, which were presumably of a similar order of magnitude to the doses given in the clinical trials mentioned in the previous section for epilepsy, although it is not possible to know for certain as the reported doses were absolute and not given relative to the bodyweight of the subjects. CBD was given 1.5-3.5 hours prior to the public speaking test and was compared with a placebo (Bergamaschi et al 2011;Zuardi et al 2017;Linares et al 2019). Participants in all three studies reported lower levels of anxiety, assessed subjectively by a visual analogue mood scale, when given CBD at doses of either 300 mg (Zuardi et al 2017;Linares et al 2019) or 600 mg (Bergamaschi et al 2011), relative to those who had received placebo.…”

“…CBD was given 1.5-3.5 hours prior to the public speaking test and was compared with a placebo (Bergamaschi et al 2011;Zuardi et al 2017;Linares et al 2019). Participants in all three studies reported lower levels of anxiety, assessed subjectively by a visual analogue mood scale, when given CBD at doses of either 300 mg (Zuardi et al 2017;Linares et al 2019) or 600 mg (Bergamaschi et al 2011), relative to those who had received placebo. However, these studies involved a limited number of subjects (n < 60 in total), included both healthy controls and individuals with social anxiety disorder, the range of CBD doses tested varied across the studies, and preparations were provided by different companies.…”