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

Ila M Linares, Antonio W Zuardi, Luis C Pereira, Regina H Queiroz, Raphael Mechoulam, Francisco S Guimarães, José A Crippa, Ila M Linares, Antonio W Zuardi, Luis C Pereira, Regina H Queiroz, Raphael Mechoulam, Francisco S Guimarães, José A Crippa

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.

Conflict of interest statement

STI-Pharm (Brentwood, UK) kindly supplied CBD at no cost. AWZ, FSG, RM and JAC are co-inventors (Mechoulam R, JAC, Guimarães FS, AWZ, Breuer A) of the patent “Fluorinated CBD compounds, compositions and uses thereof” (Pub. no. WO/2014/108899, International Application no. PCT/IL2014/050023, Def. US no. Reg. 62193296; 29/07/2015; registered in Brazil at INPI on 19/08/2015 [BR1120150164927]). The Universidade de São Paulo (USP) has licensed the patent to Phytecs Pharm (USP Resolution no. 15.1.130002.1.1). USP has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” JAC and JECH have received travel support from and are medical advisors of BSPG-Pharm. The funding agency had no role in the study design or in the decision to submit the paper for publication. The other authors report no conflicts of interest.

Figures

Figure 1. Visual Analogue Mood Scale (VAMS)…
Figure 1. Visual Analogue Mood Scale (VAMS) anxiety factor scores in each phase of the simulated public speaking test (SPST) for groups treated with cannabidiol (CBD) 150, 300, and 600 mg or placebo (points in the curve refer to mean scores and vertical lines refer to mean standard errors).* Lower anxiety levels in the group treated with CBD 300 mg relative to the placebo phase (p = 0.042). PT = pre-test; A = anticipatory anxiety; S = speech; F1= post-test 1; F2 = post-test 2.

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