Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life

Abstract

The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). The subjects were underwent a test of public speaking in a real situation (TPSRS) where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes) after administration of the drug/placebo, as time 0: -5 (baseline), 80 (pre-test), 153 (speech), and 216 (post-speech). Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.

Cannabidiol provides viable treatment opportunity for multiple neurological pathologies of autism spectrum disorder

“…CBD also reduced anxiety induced by simulated public speaking in both healthy volunteers and patientswith social anxiety disorders [32,33]. Consistent with animal studies, acute administration of CBD induced anxiolytic effects in healthy subjects with moderate (300 mg), but not lower (100 mg) or higher (900 mg) doses [34]. CBD can also attenuate anxiety related sleep problems.…”

Pharmacological challenge studies with acute psychosocial stress

“…In another study (Guimarães et al, 1987), lorazepam (1mg) decreased subjective ratings of anxiety, but tended to increase HR responses to stress. Lastly, Zuardi et al (2017) found that clonazepam (1 mg) decreased ratings of anxiety during and after a public speaking task, but increased HR response to the stress.…”

“…CBD did not alter cardiovascular function, and cortisol was not measured. In a second study, Zuardi et al (2017) compared effects of several doses of CBD (100 mg, 300 mg, 900 mg) using a variant of a public speaking task in which 12 participants were tested at once. They found a nonlinear dose-response function such that only the moderate dose (300 mg) reduced ratings of anxiety during and after a public speaking task, despite slightly increasing BP during the task.…”

Wirksamkeit von Cannabidiol: Klinische Studien mit Cannabidiol und Cannabidiol-haltigen Extrakten

“…In der Phase nach der Rede (3,5 h nach Einnahme) zeigten Clonazepam und 300 mg CBD eine angstlösende Wirkung -nicht aber 100 mg und 900 mg CBD [10]. 24 Patienten mit sozialen Angststörungen wurden in einer Doppelblindstudie mit 600 mg CBD oder Placebo behandelt: CBD zeigte eine signifikante vermindernde Wirkung bei der subjektiven Beurteilung der Angst und der kognitiven Beeinträchtigung [11].…”

“…In einer grösseren Studie konnte dies für 300 mg -nicht aber für 100 und 900 mg -bestätigt werden [10]. Die klinische Relevanz dieser Erkenntnis ist noch offen.…”