More CBD Did Not Produce More Anxiety Relief in a Public-Speaking Experiment

A public-speaking experiment found a CBD benefit at an intermediate dose, but not at lower or higher tested doses. This supports caution about assuming that increasing CBD necessarily increases anxiety relief.

Five small groups and a structured stressor

Sixty healthy adults were assigned to placebo, clonazepam 1 mg, or CBD at 100, 300 or 900 mg. Participants spoke in front of other volunteers in a real public-speaking challenge, with subjective anxiety, sedation and cardiovascular measures assessed at specified phases.

This was human experimental evidence in healthy volunteers. It was not a chronic-treatment trial in people diagnosed with an anxiety disorder, nor a test of an ordinary mixed-cannabinoid retail product.

The significant finding depended on dose and phase

CBD at 300 mg reduced subjective anxiety relative to placebo in the post-speech phase. The same effect was not demonstrated at 100 or 900 mg. The authors described a pattern consistent with an inverted-U dose response.

That pattern does not locate an optimal clinical dose precisely. Only three CBD doses were examined, and small groups cannot map the entire dose–response curve. A phase-specific subjective effect also should not be described as normalization of every physiological stress response.

Mechanisms remained hypotheses

The authors discussed receptor-based explanations informed partly by animal experiments. Those explanations were not established by direct receptor measurements in the volunteers. Plasma CBD was not measured to connect individual exposure with anxiety changes.

Sedation comparisons with clonazepam supplied additional context, but they did not establish a universal safety advantage in all patients. The appropriate conclusion is a nonmonotonic pattern under a defined acute challenge, with further work needed before assigning treatment ranges for a particular disorder.

Related: Why treatment outcomes require attention to study design.

Primary research

Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life. Frontiers in Pharmacology (2017).