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. 2022 Dec;36(12):1299-1314.
doi: 10.1177/02698811221124792. Epub 2022 Oct 14.

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool

Caroline Mb Kwee  1   2 , Joop Ma van Gerven  3 , Fleur Lp Bongaerts  1 , Danielle C Cath  4   5 , Gabriël Jacobs  3 , Johanna Mp Baas  1 , Lucianne Groenink  6
Affiliations

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool

Caroline Mb Kwee et al. J Psychopharmacol. 2022 Dec.

Abstract

Background: Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however lacking.

Aim: We aimed to predict the therapeutic window for anxiety-reducing effects of CBD in humans based on preclinical models.

Methods: We conducted two systematic searches in PubMed and Embase up to August 2021, into pharmacokinetic (PK) and pharmacodynamic (PD) data of systemic CBD exposure in humans and animals, which includes anxiety-reducing and potential side effects. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. A control group was an inclusion criterion in outcome studies. In human outcome studies, randomisation was required. We excluded studies that co-administered other substances. We used the IB-de-risk tool for a translational integration of outcomes.

Results: We synthesised data from 87 studies. For most observations (70.3%), CBD had no effect on anxiety outcomes. There was no identifiable relation between anxiety outcomes and drug levels across species. In all species (humans, mice, rats), anxiety-reducing effects seemed to be clustered in certain concentration ranges, which differed between species.

Discussion: A straightforward dosing recommendation was not possible, given variable concentration-effect relations across species, and no consistent linear effect of CBD on anxiety reduction. Currently, these results raise questions about the broad use as a drug for anxiety. Meta-analytic studies are needed to quantitatively investigate drug efficacy, including aspects of anxiety symptomatology. Acute and (sub)chronic dosing studies with integrated PK and PD outcomes are required for substantiated dose recommendations.

Keywords: CBD; Cannabidiol; IB-de-risk; anxiety; anxiolytic; pharmacokinetic; safety; systematic review; translational.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flowchart displaying the study selection process. AEA: anandamide; CBD: cannabidiol; CB1R: cannabinoid type 1 receptor; THC: Δ9-tetrahydrocannabinol.
See this image and copyright information in PMC

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