# Identifying the optimal dose of cannabidiol by intrabuccal administration in Kramnik (C3HeB/FeJ) mice

## TL;DR

This study finds that a 10 mg/kg dose of cannabidiol (CBD) administered intrabuccally in mice is optimal for brain penetration with minimal variation and no sex-based differences.

## Contribution

The study identifies the optimal CBD dose via intrabuccal administration in mice and evaluates sex as a potential confounding factor.

## Key findings

- CBD and its metabolites were detected in brain, urine, and blood samples after intrabuccal administration.
- The 10 mg/kg dose showed the least variation in CBD metabolite concentrations.
- Sex only became a confounding factor at the highest dose (30 mg/kg).

## Abstract

Cannabidiol (CBD) has numerous therapeutic properties, and is used to treat neurological conditions, such as neuroinflammation. However, the optimal dose of CBD to penetrate the brain requires further investigation. The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain. The secondary aim was to determine whether sex is a confounding factor.

Thirty adult Kramnik mice, divided equally into three groups, were administered CBD oil intrabuccally at three doses—10, 20, and 30 mg/kg, euthanized 6 h later, and whole brain, urine, and blood samples were collected. Liquid chromatography with tandem mass spectrometry was used to analyze the collected samples.

CBD and its three metabolites—7‐carboxy cannabidiol (7‐COOH‐CBD), 7‐hydroxy cannabidiol (7‐OH‐CBD) and 6‐hydroxy cannabidiol (6‐OH‐CBD), were identified and quantified in all samples. The 10 and 20 mg/kg doses of CBD produced similar results in the brain, but the group given the 10 mg/kg dose had the least variation. The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples, but also the greatest variation. Sex only became a confounding factor at 30 mg/kg.

This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples, with the least variation among the doses, and sex was not a confounder at 10 mg/kg.

Cannabidiol (CBD) has numerous therapeutic properties, and is used to treat neurological conditions, such as neuroinflammation. However, the optimal dose of CBD to penetrate the brain requires further investigation. The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain. The secondary aim was to determine whether sex is a confounding factor. Thirty adult Kramnik mice, divided equally into three groups, were administered CBD oil intrabuccally at three doses—10, 20, and 30 mg/kg, euthanized 6 h later, and whole brain, urine, and blood samples were collected. Liquid chromatography with tandem mass spectrometry was used to analyze the collected samples. CBD and its three metabolites—7‐carboxy cannabidiol (7‐COOH‐CBD), 7‐hydroxy cannabidiol (7‐OH‐CBD) and 6‐hydroxy cannabidiol (6‐OH‐CBD), were identified and quantified in all samples. The 10 and 20 mg/kg doses of CBD produced similar results in the brain, but the group given the 10 mg/kg dose had the least variation. The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples, but also the greatest variation. Sex only became a confounding factor at 30 mg/kg. This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples, with the least variation among the doses, and sex was not a confounder at 10 mg/kg.