Cannabidiol metabolites identified by LC-QTOF after controlled dosing

Area of Science:

• Pharmacology
• Analytical Chemistry

Background:

• Cannabidiol (CBD) is a non-intoxicating cannabinoid with therapeutic potential, widely available after the 2018 Farm Bill.
• Accurate measurement of CBD and its metabolites in biological samples is crucial due to increased usage.
• Existing research has identified some CBD metabolites, but a comprehensive analysis is needed.

Purpose of the Study:

• To identify and characterize CBD metabolites in human urine.
• To determine if 7-hydroxy-CBD and 7-carboxy-CBD are the major urinary metabolites of CBD.
• To investigate the impact of different CBD formulations and administration routes on metabolite profiles.

Main Methods:

• Analysis of 34 urine samples from controlled CBD dosing (100 mg) using liquid-chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).
• Samples were collected at various time points (1.5-22 hours) and represented different formulations (Epidiolex, syrup, vaporized).
• Urine samples were analyzed with and without hydrolysis to assess metabolite conjugation.

Main Results:

• Thirteen CBD metabolites were identified, including hydroxylation, carboxylic acid formation, alkyl loss, and dihydrodiol formation.
• The most abundant metabolites were 7-hydroxy-CBD, 6α-hydroxy-CBD, and a novel pentyl sidechain hydroxylated metabolite.
• Over 90% of metabolites were conjugated, necessitating hydrolysis for detection; metabolite concentrations peaked 4-6 hours post-oral administration.

Conclusions:

• 7-hydroxy-CBD is a suitable marker for assessing CBD exposure in hydrolyzed urine.
• Novel CBD metabolites were identified, enhancing the understanding of CBD pharmacokinetics.
• CBD concentrations varied based on formulation, with Epidiolex showing higher levels compared to oral syrup or vaporized CBD.