How your body breaks down CBD: 13 metabolites revealed

Cannabidiol metabolites identified by LC-QTOF after controlled dosing.

Journal of analytical toxicology • • Moderately Relevant
🤖

AI Summary

This study identified 13 distinct metabolites of CBD in human urine samples after controlled dosing of 100 mg, using advanced liquid-chromatography mass spectrometry. Researchers analyzed samples from three different administration methods (Epidiolex pharmaceutical, oral syrup, and vaporized) collected at various timepoints between 1.5 and 22 hours after dosing. The findings reveal that CBD undergoes complex metabolic transformations in the body, including hydroxylation, carboxylic acid formation, and novel modifications on the pentyl side chain—processes similar to how the body processes THC.

A critical discovery is that over 90% of CBD metabolites are conjugated (bound to other molecules) in urine, meaning they require chemical hydrolysis to be detected. This has important implications for testing: standard urine tests without hydrolysis would miss most metabolites. The study confirmed that 7-hydroxy-CBD and 6α-hydroxy-CBD are the most abundant metabolites, validating the use of 7-hydroxy-CBD as a marker for measuring CBD exposure in medical and research settings. Additionally, metabolite levels peaked at 4-6 hours after dosing, providing useful timing information for when detection is most reliable.

The research also revealed practical differences between CBD sources: Epidiolex (FDA-approved medication) produced higher detectable concentrations compared to synthetic CBD in oral syrup or vaporized forms. This suggests bioavailability varies significantly by formulation type—important information for patients, researchers, and quality control in the rapidly expanding CBD market. These findings advance our understanding of how the body processes CBD and provide a foundation for more accurate testing and dosing recommendations.

📄 Original Abstract

Cannabidiol (CBD) is a non-intoxicating cannabinoid found in cannabis and often used for its purported therapeutic benefits. In the form of Epidiolex®, CBD is an FDA-approved treatment for seizure disorders in children. After the 2018 Farm Bill removed hemp (cannabis with <0.3% THC) from the Controlled Substance Act in the United States, non-pharmaceutical CBD became widely available on the retail market. With increased use of CBD, it is important to measure CBD in various biological matrices. In urine, previous studies have measured 7-hydroxy-CBD and 7-carboxy-CBD, analogous to the major metabolites of Δ9-tetrahydrocannabinol (THC). The aim of this study was to identify metabolites of CBD and verify if 7-hydroxy-CBD and 7-carboxy-CBD are the major metabolites. To identify CBD metabolites, 34 urine samples collected after controlled dosing of 100 mg CBD, representing a wide range of time points (1.5-22 hours), and formulations (Epidiolex, syrup, and vaporized administration) were analyzed by liquid-chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) with and without hydrolysis and compared to 11 samples collected after placebo dosing. Thirteen CBD metabolites were identified, including hydroxylation, carboxylic acid formation, alkyl loss, and dihydrodiol formation. The most abundant metabolites included 7-hydroxy-CBD, 6α-hydroxy-CBD, and a novel metabolite indicating hydroxylation on the pentyl sidechain. Most metabolites were >90% conjugated demonstrating that hydrolysis is required for detection in urine. After oral dosing, metabolite concentrations were higher in urine samples collected 4 and 6 h after dosing compared to 1.5 and 11-22 h. CBD concentrations were higher when CBD was administered as Epidiolex compared to synthetically derived CBD in oral syrup or vaping. In conclusion, the results support the use of 7-hydroxy-CBD as a marker of CBD exposure in hydrolyzed urine but also identified several novel metabolites that might further our understanding of CBD pharmacokinetics.

Explore More Research

Stay informed about the latest cannabis science.

Your stash, decoded.