We recently took a stroll through the inner world of 11-OH-THC (11-hydroxy-delta-9 tetrahydrocannabinol). The OH signifies that this molecule is an alcohol. This cannabinoid is a well-known metabolite of delta-9-THC that occurs in our bodies as a result of orally consuming THC. It doesn’t produce quite the peak high that inhaling THC does, but its effects are long-lasting.
Another metabolite of THC is THC-COOH, or 11-nor-9-carboxy-9-tetrahydrocannabinol. It’s been reported that 15 to 20% of a THC dose is metabolized to THC-COOH, which is subsequently excreted in the urine. [1] Thus, it is this cannabinoid that is mined in a urinalysis drug test.
Naturally, cannabidiol (CBD) has metabolites too. [2] These were first identified in 1973, when a study evaluated metabolites extracted from rat liver homogenate. The researchers detected the alcohols 7-OH-CBD and 3”-OH-CBD. [3] In all, there have been reported to be approximately 100 downstream metabolites of CBD across multiple organisms. [4]
Some studies have shown that a large portion of CBD is excreted intact or as its glucuronide derivative. [4] A glucuronide is formed when a molecule is linked with glucuronic acid in a process that facilitates the excretion of substances that can’t be used as energy sources. These substances are excreted by the kidneys as urine.
As with oral consumption of THC, the bioavailability of CBD when eaten is low. Research has shown that the main metabolites of CBD include hydroxylated 7-COOH derivatives, as depicted in the below figure. [2]
The chemical structures of the major metabolites of CBD as identified by GC-MS. Reprinted with permission from Cannabis and Cannabinoid Research.
For example, one study showed that CBD administered intravenously produced 7-COOH-CBD as its main metabolite. [1] In another study, following the daily oral dosing of 600 mg of CBD, the analysis of urinary metabolites using gas-chromatography-mass spectrometry identified the O-glucuronide conjugate of CBD as comprising roughly 13% of the excretion products. [5] Intact CBD made up about 12% of the excreted cannabinoids.
Interestingly, this study also identified delta-8- and delta-9-THC, despite the study participants being dosed strictly with CBD, which the researchers posited as having formed from the cyclization of CBD. Cannabinol was also present in the urine which likely originated from the further degradation of the two THC molecules.
The molecules 7-OH- and 7-COOH-CBD have been labeled as anti-inflammatories in a 2010 patent out of Raphael Mechoulam’s laboratory. Another CBD-derived molecule to come out of Mechoulam’s lab, called HU-331 (HU for Hebrew University), has shown anticancer properties. [6] Despite this, while not federally regulated in the US, two states, Florida and Wisconsin, have banned this drug, listing it as schedule I.
References
- Wall ME, Brine DR, Perez-Reyes M. “Metabolism of Cannabinoids in Man.” The Pharmacology of Marihuana, edited by MC Braude and S Szara, Raven Press, 1976, pp. 93–113.
- Ujváry, I. and Hanuš, L. “Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy.” Cannabis and Cannabinoid Research, volume 1, no. 1, 2016, p. 90-101. [journal impact factor = N/A; cited by 28 (ResearchGate)]
- Nilsson I. et al. “Two Cannabidiol Metabolites Formed by Rat Liver.” J Pharm Pharmacol, vol. 25, 1973, p. 486–487. [journal impact factor = 2.405; cited by 18 (ResearchGate)]
- Harvey DJ. “Metabolism and Pharmacokinetics of the Cannabinoids.” Biochemistry and Physiology of Substance Abuse, edited by RR Watson, CRC Press, Boca Raton, 1991, pp. 279–365.
- Harvey DJ, Samara E, Mechoulam R. “Urinary Metabolites of Cannabidiol in Dog, Rat and Man and Their Identification by Gas Chromatography–Mass Spectrometry.” J Chromatogr A, vol. 562, 1991, p. 299–322. [journal impact factor = 4.169; cited by 18 (ResearchGate)]
- Kogan, N. et al. “HU-331, a Novel Cannabinoid-Based Anticancer Topoisomerase II Inhibitor.” Molecular Cancer Therapeutics, vol. 6, no. 1, 2007, p. 173-183. [journal impact factor = 5.373; cited by 42 (ResearchGate)]
Image Credit: Oregon CBD Seeds
From reference 2: “The urinary excretion profile of CBD metabolism has been reported only for a single case, which involved a dystonic patient chronically treated with 600 mg daily oral doses of CBD.58,59”
