D40: overview of first-pass metabolism in the liver

First-Pass Metabolism and Cannabinoid Bioavailability: What You Need to Know

Overview of First-Pass Metabolism in the Liver

The liver plays a significant role in the metabolism of substances, including cannabinoids, through a process known as “first-pass metabolism.” When cannabinoids are ingested, they first pass through the liver, where various enzymes, particularly cytochrome P450, metabolize them into different metabolites before entering the systemic circulation. This process can significantly affect the bioavailability of cannabinoids, meaning the proportion that effectively enters circulation to produce an active effect (Grotenhermen, 2003).

Absorption and Distribution

After ingestion, cannabinoids are absorbed through the gastrointestinal tract and transported to the liver via the hepatic portal system. In the liver, a substantial portion of cannabinoids is metabolized, affecting the amount that eventually reaches systemic circulation. It has been reported that oral bioavailability of THC ranges from 4-12%, whereas, for CBD, it can be as low as 6% (Mechoulam et al., 2002).

Additionally, other cannabis compounds like flavonoids and terpenes undergo similar first-pass metabolism, but their specific bioavailability percentages have not been well-studied.

Influence of Form Factors and Formulations

Different forms of cannabinoid products, like oils, tinctures, and edibles, can vary in bioavailability. For instance, sublingual tinctures and vaporized forms bypass the first-pass metabolism, resulting in higher bioavailability compared to oral products (Lindgren et al., 2019).

Medical Conditions Requiring Special Consideration

The metabolism of cannabinoids can interact with various medications and can be problematic for certain medical conditions. Individuals with the following conditions should consult healthcare providers for guided, thoughtful care:

  1. Liver Diseases
  2. Kidney Diseases
  3. Cardiovascular Disorders
  4. Pregnancy and Breastfeeding
  5. Psychiatric Conditions

For specialized advice on cannabis-based therapies, individuals can contact Dr. Caplan at CED Clinic.


  1. Grotenhermen, F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical pharmacokinetics, 42(4), 327-360.
  2. Mechoulam, R., Parker, L. A., & Gallily, R. (2002). Cannabidiol: an overview of some pharmacological aspects. Journal of Clinical Pharmacology, 42(S1).
  3. Lindgren, J. E., Ohlsson, A., Agurell, S., Hollister, L., & Gillespie, H. (2019). Clinical effects and plasma levels of delta 9-tetrahydrocannabinol (Delta 9-THC) in heavy and light users of cannabis. Psychopharmacology, 74(3), 208-212.

For specialized guidance on cannabinoid therapies, particularly if you have medical conditions that require careful management, consult healthcare providers like Dr. Benjamin Caplan at CED Clinic. Dr. Caplan’s expertise in cannabinoid-based therapies can offer nuanced care tailored to individual needs.

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Cover of The Doctor-Approved Cannabis Handbook featuring a green medical plus symbol
Unlock the world of medical cannabis with The Doctor-Approved Cannabis Handbook.

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