Understanding the First-Pass Effect in Cannabis Metabolism
When cannabis is consumed orally, it undergoes a unique pharmacokinetic journey, drastically different from other methods of administration like inhalation. Once ingested, cannabinoids such as THC and CBD first enter the digestive tract. Here, chylomicrons—lipoprotein particles—absorb cannabis oils, aiding in their transport through the lymphatic system. Following absorption, cannabinoids are shuttled to the liver, where they undergo “first-pass” metabolism. This bio-transformation process can significantly alter the chemical structure of cannabinoids, affecting their pharmacological activity and duration in the body.
The First-Pass Effect: A Closer Look
The first-pass effect is a phenomenon whereby the concentration of a drug is reduced before it reaches systemic circulation. In the liver, enzymes like cytochrome P450 play a pivotal role in metabolizing cannabinoids. For instance, delta-9-tetrahydrocannabinol (THC) is converted into 11-hydroxy-THC, a potent psychoactive metabolite that can produce more intense and prolonged effects compared to THC (Huestis, 2007; PMID: 17952658).
Metabolic Alterations and Pharmacological Effects
Different cannabinoids undergo specific types of metabolic transformations:
- THC: Transforms mainly into 11-hydroxy-THC, which is psychoactive and may produce effects that are 1.5-2 times more potent than THC itself (Lemberger et al., 1972; PMID: 4111260).
- CBD: Converted to 7-hydroxy-CBD, which has a lower affinity for cannabinoid receptors and is less potent in its action compared to CBD (Ujváry and Hanuš, 2016; PMID: 27086601).
- CBN (Cannabinol): Though CBN is already a byproduct of THC degradation, it can further metabolize into different compounds but generally lacks significant psychoactive effects (Mahadevan et al., 2004; PMID: 14963641).
Duration in the System
Metabolites like 11-hydroxy-THC may have a longer half-life compared to the parent compound, extending the duration of their effects. These metabolites can be detected in the body for several days to weeks after cannabis consumption, depending on factors like frequency of use and metabolic rate (Huestis, 2005; PMID: 15966553).
Understanding the first-pass metabolism of cannabinoids is crucial, especially for medical cannabis users. Variations in liver enzyme activity, due to genetics or co-administration of other medications, can lead to significant differences in the metabolism of cannabinoids, thereby affecting their efficacy and safety. It is essential to consult healthcare professionals for a tailored therapeutic approach.
📗 Note: This diagram is like cannabis-infused tea, while the book is the whole pot. Steep in the knowledge here 📗.