Introduction to Cannabinoid Pharmacokinetics
The journey of cannabinoids like THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol) through the human body is a complex process governed by the principles of pharmacokinetics: absorption, distribution, metabolism, and excretion (ADME). Due to their high lipid-solubility, cannabinoids are rapidly absorbed into fatty tissues, where they can be stored. Their slow release from these fat stores contributes to cannabinoids being detectable in the body long after use.
The Central Role of the Liver: Metabolism Phases
The liver is the primary organ for cannabinoid metabolism, mainly utilizing cytochrome P450 (CYP450) enzymes. This process unfolds in two main phases:
Phase I: Transformation
CYP450 enzymes, particularly CYP2C9, CYP2C19, and CYP3A4, modify cannabinoids through processes like hydroxylation. THC is converted into the psychoactive 11-hydroxy-THC (11-OH-THC), which is then further metabolized into the inactive 11-nor-9-carboxy-THC (THC-COOH). THC-COOH is often the target of urine drug tests. CBD is metabolized into 7-OH-CBD and 7-COOH-CBD.
Phase II: Conjugation
Phase II makes the metabolites water-soluble by attaching them to another molecule, typically through glucuronidation. This makes compounds like THC-COOH-glucuronide easier to excrete from the body.
Adipose Tissue: The Body's Storage Reservoir
As a highly lipophilic compound, THC is readily stored in fat tissue. In regular users, THC can accumulate in fat cells faster than it can be eliminated, leading to its slow release back into the bloodstream over time. This prolonged release contributes to the long half-life of THC in chronic users (5-13 days) and the detection of metabolites for extended periods. Activities that increase fat metabolism, like exercise, can temporarily raise plasma THC levels as it's released from storage.
Excretion: The Final Exit
Metabolized cannabinoids are primarily eliminated through two routes:
- Feces: About 65% of THC and its metabolites are excreted in feces.
- Urine: Approximately 20-25% is excreted in urine, mainly as the inactive THC-COOH metabolite.
THC vs. CBD Metabolism Comparison
THC and CBD have some differences in how they are processed and eliminated by the body.
| Feature | THC (Tetrahydrocannabinol) | CBD (Cannabidiol) |
|---|---|---|
| Primary Metabolism | Metabolized into active (11-OH-THC) and then inactive (THC-COOH) forms by CYP2C9, CYP2C19, and CYP3A4. | Metabolized by a wider range of enzymes, including CYP2C19, CYP3A4, CYP1A1, and CYP2C9. |
| Excretion Form | Nearly completely metabolized before excretion, with less than 5% excreted unchanged. | A greater proportion is excreted unchanged compared to THC. |
| Primary Excretion Route | Primarily feces (~65%) and urine (~20%). | Mostly feces, with less in urine. |
| Half-Life | 1-3 days for occasional users; 5-13 days for chronic users. | 18-32 hours; up to 2-5 days with repeated oral use. |
Factors Influencing Elimination Time
The time cannabinoids remain detectable varies widely based on several factors:
- Frequency of Use: Regular users accumulate more THC in fat, leading to detection for 30+ days, compared to occasional users (3-7 days).
- Body Fat Percentage (BMI): Higher body fat allows for more THC storage, prolonging retention.
- Metabolism Rate: Individual metabolic speed, affected by genetics and health, influences how quickly cannabinoids are processed.
- Dosage and Potency: Higher amounts of THC take longer to eliminate.
- Route of Administration: While inhaled cannabis has a faster onset, ingested forms may remain in the system longer.
Conclusion
Eliminating cannabinoids from the body is a complex, variable process driven mainly by the liver and significantly impacted by their fat-soluble nature. THC is metabolized into various compounds, stored in fat tissue, gradually released into the bloodstream, and finally excreted via feces and urine. This slow process explains why cannabinoids can be detected long after consumption. Individual characteristics such as frequency of use, body composition, and metabolic rate are key determinants of the clearance timeline.
