Transformation & Metabolism of Delta-9 THC: A Chemistry Perspective
Delta-9-tetrahydrocannabinol (D9-THC), the main psychoactive compound in cannabis, undergoes a complex metabolic process in the body. This involves enzymatic conversion into various metabolites, each with their distinct biological activity and receptor affinity. Understanding the kinetics and pathways involved in the metabolism of D9-THC helps clarify its duration of action, efficacy, and safety profile.
Transformation and Metabolism of D9-THC
After consumption, D9-THC is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP2C9 and CYP3A4, into 11-hydroxy-THC (11-OH-THC) and further into 11-nor-9-carboxy-THC (THC-COOH). 11-OH-THC is psychoactive and has similar effects to its parent compound. In contrast, THC-COOH is inactive but serves as a long-term marker for cannabis consumption (Huestis, 2007). These metabolites can then be excreted via urine and feces (Grotenhermen, 2003).
D9-THC and 11-OH-THC primarily interact with CB1 receptors located in the central nervous system, thereby eliciting psychoactive effects. On the other hand, THC-COOH has negligible affinity for these receptors and is considered inactive (McPartland et al., 2015).
The onset of effects from D9-THC is rapid, usually within minutes when smoked and within 30 minutes to 2 hours when ingested. However, the metabolites can remain detectable for days to weeks, particularly THC-COOH, which is stored in fat tissues (Huestis, 2007).
Factors Affecting Metabolism
- Induction: St. John’s Wort, a herbal supplement, can induce CYP3A4, potentially accelerating THC metabolism.
- Inhibition: Grapefruit juice inhibits CYP3A4, potentially prolonging the duration of THC effects.
Comparison Table: Compounds of THC, Effects, and Methods of Breakdown
|Compound||Psychoactive Effects||Receptor Affinity||Method of Breakdown||Time to Excrete|
|D9-THC||High||CB1, CB2||CYP2C9, CYP3A4 to 11-OH-THC||Minutes to Hours|
|11-OH-THC||High||CB1||Further metabolized to THC-COOH||Hours to Days|
|THC-COOH||None||Negligible||Excreted in urine and feces||Days to Weeks|
Medical Illnesses and Diagnoses
Patients with the following medical conditions should exercise caution when considering the use of cannabinoids:
- Liver Diseases
- Cardiovascular Diseases
- Psychiatric Disorders
- Huestis, M. A. (2007). Human Cannabinoid Pharmacokinetics. Chemistry & Biodiversity, 4(8), 1770–1804.
- Grotenhermen, F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics, 42(4), 327–360.
- McPartland, J. M., Duncan, M., Di Marzo, V., & Pertwee, R. G. (2015). Are cannabidiol and Δ9‐tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. British Journal of Pharmacology, 172(3), 737–753.
📗 Note: If the diagram was a quick chat, the book’s a deep conversation over a cup of cannabis tea. Brew your thoughts here 📗