11-Nor-9-carboxy-THC Metabolism and Detectio
Examining the metabolism of and detection of 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH) is meant to better understand how the human processes cannabis with a safe and practical approach when discussing or interpreting those results in the highly sensitive area of drug testing.
THC-COOH is the main metabolite of Δ⁹-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis. THC would be metabolized by the liver after THC ingestion into an active form, then an 11-hydroxy metabolite, which is called 11-OH-THC, and eventually to an inactive form called THC-COOH. When the THC-COOH metabolite is made, it is subject to conjugation with glucuronic acid to become a water-soluble molecule and finally excreted from the organism.
The testing for the THC metabolite is warranted for the detection of potential drug detection from biological samples such as urine, blood, and hair to confirm the presence or absence of THC or cannabis. Given the long half-life of THC-COOH, metabolites that originate from those compounds may be detected the day of consumption and may result in potential findings days or weeks later, depending on frequency of use.
Metabolism of 11-Nor-9-carboxy-THC
Upon cannabis consumption, THC undergoes a series of metabolic transformations:
Hydroxylation to 11-Hydroxy-THC (11-OH-THC): THC is first metabolized by liver enzymes, primarily cytochrome P450 isoforms CYP2C9 and CYP3A4, to form 11-OH-THC, a psychoactive intermediate.
Oxidation to 11-COOH-THC: The 11-OH-THC is further oxidized to 11-COOH-THC, an inactive metabolite.
Conjugation and Excretion: 11-COOH-THC undergoes conjugation with glucuronic acid, forming a water-soluble compound that is excreted primarily through feces and urine. Wikipedia
Detection of 11-Nor-9-carboxy-THC
The detection of 11-COOH-THC is pivotal in drug testing protocols:
Urine Testing: Urine tests commonly screen for 11-COOH-THC due to its longer detection window compared to THC itself. Detection times can vary based on usage patterns: Wikipedia
Infrequent Users: Up to 3–5 days post-consumption.
Heavy Users: 1–15 days.
Chronich Users: 1–30 days or longer.
Blood Testing: 11-COOH-THC is detectable in plasma within minutes after cannabis use and remains present longer than THC itself, making it a reliable marker for recent consumption.
Hair Testing: Hair analysis can detect 11-COOH-THC, providing a longer detection window and serving as evidence of past cannabis use.
Analytical Techniques
Accurate detection of 11-COOH-THC relies on advanced analytical methods:
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): This method offers high sensitivity and specificity, capable of detecting picogram per milliliter concentrations of 11-COOH-THC in biological samples.
Gas Chromatography-Mass Spectrometry (GC-MS): GC-MS is utilized for quantifying THC and its metabolites, including 11-COOH-THC, in human samples.
Factors Influencing Detection
Several variables can affect the detectability of 11-COOH-THC:
Frequency and Quantity of Use: Chronic users may retain detectable levels of 11-COOH-THC for extended periods due to accumulation in fatty tissues.
Metabolic Rate: Individual metabolic differences can influence the rate at which THC is processed and eliminated.
Body Composition: Higher body fat percentages can lead to prolonged retention of 11-COOH-THC.
Implications in Drug Testing
The availability of 11-COOH-THC in biological samples is the main indication of cannabis consumption. The problem of this marker is that it shows a long half-life and therefore cannot indicate when the sample was collected; this has importance in settings such as work-related drug testing and in legal investigations. More advanced testing methods that can distinguish the three metabolites - THC, 11-OH-THC, and 11-COOH-THC - will improve the accuracy in dating the actual time of cannabis consumption.
Summary:
In understanding the metabolism and detection of 11-nor-9-carboxy-THC, it becomes even more important to interpret drug tests legally. Metabolic and analytical advances increase the sensitivity and accuracy in detection and quantification of this metabolite, enhancing the medical, legal, and workplace decisions made on such testing.