Cannabis Pharmacokinetics, Metabolism and Detection

THC (Δ-9-tetrahydrocannabinol) is the main psychoactive cannabinoid found in cannabis and the primary molecule used for detection among cannabis users. Therefore, it is important to understand THC’s pharmacokinetics (distribution in the body), its metabolism (how it is broken down by the body) and the basis of the laboratory tests used for its detection.

The primary routes of administration of cannabis include smoking/vaporization and ingestion. Not surprisingly, the route of administration affects the absorption characteristics of THC. When cannabis is smoked or vaporized, there is a rapid onset of action (within minutes) with absorption of roughly 10%-35% of available THC in the product (1). THC is mainly absorbed through the bloodstream (2).

Peak THC plasma concentrations (blood levels) occur within 8 minutes after smoking or vaporization (1). In contrast, onset of action following ingestion occurs within 1-3 hours with 5%-20% absorption of THC (1). Peak plasma levels are observed after 2-6 hours after ingestion (1).

THC is primarily metabolized via the liver cytochrome P450 (CYP) system into a psychoactive compound, 11-hydroxy-THC (11-OH-THC) (2). 11-OH-THC is further metabolized into several inactive forms with 11-nor-9-carboxy-▵ 9-tetrahydrocannabinol (THC-COOH) as the dominant inactive metabolite (2). Because THC is highly lipophilic (fat-loving) it is mainly distributed in adipose (fat) tissue, liver, lung and spleen (1, 2).

THC’s elimination half-life —50% elimination of the initial absorbed dose of THC—can range from 2-57 hours following inhalation. The half-life of 11-OH-THC (the active metabolite of THC) is 12-36 hours (1, 2). Twenty (20) percent of THC is excreted in the urine whereas up to 65% is eliminated in feces (2). Within 5 days, nearly 90% of THC is eliminated from the body (2).

Urine immunoassays are typically used to detect THC-COOH in persons being tested for cannabis consumption. After a single use, THC can be detected in the urine for up to 7 days. With chronic cannabis consumption, THC can be detected in urine for 10-30 days. A sensitive test called enzyme-multiplied immunoassay technique (EMIT) can detect urine levels as low as 20-100 ng/ml.

Results from these screening tests indicate prior cannabis exposure but they cannot determine the amount used or degree of clinical effects after use. At present, detection of 50 ng/mL is considered positive for employees undergoing drug testing.  False-positive results can occur with ibuprofen, naproxen, dronabinol, efavirenz, and hemp seed oil. False-positive test results are unlikely from second-hand smoke inhalation, unless this exposure occurs in an unventilated space (1).

Blood tests can also be used to detect THC; however, detected levels cannot be associated with clinical effects. Hair sampling tests that use gas chromatography and mass spectrometry assays are available for cannabis screening. These screening methods can be used to test for multiple cannabinoids, including THC, THC-OH, THC-COOH, CBN and CBD (3). Cannabinoids enter the hair through capillaries and sweat and can be detected up to 3 months after exposure (3, 4). However, detection depends on heaviness of use and potency of marijuana consumed (4). 

References

  1. Russo L, Caneva D Cannabinoid poisoning. http://emedicine.medscape.com/article/833828-overview#a5  Accessed Aug. 9, 2017
  2. Sharma P, Murthy P, Srinivas Bharath MM Chemistry metabolism and toxicology of cannabis: clinical implications Iran J. Psychiatry 2012; 7:149-156
  3. Huestis MA, Mitchell JM Cone EJ Detection times of marijuana metabolites in urine by immunoassay and GC-MS J Anal Toxicol 1995; 19:443-449.
  4. Taylor M, Henderson R, Lingford-Hughes A, Macleod J, Sullivan J, Hickman M Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users. Drug Alcohol Rev. 2017; 36-220-226.

One Reply to “Cannabis Pharmacokinetics, Metabolism and Detection”

  1. -make ALL cannabis 0.25 per gram to provide concentrates to the world, because that’s what we all want. smoking leaves past 40 is harsh. I need concentraces & edibles. smoking is a HASSLE. so the less I have to do of it; the better. thank you.

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