11-nor-Delta-9-Tetrahydrocannabinol-9-Carboxylic Acid (Carboxy-THC), Confirmation, Meconium
Detection of in utero drug exposure up to 5 months before birth
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Marijuana and other psychoactive products obtained from the plant Cannabis sativa are the most widely used illicit drugs in the world.(1) Marijuana has unique behavioral effects that include feelings of euphoria and relaxation, altered time perception, impaired learning and memory, lack of concentration, and mood changes (eg, panic reactions and paranoia).
Cannabis sativa produces numerous compounds collectively known as cannabinoids including delta-9-tetrahydrocannabinol (THC), which is the most prevalent and produces most of the characteristic pharmacological effects of smoked marijuana.(2) THC undergoes rapid hydroxylation by the cytochrome (CYP) enzyme system to form the active metabolite 11-hydroxy-THC. Subsequent oxidation of 11-hydroxy-THC produces the inactive metabolite 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH; carboxy-THC). THC-COOH and its glucuronide conjugate have been identified as the major end-products of metabolism. THC is highly lipid soluble, resulting in its concentration and prolonged retention in fat tissue.(3)
Cannabinoids cross the placenta, but a dose-response relationship or correlation has not been established between the amount of marijuana use in pregnancy and the levels of cannabinoids found in meconium, the first fecal matter passed by the neonate.(4,5) The disposition of drug in meconium is not well understood. The proposed mechanism is that the fetus excretes drug into bile and amniotic fluid. Drug accumulates in meconium either by direct deposition from bile or through swallowing amniotic fluid.(5) The first evidence of meconium in the fetal intestine appears at approximately the 10th to 12th week of gestation, and slowly moves into the colon by the 16th week of gestation.(6) Therefore, the presence of drugs in meconium has been proposed to be indicative of in utero drug exposure during the final 4 to 5 months of pregnancy, a longer historical measure than is possible by urinalysis.(5)
Positives are reported with a quantitative LC-MS/MS result.
Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by LC-MS/MS: >10 ng/g
The presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid > or =10 ng/g is indicative of in utero drug exposure up to 5 months before birth.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Since the evidence of illicit drug use during pregnancy can be cause for separating the baby from the mother, a kit is available that includes all the materials necessary to complete chain of custody to ensure that the test results are appropriate for legal proceedings.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Huestis MA: Marijuana. In Principles of Forensic Toxicology. Second edition. Edited by B Levine. Washington DC, AACC Press, 2003 pp 229-264
2. O'Brein CP: Drug addiction and drug abuse. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th edition. Edited by LL Burton, JS Lazo, KL Parker. McGraw-Hill Companies Inc, 2006. Available at URL: www.accessmedicine.com/content.aspx?aID=941547
3. Baselt RC: Tetrahydrocannabinol. In Disposition of Toxic Drugs and Chemical in Man. Edited by RC Baselt. Foster City, CA, Biomedical Publications, 2008: pp1513-1518
4. Ostrea EM Jr, Knapop DK, Tannenbaum L, et al: Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis. J Pediatr 2001;138:344-348
5. Ostrea EM Jr, Brady MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing. J Pediatr 1989;115:474-477
6. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero: mechanisms, consequences, and management. Obstet Gynecol Surv 2005;60:45-56