The Metabolism of Δ⁹‐Tetrahydrocannabinol and Related Cannabinoids in Man

Abstract

The metabolism of Δ9‐tetrahydrocannabinol (THC) and related cannabinoids in man has been studied in detail utilizing intravenous, oral, and smoking routes of administration. The general pattern of metabolism was the same in all studies involving THC and related cannabinoids. Microsomal hydroxylation allylic to the Δ9‐THC double bond occurs, the major product resulting in formation of an 11‐CH2OH moiety; minor hydroxylation occurs on the C‐8 carbon. Nonmicrosomal oxidation of the resultant 11‐OH‐Δ9‐THC to 11‐nor‐Δ9‐THC‐9‐carboxylic acid and to other more polar acids generates the major terminal metabolic products. After oral administration, approximately equal quantities of THC and its highly active 11‐hydroxy metabolite were formed, whereasthe latter metabolite is a minor constituent after administration by intravenous or smoking routes. Initial pharmacokinetic analyses of the data show that the mean terminal‐phase (β‐phase) plasma half‐life after intravenous administration of THC was about 30 hours; after oral administration, it was 23 hours. No significant statistical difference was noted between men and women as to metabolic routes or plasma terminal‐phase half‐lives.

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

“…Finally, other studies using alcohol vehicle did not report any interactions between alcohol and D-9-THC (Agurell et al, 1986;Lindgren et al, 1981;Ohlsson et al, 1980a). The elimination half-life of D-9-THC has been reported to vary from 18 h to 4.3 days (Hunt and Jones, 1980;Johansson et al, 1989;Kelly, 1992;Sadler et al, 1984;Wall et al, 1976Wall et al, , 1983Wall and Perez-Reyes, 1981). The mean interval between each test day was 10 days.…”

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography–Tandem Mass Spectrometry

“…While it does not accumulate because of its rapid oxidation to form 11-nor-9-carboxy-THC (COOH-THC), it may still remain positive for a few days as the residual THC is converted to OH-THC (17,18). COOH-THC does not have pharmacological activity (19), but it persists longer in plasma and other biological samples compared to THC and OH-THC. The glucuronide conjugate of COOH-THC is also a prominent metabolite (13).…”

Medical Marijuana and Driving: a Review

“…Delta-9-tetrahydrocannabinol is rapidly metabolized in the liver by the cytochrome P450 system [24]. The active metabolite of delta-9-THC, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC), is further oxidized to 11-nor-9-carboxy-THC (THC-COOH), the most ubiquitous THC metabolite found in urine [30,31]. Qualitative screens for this inactive metabolite may remain positive for weeks to months, depending on chronicity of marijuana use.…”