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.