Metabolism of cannabinoids

We are now developing this technique for urine using the metabolism of cannabinoids for a very specific detection of polar cannabinoids. 

In the past, studies of the distribution and metabolism of cannabinoids had been hampered by the lack of pure radiolabeled compounds. In 1973, shortly after the radiolabeled cannabinoids became available, Dr. E. G. Lelghty reported the recognition of some unidentified metabolites that were retained In rat liver and spleen up to 15 days after an acute Intravenous or multiple subacute Intraperltoneal Injections of either A -THC or A -THC ). The metabolites could be extracted by methanol and had a greater lipophilicity than the parent THC. These long-retained metabolites were also found In bone marrow ( ) and represented an Increasing percentage of the total cannabinoids found In feces, but not urine (. 

Hawks RL (1982) The constituents of cannabis and the disposition and metabolism of cannabinoids. In Hawks R (ed) The analysis of cannabinoids in biological Fluids. Research Monograph 42. National Institute on Drug Abuse, RockvUle, pp 125-137... 

Wall ME, Brine DR, Perez-Reyes M (1976) Metabolism of cannabinoids in man. In Braude MC, Szara S (eds) The Pharmacology of marihuana. Raven Press, New York, pp 93-113... 

II. IMAGING THE EFFECTS OF CANNABINOIDS ON METABOLISM AND BLOOD FLOW... 

There are over 400 constituent compounds in marijuana. More than 60 of these are pharmacologically active cannabinoids, of which 4 are the most important. The most psychoactive is delta-9-tetrahydrocannabinol (A-9-THC). The other three important natural cannabinoids are A-8-THC, cannabinol and cannabidiol (Kumar et al., 2001). In addition, some of the metabolites of THC, such as 11-hydroxy-A-9-THC, are also psychoactive. As a consequence and contrary to many other drugs, the metabolism of THC in the liver does not decrease intoxication, rather it prolongs it. 

The metabolic functionalization of cannabinoids is of continuing interest (c/. Vol. 4, p. 71 Vol. 7, p. 50). A -THC may be hydroxylated at C-4 using Mycobacterium rhodochrous (together with aromatization) or at C-4" of the side-chain with Bacillus cereus or may be oxygenated at C-5 with Streptomyces species. A -THC has been hydroxylated in both the ring system and the side-chain with Pellicularia filamentosa and Streptomyces lavendulae, and further evidence in favour of in vivo epoxy metabolites and derivatives in the mouse has been presented (cf. Vol. 4,... 

The application of GLC-MS techniques to the ill vitro and ill vivo metabolism of A9-THC (8) laid the groundwork for the quantitative analysis of other cannabinoid metabolites. The sites of metabolic hydroxylation for many cannabinoids are shown in Figure 1. 

Although animal studies indicate transfer of A -THC into the milk, comparable research has not been done on humans. It is difficult to extrapolate from animal studies to humans. The only primates studied, squirrel monkeys, are known to metabolize A9-THC differently than humans. (15) In addition, lactating human mothers in the general population ingest both A9-THC and other cannabinoids (e.g., CBN, CBD) by smoking cannabis. Information is not currently available regarding either transfer of cannabinoids into the milk of lactating humans or the effects of maternal cannabis use on infant development. 

The use of cannabinoids has been studied in 62 patients with HIV-1 infection (143). Cannabinoids and HIV are of interest because there is the chance of an interaction between tetrahydrocannabinol and antiretroviral therapy. Tetrahydrocannabinol inhibits the metabolism of other drugs (144,145) and cannabinoids are broken down by the same cytochrome P-450 enzymes that metabolize HIV protease inhibitors. The subjects were randomly assigned to marijuana, dronabinol (synthetic delta-9-tet-rahydrocannabinol), or placebo, given three times a day, 1... 

With a treatment of three intraperitoneal injections of SO mg cannabinoid per kilogram body weight per day, it was found that 11-palm-A -THC did not affect the metabolism of either Type I or Type II substrates but appeared to affect benzpyrene hydroxylase activity and that cytochrome P-448 was apparently Increased two-fold by treatment with the conjugate (Table 1). 

Guzman M, Sanchez C (1999) Effects of cannabinoids on energy metabolism. Life Sci 65 657-664... 

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