Metabolism marijuana

Relatively few human imaging studies have evaluated the effects of marijuana or THC on metabolism or blood flow. Acute intravenous THC in both normal controls and habitual marijuana users led to increased an increased regional cerebral metabolic rate (CMR) in the cerebellum. This increase is positively correlated both with concentrations of THC in the plasma and with the intensity of the subjective sense of intoxication [5]. In a 1997 PET/[lsO]water study with 32 abusers [6], THC dose-depend-ently increased cerebral blood flow (CBF) in the frontal regions, insula... 

The average increase in rCMR after THC administration was less in marijuana users than in controls, and users had lower cerebellar metabolism than the controls at baseline [8]. Thus the cerebellum shows the greatest metabolic increase in response to acute THC and responds to chronic marijuana exposure with a decrease in baseline CMR. Habitual users but not controls responded to THC administration with increased rCMR in prefrontal cortex, orbitofrontal cortex, and basal ganglia. In contrast to the robust effects of THC on relative rCMR, changes in global CMR in response to THC were quite variable, with increases, decreases, and no changes seen in equal numbers of subjects. There was also variability in subjective effects, which were pleasurable for most subjects but either minimal or unpleasant (anxiety or paranoia) for others. 

Volkow ND, Gillespie H, Mullani N, Tancredi L, Grant C, Valentine A, Hollister L. Brain glucose-metabolism in chronic marijuana users at baseline and during marijuana intoxication. Psychiatr Res Neuroimaging 1996 67 29-38. 

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. 

Marijuana may also be eaten (baked into cookies or brownies), brewed in tea, or swallowed in pill form. Much of oral THC is destroyed in the stomach, and more is destroyed via first-pass metabolism. THC is metabolized primarily in the liver to an active metabolite, 11-hydroxy-THC (11-OH-THC), that is further converted to the inactive carboxylated compound 11-nor-delta 9-THC-9-COOH (THC-COOH) and its glucuro-nide form. It is these metabolites that are tested for in urine samples. 

Metabolism is the major route of elimination of THC from the body as little is excreted unchanged. In humans, over 20 metabolites have been identified in urine and feces 26 Metabolism in humans involves allylic oxidation, epoxidation, aliphatic oxidation, decarboxylation, and conjugation. The two monohydroxy metabolites (Figure 4.7) 11-hydroxy (OH)-THC and 8-beta-hydroxy THC are active, with the former exhibiting similar activity and disposition to THC, while the latter is less potent. Plasma concentrations of 11-OH-THC are typically <10% of the THC concentration after marijuana smoking. Two additional hydroxy compounds have been identified, namely, 8-alpha-hydroxy-THC and 8,11-dihydroxy-THC, and are believed to be devoid of THC-like activity. Oxidation of 11-OH-THC produces the inactive metabolite, ll-nor-9-carboxy-THC, or THC-COOH. This metabolite may be conjugated with glucuronic acid and is excreted in substantial amounts in the urine. 

Users often experience a mellow sense of wellbeing and relaxation that makes them feel expansive, creative, and more sensitive to all types of stimuli. Perception of time slows, and ability to gauge distance, depth, and speed accurately is distorted. Users can also spiral downward into anxiety, paranoia, panic attacks, and hallucinations. This effect is more pronounced when larger doses of THC are ingested, such as when hashish or other more concentrated forms of marijuana are used. Higher doses are also possible when marijuana is eaten rather than smoked this occurs when more of the drug is ingested before it can be metabolized. 

Burstein, S., in "Marijuana, Chemistry, Pharmacology, Metabolism and Clinical Effects", Ed. 

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... 

Leuchtenberger C, Leuchtenberger R. Cytological and cytochemical studies of the effects of fresh marihuana smoke on growth and DNA metabolism of animal and human lung cultures. In Braude MC, Szara S, editors. The Pharmacology of Marijuana. New York Raven Press, 1976 595-612. 

L. Lemberger, N.R. Tamarkin and J. Axelrod. A9-Tetrahydrocannabinol metabolism and disposition in long term marijuana smokers. Science 178, 72-74, 1971. 

We begin this chapter with a historical overview of marijuana and its use through the centuries. This is followed by a section on the epidemiology of current marijuana use. Next we provide information on absorption, distribution, metabolism, and excretion mechanisms of action and tolerance and dependence. Follow ing this is an overview of the medical and p-sychotherapeutic uses of marijuana. The chapter s final sections concern the physical, psychological, and social/environmental effects of marijuana. 

Mechtxilam, R. (1973). Cannabinoid chemistry. In R. Mechoulam (Ed.), Marijuana Chemistry, pharmacology, metabolism, and clinical effects pp. 2-99). 

Microsomal hydroxylation at allylic carbon atoms is commonly observed in drug metabolism. An illustrative example of allylic oxidation is given by the psychoactive component of marijuana. J -tetrahydnx annabinol J -THC. This molecule contains three allylic carbon centers (C-7. C-6. and C-3). Allylic hydroxylation occurs cxten.sively at C-7 to yield 7-hydroxy- j -THC as the major pla.sma metabolite in humans. " Pharmacological studies show that this 7-hydroxy metabolite is as active as, or even more active than. J -THC per se and may contribute significantly to the overall central nervous system (CNS) p.sychotomimctic effects of the parent compound. Hydroxylation also occurs to a minor extent at the allylic C-6 position to give both the epimeric ba- and 6/3-hydroxy metabolites. " Metaboli.sm does not occur at C-3, presumably becau.se of steric hindrance. 

Mechoulam, R., and Edery, H. Structure activity relationships in the cannabinoid series. In Mechoulam, R., ed. Marijuana Chemistry, Metabolism, Pharmacology and Clinical Effects. New York Academic Press, 1973. pp. 101-136. 

The balance between medicinal use of a drug and the abuse potential is a delicate balance. One of the main points brought by the medicinal marijuana proponents is the fact that the currently available soft gelatin capsule formulation is very expensive and lacks consistency in its effects. The latter point could be explained based on the fact that oral THC has erratic absorption from the gastrointestinal tract, is subject to the first-pass effect resulting in heavy metabolism with production of high levels of 11-OH-THC, and undesirable side effects. 

Immunoassay. THC is extensively metabolized to a large number of compounds, most of which are inactive. The principal urinary metabolite is U -nor-A -tetrahydro-cannabinol-9" carboxylic acid (THC-COOH) and its glucuronide conjugate (see Figure 34-30). Immunoassays designed to screen urine samples for marijuana use measure this and other THC metabolites. These assays are calibrated with THC-COOH, but because of cross-reactivity with many other THC metabolites, quantitative results based on them are 1.5 to 8 times greater than the actual concentration of THC-COOH as determined by GC-MS. Therefore... 

Marijuana constituents, metabolism, pharmacology, toxicology of 86YZ537. 

Tetrahydrocannabinol (marijuana) is rapidly metabolized in the body to the tetrahydrocannibinol carboxylic acid or THC (Fig. 8.5). It is the THC metabolite that is commonly monitored in urine for drug analysis of marijuana. Because the THC structure contains both a phenolic hydroxyl group and a car-... 

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