A9-tetrahydrocannabinol THC

There are approximately 400 chemicals in the cannabis plant, 61 of which are unique and may be called cannabinoids. The most common psychoactive cannabinoid is A9-tetrahydrocannabinol (A9-THC) (Robbers et al. 1996) (figure 10.4). Other psychoactive cannabinoids include A8-tetrahydrocannabinol (A8-THC), ll-hydroxy-A8-tetrahydrocannabinol (11-OH-A9-THC), and 9-nor-9 j8-hydroxyhexahydrocannabinol p-... 

At least 60 bioactive compounds are contained in herbal cannabis. A9-Tetrahydrocannabinol (A9-THC) (Mechoulam and Gaoni, 1967), cannabidiol and cannabinol are the major psychoactive or adjuvant ingredients. Cannabinoids act through at least two different G-protein coupled receptors named CBi and CB2 receptors. 

A9-Tetrahydrocannabinol (A9-THC) is considered to be the predominant compound in preparations of C. sativa (marijuana, hashish, bhang) that is responsible for the central nervous system effects in humans. The recognized central nervous system responses to these preparations include alterations in cognition and memory, euphoria, and sedation. Potential therapeutic applications of cannabis preparations that are of either historical or contemporary interest include analgesia, attenuation of the nausea and vomiting of cancer chemotherapy, appetite stimulation, decreased intestinal motility of diarrhea, decreased bronchial constriction of asthma, decreased intraocular pressure of glaucoma, antirheumatic and antipyretic actions, and treatment of convulsant disorders. These effects have been reviewed recently (Howlett, 1995). 

FIGURE 18.2 Chemical structures of A9-tetrahydrocannabinol (A9-THC) derived from marijuana, and the endogenous cannabimimetic eicosanoid, anadamide (arachidonylethanolamide), identified in the human brain. 

Note The cannabis plant has been cultivated for centuries both for the production of hemp fiber and for its presumed medicinal and psychoactive properties. The smoke from burning cannabis contains many chemicals, including 61 different cannabinoids that have been identified. One of these, A9-tetrahydrocannabinol (A9-THC), produces most of the characteristic... 

Marijuana refers to varieties of Cannabis having a high content of A9-tetrahydrocannabinol (A9-THC), which is the psychoactive ingredient of marijuana whereas industrial hemp refers to varieties of the Cannabis plant that have a low content of A9-THC. 

Cannabinoid compounds are components which can be isolated from Cannabis spp. Due to its physiological activity trans-delta-9-tetrahydrocannabinol (A9-THC) is of substantial significance. This compound is also referred to as 6a,7,8,10a-tetradydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-l-ol. 

Ring condensation may be used to produce the rans-delta-9-tetrahydrocannabinol (A9-THC) from 6,12-dihydro-6-hydroxy-cannabidol. This reaction is performed in a suitable solvent with the use of suitable catalysts and water binding substances. The solvent is in the form of a hydrocarbon, as for instance hexane, heptane, cyclohexane, petroleum ether, aromatic hydrocarbons, such as for instance benzene, toluene, chorinated hydrocarbons, such as for instance methylene chloride, chloroform and dichloroethane. Preferably methylene chloride and chloroform are used. Furthermore mixtures of the solvents may be used. 

This compound and its related acidic form, A8-tetrahydrocannabinolic acid (A8-THCA, 2.13) are structural isomers of A9-THC. Although it is the thermodynamically stable form of THC, A8-THC (2.14) contributes approximately only 1% to the total content of THC in C. sativa. In the synthetic production process, A8-THC is formed in significantly higher quantities than in plants. 

Synthesis of A9-Tetrahydrocannabinol from Natural Cannabidiol (Semisynthetic A9-THC)... 

So, the 20th century actually led to an almost total disappearance of C. sativa for medicinal purposes. The only source for THC, which became the focus of scientific research, was fhe rafher fedious exfracfion and purification from confiscated hashish or marihuana. In 1972 the first commercially viable total synthesis of A9-THC was established and it became the first cannabinoid available as a modern medicine in the form of soft gel capsules (the active ingredient being called dronabinol from tetrahydrocannabinol) under the trade name Marinol for the prevention of nausea and vomiting during cancer chemotherapy. 

The psychoactive ingredients of cannabis sativa are finally formed when its leaves are dried at elevated temperature so that e.g. tetrahydrocannabinolic acid is decarboxylated to A9-THC. 

THC undergoes metabolic degradation in the liver, where it is hydroxylated to 11-hydroxy tetrahydrocannabinol (THC-llOH). The latter, still with psychoactive activity, is oxidized to A9-THC-COOH, an inactive metabolite which is conjugated as 1 l-nor-A9-tetrahydrocannabinol-9-carboxy-glucuronide (A9-THC-COOH-glu), more hydrophilic metabolite and therefore easily excreted in the urine [32],... 

Keywords Cannabinoids Cheniokines Cocaine Cytokines Immunosuppression Morphine Opioids T-helper 1/T-helper 2 (Thl/Th2) A9-tetrahydrocannabinol (A -THC) Tolerance Withdrav al... 

The primary active component of cannabis is A9-tetrahydrocannabinol (THC), which is responsible for the greater part of the pharmacological effects of the cannabis complex. A8-THC is also active. However, the cannabis plant contains more than 400 chemicals, of which some 60 are chemically related to A9-THC, and it is evident that the exact proportions in which these are present can vary considerably, depending on the way in which the material has been harvested and prepared. In man, A9-THC is rapidly converted to 11-hydroxy-A9-THC (3), a metabolite that is active in the central nervous system. A specific receptor for the cannabinols has been identified it is a member of the G-protein-linked family of receptors (4). The cannabinoid receptor is linked to the inhibitory G-protein, which is linked to adenyl cyclase in an inhibitory fashion (5). The cannabinoid receptor is found in highest concentrations in the basal ganglia, the hippocampus, and the cerebellum, with lower concentrations in the cerebral cortex. 

In order to identify cannabis products, one of the most frequently used methods is gas chromatography-mass spectrometry (GC-MS). The identification relies on the presence of A9-THC, CBD and CBN in the sample, and to a lesser extent, the presence of A8-THC (the isomer of the active principle of cannabis) and A9-tetrahydrocannabinolic acid. The following presents a method that has been found to work, although there are a number of similar methods reported in the literature [9], The sample is prepared for GC-MS analysis as follows ... 

Cannabinoids.—New compounds (259 OH at C-8 or at C-10)847 and (259 OH at both C-9 and C-10)848 have been isolated from Cannabis sativa. p-Menth-2-ene-1,8-diol is an excellent synthon for the A9-tetrahydrocannabinol (THC) skeleton, coupling (ZnCl2-catalysed) with olivetol (3-n-pentylresorcinol) to form the (—)-parent compound, and forming the biologically potent 3-OH metabolite by appropriate modification of the reaction.849 The structurally equivalent substrate p-menth-1,8-dien-1 -ol reacted with other substituted resorcinols and led to A8- and A9-THC analogues differing in the side-chain attached at C-3.850-851 Use of the synthon (260) in a similar manner gave 2, 1 l-dihydroxy-A9-THC this was claimed... 

Group of compounds which naturally occur in the hemp plant, Cannabis saiiva. Most of them are unsoluble in water. The most abundant cannabinoids are A9--tetrahydrocannabinol (THC), its precursor cannabidiol and cannabinol, which is formed spontaneously from THC. Cannabinoids exert their effects through G-protein coupled cannabinoid receptors (CBi/CB2). 

The plant Cannabis sativa produces the psychoactive diug A9-tetrahydrocannabinol (THC). Recreationally, THC is consumed in form of marijuana (dried flowers and leaves) or hashish (resin). The cultivation and possession of Cannabis for recreational use is not... 

A9-Tetrahydrocannabinol (THC) Antidiabetic Drugs AMP-activated Protein Kinase Adipokines PPARs... 

Alternatively, A9-tetrahydrocannbinol or simply tetrahydrocannabinol is frequently used in the scientific community. When using the short name tetrahydrocannabinol or just THC it always imphes the stereochemistry of the A 9-isomer. 

As it can be observed in Fig. 2, three out of the 16 investigated compounds, namely, heroin, lysergic acid diethylamide (LSD), and its metabolite 2-oxo, 3-hydroxy-LSD (O-H-LSD), were not detected in any wastewater sample. Two other target analytes, 6-acetyl morphine (6ACM) and A9-tetrahydrocannabinol (THC), were only present in influent wastewaters and with low detection frequencies. The most ubiquitous compounds, present in all influent and effluent wastewater samples analyzed, were the cocaine metabolite benzoylecgonine, and the amphetamine-like compounds ephedrine (EPH) and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). Cocaine, cocaethylene (CE, transesterification product of cocaine formed after the joint consumption of cocaine and ethanol), and morphine (MOR) were detected in all influent, but not in all effluent wastewaters (see Fig. 2). 

Marijuana (reefer, pot, grass, weed) is the most commonly used illicit drug. The principal psychoactive component is A9-tetrahydrocannabinol (THC). Hashish, the dried resin of the top of the plant, is more potent than the plant itself. Pharmacologic effects begin immediately and last 1 to 3 hours. 

Neuropharmacologic classification of addictive drugs by primary target (see text and Table 32-1). DA, dopamine GABA, 7-aminobutyric acid GHB, 7-hydroxybutyric acid GPCRs, G protein-coupled receptors THC, A9-tetrahydrocannabinol. 

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