A 9-Tetrahydrocannabinol

Gannabinoids. Like the BZ receptor, the cannabinoid receptor was initially identified using psychotropic alkaloids such as A -tetrahydrocannabinol (A-THC) (78) that were known to affect mammalian CNS function (see PsYCHOPHARMACOLOGiCALAGENTs). The CNS receptor,... 

Gallager, D. W., Sanders-Bush, E., and Sulser, F. (1972) Dissociation between behavioral effects and changes in metabolism of cerebral serotonin following A -tetrahydrocannabinol. Psychopharmacology, 26 337-345. 

The advances in isolation methods made possible a clarification of the chemistry of cannabis. In 1963, our group reisolated CBD and reported its correct structure and stereochemistry. A year later we finally succeeded in isolating pure A -tetrahydrocannabinol (A -THC), elucidated its structure, obtained a crystalline derivative and achieved a partial synthesis from CBD. Several years later, a minor psychotomimetically active constituent, A -THC, was isolated from marijuana. Whether this THC isomer is a natural compound, or an artifact formed during the drying of the plant, remains an open problem. 

Turner CE, El-Sohly MA, Constituents of Cannabis sativa L. XVI. Possible decomposition pathway of A -tetrahydrocannabinol to atnn moX, J Pleterocycl Chem 16 1667-1668, 1979. 

Adams R, Baker BR, Structure of Cannabidiol. VII. A Method of Synthesis of a Tetrahydrocannabinol which Possesses Marihuana Activity, J Amer Chem Soc 62 2405-2408, 1940. 

Hewlett AC, Champion TM, Wilken GH, Mechoulam R, Stereochemical effects of 11-OH-A -tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor. Neuropharmacology 29 161—165, 1990. 

Biotransformation of (+)- and -)-cis/trans- etheno s to (-f)-verbenone has been achieved by a cell-free system of Cannabis sativa Callus.The (—)- and (+)-verbenone (via verbenol) were the starting materials for the first synthesis of the (—)- and (+)- enantiomers of A -tetrahydrocannabinol. 

Tetrabenazine, 350 Tetracaine, 10 Tetracycline, 212, 213 A -Tetrahydrocannabinol, 394 Tetrahydropyrimidines, synthesis, 266... 

The psychological effects of cannabis are due to cannabinoids such as A -tetrahydrocannabinol (THC) which interact with specific cannabinoid receptors in the brain (Devane et al.,1988 Matsuda et al., 1990). The functions of these receptors are not known but high concentrations are present in sensory and limbic areas, and THC also increases dopamine release from the nucleus accumbens and frontal cortex (Tanda et al., 1987) and decreases the release of acetylcholine (Trzepacz, 2000). 

The major psychoactive constituent in marijuana use is A -tetrahydrocannabinol (THC), the prototypical can-nabinoid. Although marijuana contains a large number of cannabinoids, they lack behavioral activity with the exception of cannabinol, which is approximately one-tenth as potent as THC. The THC content in hashish is more than double that in marijuana. 

A -3,4-cis-THC has now been found in Cannabis sativa (Phenotype III) other papers reporting the characterization of compounds from Cannabis sativa concern conclusive identification and synthesis of cannabinodiol, " which is known to result from the photochemical irradiation of cannabinol (Vol. 7, p. 51), and the identification of A -tetrahydrocannabinolic acid " and (+)-cannabitriol (263) " (263) and the corresponding C-2 ethyl ether may be epoxide-derived. " ... 

Lepore, Marino, Xinhe Liu, Virginia Savage, Daniel Matalon, and Eliot L. Gardner. 19%. "Genetic Differences in A -Tetrahydrocannabinol-Induced Facilitation of Brain Stimulation Reward as Measured by a Rate-Frequency Curve-Shift Electrical Brain Stimulation Paradigm in Three Different Rat Strains." Life Sciences lPharmacology Letters) 25 PL365-72. 

E.T. Uyeno, A-Tetrahydrocannabinol administration during pregnancy of the rat, Proc. West. Pharmacol. Soc., 16 (1973) 64-67. 

Pharmacological and metabolic studies on cannabinoids (Fig. 1) have suffered from a lack of knowledge of their physico-chemical properties and the insensitivity of assays of A -tetrahydrocannabinol 1, and its metabolites in biological fluids. Unambiguous, sensitive, specific and accurate quantification is required for forensic toxicology and pharmacokinetic studies which can be correlated with the time course of the psychoactive effects (2). 

The determination (3) of physical and chemical properties such as solubility, stability, pKa, glassbinding and protein-binding of A -tetrahydrocannabinol 1 and correlated congeners were only possible after the development of new high pressure liquid chromatography (HPLC) techniques and the modification of gas liquid chromatography (GLC) technologies. 

Clinical investigations of A -tetrahydrocannabinol (4,5) and ll-hydroxy-A -tetrahydrocannabinol (6) have relied upon analysis by radioactive labeling. However, the study of distribution, metabolism and excretion of the drug and its metabolites under chronic or "street" conditions demands nonradioactive analytical procedures. When plasma suspensions of l c-A -tetrahydrocan-nabinol were administered intravenously to three dogs at doses of 0.1 - 2.0 mg/kg and plasma levels of 1 were followed for up to 7000 minutes, no significant differences were seen in 1 plasma levels as determined by liquid scintillation and electron capture detection (GLC) after HPLC collection. 

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