THC

Other Names Ll9-tetrahydrocannabinol, .1.9-THC, delta-9-THC, Lll-3,4-trans-tetrahydrocannabinol, tetrahydro-6,6,9 -trimethyl-3-pentyl-6H-di-benzo [b,d]pyran-l-ol, trans-THC Substance type: cannabinoid, pyrane derivative, pyranol derivative THC is the main active constituent of the three hemp species Cannabis indica, Cannabis ruderalis, and Cannabis sativa. THC has not yet been found in any other plants. The information suggesting that THC is pyrochemically synthesized when olibanum (the resin of Boswellia sacra) is burned is contradictory. Similarly, no trace of THC or its analogs has yet been found in hops (Humulus lupulus). THC and its metabolites have been found in Egyptian mummies (Balabanova et al. 1992*). While trans-THC is psychoactive, the isomer cis-THC is not (Kempfert 1977): The effective dosage of THe when smoked is between 2 and 22 mg and when taken orally is between 20 and 90 mg. When smoked under normal conditions, 16 to 19% of the THe is consumed and the rest is pyrolized. No lethal dosage is known. However, experiments with animals indicate that the ratio between an effective and a lethal dosage can be estimated to be 4,000 to 40,000. In comparison, this ratio for alcohol is 4 to 10. (Fromberg 1996,37) In the blood, THC is transformed into the active metabolite 11-hydroxy-Ll9-THC. This substance is absorbed by fatty tissues after about thirty minutes and is then released back into the blood, metabolized, and excreted. After only a few days, all of the substance has been excreted by the body. With chronic use, 11-hydroxy-THC accumulates in the fatty tissues and in the liver and can be detected for a longer period of time (urine tests!; cf. Rippchen 1996). THC receptors have been discovered both in the central nervous system and in the peripheral pathways (Compton 1993; Devane et al. 1989; Matsuda et al. 1990). The THC or cannabinoid receptor in the nervous system has now been studied extensively and is very well understood (Pertwee 1995). Normally, endogenous neurotransmitters known as anandamides bind to these receptors (Devane et al. 1992; Devane and Axelrod 1994; Kruszka and Gross 1994). Nerve diseases (such as multiple sclerosis) can result if the body does not produce sufficient amounts of anandamides. If anandamide deficiencies are responsible for these diseases, it is possible that they could be successfully treated with THC (Mechoulam et al. 1994). Anandamide (= arachidonylethanolamide)the name is derived from the Sanskrit word ananda, "bliss"-binds to THC receptors in the brain and is the endogenous THC analog, even though the inner structures of the two are quite different. Recently, anandamide has been discovered in chocolate and cocoa beans (Theobroma cacao) as well as in red wine (cf. Vitis vinifera) (Grotenhermen 1996). Since 1971, cannabis products have been tested experimentally as medicines for treating alcoholism, heroin and amphetamine addiction, emotional disturbances, muscle spasms, and glaucoma. In 1990, the microbiologist Gerald Lancs of the University of South Florida discovered that marijuana kills the herpes virus (AFP announcement on May 16, 1990), providing scientific validation of an old Roman remedy for herpes. The traditional use of hemp products for asthma has also received scientific support: "THC dilates the bronchial passages. Like other medicines, it can be inhaled as an aerosol to treat bronchial asthma and produces equally positive effects" (Maurer 1989,48). The medicinal use of THC and its analogs for the treatment of glaucoma has become an established practice. No other substance has been demonstrated to be better tolerated or more effective than THC (Maurer 1989). A Swiss group of researchers was able to show that THC relaxes the muscular cramping associated with central nervous system spasticity (e.g., due to multiple sclerosis or spinal cord injury) (Maurer et al. 1990). The researchers found that THC (at a dosage of 5 mg) produces effects that are similar to those of codeine but more effective and that THC is also more easily tolerated. There have also been encouraging attempts to utilize THC in the clinical treatment of spasticity and the associated pain (Hagenbach 1996). The potential applications [of synthetic THC] range from the treatment of epilepsy, chronic pain, multiple sclerosis, and lack of appetite to a reduction in the "addictive pressure" associated with opiate addiction. (Schmidt 1996,30) Synthetic THC is better known by the trade name Marinol. A dosage of 20 to 45 mg of Marinol induces a "high" that lasts for only sixty to ninety minutes. Many patients in the United States who take Marinol complain that the expensive medicine is ineffective compared to marijuana when either smoked or eaten (Jack Herer, pers.comm.). Pharmacological research is now under way to develop synthetic THC analogs that could be marketed as medicines. The goal is to isolate the medically useful properties of THC while removing the psychoactive ones (Evans 1991). One of the products that has been synthesized as a result of this research is the cannabinoid analog HU-210) chemically known as (-)1l-0H-Ll8-THC-dimethylheptyl. This substance not only is psychoactive but is some one hundred to eight hundred times more potent than natural THC (Ovadia et al. 1995). However) government health departments and pharmaceutical companies are more interested in THC analogs that are devoid of psychoactive effects. Some critics of this research take a different position) arguing that the therapeutic effects of THC are directly related to its psychoactivity.

Commercial Forms and Regulations In principle) THC is an illegal substance throughout the world (cf. Cannabis indica). However) for the past several years certain prescription drugs containing THC have been available in the United States under the trade names Canasol and Marinol. Physicians may prescribe these for glaucoma and cancer patients. In Europe) these drugs can be obtained only from pharmacies that sell foreign medicines, and they are extremely expensive. Recently) there have been efforts in several states in the United States as well as in several European nations to make THe and/or Cannabis products more readily available to patients suffering from a variety of conditions. There is) however) considerable resistance to such liberalization efforts. In spite of the very long history of use of THC and Cannabis in numerous .cultures and for a wide variety of purposes (see Ratsch 2001 *) it remains to be seen whether these substances will ever become widely accepted and legitimately used. Literature See also the entries for Cannabis indica and Cannabis sativa. Compton, David R, Kenner C. Rice, Brian R. de Costa, Raj K. Razdan, Lawrence S. Melvin, M. Ross Johnson) and Billy R Martin. 1993. Cannabinoid structure-activity relationships: Correlation of receptor binding and in vivo activities. The Journal ofPharmacology and Experimental Therapeutics 265:218-26. Devane) William A.) and Julius Axelrod. 1994. Enzymatic synthesis of anandamide) an endogenous ligand for the cannabinoid receptor, by brain membranes. Proceedings ofthe National Academy ofScience, USA 91:6698-701. Devane, William A., Francis A. Dysarz III, M. Ross Johnson) Lawrence S. Melvin) and Alynn C. Howlett. 1988. Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology 34:605-13. Devane) William A.) Lumir Hanus) Aviva Breuer) Roger G. Pertwee, Lesley A. Stevenson) Graeme Griffin) Dan Gibson) Asher Mandelbaum) Alexander Etinger) and Raphael Mechoulam. 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946-49. Evans) Fred J. 1991. Cannabinoids: The separation of central from peripheral effects on a structural basis. Planta Medica 57 supp!. (1): 60-67. Fromberg, Erik. 1996. Die Pharmakologie von Cannabis. In Cannabis, ed. Jurgen Neumeyer) 36-42. [Munich]: Packeispresse Verlag Hans Schickert. Grotenhermen) Franjo. 1996. Schokolade) Haschisch undAnandamide. Hanft 12/96:14-15. Hagenbach, Ulrike. 1996. Spinale Spastik und Spasmolyse: 1st die Therapie mit THC eine unerwartete Bereicherung? In Jahrbuch des Europiiischen Collegiums fur Bewufltseinsstudien (1995) 199-207. Berlin: VWB. Iversen) Leslie 1. 1993. Medical uses of marijuana? Nature 365:12-13. Kettenes-van den Bosch, J. J., and C. A. Salemink. 1980. Biological activity of the tetrahydrocannabinols. Journal of Ethnopharmacology 2:197-231. (Very good bibliography.) Kruszka) Kelly K.) and Richard W. Gross. 1994. The ATP- and coA-independent synthesis of arachidonoylethanolamide: A novel mechanism underlying the synthesis of the endogenous ligand of the cannabinoid receptor. The Journal of Biological Chemistry 269 (20): 14345-48. Matsuda) Lisa A.) Stephen J. Lolait) Michael J. Brownstein, Alice C. Young, and Tom 1. Bonner. 1991. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561-64. Maurer, Maja. 1989. Therapeutische Aspekte von Cannabis in der westlichen Medizin. In 3. Symposion uber psychoaktive Substanzen und veranderte Bewufltseinszustande in Forschung und Therapie, ed. M. Schlichting and H. Leuner, 46-49. Gottingen: ECBS. Maurer, M., V. Henn, A. Dittrich, and A. Hofmann. 1990. Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. European Archives of Psychiatry and Clinical Neuroscience 240: 1-4. Mechoulam, Raphael, Zvi Vogel, and Jacob Barg. 1994. CNS cannabinoid receptors: Role and therapeutic impl·cations for CNS disorders. CNS Drugs 2 (4): 255 60. Mestel, Rosie. 1993. annabis: The brain's other supplier. New Sc entist7/93:21-23. Ovadia, H., A. Wohlman, R. Mechoulam, and J. Weidenfeld. 1995. Characterization of the hypothermic effect of the synthetic cannabinoid HU-210 in the rat: Relation to the adrenergic system and endogenous pyrogens. Neuropharmacology 34 (2): 175-80. Pertwee, Roger, ed. 1995. Cannabinoid receptors. New York: Harcourt Brace Jovanovich. Rippchen, Ronald, ed. [1996]. Mein Urin gehort mir. Lorbach: Edition Rauschkunde. Schmidt, Sebastian. 1996. Die THC-Pille auf Rezept. Hanfblatt3 (20): 30-31. Smith, R. Martin, and Kenneth D. Kempfert. 1977. ~.l-3,4-cis-tetrahydrocannabinol in Cannabis sativa. Phytochemistry 16:1088-89. Zeeuw, Rokus A. de, and Jaap Wijsbeek. 1972. Cannabinoids with a propyl side chain in cannabis: Occurrence and chromatographic behavior. Science 175:778-79