Chemical structure of tetrahydrocannabinol
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Dronabinol

Tetrahydrocannabinol, also known as THC, Δ9-THC, Δ9-tetrahydrocannabinol (delta-9-tetrahydrocannabinol), Δ¹-tetrahydrocannabinol (using an older numbering scheme), or dronabinol, is the main psychoactive substance found in the Cannabis plant. It was isolated by Raphael Mechoulam and Yechiel Gaoni from the Weizmann Institute in Rehovot, Israel in 1964. In pure form it is a glassy solid when cold and becomes viscous and sticky if warmed. more...

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THC has a very low solubility in water, but a good solubility in most organic solvents such as pure ethanol or hexane.

Pharmacology

Its pharmacological actions are the result of its binding to the cannabinoid receptor CB1, located in the brain. The presence of these specialized receptors in the brain implied to researchers that endogenous cannabinoids were manufactured by the body, so the search began for a substance normally manufactured in the brain that binds to these receptors, the so-called natural ligand or agonist, leading to the eventual discovery of anandamide and some related compounds. This story resembles the discovery of the endogenous opiates (endorphins, enkephalins, and dynorphin), after the realization that morphine and other opiates bound to specific receptors in the brain.

Effects include: relaxation, euphoria, altered space-time perception, alteration of visual, auditory, and olfactory senses, disorientation, fatigue and appetite stimulation. It also has anti-emetic (anti-nauseant) properties.

Toxicity

THC has a LD50 value of 1270 mg/kg (male rats) and 730 mg/kg (female rats) administered orally dissolved in sesame oil.

If this were scaled up to an adult human, the lethal dose would be between approximately 50 and 86 g for a 68 kg (150 lb) person. This would be equivalent to 1-1.8 kg of marijuana with a 5% THC content (roughly average) taken orally (much more if smoked). It is important to note, however, that toxicity studies in animal models do not necessarily correlate to human toxicity. THC receptor distribution in the rat CNS is different than that of humans, meaning that there is the significant possibility that toxicity in humans varies from the published animal LD50 studies. There has never been a documented fatality from marijuana or THC overdose.

Studies of the distribution of the cannabinoid receptors in the brain explain why THC's toxicity is so low (i.e., the LD50 of the compound is so large): parts of the brain that control vital functions such as respiration do not have many receptors, so they are relatively unaffected even by doses larger than could ever be ingested under any normal conditions.

Research

A number of studies indicate that THC may provide medical benefits for cancer and AIDS patients by increasing appetite and decreasing nausea, and by blocking the spread of some cancer-causing Herpes simplex viruses. It has been shown to assist some glaucoma patients by reducing pressure within the eye, and is used in the form of cannabis by a number of multiple sclerosis patients to relieve the spasms associated with their condition. Government studies indicate a variety of negative effects associated with constant, long-term use, including memory loss, depression and loss of motivation. The long-term effects of THC on humans have been disputed because its status as an illegal drug almost everywhere prevents free research into the subject. The issue has become deeply politicized.

Read more at Wikipedia.org


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New Forms of Medicinal Cannabis Under Development - Marinol - Brief Article
From Family Pratice News, 8/15/00 by Sherry Boschert

SAN FRANCISCO -- New modes of delivering medicinal cannabis may soon provide alternatives to smoked marijuana and Marinol.

The difficulty of titrating oral Marinol (dronabinol), a prescription drug, and the problems of psychoactive and harmful effects from smoked marijuana have spawned efforts to develop inhalers, sublingual drops and sprays, skin patches, and parenteral delivery.

A sublingual cannabis extract containing tetrahydrocannabinol (THC) and cannabidiol was easily titrated, well tolerated, and effective for chronic pain in a double-blind pilot study of six patients, Dr. William Notcutt said at a conference on cannabis therapy sponsored by the University of California, San Francisco.

Four patients had multiple sclerosis, one had chronic back pain, and one had post--spinal surgery pain in the back and legs. All had smoked marijuana previously for pain relief, said Dr. Notcutt, of the University of East Anglia, Norwich, England.

The spray was made by GW Pharmaceuticals, Salisbury, England, which the British government authorized in 1997 to cultivate and distribute cannabis for medical research. The company blends extracts from a warehouse full of cloned marijuana plants to test formulations of cannabinoids.

"If we can get rid of the psychoactive effects, randomized controlled trials are doable," company chairman Geoffrey W Guy said. Other clinical trials should start in Canada and possibly in the United States later this year, he added.

Also, the American Cancer Society has awarded a 3-year, $361 ,000 grant to researchers at the Albany (N.Y.) College of Pharmacy to develop a marijuana skin patch to control chemotherapy-related nausea and vomiting. Marinol and other oral drugs are approved for this indication, but vomiting can preclude their effectiveness.

The Food and Drug Administration approved an application to begin clinical trials of CT-3. This synthetic derivative of THC is intended for use as an analgesic and anti-inflammatory drug and has no psychoactive effect. Atlantic Technology Ventures Inc., New York, has a phase-I trial using oral and parenteral formulations underway in France.

COPYRIGHT 2000 International Medical News Group
COPYRIGHT 2001 Gale Group

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