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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Medical Marijuana Has Some Support - Brief Article
From Family Pratice News, 8/15/00 by Sherry Boschert

SAN FRANCISCO -- Marijuana probably can play a role as an analgesic, antiemetic, and appetite stimulant for patients suffering Simultaneously from pain, nausea, and appetite loss, Dr. John A. Benson said at a conference on cannabis therapy sponsored by the University of California, San Francisco.

Typically these patients are getting chemotherapy or have AIDS and haven't found relief from any other single agent, said Dr. Benson, professor of medicine and dean emeritus at Oregon Health Sciences University Portland.

But smoked marijuana delivers many of the same harmful substances to the lungs as are in tobacco smoke, and some patients become dependent on smoked marijuana.

An oral synthetic cannabinoid, dronabinol (Marinol) is available by prescription, but its efficacy can be limited in patients with vomiting.

Dr. Benson based his comments on conclusions of an Institute of Medicine panel he cochaired on the medicinal use of cannabinoids, the active ingredients in marijuana. Some of the conclusions in its 1999 report are:

* Cannabinoids may have a natural role in pain modulation, movement control, and memory.

* In cancer patients, the analgesic effectiveness of 10-15 mg of THC (tetrahydrocannabinol, the main psychoactive ingredient) is comparable to 60 mg of codeine.

* Cannabinoids use a different receptor system than opioids to provide analgesia, so adjunctive synergistic therapy is possibile.

* Marijuana used to treat pain should be targeted to chemotherapy patients; patients with postoperative pain (using an opioid adjunct); and patients with spinal cord injury peripheral neuropathic pain, or central poststroke pain. Those with chronic pain and insomnia or patients who have AIDS and neuropathy should also be targeted.

* Oral THC is comparable to Compazine but less effective than metoclopramide in treating chemotherapy-induced vomiting. Marijuana is poorly tolerated as an antiemetic by one-fourth of patients. Antiemesis with oral serotonin receptor antagonists plus dexamethasone taken an hour before chemotherapy works better.

* Cannabinoids don't restore lean body mass in patients with AIDS wasting syndrome but might be useful adjunctive therapy for stimulating appetite and reducing nausea, vomiting, pain, and anxiety.

* The IOM panel was not impressed by claims that cannabinoids can treat glaucoma. The drug reduces intraocular pressure, but the effect lasts 3 hours or less.

* "The lung cancer risks worry us," Dr. Benson said. Chronic marijuana smoking has the same risks as cigarette smoking. Other adverse effects are within the range tolerated for other medications. Driving after smoking is discouraged due to diminished psychomotor performance.

* Troubled adolescents and those with psychiatric disorders are at greatest risk for marijuana dependence.

Among 46% of the U.S. population that has tried marijuana, 9% ever became dependent. That's lower than dependency rates among people who have tried tobacco (32%), alcohol (15%), cocaine (17%), or heroin (23%), and comparable with dependency among anxiolytics (9%).

* Existing data suggest that sanctioning the medical use of marijuana will not increase use among the general population, as feared, he added.

COPYRIGHT 2000 International Medical News Group
COPYRIGHT 2001 Gale Group

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