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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Cancer therapy, supportive
From Gale Encyclopedia of Medicine, 4/6/01 by Nancy Ross-Flanigan

Definition

Supportive cancer therapy is the use of medicines to counteract unwanted effects of cancer treatment.

Purpose

Along with their beneficial effects, many cancer treatments produce uncomfortable and sometimes harmful side effects. For example, cancer drugs may cause nausea or vomiting. They may also destroy red or white blood cells, resulting in a low blood count. Fortunately, many of these side effects can be relieved with other medicines.

Description

Different kinds of drugs are used for different purposes in supportive cancer therapy. To relieve nausea and vomiting, a physician may prescribe dolasetron (Anzemet), granisetron (Kytril) or ondansetron (Zofran). Drugs called colony stimulating factors are used to help the bone marrow make new white blood cells to replace those destroyed by cancer treatment. Examples of colony stimulating factors are filgrastim (Neupogen) and sargramostim (Leukine). Another type of drug, epoetin (Epogen, Procrit), stimulates the bone marrow to make new red blood cells. It is a synthetically made version of human erythropoietin that is made naturally in the body and has the same effect on bone marrow.

Some physicians who treat cancer recommend that their patients use marijuana to relieve nausea and vomiting. This practice is controversial for several reasons. Using marijuana, even for medicinal purposes, is illegal in most states. Also, most of the evidence that marijuana effectively relieves nausea and vomiting comes from reports of people who have used it, not from carefully designed scientific studies. An oral medication that contains one of the active ingredients of marijuana is available with a physician's prescription and sometimes is used to treat nausea and vomiting in patients undergoing cancer treatment. However, the drug, dronabinol (Marinol), takes longer to work than smoked marijuana and may be difficult for patients with nausea and vomiting to swallow and keep down.

In 1997, the National Institutes of Health issued a report calling for more research into medical uses of marijuana. The panel of experts who wrote the report also recommended that researchers investigate other ways of getting the active ingredients of marijuana into the body, such as nasal sprays, skin patches and inhalers.

Patients who want to use marijuana to relieve side effects of cancer treatment should talk to their physicians and should carefully consider the benefits and risks, both medical and legal.

Recommended dosage

The recommended dosage depends on the type of supportive cancer therapy. Check with the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage.

Precautions

Dolasetron, granisetron and ondansetron

If severe nausea and vomiting occur after taking this medicine, check with a physician.

The use of ondansetron after abdominal surgery may cover up symptoms of stomach problems.

People with liver disease may be more likely to have side effects from ondansetron.

Colony stimulating factors

Certain cancer drugs reduce the body's ability to fight infections. Although colony stimulating factors help restore the body's natural defenses, the process takes time. Getting prompt treatment for infections is important, even while taking this medicine. Call the physician at the first sign of illness or infection, such as a sore throat, fever or chills.

Seeing a physician regularly while taking this medicine is important. This will give the physician a chance to make sure the medicine is working and to check for unwanted side effects.

People with certain medical conditions may have problems if they take colony stimulating factors. In people who have kidney disease, liver disease or conditions caused by inflammation or immune system problems, colony stimulating factors may make these problems worse. People with heart disease may be more likely to have side effects such as water retention and heart rhythm problems when they take these drugs. And people with lung disease may be more likely to have shortness of breath. Anyone who has any of these medical conditions should check with his or her physician before using colony stimulating factors.

Epoetin

This medicine may cause seizures (convulsions), especially in people with a history of seizures. Anyone who takes these drugs should not drive, use machines or do anything else that might be dangerous if they have had a seizure.

Epoetin helps the body make new red blood cells, but it cannot do its job unless there is plenty of iron in the body. The physician may recommend taking iron supplements or certain vitamins that help get iron into the body. Follow the physician's orders to make sure the body has enough iron for this medicine to work. Do not take iron supplements unless they are prescribed by a physician.

In studies of laboratory animals, epoetin taken during pregnancy caused birth defects, including damage to the bones and spine. However, the drug has not been reported to cause problems in human babies whose mothers take it. Women who are pregnant or who may become pregnant should check with their physicians for the most up-to-date information on the safety of taking this medicine during pregnancy.

People with certain medical conditions may have problems if they take this medicine. For example, the chance of side effects may be greater in people with high blood pressure, heart or blood vessel disease or a history of blood clots. Epoetin may not work properly in people who have bone problems or sickle cell anemia.

Dronabinol

This medicine contains sesame oil and one of the active ingredients of marijuana. Anyone who has had allergic or unusual reactions sesame oil or marijuana products should let his or her physician know before taking dronabinol.

Because dronabinol works on the central nervous system, it may add to the effects of alcohol and other drugs that slow down the central nervous system. Examples of these drugs are antihistamines, cold medicine, allergy medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants. Dronabinol may also add to the effects of anesthetics, including those used for dental procedures. Anyone taking dronabinol should not drink alcohol and should check with his or her physician before taking any of the drugs listed above.

This drug makes some people feel drowsy, dizzy, lightheaded or "high," with a sense of well-being. Because of these possible reactions, anyone who takes dronabinol should not drive, use machines or do anything else that might be dangerous until they have found out how the drug affects them. The dizziness and lightheadedness are especially likely when getting up after sitting or lying down. Getting up gradually and holding onto something for support should lessen the problem.

In laboratory studies, giving high doses of dronabinol to pregnant animals increased the risk of the unborn baby's death. The medicine's effects on pregnant women have not been studied. Women who are pregnant or who may become pregnant should check with their physicians before taking this medicine.

Dronabinol passes into breast milk and may affect nursing babies whose mothers take the medicine. Women who are breastfeeding their babies should check with their physicians before using dronabinol.

Because of its possible mind-altering effects, dronabinol should be used with care in children and older people. Both children and older people should be watched carefully when they are taking this medicine.

Using dronabinol may worsen some medical conditions, including high blood pressure, heart disease, bipolar disorder and schizophrenia.

General precautions for all types of supportive cancer therapy

Anyone who previously has had unusual reactions to drugs used in supportive cancer therapy should let his or her physician know before taking the drugs again. The physician should also be told about any allergies to foods, dyes, preservatives, or other substances.

Side effects

Dolasetron, granisetron and ondansetron

The most common minor side effects are headache, dizziness or lightheadedness, drowsiness, dry mouth, diarrhea, constipation, abdominal pain or stomach cramps and unusual tiredness or weakness. These problems usually do not require medical treatment.

Check with a physician as soon as possible if fever occurs after taking granisetron.

If any of these symptoms occur after taking ondansetron, check with a physician immediately:

  • Breathing problems or wheezing
  • Chest pain or tightness in chest
  • Skin rash, hives or itching.

Colony stimulating factors

As this medicine starts to work, it may cause mild pain in the lower back or hips. This is nothing to worry about, and it will usually go away within a few days. If the pain is too uncomfortable, the physician may prescribe a painkiller. Be sure to let the physician know if the painkiller does not help.

Other possible side effects include headache, joint or muscle pain and skin rash or itching. These side effects usually go away as the body adjusts to the medicine and do not need medical treatment. If they continue or they interfere with normal activities, check with a physician.

Epoetin

This medicine may cause flu-like symptoms, such as muscle aches, bone pain, fever, chills, shivering, and sweating, within a few hours after it is taken. These symptoms usually go away within 12 hours. If they do not, or if they are troubling, check with a physician. Other possible side effects that do not need medical attention are diarrhea, nausea or vomiting and tiredness or weakness.

Certain side effects should be brought to a physician's attention as soon as possible. These include headache, vision problems, increased blood pressure, fast heartbeat, weight gain and swelling of the face, fingers, lower legs, ankles or feet.

Anyone who has chest pain or seizures after taking epoetin should check with a physician immediately.

Dronabinol

Side effects such as dizziness, drowsiness, confusion and clumsiness or unsteadiness usually do not need medical attention unless they are long-lasting or they interfere with normal activities.

Other side effects or signs of overdose should have immediate medical attention. These include:

  • Fast or pounding heartbeat
  • Constipation
  • Trouble urinating
  • Red eyes
  • Slurred speech
  • Mood changes, including depression, nervousness or anxiety
  • Confusion
  • Forgetfulness
  • Changes in sight, smell, taste, touch or hearing
  • A sense that time is speeding up or slowing down
  • Hallucinations.

General advice on side effects for all types of supportive cancer therapy

Other side effects are possible with any type of supportive cancer therapy. Anyone who has unusual symptoms during or after treatment with these drugs should get in touch with his or her physician.

Interactions

Anyone who has supportive cancer therapy should let the physician know all other medicines he or she is taking. Some combinations of drugs may interact, which may increase or decreases the effects of one or both drugs or may increase the risk of side effects. Ask the physician whether the possible interactions can interfere with drug therapy or cause harmful effects.

Key Terms

Bipolar disorder
A severe mental illness in which a person has extreme mood swings, ranging from a highly excited state -- sometimes with a false sense of well-being -- to depression
Bone marrow
Soft tissue that fills the hollow centers of bones. Blood cells and platelets (disk-shaped bodies in the blood that are important in clotting) are produced in the bone marrow.
Hallucination
A false or distorted perception of objects, sounds, or events that seems real. Hallucinations usually result from drugs or mental disorders.
Immune system
The body's natural defenses against disease and infection.
Inflammation
Pain, redness, swelling, and heat that usually develop in response to injury or illness.
Schizophrenia
A severe mental disorder in which people lose touch with reality and may have illogical thoughts, delusions, hallucinations, behavioral problems and other disturbances.
Sickle cell anemia
An inherited disorder in which red blood cells contain an abnormal form of hemoglobin, a protein that carries oxygen. The abnormal form of hemoglobin causes the red cells to become sickle- or crescent-shaped. The misshapen cells may clog blood vessels, preventing oxygen from reaching tissues and leading to pain, blood clots and other problems. Sickle cell anemia is most common in people of African descent and in people from Italy, Greece, India, and the Middle East.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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