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Uses. This cough and cold medicine has been used in the United States since the 1950s. Because the drug is an opiate analogue and is related to levor-phanol, for convenience this book lists dextromethorphan as an opioid. Nal-oxone, a chemical used to provoke withdrawal symptoms in persons who have dependence with opiates and opioids, can bring forth those symptoms in addicts who have switched from methadone to dextromethorphan. That finding is consistent with dextromethorphan being an opioid; nonetheless, the substance is not generally classified as an opioid.

The drug resembles codeine but is considered weaker in humans, although a cat experiment measured dextromethorphan as three times stronger than codeine. Body processes break down dextromethorphan into other substances including dextrorphan.

Urinalysis comparing the amounts of dextromethorphan and its breakdown product dextrorphan can identify a person's susceptibility to lung cancer. Case reports tell of dextromethorphan's success in treating infants' brain seizures. One experiment found the substance to be a useful supplement in treating older epileptics, but another study detected no improvement. Parkinson's disease patients have shown encouraging response to treatment with the drug, but using it against Huntington's disease and Lou Gehrig's disease has brought disappointment. Animal research suggests that the substance may be useful in treating stroke. A mice experiment in France tested whether dextro-methorphan can protect against the effects of the chemical warfare agent so-

man, but the results were negative. A U.S. Army experiment with guinea pigs also found dextromethorphan to have little value as protection against soman poisoning.

Dextromethorphan is considered ineffective as a general pain reliever but does reduce certain kinds of pain: Experiments show the drug can relieve pain from diabetes, and researchers speculate that the drug may also provide similar benefit to AIDS (acquired immunodeficiency syndrome) sufferers.

Drawbacks. Most persons find the drug unpleasant if the medically recommended dosage is exceeded, with unwanted effects such as easy excitability, memory trouble, nausea, itching, interference with male sexual function, slurred speech, trouble with thinking, and difficulty with moving arms and legs. Some persons become tired and woozy even on normal doses. Nonetheless, one study of cough medicines found that volunteers preferred dextro-methorphan to other remedies that were effective, leading the researchers to speculate that the drug was providing pleasure unrelated to effectiveness in relieving cough. Indeed, some users feel more sociable and report euphoria and hallucinations. Cases of mania are known, likened to the kind of stereotypical behavior popularly associated with PCP. In one instance, the compound allowed a lawyer to work industriously for weeks with little sleep, followed by mental collapse requiring hospitalization. This individual had engaged in manic episodes and drug abuse in the past, however. A patient in another mania case report also had a medical history of drug abuse. Persons without such a history may well be susceptible to manic reactions from overuse of dextromethorphan, but the examples just cited raise the question of whether persons prone to drug abuse are particularly susceptible.

Investigators examining dextromethorphan's potential for treating juvenile bacterial meningitis called off the experiment when patients began developing diabetes after receiving high doses of the drug (possibly because of action on the pancreas inhibiting insulin production), and reports exist about other instances of juveniles developing diabetes when being treated with the compound.

Abuse factors. Accounts of persons abusing dextromethorphan began appearing in science journals during the 1960s. In the 1990s news media reports described the substance as popular among teenagers, who sometimes referred to this drug use as "robo-copping." Usage by persons of that age group is not limited to the United States. For example, authorities in Korea have expressed concern about fatal overdoses among young illicit users, particularly when they combine dextromethorphan with another drug to intensify effects.

In the 1960s human addiction to dextromethorphan was dismissed as highly unlikely. Subsequently, researchers who documented behavior of rats exposed to drug combinations concluded that dextromethorphan has abuse potential. Human addiction has indeed been reported, although this is described as unusual. Scientists have not found dependence or withdrawal symptoms. A rat study determined that dextromethorphan can reduce alcohol withdrawal symptoms, and experiments with rats and mice show that dextromethorphan can reduce morphine withdrawal symptoms. One human study found that dextromethorphan by itself did not relieve methadone abstinence, but different research shows that in combination with other substances dextromethor-

phan can relieve abstinence symptoms experienced by heroin addicts. Such results do not demonstrate whether dextromethorphan has cross-tolerance with all the drugs just named, allowing it to be substituted for any of them; their withdrawal syndromes all include elements mimicking the common cold and flu, and dextromethorphan may simply be able to relieve flulike symptoms regardless of cause.

Rats that dose themselves with intravenous cocaine have shown less interest in that drug after receiving dextromethorphan, but the meaning of that reduced interest is unclear: Does dextromethorphan promote abandonment of drug use, or do the animals find dextromethorphan so preferable that cocaine cannot compete?

Drug interactions. Dextromethorphan can boost pain relief actions of morphine, allowing patients to use less of that opiate. Research has also found that dextromethorphan does not boost euphoria or dependence produced by morphine, leading one investigator to conclude that morphine's illicit attractions are not increased by dextromethorphan.

Dangerous interactions may occur if dextromethorphan is taken along with MDMA, with monoamine oxidase inhibitors (MAOIs, found in some antidepressants and other medicine), or with serotonin uptake reinhibitors (a type of antidepressant). When taken with dextromethorphan the latter substances could provoke the "serotonin syndrome," a potentially fatal emergency involving muscle tremors, heartbeat and blood pressure abnormalities, changes in mental state, and loss of consciousness. In rats the drug reduces effects produced by PCP. Dextromethorphan can cause false positives for PCP in urine tests, but an experiment failed to produce positives for opioids.

Cancer. Not enough scientific information to report.

Pregnancy. The drug has been widely used for decades without report of congenital malformations. After chicken embryo experiments in the 1990s suggested that dextromethorphan might cause birth defects, a study in Canada compared women who used the drug during pregnancy with those who did not and found no increase of congenital defects in the drug group. A study looking for birth malformations in Spain found none that could be attributed to dextromethorphan and concluded that normal medical used of the drug did not produce birth defects. Those negative findings have not surprised experts familiar with drawbacks in using chicken embryos to test for birth defects; chicken development can be harmed by conditions having no effect on humans, and chicken embryo tests are no longer accepted as indicating human risk of birth defects. Several human studies, however, have found a slight increase in risk of birth defects among pregnant women using dextro-methorphan. The risk is close to negligible, but, as one authority points out, that is not the same as zero risk. The small chance can be reduced to zero by avoiding the drug during pregnancy.

Additional scientific information may be found in:

Darboe, M.N. "Abuse of Dextromethorphan-Based Cough Syrup as a Substitute for Licit and Illicit Drugs: A Theoretical Framework." Adolescence 31 (1996): 239-45. Einarson, A., D. Lyszkiewicz, and G. Koren. "The Safety of Dextromethorphan in Pregnancy: Results of a Controlled Study." Chest 119 (2001): 466-69.

Hinsberger, A., V. Sharma, and D. Mazmanian. "Cognitive Deterioration from Long-Term Abuse of Dextromethorphan: A Case Report." Journal of Psychiatry and Neuroscience 19 (1994): 375-77.

Martinez-Frias, M.L., and E. Rodriguez-Pinilla. "Epidemiologic Analysis of Prenatal Exposure to Cough Medicines Containing Dextromethorphan: No Evidence of Human Teratogenicity." Teratology 63 (2001): 38-41.

Pender, E.S., and B.R. Parks. "Toxicity with Dextromethorphan-Containing Preparations: A Literature Review and Report of Two Additional Cases." Pediatric Emergency Care 7 (1991): 163-65.

Polles, A., and J.L. Griffith. "Dextromethorphan-Induced Mania." Psychosomatics 37 (1996): 71-74.

Rammer, L., P. Holmgren, and H. Sandler. "Fatal Intoxication by Dextromethorphan: A Report on Two Cases." Forensic Science International 37 (1988): 233-36.

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