Strategies Against Methamphetamine and Cocaine Described at ASAM Meeting

Widespread media reports and billboard campaigns decrying a methamphetamine epidemic are drawing attention away from the greater and more entrenched use of cocaine, according to a National Institute of Drug Abuse (NIDA) scientist speaking at the American Society of Addiction Medicine's (ASAM) 38th Annual Medical-Scientific Conference, held in Miami, April 26 to 29.

In a symposium sponsored by the NIDA, Wilson Compton, MD, director of the Division of Epidemiology, Services and Prevention Research, said that cocaine remains the recreational stimulant drug of choice, used by 5% to 6% of the US population, compared with 1.5% to 2.5% of the population using methamphetamine.

There are regional and racial differences in use, however, and Compton noted a relatively higher use of methamphetamine among Hawaiian and Native American populations, and an apparent progression of use from Pacific islands and the western United States toward the East Coast.

Compton attributed the increasing news coverage, despite relatively stable levels of methamphetamine use, to the means of manufacturing and trafficking the drug, as well as to possible increases in toxicity. In contrast to the concealed transport of cocaine across borders, methamphetamine laboratories have been found and "busted" in residential neighborhoods, with families in proximity to the toxic, unstable compounds. Families are also aware of, and affected by, the nationwide restrictions on pseudoephedrine(Drug information on pseudoephedrine), an ingredient in popular cold and flu remedies and a principal component in the manufacture of methamphetamine.

In addition, the pattern of use, spreading from the western states toward the East, gives credence to the "gathering threat" of methamphet-amine. Methamphetamine use is also increasingly associated, Compton noted, with both HIV infection and medication-resistant HIV infection, in a manner previously observed with crack cocaine. There has also been an increase in the number of methamphetamine users seeking treatment for medical complications and for detoxification, Compton indicated. "There is a distinction between the public health--the population-based survey showing, if anything, a decrease in meth use overall--and the tremendous increase in the problems associated with [it], with the admission rates."

He suggested that some increase in the presented complications from methamphetamine use may be the result of a shift in the preferred route of administration from oral and injection to inhalation by smoking. An increase in toxicity may also correspond to an increase in purity, Compton said, with imports from Mexico replacing the products from domestic laboratories that are closed or are unable to obtain the pseudoephedrine base or other manufacturing components.

Domestic producers persist, however, as reflected in a July news report in the Des Moines Register of Iowa farmers securing their fertilizer tanks against the pilfering of anhydrous ammonium nitrate for use in manufacturing meth-amphetamine. More than 4000 locks for the tanks have been distributed in the state, and there are plans to add calcium nitrate to render the mixture unsuitable for the methamphetamine labs. These measures were characterized in a news conference by Lt Gov Patty Judge as "one more success in Iowa's fight against the substance."

Kathleen Brady, MD, PhD, professor of psychiatry and director of the Clinical Neurosciences Program at the Med- ical University of South Carolina in Charleston, described several neurotransmitter targets for research in developing medications to treat methamphetamine, cocaine, and other stimulant drug addictions. She said that the excitatory glutamate pathways to the mesolimbic dopamine(Drug information on dopamine)rgic cell groups of the nucleus accumbens and ventral tegmental area (VTA) have been associated with mechanisms for associative learning. Glutamate helps in forming memories and associations via long-term potentiation through stimulating dopamine release in the VTA, Brady explained.

These pathways, she suggested, are "laying the tracks for the context, memory, and emotional valence that's associated with drug use and drug cues."

Although Brady considers topiramate(Drug information on topiramate) (Topamax) to be one of the more promising agents to affect the glutamatergic system for this purpose, she notes that it is not easy to use in this population because it requires gradual dose titration to avoid cognitive dysfunction and other adverse effects. When the daily dose is raised to 200 mg, however, there are promising data on reduced cocaine use compared with placebo, with more subjects maintaining urine test evidence of drug abstinence for 3 consecutive weeks.

Other agents affecting the glutamatergic system that are being assessed as applications for stimulant substance abuse include N-acetyl-l-cysteine (NAC), an antidote for acetaminophen overdose, which interferes with the cysteine(Drug information on cysteine)-glutamine exchange, increasing glutamate and, in early testing, appears to reduce cue-induced craving; and D-cycloserine (DCS), an antituberculosis agent and N-methyl-d-aspartate agonist that has been used to facilitate exposure-based extinction therapies in anxiety disorders and for which there is preliminary evidence that it facilitates extinction of response to cocaine cues.

Modafinil (Provigil) also affects the glutamatergic system, Brady said. Charles Dackis, MD, chief of psychiatry at the Penn Presbyterian Medical Center in Philadelphia, commented that it was originally considered for trials with cocaine because its therapeutic effects appear to be the opposite of symptoms that occur in cocaine detoxification. "It relieves nearly all of the symptoms of cocaine withdrawal," Dackis said, "over-sleeping, over-eating, decreased energy, and poor concentration."