Chemistry Special to DRCNet by Steve Beitler

"Who remembers when this ad came out?" The speaker's slide was a still image of the classic egg and frying pan ad, "This is Your Brain on Drugs." The speaker, Timothy Condon of the National Institute on Drug Abuse (NIDA), answered his own question. "It was 1987... not that long ago. But, today, this is your brain on drugs."

His next slide showed aerial views and cross-sections of the brain, two rows of four neatly ordered ellipses of gray matter mottled with bright reds and greens. "Look how far we've come," Condon said. "This shows how we're mapping the impact of drugs of abuse on the brain. We're making incredible strides in the neurobiology of addiction."

Condon's talk, on October 4 at Stanford University, kicked off a highly technical symposium entitled "Addiction and the Brain." Hosted by Stanford's medical school, the program featured Condon and six researchers, each of whom addressed a different aspect of the same question: How are the brain's chemical interactions and "circuitry" implicated in creating or sustaining addiction? The scientists reviewed recent studies on changes in brain chemistry that appear to alter the brain's mechanisms that control euphoria, aversion, reinforcement and subtle aspects of learning and memory.

Lurking behind the onslaught of obscure terms, overcrowded slides and non-stop obeisance to academic colleagues was the belief that what happens to complex chemicals in molecular-level interactions might hold the key to understanding the profound reality that is addiction. Also lurking behind the symposium was NIDA, whose hefty packets were available as people arrived at the auditorium and whose funding had supported a good bit of the research discussed at Stanford.

Condon's opening talk was the most accessible to the non-specialist. "Drug addiction is our number one public health problem," he said. He showed a slide depicting what he called "the history of serial epidemics" -- surges in the use of heroin, crack cocaine and amphetamines over the last 40 years. "Just when you get a handle on one, another one pops up," he noted, ignoring the policy implications of that fact.

Condon pegged the dollar cost to society of illegal drug use at $161 billion per year, midway between the $185 billion toll extracted by alcohol and the $138 billion cost impact from tobacco. But Condon was hopeful. "Science has revolutionized our view of addiction," he said. He let the ideological cat peek out of the bag when he praised the Partnership For a Drug-Free America, the gang that created the egg-and-frying-pan ad, as "good people with whom NIDA partners a lot."

Rob Malenka of Stanford focused on the brain's synapses, those infinitesimal spaces between neurons that are important pathways for the complex interactions of brain chemicals and cells. With a keen eye for the obvious, he noted that, "a major problem in treatment is the persistence of addiction." He noted the difference between relapses that are stress-related and those that are cue-related. As an example of the latter, Malenka described an experiment that showed differences in neurochemical levels and activity when people with a history of cocaine use were shown two videos: one of scenes of nature, and the other showing people using cocaine.

The molecular mechanisms of drug addiction were the topic for Eric Nestler of the University of Texas. He discussed gene expression, which is the mechanism by which genes encode the proteins that do the heavy lifting when it comes to determining each person's genetic endowment. "Drugs of abuse act on these proteins at the synapses," Nestler said. "Chronic exposure to drugs produces changes in the proteins that we're just starting to understand." The changes in these molecules that take place among drug users could be similar to the changes observed in lab rats that develop what Nestler termed "natural addictions." "One rat in our lab was running as many as 20 miles a day on his little wheel," Nestler noted. "That's quite a lot for a rodent." He also noted that chronic amphetamine use leads to changes in the dendrites, which are part of brain cells. "That might be a potential target for intervention (read: a vaccine) to treat addiction."

Charles O'Brien of the University of Pennsylvania concluded the symposium with a review of the history of naltrexone, an opioid antagonist or blocker that was approved by the FDA in the 1980's for the treatment of heroin addiction. Later research showed that naltrexone had promise as a treatment for alcoholism, and its use for that disease remains controversial. As part of the lead-in to his discussion of naltrexone, O'Brien cited some intriguing numbers. Seventy-five percent of people surveyed had tried tobacco at least once; of this number, 24 percent of them became addicted. Forty-six percent of his respondents tried marijuana at least once, and 9 percent of them were classified as "addicted." Only 1.5 percent of the people O'Brien questioned had ever tried heroin, with 23 percent of them eventually succumbing to addiction.

"NIDA has always been big on brain research, and they tend to accept the results of these studies pretty uncritically," said Marsha Rosenbaum, director of the San Francisco office of the Drug Policy Alliance. "They're selective on what they choose to publicize, and what bothers me is what they don't talk about or acknowledge." She cited the recent controversy over an article published in the journal Science, in which a team led by Dr. George A. Ricuarte of The Johns Hopkins University School of Medicine claimed to find that the amount of Ecstasy that some recreational users take in a single night may cause brain damage and may help hasten the onset of Parkinson's disease. The Ricuarte study has been savaged by other scientists, who say that the monkeys and baboons in the research were given massive amounts of Ecstasy and that the kinds of damage purportedly seen by the Johns Hopkins researchers have never been observed in autopsies or brain scans of people who were not shy about taking the drug.

The frontiers of brain chemistry aren't as germane to policy reform as the front lines of the battle for medical marijuana or prison reform, but they are an intriguing intersection of policy and science. Advances in our understanding of how the brain works, coupled with growing knowledge of the genetic basis of disease, health and perhaps behavior, will slowly deepen our understanding of the role of neurochemistry and genetics in aspects of drug use and abuse. While the scientists at Stanford would probably disclaim any link between their research and policy, reformers need to confront the fact that, so far, policy has had a bigger impact on science than science has had on policy.

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