Fighting Fire With Fire

Page 5 of 7

Three of Dr. Adinoff's assistants huddle around the monitor. They're helping with an experiment that seeks to identify what causes relapse among addicts. The scientists make weekly visits to local shelters and rehab clinics like Homeward Bound and Nexus Recovery Center, looking for addicts who are willing to have their brains monitored within four to six weeks of their last drug use.

The man in the scanner today isn't an addict; he's a control subject. As he lies inside the scanner punching buttons on a videogame control box, the machine makes a chugging noise and clicks away as it rapidly snaps images. In just one second, the machine captures the entire volume of the brain in 36 different "slices."

Adinoff designed the experiment to test his hypothesis that addicts' brains have a hard time reversing or stopping habits based on certain cues. While in the scanner, people play a videogame in which they choose a sequence of shapes likely to win them money. When the cues are switched—meaning the shape combinations that win money versus lose money are reversed—the subjects must switch their choice accordingly. The process is based on the misfiring reward-response process of addicts, who continue to abuse drugs even when the pleasant payoff of getting high is replaced by negative consequences.

Adinoff predicts that when all the data is analyzed, it will show that addicts have more trouble "reversing their response" because of a problem with their orbital frontal cortex—the part of the brain just behind the forehead that's responsible for reasoning and logical decisions. That part, whether because of substance abuse or the genetic factors that preceded it, tends to suffer from low blood flow in addicts, he says, and therefore lacks the energy it needs to inhibit impulsive behavior.

Laurry Michlin, a retired clothing salesman who snorted cocaine for more than three decades and figures he spent about $25,000 per year on the drug, describes the struggle between various parts of the brain this way: "I'd go have lunch and give myself eight reasons not to use—it could lead to a heart attack or stroke, isolate me from family and friends, make me paranoid, and it costs a lot of money. But my middle brain would drive me over to East Dallas to buy cocaine."

Parts of the brain such as the amygdala and the insula, which record emotional and experiential memory, stoke cravings. At the same time, the orbital frontal cortex synthesizes information coming from various parts of the brain and drives more logical decision-making, such as the reasons not to reach for the bottle or the pipe.

The scenario is a biological version of the devil and angel over the shoulder. Philosophers and physicians, scientists and spiritual leaders have debated the mind-body connection for thousands of years, and according to Adinoff, the growing field of brain research points to an increasingly faint divide between the physical and the psychological.

He's conducting experiments to determine the role emotional trauma plays in relapse—powerful life experiences, especially negative ones, impact brain circuitry—as well as another to examine the impact of stress. Alcoholics eventually lose the ability to produce normal levels of cortisol, the steroid that helps the body cope with stress, which may make them more likely to relapse during a tense moment.

"All of this is to identify the brain mechanisms that make relapse more likely and then develop treatments specific to those brain areas, receptors and behaviors," he says. "The more we can isolate these regions and understand what's happening, the more we can design specific medications or psychosocial treatments. None of us are able to take a picture of someone's brain and say, 'this person has schizophrenia,' 'this person has depression' or 'this person has cocaine addiction,' but that's one of the major goals."

Past experiments, many of them involving modern scanning technology, yielded discoveries that gave rise to a host of current treatments. Prometa is hardly the first medicine purported to treat addiction, and it follows an array of more mainstream innovations.

Vigabatrin, a medicine for cocaine users that's being tested in double-blind, placebo-controlled trials, stimulates production of GABA, the inhibitory neurotransmitter. Naltrexone blocks opiate receptors in the brain from binding with opiates like heroin, and it's also effective for alcoholics because it regulates the release of the neurotransmitter dopamine, which is involved in the progression of addictive disorders.

According to NIDA's Vocci, the fact that the brain mechanisms involved in addiction are interrelated and that naltrexone can alleviate dependence on more than one drug means we're headed toward a one-size-fits-all cocktail that could curb a range of bad habits. There are even numerous vaccines in the works. Tom and Therese Kosten, a husband and wife team at the Baylor College of Medicine in Houston, have developed one for cocaine that could be on the market as early as 2010. Still in clinical trials, the inoculation enables the immune system to attack drug molecules and bar them from the brain.

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Megan Feldman
Contact: Megan Feldman