Addiction
Addiction is one of the nation’s biggest public health problems, costing $524 billion (including lost wages and costs to the public health care and criminal justice systems) each year. The majority of the estimated 20 million alcoholics and drug addicts in America (and millions more compulsive gamblers, overeaters and sex addicts, if you accept an expanded understanding of addiction) never get help. Those who do often relapse repeatedly, sometimes returning to treatment centers 5, 10 or 15 times (if they don’t die first). And many of those who “recover” simply trade one addiction for another.
Dopamine, a neurotransmitter that sends signals between cells in the brain, affects a variety of critical functions, including learning, memory, movement, emotional response and feelings of pleasure and pain.
Scientists now believe that dopamine is a predictor of salience — that is, it tells us, and then helps us to remember, what we should focus on. When you see a person you are strongly attracted to, scientists can now see a spike of dopamine in your brain. If you are hungry and smell a food you like, dopamine also increases. But even unpleasant experiences — like physical pain or the fear of an intruder in the house — can cause a dopamine spike.
Drugs, particularly cocaine and methamphetamines, cause a large increase in the amount of dopamine secreted and pooling between brain cells, leading to feelings of euphoria. With regular, repeated “addictive” drug use, though, the brain eventually responds by reducing its normal release of dopamine. Studies also show a simultaneous decrease in the number of dopamine receptors created. That, in turn, makes the brain’s reward system less likely to respond to behaviors (romance, a good meal, the company of friends) that produce a normal dopamine surge. The addicted brain essentially becomes pathologically selective, dependent on bigger and bigger blasts of, say, cocaine to feel rewarded.
An increase in dopamine creates a craving — and an expectation of a reward. Nina Volkow used a brain scan to look at the dopamine releases in 18 cocaine addicts while they watched two videos: one of nature scenes, the other of people using cocaine. Volkow found that dopamine increased while the addicts watched the cocaine video and that the severity of the increase matched their self-reported level of craving for the drug. For these people, their lives and experience had taught them that when they see others using cocaine, they’re probably about to get rewarded with drugs, too.
Dopamine also travels to the parts of the brain responsible for solidifying memory, like the amygdala, which learns and stores emotional memories (including the high of drugs).
Studies in both animals and humans have indicated that those with low levels of dopamine D2 receptors, which regulate the release of dopamine in the brain, are more likely to find the experience of taking drugs pleasurable.
In one experiment, Volkow increased the level of dopamine D2 receptors in rats that had low levels. After the increase, the rats significantly curtailed their intake of alcohol, which they had eagerly gulped down before.
Walter Ling likes to explain complex brain processes using simple metaphors. GABA (gamma-aminobutyric acid) is to a brain what a braking system is to a car.
GABA’s role is to keep glutamate, the main excitatory transmitter, from overwhelming us. In the extreme, too much glutamate can cause a seizure and too much GABA can put us in a coma.
Frank Vocci: “What’s been shown is that people with alcohol and cocaine problems have less GABA in their brains, and we do know that medications that increase GABA have shown some efficacy in treating addiction.” (It isn’t yet clear whether the absence of GABA is a cause of addiction or a result.) The seizure medication topiramate, for example, works on both GABA and glutamate and has helped some alcoholics in initial trials quit or cut back on their drinking. The muscle relaxant baclofen, which essentially mimics the effects of GABA, may also help some cocaine addicts quit.
Hythiam is aggressively marketing its Prometa protocol for cocaine, alcohol and methamphetamine addiction, which involves therapy and medications, both oral and intravenously injected, not usually used to treat addiction: flumazenil, approved by the F.D.A. to treat overdoses of Valium and Xanax, and gabapentin, approved to relieve neuropathic pain. Addiction-medicine doctors around the country who have administered the protocol report encouraging results. Prometa appears to reduce anxiety and craving by enhancing the brain’s GABA receptors.
Xenova Group Plc has created what it says are effective vaccines for cocaine and nicotine addiction (NABI Biopharmaceuticals in Florida has also developed a nicotine vaccine). The vaccines, which the institute on drug abuse and others are testing, work by producing antibodies to a specific drug, binding to the drug when it enters the bloodstream and keeping it from entering the brain. An effective vaccine won’t stop craving or treat any underlying pathology, but it will make it nearly impossible for an addict to get high on that particular substance.
Beginning in the late ’70s, Bruce Alexander set out to study the role of our environment on addictive behavior. Until that point, most scientists studying addiction put rats in small, individual cages and watched as they eagerly guzzled drug-laced solutions and ignored water and food, sometimes dying in the process. This phenomenon was noted — first by researchers, then drug czars, then parents trying to keep their children off drugs — as proof of the inherently addictive quality of drugs and of the inevitable addiction of any human who used them. This was false. Most people who use drugs don’t become addicted.
Alexander had a simple hypothesis: The rats became addicts because they had awful lives. To prove it, Alexander created a lab-rat heaven he called Rat Park. The 200-square-foot residence featured bright balls and tin cans to play with, painted creeks and trees to look at and plenty of room for mating and socializing.
Alexander took 16 lucky rats and plopped them into Rat Park, where they were offered water or a sweet, morphine-based cocktail (rats love sweets). Alexander offered the same two drinks to the control group of rats he left isolated in cages. The results? The rat-parkers were apparently having too much fun to bother with artificial highs, because they hardly touched the morphine solution, no matter how sweet Alexander and his colleagues made it. The isolated and arguably depressed rats, on the other hand, eagerly got high, drinking more than a dozen times the amount of the morphine solution as the rats in paradise.
Studies show that animals, including humans, who are stressed during early development are more likely to self-administer drugs later in life and that living in an enriched environment appears to protect animals from developing addictive behavior.
In 2003, researchers at the Wake Forest School of Medicine measured the levels of dopamine D2 receptors of 20 macaque monkeys while they were housed in isolation. They then assigned the monkeys to social groups of four monkeys each, letting natural social hierarchies develop. Three months later, they tested the levels of D2 receptors again.
The dominant monkeys had 20 percent higher D2 receptor function, while the submissive ones were unchanged. When the monkeys were then taught how to self-administer cocaine by pressing a lever, the dominant monkeys took significantly less cocaine than the subordinate ones.
Interestingly, though, when the animals that seemed to be protected from addiction were given cocaine repeatedly, the number of their D2 receptors eventually went down, and they then became addicted.
“Some people may be naturally better protected against addiction than others,” Volkow says, “but that’s not enough to keep someone from becoming addicted. The same thing is true for those who are genetically predisposed. We know from twin and family studies that about 50 percent of a person’s vulnerability to addiction is genetic. But if you’re never exposed to illegal drugs, or if you grow up and live in an environment without trauma and too many stressors, you probably won’t become addicted.”
Neurologists at the University Medical Center Hamburg-Eppendorf in Germany found that pathological gamblers, like drug addicts, have a sluggish reward system that doesn’t react normally to pleasing stimuli. The scientists used an M.R.I. scanner to compare the brain responses of 12 gambling addicts and 12 nonaddicted people to a card-guessing game. Subjects were told to pick a playing card, and if the card turned out to be red, they won a euro.
The game activated the ventral striatum, an important part of the brain’s reward system. Those nonaddicts who picked a winning card had increased blood flow to the striatum, but the gambling addicts who picked the right card had much less of it (their reward system was less active). The same kind of indifference to basic rewards has been seen in the ventral striatum of cocaine addicts.
Gamblers have to increase their bets to get the same level of excitement, just like someone addicted to drugs who has to keep using more to get an effect.
Obese people have lower levels of dopamine D2 receptors than those who eat normally.