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Authors: Ira Flatow

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SPOTTING THE SIGNS

But how easy is it for physicians, nurses, and other health care providers to spot signs of substance abuse and addiction? Greenfield says physicians and nurses are often not trained well enough to see evidence that might be right in front of them.

“In fact drug and alcohol addiction are among the largest, most prevalent problems that we have; they present a major public health
problem in addition to an individual and family problem. And at almost every health care setting, whether it’s a physical health care setting or mental health care setting, patients present themselves for other types of disorders and they also have a co-occurring substance use disorder.” This presents an opportunity for physicians and nurses to actually engage and screen patients. Are they using alcohol or drugs in a harmful way? Have they already become addicted or dependent on these substances? “A doctor can actually catch a patient, where something is moving forward into becoming a major abuse or dependence problem, and can help by educating a patient and referring them to treatment, to intervening earlier on in the course of the disease process. Of course, in every area of medicine, what we try to do is intervene as early as possible. But often doctors and nurses haven’t had adequate clinical training to screen and diagnose and to understand what the treatment processes are.”

In many cases, says Volkow, doctors in emergency departments are afraid to ask patients if they are addicted to drugs. “Why don’t they ask the question? Because drug addicts are stigmatized and doctors feel uncomfortable asking the patients do they drink, do they take cocaine. And they don’t even know how to ask that question sometimes—and certainly they don’t recognize it.” And even if they do know to ask the right questions, they may not know how to follow them up. “Unfortunately, there is no parity for the treatment of drug addiction. So as a result of that, many medical insurances will not cover the cost of doing an evaluation for drug addiction and proper referral. A patient that is addicted when they have a job or they are referred by their physician is very different from the situation of a person that is homeless, that doesn’t have a job, that doesn’t have a family, that ends up in the emergency room, and you are actually hand-tied in terms of what you can offer.”

And many times, people with addiction problems may never show up in a physician’s office or emergency department. Though they appear in countless television and film plots, the people who
continually show up in clinics for treatment represent just the tip of the iceberg, says Greenfield. “In fact, the vast majority of folks who have substance abuse disorder problems, many are working every day. They are taking care of various kinds of responsibilities out in the world, and they are actually having problems with addiction. Sometimes those things manifest themselves at home rather than at work. Sometimes they may not show up in an emergency room, but they may show up, maybe, in a mental health care clinic or a physical health care clinic.

“So this is not just in the emergency room with someone who’s coming in acutely, multiple times, but it’s much more generalizable to all sorts of health care settings where we, as medical professionals, can do a much, much, much better job at diagnosing early and referring for treatment many, many individuals who could actually benefit from all the available treatments that do exist and are actually effective.”

“THIS IS YOUR BRAIN ON DRUGS…”

Remember that commercial? Really an anticommercial, about the dangers of drugs? The frying pan, the burned egg? It sent a clear message that addiction is not just a bad habit but is also a complex chemical interaction in your brain. And one of the breakthroughs in the addiction field was the realization, says Dr. Rob Malenka, professor in psychiatry and behavioral sciences at Stanford University, that whether it’s nicotine or alcohol or cocaine or heroin, they all work on the brain’s reward circuitry.

“Through evolution, the brain has evolved to tell us what feels really good, what is rewarding, what is important for our survival. And we now know that all these different drugs of abuse act on this specific circuit in these specific brain areas.” One of the key chemical messengers in the brain circuits is a substance called dopamine. “It’s a substance we term a neurotransmitter, and it turns out that all these different addictive substances increase the actions or the release of dopamine.” And while the effects and actions of dopamine
are just now being understood, the release of dopamine in certain brain structures tells the person that this substance is reinforcing or rewarding.

“And then, for certain genetically vulnerable individuals, there are long-lasting changes in these circuits that lead the person to believe that the pursuit of this substance is the most important thing in their life.” These long-lasting changes occur in the connections between nerve cells, called synapses. “So the communication between individual nerve cells that are part of this circuit starts to change. There are molecular changes in these cells that are part of these circuits. We’re beginning to learn a reasonable amount about what are these changes in specific connections between nerve cells. And that’s the first step towards trying to understand how to reverse those changes.”

Because reversal is the key to drug addiction. As Mark Twain once said about his own addiction, “I don’t have much trouble giving up smoking. I’ve done it a hundred times.” In many cases it’s possible to stop the addiction, give up the cigarettes or cocaine. But what happens is that people go back to smoking or snorting. They can’t stay away. Once those chemical and neurological changes take place in the brain, reversing them is not very easy. The addiction has rewired the brain and, very importantly, brought into that rewiring the part of the brain that encodes memories, so that a relapse may occur without the person even being exposed to the addictive substance but simply to the memory of that exposure.

“It’s extraordinarily important,” says Volkow, “in the terms of why it’s so difficult to treat addiction and why people, despite the fact that they face catastrophic consequences—not negative, catastrophic—and they don’t want to take the drug anymore, they relapse. It’s almost like a reflex.” Volkow is very clear and determined on this important point. She wants to make sure you understand just how difficult it is for someone to not relapse when exposed to that memory. It’s almost like uncontrolled salivating when you think about a great dessert.

“Inside your brain, there is a release of dopamine when the person that’s addicted sees stimuli associated with the drug that activates the motivational circuit almost in a reflexlike way. And that drives him or her to do that behavior. And that’s evidently one of the mechanisms why relapse occurs and it’s so difficult to ‘kick the habit.’”

So finding a way to erase that emotional circuitry is one of the great challenges. “Indeed, that’s one of the strategies that we’re now trying to encourage investigators to look at: the development of medications that can either erase those memories associated with the drug or, alternatively—very important—can create stronger memories that can overcome those learned responses. So that your behavior is not driven by what we call conditioning, but by these new learned experiences.”

There is ongoing research to erase those neurological pathways, but so far only in lab animals. “But there are some real interesting positive results that suggest that this strategy may, in fact, prove beneficial in helping people through the therapeutic process.”

But what about other addictions that do not start out with well-known street drugs such as nicotine or alcohol but instead with addictive behavior about activities such as gambling, eating, or playing video games. Is the brain laying down the same kind of new pathways? Malenka says the general consensus among scientists is that “yes, a lot of these other kinds of compulsive, especially rewarding behaviors, or reinforcing behaviors like gambling, like overeating, like perhaps even video game playing, certainly effect these so-called reinforcement reward circuits, they do effect the release of this chemical messenger dopamine. Work done by Volkow and others has shown that it’s not only the release of dopamine but also how much is released and how fast it’s released that is important.

“And it turns out, the highly addicting substances, like cocaine, can really cause a much more rapid, stronger increase in this chemical messenger than, for instance, what I do all the time, which is eat
doughnuts, or eat a quart of Häagen-Dazs ice cream, which is highly rewarding for me. But I can kick the habit when I choose to.”

WATCHING THE CRAVING IN THE BRAIN

Volkow agrees. She says it’s a “very interesting question that has started to intrigue many of the scientists; certainly, it has intrigued me for many years.” Using brain imaging, Volkow and her colleagues at the Brookhaven National Laboratory in Upton, New York, have watched the brain in action as it reacts to different stimuli, “specifically in pathological eating in obesity, versus those that we see in addiction.” And what she sees are both similarities and differences. The similarities: there is a marked disruption of the functioning of the dopamine system, which is directly affected by drugs, “but it’s also the one that motivates our behavior vis-à-vis natural activities like eating or doing social interactions or engaging in procreation—sexual behaviors.”

The dopamine system becomes dysfunctional, she says, in both addiction and overeating. The dopamine is not released in as great a quantity as it was before, so that it does not produce that terrific sense of well-being—the high—as it used to. “And it is believed that one of the reasons why there is a motivation to either continue taking the drug or to compulsively eat is that it’s a mechanism to compensate for this deficit.” In other words, you eat more or take more drugs to stimulate more dopamine release. It takes more to achieve the “high.”

On the other hand, what’s uniquely different in this case—eating versus drugs—in pathologically obese people “is that their brain is particularly sensitive to the pleasurable aspects associated with food. Evidently, that is the reason why they are favoring these particular stimuli—in this case, food—over other ones. So this is why some people become addicted specifically to a certain substance and others may become addicted to behavior, because each one of our brains responds with a different sensitivity to the rewarding effects of the stimuli.”

THIS IS YOUR BRAIN UNDER STRESS…

It’s well known that stress can make people relapse: I need that drink, just one bite of cheesecake. What link is there to addiction? “It turns out that the circuits in the brain that respond to stress,” says Malenka, “that release certain hormones in response to stress, are heavily interconnected with the exact circuits we’ve been talking about, the so-called reward circuits, the circuits that use dopamine. And work from many labs has shown that in humans as well as in animal models of addiction, stress is a very important factor in causing the continued use of a substance, as well as leading to relapse.” It appears that “the brain’s response to stress is actually pretty similar, under certain cases, to the brain’s response to certain drugs of abuse.”

For example, in a classic set of experiments it’s been shown that “if you train an animal to self-administer a drug—this happens in human beings too—and then you take the drug away for many weeks or months, an acute stressful event can have that person or animal start using the drug again. We believe that’s because that stress is causing perhaps the same release of dopamine” that substance abuse causes.

Volkow points out that there is an overlap in the circuits and brain areas that are affected by drugs and stress. And what ties those areas together? What commonality do they have? It all boils down to dopamine. “Dopamine is there not only to signal pleasure but actually to signal saliency, and as you recognize, of course, pleasurable events are very salient.” We need to learn from them. “But a stress is also very salient, because if we do not learn from it, when we are exposed to it again we may not avoid it.

“So anything that has importance, in terms of the survival of the species, that connotes a need to learn an experience, so you can change your behavior accordingly, will involve dopamine. When you are exposed to a stress, you are going to be releasing dopamine. And that’s going to drive a similar circuitry to that that we see in drug addiction.”

In individuals who are addicted, the increase in dopamine by itself
is a conditioned response. “It’s a learned memory response that’s associated with the drug. And this is probably one of the reasons why, when a person that’s going through recovery is stressed, and then they relapse, it’s in a way similar to the way they relapse when they get exposed to a stimulant that, in the past, they had associated with the use of drugs.”

STIGMA: ROADBLOCK TO RESEARCH

Is there any way, medically, to reverse the addictive wiring in the brain, perhaps through new medications? Volkow says it’s a “very challenging question indeed.” The federal government is trying to encourage researchers using laboratory animals “to do exactly that. Can you strengthen certain pathways that have been damaged by the chronic use of drugs? There are some very interesting compounds that, for example, are targeting the disruptions that exist in the memory circuit. We’re also looking to strengthening the ability of your brain, through cognitive operations, to regulate your emotions and your desires. And this is, of course, a pathway that is badly eroded by the usage of drugs. Those compounds are currently being investigated in animal studies, some with actually fascinating positive results. But it’s very difficult to get these compounds into the clinic.”

Why can’t we move toward testing these drugs in humans? First, says Volkow, because the process is very, very expensive, and as is the norm in developing new drugs, that burden falls on the pharmaceutical industry, “and here in the pharmaceutical industry, it’s not one of their primary interests.” It’s not just the expense that turns them away. Drug companies routinely spend hundreds of millions of dollars developing a new drug. In this case, Volkow believes the reason is quite different. Drug companies fear “that drug addiction is stigmatized.” And drug companies don’t want to be associated with unpopular illnesses. “That certainly doesn’t help the translation of potentially promising medications into the practice. We cannot get them into the clinics. We cannot get that translation from the ani
mal experiments into the humans as fast as we could, because of restriction and budgets. The government has to carry the costs that are associated with these medication developments.”

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