by Ira Flatow
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 animal 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.”
What may change this attitude is the profit motive. Drug companies understand profits. Drug addicts may not constitute a large enough market to be profitable, especially if many of them are not covered by health insurance. But what is slowly dawning on researchers and the drug industry—with the prodding of Volkow and researchers like her—is the potential for much larger profits from a much larger pool of customers. “You don’t necessarily need to address it as a medication for cocaine addiction but rather a medication for addiction in general. And then you can start to recognize that, indeed, the market could be very large because some of these processes also underline some of the behavior of compulsive disorders, such as pathological gambling or compulsive eating. These medications could also be beneficial in addressing some of the disruption that we see in these individuals.” Imagine a drug that stops you from overeating. Or treats gambling. Just think of the numbers of potential customers. Tens of millions. Hundreds of millions. Billions, worldwide. Even on a smaller scale, says Volkow, “the ability to develop a medication to treat methamphetamine addiction would be quite extraordinary.”
TREATING ADDICTION LIKE OTHER CHRONIC DISEASES
Until these new brain drugs are developed, therapists will treat patients the best way they can with the drugs currently available. Dr. Greenfield stresses that understanding the neurological changes in the brain can help explain to patients and their physicians why getting well and into recovery can be so difficult. “On the other hand, the other part that’s so important for people to understand is, like other types of medical disorders, addiction is a treatable disorder and people do actually get better. But like other medical disorders, like diabetes, hypertension, heart disease, people generally don’t get better with a single treatment. They often require several different treatments, sometimes different types of treatments over time, to slowly but surely regain their health—their physical health and their mental health.
Greenfield believes that people have an outdated view of addiction and its treatments. “This stigmatization has really held back the general public’s understanding of all the gains that have been made over the last 20 years: People actually get better; people do much better. It’s a classic ‘bench to bedside’ story: basic biology and treatment-related research demonstrating over and over again that many, many patients can be helped. We are able to treat a vast majority of folks, and in many instances, have people who are in recovery for many years, sometimes with relapses that occur periodically. Hopefully, if they remain connected to treatment and to a treatment community, they can recognize a relapse quickly and associate themselves again with treatment that’s been helpful and shorten the actual duration of their actual relapse or lapse.
“And that’s what we aim for: to keep people as healthy as we can over time, and if they do slip—a relapse—to shorten the duration of that and to return them as quickly as possible to their best-functioning selves.”
The treatments may not be solely through drugs, says Volkow. “There’s actually behavioral cognitive group therapies that have been unequivocally shown that they work. They are effective in the treatment of drug addiction, and yet they are not necessarily all the time accepted as such.” What’s not accepted or understood by the general public is that addiction should be looked at and treated like other chronic diseases.
“This relates to the whole stigmatization aspect of it, very differently from the way that we treat other diseases, in terms of what we expect of the treatment of drug addiction. We expect a cure. Yet we know that it’s a chronic disease. So we are treating. Very rarely do we cure right now.”
Greenfield cannot stress that point enough. “If you follow along on that model and continue to think about it—for someone who’s being treated for diabetes or heart disease or hypertension, what you hope you would do is you would help them in the acute first illness that they had, and then you enter them into treatment. And you want them to be monitored over the long term to keep them healthy and hopefully to prevent any more acute episodes.
“This is very similar to substance abuse treatment. People come in with an acute problem, you treat them, and then what you’d really like to do is enter them into care where they’re followed to keep them as healthy as possible. If people are connected to care, if there is a stressful life event or something else that comes up, they’re already hooked into care and they can usually continue how they’re doing or circumvent any exacerbation in their condition, hopefully avoiding, if possible, another major episode.
“This is truly a model of keeping people well over time, one that it’s really important we begin to implement for people with substance use disorders. We have many models in chronic disease care that work. We know that this is a kind of model that will work for substance abuse as well, over the long term.”
LOOKING AHEAD
Researchers are always looking for new questions to answer. What would we like to know about the brain that we don’t know now, and how could we get to know it? Where should the limited dollars for research be invested?
“I would put more money into really defining both the molecular changes in the brain that happen in response to substances of abuse or during addiction, but really beef up the imaging approaches so we can really understand, because the devil is always in the details,” says Dr. Malenka. “Which specific brain areas, which specific connections, which circuits in the brain are really being modified in a semipermanent way during addiction?”
Malenka also thinks we should invest in trying to identify both genetically and through other approaches those people who’re going to be most vulnerable to developing addiction, especially kids. “I believe people really start developing their problems mostly during adolescence, late adolescence to early adulthood, and I think it would be wonderful if we could identify those specific individuals that are going to be particularly susceptible and vulnerable to addictions.”
As for Volkow? “I’d like to be able, with the money, to create the knowledge that would allow us to have devoutness for substance abuse—the knowledge that would drive and motivate and intensify the pharmaceutical industry to be able to fund medications into clinical practice. And finally, to use that knowledge to create more targeted prevention, such that less people get exposed to drugs.”
CHAPTER FIVE
SLEEP AND LEARNING: CAFFEINE IN YOUR BEER
Laugh and the world laughs with you, snore and you sleep alone.
—ANTHONY BURGESS
Birds do it. Bees don’t. We do it more than elephants but less than bats or opossums. Of course, I’m talking about sleep—something you can’t do without, yet few of us, it appears, get enough of it.
Writers, poets, and scientists have pondered this mysterious state of consciousness for centuries, asking questions such as: Why do we even need to sleep? Why would evolution favor sleep? Think about it. When you’re asleep you’re in your most vulnerable position. You’re unable to defend yourself from an enemy. So what’s the payoff here? Are there crucial biological functions that can take place only when we sleep? And if so, what happens when you don’t get enough sleep? Does memory suffer? Are there deep psychological things that are going on when we sleep that we don’t even know about?
Yet millions of people are not getting enough sleep. Whether it’s because of snoring, restless leg syndrome, or sleepwalking with a pint of ice cream, a staggering number of people don’t sleep well at night.
SO WHY DO WE NEED TO SLEEP?
Sleep is much more important than serving as a simple mind refresher and “cobweb” clearer. Researchers are now able to peer into the brain and watch what happens when we sleep. They are finding that sleep is quite necessary if we are to learn, remember, solidify, and improve new skills. And a good night’s sleep may also be necessary for repairing an injured brain.
First, to debunk a myth: when you go to sleep, while you may be unconscious lying there in bed, your brain is far from being “asleep.”
“There are probably many, many things that are occurring during sleep that are beneficial, things that have been assigned by evolution to that part of the night,” says Dr. Robert Stickgold, associate professor of psychiatry at Harvard Medical School.
“My own personal favorite, and the one that I think has the best explanation for why it would have evolved originally, is that while we’re asleep the brain is going through our memory stores and trying to see what’s worth keeping, what’s worth throwing out, and how things should be strengthened and put together.”
That doesn’t mean that our bodies are not using sleep to replenish and refresh us. The bottom line on sleep, says Dr. Carlos Schenck, senior staff physician at the Minnesota Regional Sleep Disorders Center in Minneapolis, is how well you feel in the morning.
“If someone says, ‘I don’t think I’m getting enough sleep,’ and yet they wake up refreshed and they function, they may be a short sleeper and may not need nearly as much sleep as the average person. So you always have to focus on the functional consequence.”
Judging how much sleep you need is very difficult. But research now shows that if you can function well during the day, and people tell you that you’re looking well and not drowsy, then you’re probably getting enough sleep.
But “if you need a double grande to get that morning going, then you’re probably not getting enough sleep,” says Stickgold, referring, of course to the caffeine jolt of coffee.
“And there’s another ominous event that’s taking place now,” warns Schenck. “There are new beers on the market that are loaded with caffeine, and so people will drink a beer in the evening and the caffeine makes them feel more alert, and yet it will greatly prolong their onset for sleep, and that could have a devastating effect on their sleep–wakefulness rhythm. You’ll be hearing more and more about these types of beers loaded with caffeine. I think it’s really going to have a very devastating effect.”
CEMENTING NEW SKILLS
But getting back to that memory consolidation idea, where it appears that our minds are using sleep to sort through what we learned during the day, Stickgold and other scientists have conducted tests that show just how crucial a good night’s sleep is to learning new skills.
Scientists noticed that when they trained study subjects on a new task and then tested them on the task a few hours later, they didn’t show any improvement at all. What they did find is that the improvement would show up later—the next day!
They discovered that people really do need to sleep on it to cement their new learning experience.
“Even if we trained them right before they went to bed, the next day they show improvement,” says Stickgold. “And it’s pretty consistent from person to person. But it varies with how much sleep they g
ot. And the thing we saw that I scare my college students with is that the study subjects who had less than six hours of sleep showed no improvement at all the next day.”
How many college kids get six hours’ sleep?
“Although when you talk to those students who cram for exams, they’ll tell you, ‘I did fine,’ the next day. But two days later, it’s all gone. And that might be a sleep connection. We don’t know that yet. But for this particular test, the more sleep you had in excess of six hours, the better you performed the next day.”
And what’s going on in your brain that you need this sleep to cement that practice? Stickgold took his students into his sleep lab to find out.
“We got very surprising results.”
What he found is that when you go through a night of sleep you go through a 90-minute sleep cycle. You go down into deep sleep and then come out of it into REM sleep, where you do most of your intense dreaming. This cycle gets repeated all night.
“And what we discovered is that to show improvement on the next day, you need good slow-wave—or deep—sleep in the first couple of hours of the night. And you need REM sleep, but only after six hours. And that’s probably why those students who got less than six hours didn’t show improvement.
“So you need two things to happen at night. You need to have something happen while you’re in deep sleep, earlier in the night. There’s three or four hours that have to pass. I don’t know what’s happening. I describe it as ‘the dough is rising.’ And then at the end of the night, you need REM sleep, where presumably something else happens. And that’s what finally cements it all together.”