August 31, 2010

USA: Lasting Pleasures, Robbed by Drug Abuse

NEW YORK, NY / The New York Times / Health / Views / August 31, 2010


Of all the things that people do, few are as puzzling to psychiatrists as compulsive drug use.

Sure, all drugs of abuse feel good — at least initially. But for most people, the euphoria doesn’t last. A patient of mine is all too typical.

“I know this will sound strange,” he said, as I recall, “but cocaine doesn’t get me high any more and still I can’t stop.”

When he first started using the drug, in his early 30s, my patient would go for days on a binge, hardly eating or drinking. The high was better than anything, even sex.

Within several months, though, he had lost the euphoria — followed by his job. Only when his wife threatened to leave him did he finally seek treatment.

When I met him, he told me that he would lose everything if he could not stop using cocaine. Well, I asked, what did he like about this drug, if it cost him so much and no longer made him feel good? He stared at me blankly. He had no clue.

Neither did most psychiatrists, until recently.

We understand the initial allure of recreational drugs pretty well. Whether it is cocaine, alcohol, opiates, you name it, drugs rapidly activate the brain’s reward system — a primitive neural circuit buried beneath the cortex — and release dopamine. This neurotransmitter, which is central to pleasure and desire, sends a message to the brain: This is an important experience that is worth remembering.

We would not have gotten very far as a species without this brain system to motivate us to seek out rewards like food and a nice mate. The trouble is that while such natural reinforcers activate the reward system, mind-altering drugs do it much more powerfully, causing a far greater dopamine release.

In other words, drugs have a competitive advantage over these natural rewards and can hijack the brain’s reward system.

Even so, the acute pleasure fades when the neurons in the reward circuit get used to all that dopamine. Eventually, as with my patient, even higher and higher doses cease to feel good as users try in vain to recapture the initial high.

So what explains compulsive drug use, especially when it brings the user to the brink of personal ruin?

I got a clue from my patient’s recent relapse. After nearly six months of abstinence, he found himself inexplicably craving cocaine on the way home from work.

It happened that he had run into an old friend just outside his office with whom he had used drugs years earlier. Although he did not consciously associate the friend and the drugs, his brain had not forgotten, and the meeting touched off the urge to use again.

In short, recreational drugs like cocaine don’t just usurp the brain’s reward circuit; they have powerful effects on learning and memory.

Many brain imaging studies, using positron emission tomography, show that cues like viewing drug paraphernalia are enough by themselves to activate memory circuits and unleash drug craving. Where you are and what you are doing when you use a drug like cocaine is inextricably linked with the high. And these associations are stored not just in your conscious memory, but also in memory circuits outside your awareness.

This kind of pathologic learning lies at the heart of compulsive drug use. Long after someone has apparently kicked the habit, long after withdrawal symptoms subside, the individual is vulnerable to these deeply encoded unconscious associations that can set off a craving, seemingly out of the blue.

I could not rewire my patient’s brain. But at least I could try to help him reconfigure his environment by avoiding cues that might provoke cocaine craving. I had him make an inventory of all the people and places he associated with his drug use — and then had him steer clear of as many as he could. Lucky for him that he never used drugs at home.

His problems did not end there, however. Although he has been cocaine-free for nearly two years, he feels life is lackluster and little excites him. And that experience is consistent with recent evidence that the effects of drugs like cocaine can endure long after use has ended.

Dr. Nora D. Volkow, a psychiatrist who is director of the National Institute on Drug Abuse, has shown using PET scans that methamphetamine-dependent subjects have about 25 percent fewer dopamine transporters in critical brain regions compared with normal volunteers. Since the transporters ferry dopamine in and out of neurons, this decrease means less dopamine release and a less responsive reward circuit.

Alarmingly, this reduction in dopamine transporters was present in subjects who had not used methamphetamine for at least 11 months, suggesting that the effect was long-lasting — perhaps even permanent.

Though my patient had not used methamphetamine, cocaine has similar effects in the brain. With years of abuse, he could have lost enough dopamine transporters that his own reward circuit would become dulled to everyday pleasures. After all, to most brains a fine dinner with friends or a beautiful sunset is no match for the euphoria of cocaine.

We do not yet know whether the loss of dopamine transporters is permanent or eventually reversible. But why take the chance and endure a dulled life? The plain truth is that drug-induced pleasure is a cruel illusion: it never lasts.

Dr. Richard A. Friedman is a professor of psychiatry at Weill Cornell Medical College.

Copyright 2010 The New York Times Company