The other effects of getting high

The son of a friend of mine is 17, tall, good-looking, quiet -- and a prime example of how much and yet how little many kids know about illegal drugs.

Asked what he has used, the teen rattles off pot, alcohol and ‘shrooms (mushrooms), which he and a friend grow. But he’s also done acid (LSD), crack (cocaine), crystal meth (a form of methamphetamine), prescription tranquilizers and painkillers such as Valium and Percocet, and, oh, yeah, GHB, Ecstasy (and its variants) and mescaline. Asked if he wants to get clean, he says, “Not right now. My use is just recreational.”

And perhaps it is. But the latest government figures released in September show that illegal drug use is up among young adults between 18 and 25. There may be much that my friend’s son, and America’s other 16 million illicit drug users, don’t know about how street drugs affect the brain.

One main class of street drugs is the psychostimulants, which include amphetamines (such as methamphetamines and MDMA, or Ecstasy) and methylphenidate and cocaine. In low doses, amphetamines generate feelings of euphoria and alertness. But at higher doses, these drugs can trigger paranoia and psychosis.

Amphetamines are psychologically and physically addicting. Also called speed, they can increase blood pressure and heart rate. Because they constrict blood vessels, they “deprive the heart of blood flow while forcing it to do more work,” says psychopharmacologist Glen Hanson, acting director of the National Institute on Drug Abuse.

In the brain, Hanson says, amphetamines and methamphetamines act as “releasers” of neurotransmitters, forcing the brain to pump out 30 to 40 times the normal levels of these neurotransmitters, most notably dopamine, serotonin and norepinephrine. The immediate effect is to activate the brain’s “reward” circuits. But over-revving this circuitry can also cause violent behavior. Chronic stimulation depletes brain cells so that they can no longer produce neurotransmitters.

MDMA, or Ecstasy, now used by nearly a million people, according to federal figures, works somewhat differently. As one might guess from its chemical name (3,4-methylenedioxymethamphetamine), MDMA is an amphetamine.

Until recently, scientists thought that MDMA worked primarily on serotonin, creating such a flood of good feeling that users called it the “love drug.”

In one set of studies, Dr. Una D. McCann, associate professor of psychiatry and behavior sciences at Johns Hopkins School of Medicine and her husband, Dr. George A. Ricuarte, associate professor of neurology, also at Johns Hopkins, examined monkeys, baboons and humans, and found that MDMA is toxic to neurons that make serotonin.

In humans, McCann and Ricuarte have documented damage using PET scans, a brain imaging technique, and tests for 5-HIAA, a breakdown product of serotonin. The implications are serious -- without sufficient serotonin, sleep, mood, memory and other crucial brain functions may be disrupted.

Indeed, MDMA users often report that depression (or “E-pression”) strikes after a weekend on Ecstasy. MDMA can also induce muscle tension and trigger such high body temperatures -- 107 to 108 degrees Fahrenheit -- that seizures, multi-organ failure and even death can result.

Recently Ricuarte’s group reported in Science magazine that in animals, Ecstasy lowers levels of dopamine as well as serotonin, raising the risk of Parkinson’s disease. So far, however, there appear to be no increased rates of Parkinson’s disease among human Ecstasy users. In fairness, it’s also true that the benefits of Ecstasy are beginning to be taken seriously as well. Last fall, the Food and Drug Administration approved a study of Ecstasy as an aid to psychotherapy.

Cocaine, a psychostimulant, works in yet a different way, notes Dr. Marc Kaufman, a research pharmacologist at McLean Hospital in Belmont, Mass.

It does rev up the brain’s “reward” circuitry. But unlike other drugs, cocaine does its damage not by directly damaging neurons that make neurotransmitters but by reducing blood flow to parts of the brain. By causing blood vessels to narrow, it raises the risk of stroke and heart attack.

Some of the most popular street drugs are depressants, among them, the “date-rape” drugs. One such downer is GHB, called gamma hydroxybutyrate but also known as liquid ecstasy or Georgia HomeBoy. It can be easily slipped into a person’s drink. Like alcohol and the tranquilizer Valium, GHB acts through so-called GABA receptors, the brain’s intrinsic tranquilizer system; when GABA receptors are activated, neural activity slows down.

So far, GHB has not been shown to cause damage to neurons. But it can relax a user too far -- to the point of rendering someone incapable of resisting unwanted sex. It can also lead to coma and even to death; alcohol can enhance this effect.

Another date-rape drug, Rohypnol, has similar effects. Dubbed Roofies, Rohypnol is a benzodiazepine. Like GHB, it works through GABA receptors and receptors for benzodiazepine as well. Rohypnol, which is legally available overseas, can also trigger amnesia, making it treacherous in the hands of anyone seeking to coerce someone into sex and render his victim unable to recall events.

Ketamine, a powerful anesthesia drug often used by veterinarians, is another popular downer. Dubbed K and Special K, it is similar to PCP (phencyclidine, or angel dust) and is easy to make. It blocks NDMA receptors in the brain, producing general anesthesia.

Technically, ketamine is a dissociative anesthetic, meaning it does not directly kill pain but makes people not react to the pain they are feeling.

By contrast, heroin is a direct painkiller, acting on opiate receptors in the brain. Users who are hooked must have heroin, or its legal substitute, methadone, every day simply so they won’t feel sick. The list of drugs that are abused -- including alcohol, LSD and mescaline -- is endless. Finally, I’ll mention marijuana, a sedative and a light hallucinogen. Marijuana acts on cannabinoid receptors and is not believed to cause permanent brain damage.

The bottom line with all drugs of abuse, adds Hanson, is that recreational use can turn into a “game of Russian roulette.” Street drugs “don’t kill everyone who takes them,” and obviously not everyone becomes addicted. But he adds, “The benefits just do not warrant the kind of risk you are exposing yourself to.”

My friend’s son, among others, is not convinced.

“I think it all comes down to the person. We are all different, with such different brain chemistry,” he says.

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Judy Foreman is a lecturer at Harvard Medical School.