By Sally Squires
                  Washington Post Staff Writer
                  Wednesday, January 12, 2000; Page H01

        With names such as ecstasy, clarity, roofies, bidis, yellow sunshine and
                  pina colada, they sound intoxicating and exotic. And they are. To many
                  people, drugs seem to offer possibilities of making life better, more
                  interesting, more exciting, more varied, less painful. Sometimes they do, for
                  a while anyway. No one would take them if they didn't make people feel, if
                  not good, at least very different.

                  But we now know that their short- and long-term effects are more
                  dangerous than experts had thought even 10 years ago.

                  As scientists continue to unravel the mysteries of the brain, one thing is
                  becoming crystal clear: Merely dabbling in drugs can cause severe, and
                  often irreversible, damage to brain cells and the nervous system in general.

                  Thanks to sophisticated new imaging techniques such as functional
                  magnetic resonance (fMRI) and positron emission tomography (PET
                  scans), scientists can view the brain today in real time. Genetics research
                  has enabled researchers to identify and clone the tiny sections of brain
                  cells, called receptors, that respond to virtually every drug of abuse.

                  On the eve of a new millennium, scientists "know more about how drugs
                  act in the brain than we do about anything else in the brain," says Alan
                  Leshner, director of the National Institute on Drug Abuse (NIDA).

                  Most of the picture isn't pretty. Despite widely varying chemical structures,
                  drugs of abuse typically ignite a biochemical cascade in the brain that
                  almost always lights up reward or pleasure circuits, often by affecting the
                  messenger chemicals, called neurotransmitters, that help transmit signals
                  from one brain cell to another.

                  "Some of these changes may well be benign," Leshner says. "Some are
                  not. But you use a drug, and you have changed your brain in big or little
                  ways."

                  Nerve cells, like all cells, are equipped with several kinds of entry gates,
                  called receptors, most of which protrude out of the cell's outer skin, or
                  membrane.

                  Each receptor is designed to respond when it comes in contact with a
                  neurotransmitter molecule of a certain shape, which fits the receptor's
                  structure like a key in a lock. Drugs work because they fit those locks in
                  nearly the same way that natural neurotransitters do.

                  Many receptors trigger a channel to open and cause a brief rush of
                  chemicals into the cell. If they're the right kind of chemicals, they can
                  prompt the cell to "fire" -- that is, make it more likely to send a signal to its
                  neighbor.

                  Those are called excitatory responses. Other compounds make cells less
                  prone to fire; they are called inhibitory. Depressant drugs such as alcohol
                  cause that kind of response.

                  Some receptors are inside the cell. When activated, they cause changes in
                  the way a cell does its internal housekeeping.

                  Just as a key may fit in a lock but still not turn, some drugs merely plug a
                  receptor, preventing the natural neurotransmitter from docking there. Other
                  drugs act almost exactly like the natural compound, commanding the
                  receptor channel to open and flood the cell's interior with various kinds of
                  chemicals from outside.

                  So if drugs don't actually do much that isn't already done by naturally
                  occurring compounds, why is everybody so worried about them? There
                  are several answers, all rather grim.

                  For one thing, drugs can hit your brain in concentrations far greater than
                  neurotransmitters ever would. Moreover, drugs can change the chemistry
                  of your brain cells in temporary and permanent ways.

                  Some of them kill neurons outright or maim them so that they'll never work
                  correctly. Others alter the nerve cells for days or weeks at a time -- long
                  after the user may desperately wish to be straight -- often producing
                  extremely painful withdrawal symptoms.

                  Why, then, do we do it? Attraction to drugs sort of runs in the family. It's
                  surprisingly common in the animal world.

                  Many species will go out of their way to get intoxicated. House cats love
                  to get high on catnip. Elephants in the wild will stop what they're doing to
                  get drunk on fermented fruits. Some birds delight in eating berries that
                  make them so stoned they can't fly straight.

                  But we are the only species that can understand what we're doing to
                  ourselves.

                  For information, see NIDA's web site at http://www.nida.nih.gov.

                  Club Drugs

                  Typically found at all-night "raves" and "trances," so-called "club drugs"
                  also are popular at some dance clubs and bars. Although they have
                  benign-sounding names, many contain a potent and dangerous mix of
                  compounds. They often come from home laboratories and frequently are
                  laced with chemical contaminants that increase the risk of overdose.

                  Because many of these drugs are colorless, tasteless and odorless, they
                  have been slipped into beverages and taken by unsuspecting individuals. In
                  recent years, their use has been linked with an increasing number of date
                  rapes and other sexual assaults.

                  Although they share the common informal designation as "club drugs,"
                  these compounds belong to at least three distinct categories.

                  1. Tranquilizers and sedatives. Rohypnol -- also known as roofies, rophies,
                  roche and forget-me pill -- is a member of the same well-known class of
                  tranquilizers that includes Valium, Halcion and Xanax. All principally affect
                  GABA receptors, with results ranging from sedation to coma.

                  Rohypnol usually is produced in pill form but sometimes is ground up and
                  snorted. It is legal in many countries as a treatment for insomnia and as a
                  sedative or presurgery anesthetic but has not been approved for
                  prescription use by the Food and Drug Administration for use in the United
                  States.

                  Rophypnol affects areas of the brain involved in memory processing and
                  produces a condition called "retrograde amnesia" that is similar to a
                  blackout -- users often can't remember events that occurred while under
                  the drug's influence. The drug also lowers blood pressure and can produce
                  gastrointestinal problems, urinary retention and impaired vision.

                  A similarly abused drug is GHB (gamma-hydroxybutyrate), variously
                  known as grievous bodily harm, G, Georgia home boy and liquid ecstasy.
                  It can be a clear liquid or a white powder and produced in tablet or
                  capsule form.

                  GHB is an extremely powerful and fast-acting central nervous system
                  depressant. For reasons not well understood, it once had a reputation on
                  the steroid black market as a muscle-builder, fat-reducer and
                  antidepressant. It hasn't been shown to do any of those things.

                  It does produce sedative effects 10 to 30 minutes after being taken. At low
                  doses, it can relieve anxiety and cause drowsiness, sometimes
                  accompanied by nausea, vomiting and headache. But at higher doses,
                  GHB produces sleep and sometimes coma.

                  Like any broadly active sedative, it can slow breathing and heart rate to
                  dangerously low levels, especially if combined with alcohol. Like
                  Rohypnol, GHB frequently produces amnesia and often is implicated in
                  date rape.

                  2. Psychedelic stimulants. Ecstasy -- also called clarity, XTC, adam or
                  lover's speed -- contains MDMA, a compound very similar to
                  methamphetamines [see article at lower left]. But it also can cause
                  hallucinations equivalent to those induced by mescaline, the active
                  ingredient in peyote mushrooms.

                  The parent compound of MDMA destroys serotonin-producing brain
                  cells, and MDMA may do the same, at the long-term expense of thought
                  and memory. MDMA itself damages neurons that respond to dopamine.

                  MDMA typically results in sweating, anxiety, increased heart rate and
                  blood pressure. Muscle seizures are not uncommon, and users may
                  employ an infant pacifier or other device to lessen the effects of involuntary
                  jaw clenching.

                  3. Psychedelic anesthetics. Ketamine, sold legally to veterinarians for
                  anesthesia, often is called special K, K, vitamin K and cat valiums.

                  It is chemically similar to PCP (phencyclidine), originally developed as an
                  anesthetic but abandoned when it was seen to cause hallucinations and
                  psychotic states.

                  Taken in liquid form or as a powder often snorted or smoked with
                  marijuana or tobacco -- and in some places injected into muscle tissue --
                  Ketamine and PCP bind to a kind of receptor that was not identified until
                  the 1990s.

                  They affect the function of several neurotransmitters, particularly one called
                  NMDA, and produce a characteristic stupor similar to extreme
                  drunkenness. Panic, rage and paranoia are typical.

                  Ketamine increases blood pressure and can cause potentially fatal
                  breathing problems.

                  At low doses, it impairs attention, learning ability and memory. At higher
                  doses, it can cause degraded motor function, delirium and amnesia.

                  Methamphetamines

                  Also known as speed, uppers, meth, copilots, crank, crystal meth, fire,
                  chalk and ice, these drugs are powerful stimulants that cause the heart to
                  race, increase blood pressure and boost the body's metabolism.

                  People taking methamphetamines often become talkative, feel anxious and
                  may experience a sense of exhilaration or euphoria. But this so-called
                  "rush" or "flash" lasts only a few minutes. These powerful stimulants are
                  highly addictive and have been showing up in recent years as part of the
                  club scene.

                  Brain changes. Methamphetamines work in the brain on the so-called
                  "pleasure circuit." They are chemically similar to two powerful
                  neurotransmitters, dopamine and norepinephrine, causing their release in
                  key areas of the brain, including the nucleus accumbens, which affects
                  emotions; the prefrontal cortex, which plays a critical role in working
                  memory; and the striatum, an area of the brain involved in movement.

                  Methamphetamines elicit pleasure through a complex chain reaction around
                  and inside nerve cells. The drugs pass easily through nerve cell membranes,
                  taken up by transporter molecules that normally would carry dopamine or
                  norepinephrine through the cell wall.

                  Inside the nerve cell, methamphetamine then enters holding tanks called
                  vesicles that contain dopamine and norepinephrine. This, in turn, prompts
                  release of more dopamine and norepinephrine. Normally, enzymes would
                  break down the overflow of neurotransmitters, but methamphetamine
                  blocks this reaction.

                  Transporter molecules then remove the excess dopamine and
                  norepine-phrine, dumping them into the synapse, or space between nerve
                  cells. As the levels of dopamine increase, so do feelings of pleasure and
                  euphoria. Norepinephrine appears to be responsible for feelings of
                  alertness and thwarts fatigue.

                  Other physical effects. Methamphetamines raise blood pressure and can
                  cause dangerous irregular heartbeats, chest pain, shortness of breath,
                  nausea, vomiting and diarrhea. They also can increase body temperature to
                  fatal levels, particularly during overdoses.

                  Biggest risks. Brain hemorrhage can cause permanent paralysis and speech
                  loss or be fatal. Laboratory research in animals also suggests that even a
                  single, high dose of methamphetamine can destroy as much as one-half of
                  nerve cells producing dopamine in the brain. A similar destruction, not
                  caused by drugs, is involved in Parkinson's disease, a progressive,
                  debilitating neurological condition.

                  Inhalants

                  The name says it all: Inhalants are chemical fumes that are sniffed or
                  inhaled. They provide one of the swiftest ways for drugs to reach the brain
                  because they enter the bloodstream directly through the lungs.

                  Also known as chemical vapors, these substances are found in a wide
                  range of common products. They have been used at least once by an
                  estimated 21 percent of eighth-graders, according to the National Institute
                  on Drug Abuse.

                  The chemicals found in inhalants are as varied as their use. Cigarette
                  lighters and refills contain the gas butane.

                  Paint thinner may have toluene, turpentine, ethyl acetate or mineral spirits.
                  Fingernail polish remover contains acetone, as does rubber cement.

                  Pressurized cans of hair spray, computer cleaner and whipped cream
                  contain fluorinated hydrocarbons.

                  Medical anesthetic gases contain ether, chloroform, halothane and nitrous
                  oxide, also known as laughing gas.

                  Brain changes. Some inhalants act somewhat like surgical anesthetics,
                  suppressing nerve action in a way not clearly understood and causing
                  various degrees of stupor. Some produce structural changes in brain cells.

                  These often affect the cerebral cortex, the cerebellum and the brain stem.
                  As a result, chronic inhalant users often move slowly and clumsily because
                  of loss of coordination.

                  The frontal cortex, a region of the brain that helps to solve complex
                  problems, also is affected by inhalants, as is the hippocampus, a part of the
                  brain involved in memory retention. Inhalants rob the brain of oxygen,
                  reducing nerve cell activity and killing some cells. That, in turn, can affect
                  thinking, memory and ability to learn.

                  Other physical effects. Permanent hearing loss, especially from inhaling
                  toluene found in paint sprays, glues and dewaxers, is a big risk for inhalant
                  users. Irreversible damage to nerves throughout the body, a condition
                  called polyneuropathy, is common. Among the most vulnerable nerves are
                  those in the back and legs.

                  Inhalants chemically attach to fatty tissues, especially the white myelin
                  sheaths that protectively coat nerve axons, somewhat like the insulation on
                  electrical wires, and speed nerve conduction. Inhalants damage the myelin
                  and destroy it. Some of these changes are temporary, but others can
                  produce long-lasting damage.

                  Elsewhere in the body, inhalants can cause a chemically induced hepatitis
                  (inflammation of the liver), liver failure and muscle weakness.

                  They also sometimes interfere with blood cell production, which can result
                  in the life-threatening condition known as aplastic anemia.

                  Biggest risks. "Sudden sniffing death" occurs when inhaled vapors replace
                  oxygen in the lungs and the brain. Inhalants also can interfere with the
                  normal heart rhythm and lead to cardiac arrest.

                  Marijuana

                  Pot, weed, grass, ganja, M.J. or whatever -- it's the most commonly used
                  illicit drug in the United States. Marijuana is the dried leaves and flowers of
                  the hemp plant, also known as Cannabis sativa. Delta-9
                  tetrahydrocannabinol (THC) is the leading active ingredient in marijuana,
                  but it includes more than 400 other compounds.

                  Marijuana is gaining popularity among youth after nearly a decade of
                  decline, although rates still haven't reached levels seen in the 1970s and
                  1980s.

                  In 1999, 22 percent of eighth-graders had tried marijuana, compared with
                  just 10 percent in 1991, according to the Monitoring the Future Study,
                  sponsored by the National Institute on Drug Abuse (NIDA). Among high
                  school seniors, Monitoring the Future found that nearly 50 percent had
                  tried marijuana in 1999, compared with 37 percent in 1991.

                  The drug is mostly smoked in hand-rolled "joints" but also can be smoked
                  from pipes, bongs or hollowed-out cigars. Some people also use marijuana
                  to brew tea, or they include it in foods, such as brownies or cookies.

                  Brain changes. For a long time, nobody knew what THC was doing in the
                  brain because there didn't seem to be a receptor for it. Only in the last 10
                  years did scientists finally find the receptor and isolate a naturally occurring
                  brain chemical called anandamide that binds to it.

                  THC also binds to the anandamide receptor and suppresses activity in the
                  hippocampus, an area of the brain pivotal for learning, memory and
                  emotions. Studies show that learned behaviors deteriorate with marijuana
                  use. That translates to problems with attention, memory and learning -- all
                  of which are impaired among college students who use marijuana heavily,
                  even after they have stopped using the drug for 24 hours.

                  On average, it takes at least 30 hours for the body to clear even half of the
                  THC from a single use. Those who begin using marijuana before college
                  show lower achievement and are more likely to engage in more deliquent
                  behavior and aggressiveness than non-users.

                  There also are lots of anandamide receptors in the basal ganglia and
                  cerebellum, both of which are involved in movement control, and in the
                  cerebral cortex, where the "high" probably is generated.

                  Other physical effects. In the lung, marijuana produces many of the same
                  health effects as tobacco smoke -- daily coughs, phlegm, chronic
                  bronchitis and increased susceptibility to chest colds. Long-term marijuana
                  use damages lungs.

                  Since marijuana smokers inhale deeply and hold the smoke in their lungs
                  for long periods of time, they also appear to be exposed to three to five
                  times the levels of carbon monoxide as tobacco smokers. Marijuana
                  increases heart rate and raises blood pressure.

                  Like nearly all drugs, marijuana doesn't mix with pregnancy. Use of
                  marijuana by expectant mothers raises the risk of delivering a baby who
                  has a low birth weight and is at increased risk for various health problems.

                  Nursing mothers who smoke marijuana pass THC to their babies through
                  breast milk and risk damaging their infant's motor development. Children
                  who breathe passive marijuana smoke display more temper tantrums,
                  thumb sucking and anger than youngsters not exposed.

                  Biggest short-term risks. Marijuana users are as uncoordinated as drunks
                  on standard driving tests, and more than 120,000 people seek treatment
                  each year for marijuana addiction, according to NIDA.

                  Alcohol and Cigarettes

                  Often dismissed as "just alcohol" or "just cigarettes," these substances
                  contain powerful drugs that are very harmful to brain and body.

                  Both are widely used. A 1999 survey conducted by the National Institute
                  on Drug Abuse found that more than half of all eighth-graders and 80
                  percent of high school seniors had imbibed alcohol at least once, despite
                  the legal drinking age of 21 years.

                  The same study showed that 44 percent of eighth-graders and two-thirds
                  of high school seniors had smoked at least once. About 14 percent of
                  eighth-graders and roughly one in four high school seniors also have used
                  smokeless tobacco.

                  Brain changes. Some of the brain's messenger chemicals excite nerve cells;
                  others dull or inhibit them. Among other activities, alcohol affects the most
                  powerful of the inhibitory systems -- those involving the neurotransmitter
                  GABA -- and that results in a general depression of many kinds of nerve
                  response.

                  Too much alcohol floods neurons and changes gene function of the cells,
                  which in turn appears to alter receptors and results in intoxication,
                  brain-cell death and, if repeated, dependence and alcoholism.

                  Nicotine, the active ingredient in tobacco, reaches the brain just eight
                  seconds after being inhaled and is both a stimulant and a sedative.
                  Chemically similar to a powerful neurotransmitter called acetylcholine,
                  nicotine activates areas of the brain in feeling pleasure and reward. It does
                  so by boosting production of dopamine, another powerful
                  neurotransmitter, in a part of the brain called the nucleus accumbens.

                  Chewed or smoked, nicotine is addictive, like heroin or cocaine -- one
                  reason that those who begin smoking before age 21 have the hardest time
                  quitting.

                  Other physical effects. Heavy alcohol use delays puberty and can slow
                  bone growth in laboratory animals, leading scientists to suspect that it could
                  do the same in humans. Elsewhere in the body, alcohol can deplete B
                  vitamins important for neurological function and optimal use of peripheral
                  nerves in fingers and toes.

                  In the liver, chronic alcohol abuse over time causes degeneration, swelling
                  and scarring of the liver (called cirrhosis) and can lead to liver failure. Light
                  drinking may provide some moderate protection against heart disease, but
                  the exact dose is dicey.

                  A recent study by researchers at the University of Pennsylvania found that
                  even social drinking increased free radicals, harmful substances linked to
                  development of premature heart disease, stroke, cirrhosis and many other
                  disorders.

                  Nicotine increases heart rate and blood pressure. It also alters breathing
                  patterns and damages the lungs. In very high concentrations, nicotine is a
                  poison. In fact, just one drop of purified nicotine on the tongue is deadly.

                  Biggest short-term risks are addiction to alcohol and nicotine and death
                  from binge drinking.

                  Long-term smokers are more likely than nonsmokers to develop lung
                  cancer (caused by smoke, not nicotine) and other tumors. Emphysema,
                  difficulty in breathing caused by destruction of air pockets in the lungs, also
                  is a major risk for smokers.

                  Women who smoke undergo menopause sooner than nonsmokers and
                  suffer the effects of aging, including wrinkled skin, earlier than their
                  nonsmoking counterparts. Alcoholics face a high risk of liver disease.
                  Alcoholics who smoke are particularly vulnerable to cancer of the throat,
                  mouth and esophagus.

                  IT'S ALL IN YOUR HEAD

                  Unlike many substances, drugs can seep through blood vessels in the brain
                  and reach nerve cells, or neurons.

                  Brain areas most affected by drugs

                  Limbic system

                  1. Striatum

                  Nucleus accumbens

                  Caudate nucleus

                  Thalamus

                  Hippocampus

                  Ventral tegmental area

                  Cerebellum

                  Brain stem

                  Cerebral cortex

                  Frontal cortex

                  Prefrontal cortex

                  Fooling receptors

                  A receptor designed to respond to a natural neurotransmitter can be either
                  blocked or activated by drug molecules that have a similar, but not
                  identical, shape.

                  Anatomy of a neuron

                  Neurons gather incoming messages -- both excitatory and inhibitory --
                  from their neighbors across narrow gaps between cells called synapses.
                  When a cell "fires," it sends a signal down its axon. Tiny pouches called
                  vesicles spray neurotransmitters across the synapse, which then affect
                  receptors on the receiving cell.

                  Five important

                  neurotransmitters . . .

                  Serotonin

                  Widespread substance that affects mood, appetite, sexual activity,
                  aggression, body temperature and sleep.

                  Norepinephrine

                  Regulates blood pressure and prompts extreme arousal, "fight or flight"
                  response, mental focus and pain reduction.

                  Dopamine

                  A key compound that is an important part of the brain's "reward" system,
                  causing feelings of wellbeing.

                  GABA

                  The brain's major inhibiting compound, involved in muscle relaxation,
                  sleep, diminished emotional reaction and sedation.

                  Acetylcholine

                  Involved in muscle action all over the body; in the brain affects arousal,
                  attention, learning, mood and sleep.

                  . . . and drugs that interfere with them

                  Ecstasy (MDMA)

                  Damages or destroys serotonin neurons, alters balance and action of
                  norepinephrine and dopamine.

                  Methamphetamines

                  Increase concentrations of norepinephrine and dopamine in nucleus
                  accumbens, caudate nucleus and prefontal cortex, among other structures.

                  Alcohol, Tranquilizers

                  Alcohol increases activity of GABA, inhibits release of acetylcholine and
                  excites dopamine neurons in ventral tegmental area activity.
                  Benzodiazepine tranquilizers, such as Rohypnol, boost GABA activity in
                  cerebellum, brain stem and spinal cord.

                  Psychedelics

                  Activate some serotonin receptors on post-synaptic cells, change balance
                  and action of norepinephrine and dopamine.

                  Ketamine

                  Affects special PCP receptors, inhibiting two key neurotransmitters
                  (NMDA and glutamate) and stifling neural activity.

                  SOURCES: A Primer of Drug Action, 7th Edition by Robert M. Julien
                  (W.H. Freeman, 1995); Drugs and the Brain by Solomon H. Snyder
                  (Scientific American Library, 1996); NIDA

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