Ecstasy
 New studies show that users of Ecstasy risk the possibility of brain damage from prolonged use. Law enforcement is intensifying its efforts to stop the growing demand for Ecstasy and to halt organized crime's penetration of the market.

The pill, at $20 or so a pop, acts a little like stimulants such as methamphetamine and a little like a hallucinogen such as LSD. A hit produces a warm, fuzzy sense of well-being and the manic energy to dance until dawn. However, studies indicate that Ecstasy, the nickname for the drug compound 3,4 methylenedioxy-methamphetamine (MDMA), clicks off brain cells crucial to memory and sleep.

"The party's over,'' says Alex Stalcup, a physician who runs a drug treatment center in Concord, Calif. ''Ecstasy hurts the brain. It is no longer a hypothesis. The drug is toxic. It is no longer appropriate to consider it a recreational drug.''

Dangers of Ecstasy

Yet the urgency to get the drugs out of reach of teenagers has intensified as new scientific studies warn that Ecstasy causes brain damage.  Stalcup, the drug addiction doctor who describes himself as a prototypical aging hippie'' and has tried Ecstasy, often spends Saturday nights at San Francisco-area raves, where he treats overheated and dehydrated teenagers.

 Scientists have studied images of the brain before and after Ecstasy. Stalcup describes the differences as ''graphic and gruesome.'' Ecstasy kills off part of the nerve in the brain that releases serotonin, the chemical that controls sleep, sexual function, memory, appetite and mood, says Wilkie Wilson, a neuropharmacologist at Duke University who co-wrote Buzzed, a guide to abused drugs.

A study by Johns Hopkins University researcher George Ricaurte in Baltimore compared the brain scans of 14 Ecstasy users to non-users' scans and found nerve damage that persists for at least seven years. Teens have more serotonin-producers than they need, Wilson says, but some of those nerves are lost with aging. ''Ecstasy users probably don't realize this, but they are aging themselves prematurely,'' he says. ''I expect them to have clinical depression and sleep disorders down the road. It impairs learning, which is a particularly bad thing for teenagers.''

Cocaine
National Institute on Drug Abuse Research Report Series

How is cocaine used?
The principal routes of cocaine administration are oral, intranasal, intravenous, and inhalation. The slang terms for these routes are, respectively, "chewing," "snorting," "mainlining," "injecting," and "smoking" (including freebase and crack cocaine). Snorting is the process of inhaling cocaine powder through the nostrils, where it is absorbed into the
bloodstream through the nasal tissues. Injecting releases the drug directly into the bloodstream, and heightens the intensity of its effects. Smoking involves the inhalation of cocaine vapor or smoke into the lungs, where absorption into the bloodstream is as rapid as by injection. The drug can also be rubbed onto mucous tissues. Some users combine
cocaine powder or crack with heroin in a "speedball." 

Cocaine use ranges from occasional use to repeated or compulsive use, with a variety of patterns between these extremes. There is no safe way to use cocaine. Any route of administration can lead to absorption of toxic amounts of cocaine, leading to acute cardiovascular or cerebrovascular emergencies that could result in sudden death. Repeated
cocaine use by any route of administration can produce addiction and other adverse health consequences. 

How does cocaine produce its effects? 
A great amount of research has been devoted to understanding the way cocaine produces its pleasurable effects, and the reasons it is so addictive. One mechanism is through its effects on structures deep in the brain. Scientists have discovered regions within the brain that, when stimulated, produce feelings of pleasure. One neural system that appears
to be most affected by cocaine originates in a region, located deep within the brain, called the ventral tegmental area (VTA). Nerve cells originating in the VTA extend to the region of the brain known as the nucleus accumbens, one of the brain's key pleasure centers. In studies using animals, for example, all types of pleasurable stimuli, such as food,
water, sex, and many drugs of abuse, cause increased activity in the nucleus accumbens. 

Cocaine in the brain - In the normal communication process, dopamine is released by a neuron into the synapse, where it can bind with dopamine receptors on neighboring neurons. Normally dopamine is then recycled back into the transmitting neuron by a
specialized protein called the dopamine transporter. If cocaine is present, it attaches to the dopamine transporter and blocks the normal recycling process, resulting in a build-up of dopamine in the synapse which contributes to the pleasurable effects of cocaine.

Researchers have discovered that, when a pleasurable event is occurring, it is accompanied by a large increase in the amounts of dopamine released in the nucleus accumbens by neurons originating in the VTA. In the normal communication process, dopamine is released by a neuron into the synapse (the small gap between two neurons), where it binds with specialized proteins (called dopamine receptors) on the neighboring neuron, thereby sending a signal to that neuron. Drugs of abuse are able to interfere with this normal communication process. For example, resulting in an accumulation
of dopamine. This buildup of dopamine causes continuous stimulation of receiving neurons, probably resulting in the euphoria commonly reported by cocaine abusers. 

As cocaine abuse continues, tolerance often develops. This means that higher doses and more frequent use of cocaine are required for the brain to register the same level of pleasure experienced during initial use. Recent studies have shown that, during periods of abstinence from cocaine use, the memory of the euphoria associated with cocaine use, or
mere exposure to cues associated with drug use, can trigger tremendous craving and relapse to drug use, even after long periods of abstinence. 

What are the short-term effects of cocaine use?
Cocaine's effects appear almost immediately after a single dose, and disappear
within a few minutes or hours. Taken in small amounts (up to 100 mg), cocaine
usually makes the user feel euphoric, energetic, talkative, and mentally alert,
especially to the sensations of sight, sound, and touch. It can also temporarily
decrease the need for food and sleep. Some users find that the drug helps them to
perform simple physical and intellectual tasks more quickly, while others can
experience the opposite effect. 

The duration of cocaine's immediate euphoric effects depends upon the route of administration. The faster the absorption, the more intense the high. Also, the faster the absorption, the shorter the duration of action. The high from snorting is relatively slow in onset, and may last 15 to 30 minutes, while that from smoking may last 5 to 10 minutes. 

The short-term physiological effects of cocaine include constricted blood vessels; dilated pupils; and increased temperature, heart rate, and blood pressure. Large amounts (several hundred milligrams or more) intensify the user's high, but may also lead to bizarre, erratic, and violent behavior. These users may experience tremors, vertigo, muscle
twitches, paranoia, or, with repeated doses, a toxic reaction closely resembling amphetamine poisoning. Some users of cocaine report feelings of restlessness, irritability, and anxiety. In rare instances, sudden death can occur on the first use of cocaine or unexpectedly thereafter. Cocaine-related deaths are often a result of cardiac arrest or seizures followed by respiratory arrest. 

What are the long-term effects of cocaine use?
Cocaine is a powerfully addictive drug. Once having tried cocaine, an individual
may have difficulty predicting or controlling the extent to which he or she will
continue to use the drug. Cocaine's stimulant and addictive effects are thought to
be primarily a result of its ability to inhibit the reabsorption of dopamine by nerve
cells. Dopamine is released as part of the brain's reward system, and is either
directly or indirectly involved in the addictive properties of every major drug of
abuse. 

An appreciable tolerance to cocaine's high may develop, with many addicts
reporting that they seek but fail to achieve as much pleasure as they did from their
first experience. Some users will frequently increase their doses to intensify and
prolong the euphoric effects. While tolerance to the high can occur, users can also
become more sensitive (sensitization) to cocaine's anesthetic and convulsant
effects, without increasing the dose taken. This increased sensitivity may explain some deaths occurring after apparently low doses of cocaine. 

Use of cocaine in a binge, during which the drug is taken repeatedly and at increasingly high doses, leads to a state of increasing irritability, restlessness, and paranoia. This may result in a full-blown paranoid psychosis, in which the individual loses touch with reality and experiences auditory hallucinations. 

What are the medical complications of cocaine abuse?
There are enormous medical complications associated with cocaine use.
Some of the most frequent complications are cardiovascular effects,
including disturbances in heart rhythm and heart attacks; such respiratory
effects as chest pain and respiratory failure; neurological effects, including
strokes, seizure, and headaches; and gastrointestinal complications,
including abdominal pain and nausea. 

Cocaine use has been linked to many types of heart disease. Cocaine has
been found to trigger chaotic heart rhythms, called ventricular fibrillation;
accelerate heartbeat and breathing; and increase blood pressure and body
temperature. Physical symptoms may include chest pain, nausea, blurred
vision, fever, muscle spasms, convulsions and coma. 

Different routes of cocaine administration can produce different adverse
effects. Regularly snorting cocaine, for example, can lead to loss of sense
of smell, nosebleeds, problems with swallowing, hoarseness, and an
overall irritation of the nasal septum, which can lead to a chronically
inflamed, runny nose. Ingested cocaine can cause severe bowel gangrene,
due to reduced blood flow. And, persons who inject cocaine have
puncture marks and "tracks," most commonly in their forearms.
Intravenous cocaine users may also experience an allergic reaction, either
to the drug, or to some additive in street cocaine, which can result, in
severe cases, in death. Because cocaine has a tendency to decrease food
intake, many chronic cocaine users lose their appetites and can experience
significant weight loss and malnourishment. 

Research has revealed a potentially dangerous interaction between
cocaine and alcohol. Taken in combination, the two drugs are converted
by the body to cocaethylene. Cocaethylene has a longer duration of action in the brain and is more toxic than either drug alone. While more research needs to be done, it is noteworthy that the mixture of cocaine and alcohol is the most common two-drug combination that results in drug-related death.