MDMA (ecstasy)
 MDMA was developed in 1914 as an appetite suppressant, but animal tests were unimpressive, so it was never tested in humans. In the 1960s, MDMA became known as an "empathy agent," prescribed by psychiatrists to help their patients break through psychological defenses. By the mid-1980s, MDMA was being produced in illegal unlicensed laboratories and distributed for recreational use. It became classified as a schedule I controlled substance in 1985.
MDMA is the most common stimulant found in dance clubs and at raves. It usually is sold as small tablets of various colors imprinted with popular icons or words. MDMA is structurally similar to amphetamine and mescaline, which is a hallucinogen. However, it is not as stimulating or addictive as amphetamine and is much less likely to cause psychosis than LSD or other potent hallucinogens. A high proportion of MDMA pills purchased on the street are adulterated with substances such as dextromethorphan or pseudoephedrine (drugs found in many over-the-counter cold and cough preparations), caffeine, and in some cases, LSD.
The effects of an oral dose of MDMA appear within 30 to 60 minutes and last up to eight hours. Some users obtain a quicker onset of action by crushing the tablet and snorting the powder. Users describe initial feelings of agitation, a distorted sense of time, and diminished hunger and thirst, followed by euphoria with a sense of profound insight, intimacy, and well-being. MDMA ingestion increases the release of serotonin, dopamine, and norepinephrine in the brain.
Unpleasant side effects of MDMA include tightening of the jaw muscles (trismus) and teeth clenching and grinding (bruxism). Adverse effects of MDMA ingestion result from an overload of the sympathetic nervous system, and include rapid heart rate, excessive pupil dilation, excessive sweating, tremor, elevated blood pressure, irregular heart beat, muscle rigidity, shuffling gait, esophoria (tendency for eyes to turn inward), and difficulty urinating.
One particularly troublesome potential outcome of MDMA ingestion is hyperthermia - severely elevated core body temperature. Heat from the exertion of dancing in a crowded room coupled with MDMA-induced hyperthermia can lead easily to drinking excessive amounts of water and severe water intoxication (the opposite of dehydration). Possible effects include confusion, delirium, paranoia, headache, anorexia, depression, insomnia, and irritability, all of which may continue for several weeks. Repeated use of MDMA has been associated with cognitive deficits in animals and humans, with potentially permanent memory impairment.
Two days after ingesting MDMA, users typically experience depression consistent with serotonin depletion. Compared with alcohol withdrawal, people who withdraw from MDMA are often more depressed, irritable, and unsociable.
A number of products sold legally as "herbal ecstasy" typically contain stimulants such as ephedra, caffeine, and guarana. People who use these products may believe they are safe alternatives to MDMA, but several cases of toxic overdose from the intense stimulation of ephedrine or excessive caffeine have been reported.
Gamma Hydroxybutyrate (GHB)
 GHB, a derivative of the inhibitory neurotransmitter g-aminobutyric acid, occurs naturally in the central nervous system, where it is believed to mediate sleep cycles, body temperature, and memory. Street names for GHB include G, liquid ecstasy, Grievous Bodily Harm, gib, soap, scoop, and nitro.
GHB was first synthesized in France in 1960 as an anesthetic. It later achieved popularity as a recreational drug and a nutritional supplement marketed to bodybuilders. Nonprescription sales in the United States were banned in 1990 because of adverse effects, including uncontrolled muscle movements and depression of the respiratory and central nervous system. In 2000, with 60 deaths reported from overdose and concern over its use as a "date rape" drug, GHB was reclassified as a schedule I controlled substance.
GHB is easily manufactured from industrial chemicals. Web sites offer instructions for home production and sell kits with the requisite materials. The salty powder usually is dissolved in water and sold at $5 to $10 per dose. Overdose is common because the strength of the solution is often unknown. The unpleasant salty or soapy taste of the drug may be masked in flavored or alcoholic beverages.
Effects of GHB appear within 15 to 30 minutes of oral ingestion and peak after 20 to 60 minutes, depending on whether it is mixed with food. Toxicity increases if taken with alcohol or other CNS depressants. GHB produces euphoria, progressing with higher doses to dizziness, excessive salivation, abnormally low heart rate, hypothermia (a decrease in the core body temperature), and amnesia. Overdose may result in a condition named Cheyne-Stokes (an abnormal type of breathing seen especially in comatose patients, characterized by alternating periods of shallow and deep breathing), seizures, coma, and death. Chronic use of GHB may result in dependence and withdrawal symptoms including anxiety, insomnia, tremor, and in severe cases, psychoses that do not respond well to treatment.
Ketamine
 Ketamine was derived from phencyclidine (PCP) in the 1960s for use as an anesthetic. Currently, about 90% of the ketamine sold legally is intended for veterinary use. Street names include K, special K, super K, vitamin K, kit-kat, keets, super acid, jet, and cat valium.
Ketamine causes anesthesia without respiratory depression by inhibiting the neuronal uptake of norepinephrine, dopamine, serotonin, and glutamate. It can cause bizarre thoughts and hallucinations - side effects that limited its original medical use but appeal to recreational drug users.
Ketamine is difficult to manufacture, so distributors direct most of the illicit supply from human and veterinary anesthesia products. As a pharmaceutical, ketamine is distributed in a liquid form that can be ingested or injected. In clubs, it is usually found as a dried powder that is smoked in a mixture of marijuana or tobacco. It can also be snorted, typically using a nasal inhaler, called a "bullet" or "bumper." One inhalation is called a "bump." Ketamine sometimes is taken in "trail mixes" of methamphetamine, cocaine, sildenafil citrate (Viagra), or heroin.
Effects of ketamine ingestion appear rapidly and last about 30 to 45 minutes, with sensations of floating outside the body, visual hallucinations, and a dream-like state. Along with these "desired" effects, users also commonly experience confusion, anterograde amnesia (a form of memory loss where new events are not transferred to long-term memory), and delirium. They also may experience rapid heart beat, heart palpitations, elevated blood pressure, and slow or "stop and start" breathing. "Flashbacks" or visual disturbances can appear days or weeks after ingestion. Some chronic users become addicted and exhibit severe withdrawal symptoms that require medically supervised detoxification.
Flunitrazepam (Rohypnol)
 Flunitrazepam, marketed as Rohypnol, is a potent, quick acting benzodiazepine (sedative). It is available in more than 60 countries in Europe and Latin America for preoperative anesthesia, sedation, and treatment of insomnia. In the United States, imported Rohypnol came to prominence in the 1990s as an inexpensive recreational sedative and a "date rape," or "acquaintance sexual assault," drug. Street names include Mexican Valium, circles, roofies, la rocha, roche, rophies, R2, rope, and forget-me pill.
In a single 1 mg or 2 mg dose, Rohypnol reduces anxiety, inhibition, and muscular tension with a potency approximately 10 times that of diazepam (Valium). Effects occur about 30 minutes after ingestion, peak at two hours, and may last up to eight to 12 hours. Higher doses produce anterograde amnesia (a form of memory loss where new events are not transferred to long-term memory), lack of muscle control, and loss of consciousness. Some users experience reduced blood pressure, dizziness, confusion, visual disturbances, urinary retention, or aggressive behavior.
The effects of Rohypnol are much greater when mixed with alcohol or other sedating drugs. When mixed with alcohol, it can incapacitate victims and prevent them from resisting sexual assault. Rohypnol can be lethal when mixed with alcohol and/or other depressants.
Like other benzodiazepines, chronic use of Rohypnol can produce dependence. Withdrawal symptoms include headache, tension, anxiety, restlessness, muscle pain, sensitivity to light, numbness and tingling of the extremities, and seizures.
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