Benzylpiperazine/Trifluoromethyl-phenylpiperazine

What Kind of Drug Is It?

Benzylpiperazine (BZP) and trifluoromethyl-phenylpiperazine (TFMPP) are both stimulants—substances that increase the activity of a living organism or one of its parts. Neither one of these compounds has any known medical use for humans, at least not in their existing chemical forms. BZP and TFMPP are substances known as intermediaries, meaning they are at a middle stage in chemical production. Because piperazines can dissolve fats, they are often used as cleaning solutions. Usually, piperazines are made into detergents or medicines.

Overview

Chemicals known as piperazines are used for industrial purposes worldwide. A basic piperazine can be changed into a variety of different substances simply by adding different chemical groups to the original compound. For instance, a drug called piperazine citrate destroys intestinal worms, making it useful in the treatment of parasitic infections in both humans and animals. Parasites are organisms that must live with, in, or on other organisms to survive.

Other medicinal and mind-altering qualities of piperazines are being studied as possible treatments for:

• Depression, a mood disorder that causes people to have feelings of hopelessness, loss of pleasure, self-blame, and sometimes suicidal thoughts.
• Psychosis (pronounced sy-KOH-sis), a severe mental disorder that often causes hallucinations and makes it difficult for people to distinguish what is real from what is imagined.
• Alzheimer's disease, a brain disease that usually strikes older individuals and results in memory loss, impaired thinking, and personality changes; symptoms worsen over time.
• Tumors.

Official Drug Name: Benzylpiperazine (BENZ-ull-pih-PAIR-uh-zeen; BZP), trifluoromethyl-phenylpiperazine (try-FLU-roh METH-ull FENN-ull-pih-PAIR-uh-zeen; TFMPP)

Also Known As: A2, BZP, legal E, legal X, herbal ecstasy, herbal speed, the party pill, piperazine, and TFMPP

Drug Classifications: Schedule I, stimulant, hallucinogen

BZP and TFMPP are piperazine stimulants. They stimulate the brain, creating hallucinogenic experiences in some users. Both drugs have been compared to amphetamines. According to the U.S. Department of Justice, "the amphetamine-like stimulant

effects of BZP" seem to "attract the attention of drug abusers." The effects of piperazine abuse can be unpredictable. Some users report feelings of relaxation, happiness, and increased closeness with others after taking BZP and TFMPP. However, others describe their experiences with these drugs as frightening and extremely unpleasant. BZP seems to be more commonly abused than TFMPP, probably because there is a greater supply of it available for purchase. Most users of TFMPP prefer to combine it with the club drug ecstasy (MDMA).

Until March of 2004, piperazines were considered legal in the United States. Piperazines sold in bulk over the Internet made their way to the club and rave scene. They grew in popularity among adolescents and young adults, sometimes being sold as the dangerous and often-abused drug ecstasy but usually as "BZP," "legal E," "legal X," or "A2." The dangers of BZP and TFMPP stem from their stimulant effects. Rapid heart rhythms, tremors, and convulsions have been reported in some cases.

What Is It Made Of?

BZP and TFMPP are chemical compounds of carbon, hydrogen, and nitrogen. Piperazines are synthetic drugs. They cannot be grown in a garden or dug up from the ground. BZP, the more common of the two abused piperazines, is an odorless, colorless, or faintly yellow oily liquid at room temperature. Like water, it freezes at 32°F (0°C). If consumed by humans or animals in this form, it can cause burns to the skin, lungs, or intestinal tract.

How Is It Taken?

Legal piperazine preparations available in the United States and Canada are listed in the Micromedex Healthtouch prescription database "to treat common roundworms and pinworms." A drug called piperazine citrate comes in various forms, including granules (to be mixed with water), an oral suspension (a liquid medication), or tablets. It can only be obtained with a doctor's prescription. As of 2005, use among humans was limited to the treatment of parasitic worm infections.

Most illicit piperazines are sold in tablet form and contain both BZP and TFMPP. Sometimes, BZP tablets are sold as ecstasy. There is no sure way of knowing the exact dose of BZP and/or TFMPP in tablet form because all of the pills are made in illegal labs. Frequent users usually take anywhere from 35 milligrams to 150 milligrams at a time.

Mystery Ingredients

Most industrial sources supply a BZP preparation that is 97 percent pure, but manufacturers often do not list the ingredients used to prepare the other 3 percent of the compound. Many additives found in industrial chemicals may be toxic or even fatal if consumed. BZP poses a big enough threat to human health on its own. The "mystery ingredients" that are mixed in with it may add to that risk.

Illegal piperazine tablets are sometimes packaged in vitamin containers. The pills may be white, off-white, tan, or bright shades of green, orange, pink, purple, or yellow. Like ecstasy tablets, piper azine tablets resemble sweet-and-sour candies. They often feature tiny logos—a heart, a fly, a butterfly, a crown, a smiley face, a bull's head, or a squirrel, for example—etched in them. Some users have reported snorting or smoking BZP preparations. This particular method of ingestion irritates the lining of the nose, mouth, and breathing tubes.

Are There Any Medical Reasons for Taking This Substance?

Since the early 1950s, piperazines have been used widely by veterinarians as an anthelmintic drug. Anthelmintics are used to treat parasitic infections. In other words, they destroy worms. In humans, piperazine citrate serves a similar function and is used to treat pinworm and roundworm infestations in adults and children. The drug acts by paralyzing the muscles of mature worms and dislodging them from the walls of the intestines. The worms are then eliminated as part of a bowel movement.

In 1999, drug researchers in Japan found that a particular form of benzylpiperazine stimulates a brain chemical called acetylcholine. A neurotransmitter, acetycholine is involved in learning and memory. This led to the discovery of donepezil (Aricept), which helps ward off memory loss in patients with Alzheimer's and other brain diseases.

As of early 2005, other chemical substances related to BZP were being investigated for possible uses in the treatment of depression, psychosis, epilepsy, and severe pain. In addition, phenylpiperazine derivatives (substances similar to TFMPP) were being tested for their ability to kill certain types of cancerous tumors.

Usage Trends

Use of BZP was first reported in the United States and Switzerland in 2000. According to the U.S. Drug Enforcement Administration (DEA), seizure of BZP and TFMPP tablets, capsules, and powders increased steadily through 2004.

Teenagers and young adults who attend raves on a regular basis are the most frequent users of both BZP and TFMPP. Like ecstasy, piperazine has spread from the club scene to high schools and college campuses.

In the United States, BZP is usually imported in powder form and then manufactured into pills. Several hundred pounds of powdered BZP have been seized from India. Busts have been made for possession and use of piperazines throughout the United States, especially in California, Connecticut, and Texas.

In Europe, BZP—which is known there as A2—is marketed "as a cheap and safe alternative compared to illicit amphetamines," stated a DEA "Drug Intelligence Brief" released in December of 2001. As late as 2005, the drug was being sold over-the-counter in New Zealand as a legal stimulant under the brand name Nemesis. "The pills… are advertised as safe, legal alternatives to illegal highs. There is no age restriction on sales," according to a drug authority interviewed in the Ashburton Guardian.

Louise Bleakley reported in the New Zealand Press that benzylpiperazine tablets, commonly referred to there as "party pills," are "neither classified as a drug nor a dietary supplement so there is no requirement for them to be labeled." Casual drug users in New Zealand seemed "less cautious" about taking BZP, noted Bleakley, "because of the commonly used 'herbal' label" on their packaging. "In fact, herbal party pills [are] synthetic compounds."

Typical Users

The U.S. Drug Enforcement Administration reported that the typical abusers of BZP and TFMPP are "adolescents and young adults involved with the current rave culture." Of particular concern is the fact that many of its users do not even know they are taking it. Some dealers do not realize they are selling it. Not only have BZP and TFMPP tablets been found among bags of ecstasy (MDMA) tablets, the powders of all three drugs have been found mixed together in drugs being passed off as pure ecstasy.

BZP is not considered a controlled substance worldwide. In late 2004 and early 2005, it was being sold over-the-counter in New Zealand as an herbal party pill. (Oddly enough, the pills contain no herbs.) The staff of New Zealand's Christchurch Hospital, according to a New Zealand Press article, said that piperazine users admitted for emergency treatment "were usually young women in their late teens or early twenties."

According to the New Zealand Press in late 2004, hospital emergency departments in urban New Zealand reported seeing "at least six patients a weekend suffering severe paranoia and dehydration" after taking the so-called herbal drugs. "Party-goers were arriving at the hospital hysterical and requiring sedation." At that time, New Zealand's associate health minister, Jim Anderton, proposed that a new classification be added to the A, B, and C ratings given to drugs

there by law. These letter ratings are somewhat similar to the scheduling of drugs by number in the United States. Anderton's idea for a "D" rating, which would include party pills, has received considerable support.

Effects on the Body

Piperazines like BZP and TFMPP are psychostimulants. Because they affect the brain, the drugs cause a wide range of sensations and experiences. Sometimes these effects are considered pleasant by the user. Sometimes they are frightening. They can even be life threatening. Piperazines vary in their mind-altering properties. The drugs influence brain function by acting on chemicals called neurotransmitters, which can have profound effects on mood, learning, perceptions, and movement.

Animal research has shown that BZP triggers the release of neurotransmitters called dopamine and norepinephrine, two natural stimulants that the body produces on its own. TFMPP acts by stimulating nerve receptors sensitive to serotonin, another neurotransmitter.

At doses of 20 milligrams to 100 milligrams, BZP and TFMPP reportedly produce a range of mental experiences lasting six to eight hours. Amphetamine-like effects include euphoria, alertness, a reduced need for both food and sleep, a heightened sense of touch and other pleasurable sensations, and a sense of emotional closeness with others. At higher doses, though, users have reported stomach pain, vomiting, and feelings of extreme anxiety and paranoia. A tingling feeling on the surface of the skin may make users feel as if insects are crawling all over them. Some users end up in emergency rooms panic-stricken, screaming, and suffering from extreme dehydration.

BZP acts very much like amphetamines or speed. Amphetamines are illegal without a prescription from a medical doctor. They can make users jumpy, irritable, and even violent. According to the U.S. Department of Justice, "BZP is about 10 to 20 times less potent than amphetamine." However, just one or two BZP tablets can have extreme negative effects on the people who take them.

Like amphetamines, piperazines increase the heart rate, blood pressure, and body temperature, which can be dangerous or even fatal. At high doses, piperazines may produce hallucinations, convulsions, and slowed breathing that can result in death. The physical effects of piperazine use include nausea, vomiting, redness of the skin, stomach pains, thirst, dry mouth, frequent urination, bladder infection or irritation, severe headaches, and "hangover" feelings lasting up to two days. BZP and TFMPP also affect brain centers that control movement. Muscle stiffness, uncontrollable shaking, jaw clenching, and nervous tics may occur in users.

If BZP comes in contact with the eyes or skin, it can cause severe inflammation and burns. When inhaled, it irritates the respiratory tract, leaving the user with a sore throat, coughing fits, and difficulty breathing. Prolonged inhalation can cause chemical burns to the breathing tubes and the buildup of fluid in the lungs. When swallowed, piperazines are absorbed quickly through the linings of the stomach and intestines. Part of the drug is broken down by the actions of the liver and kidneys, and the rest is released from the body as urine.

Because piperazine abuse is relatively new among drug users, the harmful effects of BZP and TFMPP have not been fully determined. According to the Health and Safety Executive of the United Kingdom, piperazines are thought to have the potential to cause

asthma, although how this occurs is still unknown. The effects in children and pregnant women also remain unknown.

Former speed addicts who took BZP experienced an increase in blood pressure and short-term mental experiences similar to those brought on by amphetamines. These data suggested that BZP was likely to be addictive and abused. Results of experiments conducted on rhesus monkeys, published in Drug and Alcohol Dependence in 2005, confirmed that BZP is as addicting as amphetamines. TFMPP taken alone, however, was not considered likely to be abused. Other animal experiments suggest that the use of piperazines can actually inhibit learning.

Reactions with Other Drugs or Substances

The DEA reports that BZP and TFMPP are sometimes deliberately mixed with ecstasy by drug dealers and then sold as ecstasy. Some users hoping for an extended or intensified high from ecstasy will knowingly combine these drugs. A DEA "Drug Intelligence Brief" described the drug-related death of a 23-year-old woman in Zurich, Switzerland, after she had consumed both BZP and ecstasy. Medical evidence suggests that the drug combination made her extremely thirsty. Before going into a coma, she consumed 10 liters of water in just 15 hours. The young woman experienced high blood pressure and brain swelling prior to her death.

Users have reported combining BZP with alcohol, Xanax (a benzodiazepine), dextromethorphan, marijuana, and hydrocodone (a steroid). They have described many of their experiences as frightening or unpleasant. A New Zealand alcohol and drug service expert was quoted in the Ashburton Guardian as saying that the "herbal highs" associated with BZP use are intensified by alcohol.

Warnings are given against combining prescription piperazines, used to treat parasitic infections, with certain psychiatric medications. The combination may cause violent seizures or convulsions. Piperazines are especially dangerous when used by people with kidney disease, liver disease, or a history of epilepsy.

Treatment for Habitual Users

The need for emergency room treatment rose considerably by 2004 among users of BZP and TFMPP. Both drugs are produced illegally. In many cases, users are unaware of the dosage of the tablets they take, which increases the risk of overdose and even death. Because piperazine abuse has been recognized only recently, specific programs for rehabilitation have not yet been developed. Treatment will most likely include psychological counseling.

Weighty Issues

People who use BZP or TFMPP usually lose interest in food and may stop eating altogether. After about two weeks on the drug, however, the effects on food intake and weight loss level off. When the drug is stopped altogether, a "rebound effect" on the appetite center of the brain may occur, leading to excessive eating and weight gain.

Consequences

Piperazines are capable of disrupting a person's ability to think, communicate, and act sensibly. As with other mind-altering substances, use of BZP or TFMPP may jeopardize work or school performance, ruin relationships, and increase the likelihood of involvements in accidents. Loss of control or inappropriate behavior may cause other people to view the user with suspicion. Addiction can lead the user to abandon educational goals and engage in criminal activity.

The Law

In the United States, the Controlled Substances Act (CSA) of 1970 called for the assignment of all controlled drug substances into one of five categories called schedules. These schedules are based on a substance's medicinal value, possible harmfulness, and potential for abuse and addiction. Schedule I is reserved for the most dangerous drugs that have no recognized medical use.

In 2003, Drug Topics reported that the DEA was working to have both BZP and TFMPP added to the list of Schedule I drugs under the CSA. The reasoning behind these actions was that the drugs "have hallucinogenic or amphetamine-like activity and have been abused by individuals who have bought them through Internet companies." Until they were scheduled, BZP and TFMPP could be purchased legally from chemical supply houses. However, they were not intended for human consumption. Buyers got around this specification by lying about the intended use of the drug.

On March 18, 2004, the DEA officially classified BZP as a Schedule I drug, so its use in the United States is now regulated by federal law. Any person convicted of possessing and/or selling a Schedule I drug can face a lengthy prison term and hundreds of thousands of dollars in fines. Repeat offenders receive even harsher punishment.

For More Information

Periodicals

Bleakley, Louise. "Party Pill Labelling Frustrates." New Zealand Press (December 28, 2004).

De Boer, D., and others. "Piperazine-Like Compounds: A New Group of Designer Drugs-of-Abuse on the European Market." Forensic Science International (September, 2001): pp. 47-56.

"Doctors Warn of Dangers of 'Herbal High' Pills." New Zealand Press (November 15, 2004).

Fantegrossi, W. E., and others. "Reinforcing and Discriminative Stimulus Effects of 1-Benzylpiperazine and Trifluoro methyl-phenylpiperazine in Rhesus Monkeys." Drug and Alcohol Dependence (February 14, 2005): pp. 161-168.

"Three Substances Shift to Schedule I." Drug Topics (August 5, 2002): p. 12.

"Warning over Herbal Highs." Ashburton Guardian (February 4, 2005).

"What's Being Added to, Dropped from CS List." Drug Topics (October 6, 2003): p. 7.

Web Sites

"BZP and TFMPP: Chemicals Used to Mimic MDMA's Effects. Drug Intelligence Brief, December 2001." U.S. Department of Justice, Drug Enforcement Administration, Intelligence Division. http://www.usdoj.gov/dea/pubs/intel/02005/02005.pdf (accessed June 30, 2005).

"Drugs and Chemicals of Concern: N-Benzylpiperazine." U.S. Department of Justice, Drug Enforcement Administration: Diversion Control Program.http://www.deadiversion.usdoj.gov/drugs_concern/ (accessed June 30, 2005).

"Manufacture and Distribution of Unapproved Piperazine Products." U.S. Food and Drug Administration, Center for Veterinary Medicine. (Guideline No. 102). http://www.fda.gov/cvm/guidance/pipera.html (accessed June 30, 2005).

Pendleton, Robert. "BZP (1 Benzylpiperazine): Frequently Asked Questions." The Lycaeum Drug Archives.http://www.lycaeum.org/ (accessed June 30, 2005).

"Piperazine (Systemic)." Healthtouch Online.http://www.healthtouch.com/ (accessed June 30, 2005).

"Piperazine Citrate." Nurses PDR.http://www.nursespdr.com/ (accessed June 30, 2005).

"Proposed Maximum Exposure Limit for Piperazine and Piperazine Dihydrochloride." Health & Safety Executive Regulatory Impact Assessment.http://www.hse.gov.uk/ria/chemical/piperaz.htm (accessed June 30, 2005).

See also: Amphetamines; Designer Drugs; Ecstasy (MDMA)