The use of piperazine derivatives, colloquially named ‘party pills’, has been escalating in New Zealand and worldwide since their introduction in the 1990s. Benzylpiperazine (BZP) is often used alone, or can be combined with trifluoromethylphenylpiperazine (TFMPP). Taken together as an oral dose, they have been reported to produce effects similar to 3, 4-methylenedioxymethamphetamine (MDMA). While the pharmacokinetic data have recently been published, little research has been conducted on the subjective effects of these piperazines on humans. This paper outlines the subjective effects observed following oral doses of BZP (200 mg) and TFMPP (60 mg) alone, or in combination (100/30 mg) compared to placebo.
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. Use of BZP was first reported in the United States and Switzerland in 2000. Drug Enforcement Administration (DEA), seizure of BZP and TFMPP tablets, capsules, and powders increased steadily through 2004. In 1999, drug researchers in Japan found that a particular form of benzylpiperazine stimulates a brain chemical called acetylcholine.
About BZP/piperazines
- BZP appears to be metabolised by cytochrome P450 (possibly involving the CYP2D6 iso-enzyme) and catechol-O-methyl-transferase (COMT).
- The pills may be white, off-white, tan, or bright shades of green, orange, pink, purple, or yellow.
- How long the effects last and the drug stays in your system depends on how much you’ve taken, your size and what other drugs you may have also taken.
- The DPIC was consulted about 35 NPS exposures in 2013, most frequently involving 4-FA, mephed…
- 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.
- BZP is banned in several countries, including the USA, Republic of Ireland, Australia and New Zealand, but is available on a more or less restricted basis in many jurisdictions.
Although piperazine itself is used as an anthelminthic drug, neither BZP nor any other piperazine derivative is licensed for this purpose. As an agonist at the 5HT2C receptor, and an antagonist at the 5HT2B receptor, mCPP has been widely used as a probe of serotonin function in psychiatric research. An industrial use of mCPP is as an intermediate in the production of trazodone and three related substances.Trazodone is licensed in a number of Member States for the treatment of depression and other disorders. The substance 1-(3-chlorophenyl)-4-(3-chloropropyl)-piperazine (mCPCPP) is a precursor used in the manufacture of antidepressant drug nefazodone. BZP was created by Burroughs Wellcome as a potential antidepressant drug, but was never developed commercially because it produced similar effects to d-amphetamine, although the relative potency was only 10 %.
MeSH Terms
BZP is illegal in many countries including the United States of America and Australia, yet it remains legal in the United Kingdom, Canada and New Zealand. There has been little research, to date, on the neurological consequences of high dose or chronic exposure of BZP. Here we provide a comprehensive review of the information currently available on BZP and suggest a need for further research into the mechanisms of action, long-term effects and potentially addictive properties of BZP. 1-Benzylpiperazine (BZP; see Molecular structure 1) is one of a small group of benzyl-substituted piperazines, but a much larger group comprises the phenylpiperazines (see Tables 1 and 2). Despite claims by some tablet and capsule suppliers that they are herbal products, piperazine and its derivatives are synthetic substances that do not occur naturally. The large-scale misuse of certain piperazine derivatives (often known as ‘party pills’) started in New Zealand several years ago, but became common in Europe only after 2004.
Legal Status
Whilst it has been linked to a number of fatalities in association with BZP, there are no documented cases of it being toxic in its own right 1.
Addictive Effects
The “mystery ingredients” that are mixed in with it may add to that risk. Mixing drugs is always risky but some mixtures are more dangerous than others. How long the effects last and the drug stays in your system depends on how much you’ve taken, your size and what other drugs you may have also taken. The best known piperazines are BZP (benzylpiperazine), TFMPP, DBZP and mCPP. MCPP, was developed during the late 1970s and is used as an intermediate in the manufacture of several antidepressants, e.g. trazodone and nefazodone 5. TFMPP is almost always seen in combination with BZP to produce the entactogenic 6 effects of MDMA 7.
Medical Use
(2003), ‘Central Serotonergic Effects of m-Chlorophenylpiperazine (mCPP) among Normal Control Adolescents’, Neuropsychopharmacology, Volume 28, pp. 133–139. (2008), ‘Investigation of the first deaths in the United Kingdom involving the detection and quantitation of the piperazines BZP and 3-TFMPP, Journal of Analytical Toxicology, Volume 32, No 2, pp. 172–177. (1999), ‘The forensic examination of benzylpiperazine and phenylpiperazine homologs’, Presented at the 9th Annual Clandestine Laboratory Investigating Chemists Association (CLIC) Technical Training Seminar, Toronto, Ontario, Canada, 8–11 September, 1999. This repository is under review for potential modification in compliance with Administration directives.
The drug acts by paralyzing the muscles of mature worms and dislodging them from the walls of the intestines. TFMPP is controlled in Texas under Penalty Group 2, as a hallucinogenic substance. Since 2012, TFMPP has been listed as a Schedule III controlled substance in Canada,18 making possession of TFMPP a federal offence.
Following oral administration of mCPP to healthy human male volunteers, the elimination half-life ranges from 2.6 to 6.1 hours with a wide variation in peak blood levels and bioavailability. The hydroxy metabolites are partly excreted as the corresponding glucuronides and/or sulphates, and the chloroanilines are partly excreted as the acetylated derivatives. Physiological and subjective effects reach their peak 1 to 2 hours after oral administration and can last 4 to 8 hours. The negative effects of mCPP, often typical of a serotonin syndrome, include anxiety, dizziness, confusion, shivering, sensitivity to light and noise, fear of losing control, migraine and panic attacks. The subjective effects of mCPP and MDMA are somewhat comparable, but unlike MDMA and BZP, mCPP has little effect on the dopaminergic system. Piperazines have been found to act as stimulants as a result of dopaminergic, noradrenergic, and predominantly serotoninergic effects produced in the brain.
Following a risk assessment in 2007, a Council Decision of 2008 introduced controls on BZP in the European Union. There are several routes to the synthesis of mCPP, the most common of which is the reaction of diethanolamine with m-chloroaniline. Other methods involve the reaction of m-chloroaniline with bis(2-chloroethyl)amine or the reaction of piperazine with m-dichlorobenzene. The other two isomers of CPP could be made in a similar way.It is unlikely that the mCPP found in illicit products has been synthesised in clandestine laboratories since it is available commercially as the base or as the hydrochloride salt.
Other Products Of Interest:
These are reported substrates of CYP2D6, CYP1A2, and CYP3A4 respectively. Greater enzyme inhibition was observed in TFMPP microsomal assays in comparison to those using BZP. The metabolism of omeprazole was not affected, suggesting that BZP and TFMPP do not have a signif… Aims Decisions on whether and how to ‘schedule’ drugs (i.e. to determine their legal status and penalties to be applied for sale or possession) are often heavily criticized. We sought to assess more comprehensively the results of such decisions for newly emerging drugs.
Benzylpiperazine
Usually, piperazines are made into detergents or medicines. Matt Bowden, one of the original distributors of such pills4 was interviewed when issues involving party pills arose in the media. A clinical trial by ClubStargate for a pill named Ease was suspended because it contained methylone, which was claimed by the Ministry of Health to fall under New Zealand controlled drug analogue laws (although this was never proven in court).
If you or someone else needs urgent help after taking drugs or drinking, call 999 for an ambulance. Like drink-driving, driving when high is dangerous and illegal. If you’re caught driving under the influence, you may receive a heavy fine, driving ban, or prison sentence.
BZP showed significant dexamphetamine-like stimulant effects, inducing euphoria, sociability, and drug liking, whereas TFMPP induced fewer stimulant-like effects and increased anxiety, via its serotonergic effects. The combination of BZP and TFMPP induced similar subjective effects, along with well-characterized dexamphetamine- and MDMA-like effects. These subjective data allow for obvious comparisons to be made between party pill drugs and other commonly known stimulants. However, despite estimates of over 20 million doses sold in New Zealand alone and increasing seizures by the Drug Enforcement Administration in the USA, there are no published cases of dependence worldwide. The long-term effects of regular party pill use are also unknown, and create the potential for future research. The combination of BZP and TFMPP induced similar subjective effects, along with well-characterized dexamphetamineand MDMA-like effects.
In the late 1990s, BZP emerged in New Zealand as a ‘legal alternative’ for MDMA and methamphetamine 3. In Europe, its use was first reported in Sweden in 1999, but it only became widespread as a NPS from 2004 onwards until controls over the substance were introduced in 2008, in the European Union 4. Amphetamines are illegal without a prescription from a medical doctor. 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. 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.
Other frequently cited 849 drug combinations included cocaine and marijuana, ecstasy and marijuana, LSD and marijuana, and cocaine and alcohol. These data highlight the need to develop drug health-education and prevention messages targeted at polydrug usage. There is emerging evidence of increasing use of legally available synthetic compounds as recreational drugs. In addition, there are very few “user reports” of effects when TFMPP is taken alone or in combination with BZP 1-benzylpiperazine. Three patients presented to our emergency department after ingesting 4 tablets thought to be 3,4-methylenedioxy-N-methylamphetamine (MDMA, street name “Ecstasy”) over the course of an even… BZP is banned in several countries, including the USA, Republic of Ireland, Australia and New Zealand, but is available on a more or less restricted basis in many jurisdictions.
Many participants had reduced the frequency with which they used BZP-party pills due to adverse effects. Potentially risky behaviours identified included taking large doses, mixing BZP-party pills with alcohol and other substances, and driving whilst under the influence of BZP-party pills. Conclusion Findings suggest that young people in this study were not suffering excessive or dangerous adverse effects. However, potentially risky use of these products raises the issue of the need for developing harm reduction interventions. Over the last decade, New Zealand has led the world in the legal sale and uncontrolled use of the recreational drug benzylpiperazine (BZP), the active ingredient of ‘party pills’.
A range of other piperazine derivatives have also been sold as ingredients in party pills, and many of these branded “proprietary blends” have subsequently been sold in countries around the world. Health care providers are seeing an increased number of patients under the influence of several new psychoactive drug classes. Synthetic cannabinoids, cathinones, and piperazines are sought by users for their psychoactive effects, perceived safety profile, minimal legal regulations, and lack of detection on routine urine drug screening. However, these drugs are beginning to be recognized by the medical community for their toxic effects. The neuropsychiatric and cardiovascular toxicities are among the most common reasons for emergency medical treatment, which in some cases, can be severe and even life-threatening. Management strategies are often limited to supportive and symptomatic care due to the limited published data on alternative treatment approaches.
