Benzylpiperazine 1257861 223888096 2008-07-06T10:17:45Z Dan88888 4344075 /* Legal issues */ {{Drugbox| |IUPAC_name = 1-benzylpiperazine | image = Benzylpiperazine.svg | image2= BZP3d.png | CAS_number= 2759-28-6 | ATC_prefix= | ATC_suffix= | PubChem= 75994 | smiles = C1=C(C=CC=C1)CN2CCNCC2 | DrugBank= | C=11 | H=16 | N=2 | molecular_weight = 176.258 g/mol | bioavailability= | metabolism = hepatic | elimination_half-life= | excretion = renal | pregnancy_category = | legal_status = [[Drug Enforcement Administration|DEA]] Schedule 1 drug; legal in some countries | routes_of_administration= oral, intravenous, insufflation }} '''Benzylpiperazine''' (with trade names such as "A2", "Frenzy" and "Nemesis",<ref name="BLTC">{{cite web | title = Clubbers snap up new legal high | url= http://www.guardian.co.uk/society/2005/dec/13/drugsandalcohol.drugs | publisher = The Guardian | author= David McCandless | date= 2005-12-13 | accessdate = 2008-05-26}}</ref> commonly referred to as '''BZP''') is a [[recreational drug]] with [[Euphoria (emotion)|euphoric]], [[stimulant]] properties. Its dopamine and serotonin agonist [[mechanism of action]] is believed to be similar to [[MDMA]] and the effects produced by BZP are comparable to those produced by [[amphetamine]]. Adverse effects have been reported following its use including [[psychosis|acute psychosis]], [[renal]] toxicity, and [[seizures]]. It does not appear to be very addictive and no deaths have been reported following a sole ingestion of BZP, although there have been at least two deaths from the combination of BZP and MDMA. Its sale is banned in a few countries, including the [[United States]], [[Australia]], [[New Zealand]] and in parts of [[Europe]].<ref>{{cite web | title =Legal dance drug faces ban amid fears over side-effects | author= Alexandra Topping|publisher = The Guardian | date = 2007-06-18 | url =http://www.guardian.co.uk/drugs/Story/0,,2105482,00.html | format = | doi = | accessdate = 2008-05-26}}</ref> However, its [[legal status]] is currently less restrictive in some other countries such as [[Ireland]] and [[Canada]], although investigations and regulations are pending under [[European Union]] laws. ==History== ===Development history=== It is often claimed that BZP was originally synthesized as a potential [[antihelminthic]] (anti-parasitic) agent for use in farm animals.<ref>{{cite web | last = | first = | title = Lay off the party pills | publisher = New Zealand Medical Association | date = 2006-11-01 | url =http://www.scoop.co.nz/stories/GE0611/S00001.htm | accessdate = 2007-04-22 }}</ref> However, there are some references to BZP in medical literature that predate interest in [[piperazine]]s as anthelmintics. Even so, the majority of the early work with the piperazines were investigations into their potential use as anthelmintics with the earliest [[clinical trial]]s in the literature relating to piperazine being articles in the ''[[British Medical Journal]]'' in the 1950s.<ref>{{cite journal |author=White R, Standen O |title=Piperazine in the treatment of threadworms in children; report on a clinical trial |journal=British Medical Journal |volume=2 |issue=4839 |pages=755–7 |year=1953 | url =http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=13082101 |pmid=13082101}}</ref><ref>{{cite journal |author=Standen O |title=Activity of piperazine, ''in vitro'', against Ascaris lumbricoides |journal=British Medical Journal |volume=2 |issue=4930 |pages=20–2 |year=1955 | url =http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14378628 |pmid=14378628}}</ref> It was discovered that BZP had [[Adverse drug reaction|side effect]]s and was largely abandoned as a worm treatment. It next appears in the literature in the 1970s when it was investigated as a potential [[antidepressant]] medication, but rejected when research reported that BZP had amphetamine-like effects and was liable to abuse. The study suggested that BZP “should be placed under statutory control similar to those regulating the use of amphetamine.”<ref>{{cite journal |author=Campbell H, Cline W, Evans M, Lloyd J, Peck A |title=Comparison of the effects of dexamphetamine and 1-benzylpiperazine in former addicts |journal=Eur J Clin Pharmacol |volume=6 |issue=3 |pages=170–6 |year=1973 |pmid=4586849 |doi=10.1007/BF00558281}}</ref> ===Recreational history=== In the [[1990s|early 1990s]], the United States [[Drug Enforcement Administration]] noted the drug was being used recreationally in [[California]]. It also reported that BZP was being used as an [[adulterant]] in [[Illegal drug trade|illicit drugs]]. Not long after, there was an explosion in the drug's use worldwide &mdash; a situation which was soon followed by legislative control in many countries. Since 1999, benzylpiperazine use grew sharply in New Zealand, where there was initially a complete lack of regulation. The New Zealand government attempted to ban the product as of December 18, 2007, but the necessary second reading of the bill did not happen in time for the law to be passed.<ref name="Misuse-2005">{{cite web | title =Misuse of Drugs Amendment Act 2005. | work = | publisher = New Zealand Government | date = 2005-06-17 | url =http://www.stanz.org.nz/images/ASSENT81.PDF| format = [[PDF]] | doi = | accessdate = 2007-04-22 }}</ref><ref name="Bay of Plenty Times"> {{cite web | author= Michele McPherson | title = Party Pill Ban Delayed | url = http://www.bayofplentytimes.co.nz/localnews/storydisplay.cfm?storyid=3758134 | publisher = Bay of Plenty Times | date = 2007-12-12| accessdate = 2007-12-31}}</ref> It was so widely used that an estimated 5 million pills were sold in New Zealand in 2007.<ref name="Gee-2007">{{cite journal |author=Gee P, Fountain J |title=Party on? BZP party pills in New Zealand |journal=[[The New Zealand Medical Journal|N Z Med J]] |volume=120 |issue=1249 |pages=U2422 |year=2007 | url =http://www.nzma.org.nz/journal/120-1249/2422/content.pdf |pmid=17308559}}</ref> Piperazine based stimulants began to appear in Europe in 2000<ref>{{cite journal |author=de Boer D, Bosman I, Hidvégi E, Manzoni C, Benkö A, dos Reys L, Maes R |title=Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market |journal=Forensic Sci Int |volume=121 |issue=1-2 |pages=47–56 |year=2001 |pmid=11516887 |doi=10.1016/S0379-0738(01)00452-2}}</ref> but remained virtually unavailable in the rest of the world until recently. In early 2006, pills containing the active ingredients BZP and [[TFMPP]] first began to appear in the city of [[Vancouver]], Canada, where they were used by late night party-goers as a supposedly safer alternative to the illicit street drugs available there. In the United States, it is still used as an adulterant in ecstasy mimic tablets. ==Production and distribution== [[Image:bzp brands.jpg|thumb|left|200px|A selection of products containing BZP.]] BZP is a piperazine derivative which comes as either the hydrochloride salt or a [[Freebase (chemistry)|free base]]. The hydrochloride salt is a white solid while the base form is a slightly yellowish-green liquid. BZP base is corrosive and causes burns.<ref name="DEA-2006">{{cite web | title =Drugs and Chemicals of Concern: N-Benzylpiperazine | work = | publisher = US DEA | date = June 2006 | url =http://www.deadiversion.usdoj.gov/drugs_concern/bzp_tmp/bzp_tmp.htm | format = | doi = | accessdate = 2007-04-22 }}</ref> In countries where its purchase is legal, BZP products are often produced in small specialist laboratories. The raw materials can be purchased from various chemical supply agencies and formed into tablets or capsules using relatively cheap production techniques. The resulting product can be marketed at extremely high [[markup (business)|markup]], so end-user prices can be as high as 300 times the bulk cost of raw ingredients. BZP is often marketed ostensibly as a "dietary supplement" to avoid meeting stricter laws that apply to medicines and drugs, despite the fact that BZP has no dietary value. As of late 2005, the Misuse of Drugs Act ensured it can no longer be classified or marketed as a [[dietary supplement]] in New Zealand.<ref name="Misuse-2005"/> Some retailers claim that BZP is a "natural" product, describing it as a "pepper extract" or "herbal high," when in fact the drug is entirely [[chemical synthesis|synthetic]],<ref name="Gee-2007"/> and has not been found to occur naturally.<ref name=" Alansari-2006">{{cite journal |author=Alansari M, Hamilton D |title=Nephrotoxicity of BZP-based herbal party pills: a New Zealand case report |journal=[[The New Zealand Medical Journal|N Z Med J]] |volume=119 |issue=1233 |pages=U1959 |year=2006 |pmid=16680176}}</ref> ==Pharmacodynamics== BZP has been shown to have a mixed mechanism of action, acting on the [[serotonin|serotonergic]] and [[dopamine]]rgic receptor systems in a similar fashion to [[MDMA]].<ref name="Baumann">{{cite journal |author=Baumann M, Clark R, Budzynski A, Partilla J, Blough B, Rothman R |title=Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain |journal=Ann N Y Acad Sci |volume=1025 |issue= |pages=189–97 |year= 2004|pmid=15542717 |doi=10.1196/annals.1316.024}}</ref> BZP has amphetamine-like actions on the [[monoamine transporter|serotonin reuptake transporter]], which increase serotonin concentrations in the [[extracellular fluid]]s surrounding the [[Cell (biology)|cell]] and thereby increasing activation of the surrounding serotonin receptors.<ref name="Tekes">{{cite journal |author=Tekes K, Tóthfalusi L, Malomvölgyi B, Hermán F, Magyar K |title=Studies on the biochemical mode of action of EGYT-475, a new antidepressant |journal=Pol J Pharmacol Pharm |volume=39 |issue=2 |pages=203–11 |year= |pmid=2448760}}</ref><ref>{{cite journal |author=Lyon R, Titeler M, McKenney J, Magee P, Glennon R |title=Synthesis and evaluation of phenyl- and benzylpiperazines as potential serotonergic agents |journal=J Med Chem |volume=29 |issue=5 |pages=630–4 |year=1986 |pmid=3701781 |doi=10.1021/jm00155a008}}</ref> BZP has a lower potency effect on the [[monoamine transporter|noradrenaline reuptake transporter]] and the [[monoamine transporter|dopamine reuptake transporter]].<ref name="Baumann"/> BZP has a high affinity action at the [[Adrenoceptor|alpha2-adrenoreceptor]], it is an antagonist at the receptor, like [[yohimbine]], which inhibits negative feedback, causing an increase in released [[noradrenaline]].<ref name=" BilZ0r">{{cite web | last = | first = BilZ0r | title =Neuropharmacology of BZP | publisher = Erowid.org | date = November 2003 | url =http://www.erowid.org/chemicals/bzp/bzp_article1.shtml | accessdate = 2007-04-22 }}</ref> BZP also acts as a non-selective [[serotonin receptor]] [[agonist]] on a wide variety of serotonin receptors;<ref name="Tekes"/> binding to 5HT<sub>2A</sub> receptors may explain its mild hallucinogenic effects at high doses, while partial agonist or antagonist effects at the 5HT<sub>2B</sub> receptors may explain some of BZPs peripheral side effects, as this receptor is expressed very densely in the gut, and binding to 5HT<sub>3</sub> receptors may explain the common side effect of headaches, as this receptor is known to be involved in the development of [[migraine]] headaches. There is still much that is not known about the pharmacokinetics of benzylpiperazine. Its metabolism is mainly through the enzymes [[CYP2D6]] and [[COMT]].<ref name="Gee-2007" /> ==Effects== [[Image:eye bzp.jpg|thumb|right|Typical pupil dilation]] The effects of BZP are largely similar to [[amphetamine]]s,<ref>{{cite journal |author=Fantegrossi W, Winger G, Woods J, Woolverton W, Coop A |title=Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys |journal=Drug Alcohol Depend |volume=77 |issue=2 |pages=161–8 |year=2005 |pmid=15664717 |doi=10.1016/j.drugalcdep.2004.07.014}}</ref> with one study finding that former amphetamine addicts were unable to distinguish between [[dextroamphetamine]] and BZP administered intravenously.<ref>{{cite journal |author=Campbell H, Cline W, Evans M, Lloyd J, Peck A |title=Comparison of the effects of dexamphetamine and 1-benzylpiperazine in former addicts |journal=Eur J Clin Pharmacol |volume=6 |issue=3 |pages=170–6 |year=1973 |pmid=4586849 |doi=10.1007/BF00558281}}</ref> Users report alertness, euphoria and a general feeling of well being. The perception of certain sensations such as taste, colour or music may be subjectively enhanced. The average duration is longer than that of dextroamphetamine, typically lasting 4-6 hours with reports as long as 8 hours depending on the dose.<ref name="Drug-Forum">{{cite web | title =BZP Experiences | author= |publisher = drugs-forum.co.uk | date = 2007-07-08 | url =http://www.drugs-forum.co.uk/forum/showthread.php?t=34969|Drug | format = | doi = | accessdate = 2008-05-26}}</ref> A recent study has shown that mixtures of BZP with other piperazine drugs such as [[Trifluoromethylphenylpiperazine|TFMPP]] share certain [[pharmacodynamic]] traits with [[MDMA]].<ref name="Baumann">{{cite journal |author=Baumann M, Clark R, Budzynski A, Partilla J, Blough B, Rothman R |title=N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') |journal=Neuropsychopharmacology |volume=30 |issue=3 |pages=550–60 |year=2005 |pmid=15496938 |doi=10.1038/sj.npp.1300585}}</ref> ===Subjective effects=== Upon ingestion of between 50 mg and 200 mg of BZP, the user may experience any or all of the following: Coming up:<ref name="Drug-Forum"/><ref name="Nicholson-2006"/><ref>{{cite web | title =Erowid experience vault: Lazer Light Loving BZP & TFMPP | author= |publisher = Erowid | date = 2004-10-28 | url =http://www.erowid.org/experiences/exp.php?ID=23485| format = | doi = | accessdate = 2008-05-26}}</ref> * Actual and perceived changes in [[Thermoregulation|body temperature]] * Slight [[nausea]] * [[Flushing (physiology)|Flushing]] * Mild [[xerostomia]] (dry mouth) * Rapid mood elevation * Mild jaw clenching/[[bruxism]] * Increased heart rate * Enhanced sociability * Repetitive thought patterns * [[Dilation]] of [[pupil]]s (see photo) * Decreased [[appetite]] * Slight [[urinary incontinence]], often described as "leaking" a small amount of [[urine]] after [[urinating]] (not due to loss of [[urinary bladder|bladder]] control) * "Rushing" sensation<ref name="Drug-Forum">"It gives a rushing sensation and makes one easily distracted. Sociability is good. The drug lower the inhibitions somewhat."</ref> * Enhanced appreciation of music * Skin tingling * Feelings of [[Euphoria (emotion)|euphoria]], wonder, amazement, well-being, energy and elation * Increased desire to move, also slight increase in [[stereotypy]] Coming down:<ref name="Nicholson-2006">{{cite journal |author=Nicholson T |title=Prevalence of use, epidemiology and toxicity of 'herbal party pills' among those presenting to the emergency department |journal=Emergency medicine Australasia : EMA |volume=18 |issue=2 |pages=180–4 |year=2006 |pmid=16669944 |doi=10.1111/j.1742-6723.2006.00826.x}}</ref> * Mild [[headache]] * Nausea * [[Hangover]]-like symptoms (common with high doses) * [[Fatigue (physical)|Fatigue]] * Increased hunger (and sometimes thirst) * [[Insomnia]] * [[Confusion]] * [[Anorexia (symptom)|Loss of appetite]] ===Tolerance=== Research into BZP's tolerance is sparse. [[Anecdotal evidence]] from online sources claim tolerance to the central action of BZP will develop quickly.<ref name=" BilZ0r"/> Due to tiredness associated with the body's recovery from stimulants, such as BZP, it is uncommon for users to be able to sustain a week-long intake. ===Toxic effects=== [[Image:Bzptablet.jpg|right|thumb|An 'ecstasy' tablet - seized by law enforecement in the United States - containing BZP, [[methamphetamine]], and [[caffeine]]]] As with most [[sympathomimetic]] [[stimulant]]s there appear to be significant side effects associated with BZP use. BZP reportedly produces insomnia and a mild to severe [[hangover]] after the drug effect wears off,<ref name="Nicholson-2006"/> however, some manufacturers in New Zealand have started including recovery pills which contain [[5-Hydroxytryptophan|5-HTP]] and vitamins which allegedly ease these hangovers. The major side effects include dilated pupils, blurred vision, dryness of the mouth, extreme alertness, [[pruritus]], [[confusion]], [[agitation]], tremor, extrapyramidal symptoms ([[dystonia]], [[akathisia]]), [[headache]], [[dizziness]], anxiety, [[insomnia]], [[vomiting]], [[chest pain]], [[hallucination]]s, [[paresthesia]], [[tachycardia]], [[hypertension]], [[palpitation]]s, collapse, [[hyperventilation]], sweating, [[hyperthermia]], and problems with [[urine retention]].<ref name="Nicholson-2006"/><ref name="Harnett">{{cite journal |author=Harnett MA |title=Piperazine-Based Party Drugs: Case Series of 73 Poisonings [abstract] |journal=[[Clinical Toxicology|Clin Toxicol (Phila). ]] |volume=45 |issue=4 |pages=373 |year=2007|doi=10.1080/15563650701284894}}</ref><ref name="Gee-2005">{{cite journal |author=Gee P, Richardson S, Woltersdorf W, Moore G |title=Toxic effects of BZP-based herbal party pills in humans: a prospective study in Christchurch, New Zealand |journal=[[The New Zealand Medical Journal|N Z Med J]] |volume=118 |issue=1227 |pages=U1784 |year=2005 | url=http://www.nzma.org.nz/journal/118-1227/1784/content.pdf |pmid=16372033}}</ref><ref name="Theron-2007">{{cite journal |author=Theron L, Jansen K, Miles J |title=Benzylpiperizine-based party pills' impact on the Auckland City Hospital Emergency Department Overdose Database (2002-2004) compared with ecstasy (MDMA or methylene dioxymethamphetamine), gamma hydroxybutyrate (GHB), amphetamines, cocaine, and alcohol |journal=[[The New Zealand Medical Journal|N Z Med J]] |volume=120 |issue=1249 |pages=U2416 |year=2007| url=http://www.nzma.org.nz/journal/120-1249/2416/content.pdf |pmid=17308553}}</ref> The more severe toxic effects include psychosis,<ref>{{cite journal |author=Austin H, Monasterio E |title=Acute psychosis following ingestion of 'Rapture' |journal=Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists |volume=12 |issue=4 |pages=406–8 |year=2004 |pmid=15715818}}</ref> renal toxicity,<ref name=" Alansari-2006"/> [[respiratory failure]],<ref name="Harnett"/> and [[seizure]].<ref name="Nicholson-2006"/><ref name="Gee-2005"/> ====Christchurch study==== The majority of the toxic effects information came from a study conducted between 1 April 2005 to 1 September 2005. The study recorded all presentations associated with party pill use at the [[Emergency Department]] of [[Christchurch]] Hospital, New Zealand by recording them on a prospective data collection form. The aim was to study the patterns of human toxicity related to the use of benzylpiperazine-based 'party pills'. 61 patients presented on 80 occasions. Patients with mild to moderate toxicity experienced symptoms such as insomnia, anxiety, nausea, vomiting, palpitations, dystonia, and urinary retention. Significantly, fourteen toxic [[seizures]] were recorded with two patients suffering life-threatening [[toxicity]] with [[status epilepticus]] and severe respiratory and [[metabolic acidosis]]. It was concluded that BZP appears to induce toxic seizures in neurologically normal subjects.<ref name="Gee-2005"/> The results of this study and others like it<ref name="Nicholson-2006"/><ref name="Theron-2007"/> showed that BZP can cause unpredictable and serious toxicity in some individuals, but the data and dosage collection were reliant on self reporting by drug users, which may result in under-reporting, and there were complicating factors like the frequent presence of alcohol and other drugs.<ref name="Theron-2007"/> ====Aborted Medical Research Institute of New Zealand Study==== In 2007 STANZ commissioned an independent report into the MRINZ Study on BZP which was aborted and widely reported on by the media as "proof" of BZP harm, and relied on by the Expert Advisory Committee on Drugs (EACD) when they recommended to reclassify BZP to a class C restricted substance. This independent report on the study found major biases in the study including:<ref>{{cite web | title =Report on the proposal to reclassify BZP | work = | author= Dawson M, Wodak A |publisher = AccessUTS | date = | url =http://www.savethepills.com/MRINZreview.pdf | format = | doi = | accessdate = 2008-05-26}}</ref> *That the term “seizures” was used “to refer to anything from a small twitch to a grand seizure” and that this was “too broad”. Further, there was a failure in some studies to explain if the seizures were due to withdrawal effects. *That the MRINZ study was designed to look at driving performance “under an intoxicating dose of BZP with or without alcohol” rather than at the side effects of BZP and that the results should be used to inform the study’s primary aim. *That the side effects in the MRINZ study were “were most likely heightened as participants endured at least six hours of fasting and the substance was taken when it is not normally taken”. The Committee noted this might explain the discrepancy between the subjects’ experience in the study and their prior experience with BZP. *That one Committee member expressed the view that the Committee may have placed “too much emphasis” on the MRINZ study, in part because the aborting of the trial “may have created an emotional overtone that influenced the Committee’s decision”. <!-- there was an additional bullet point here about a sample size of 16; this has been removed because it did not refer to the SHORE study; the SHORE study was NZ-wide and had +2000 respondents --> ===Attributed deaths=== According to party pill manufacturer Matt Bowden, over 20 million pills containing BZP have been consumed in New Zealand with no available record attributing deaths or lasting injuries to a single ingestion of BZP.<ref>{{cite web | last = Bowden | first =Matt | authorlink = | coauthors = | title =Call for BZP ban misses the point | work = | publisher = STANZ | date = 2005-11-02 | url =http://www.stanz.org.nz/Call%20for%20BZP%20ban%20misses%20the%20point.pdf | format = | doi = | accessdate = 2008-03-03}}</ref> Additionally, a retrospective study carried out at an [[Auckland]] emergency department found that BZP presentations only made a minor contribution to their overdose database with most cases not producing any significant toxicity.<ref name="Theron-2007"/> Several cases where BZP individually or combined with alcohol or other medicines or illicit drugs resulting in complications exist. One such example is the well publicised case of a combination of BZP and [[MDMA]] by a 23 year old from [[Greymouth|Greymouth, New Zealand]]. Ben Rodham, a DJ, ingested a combination of BZP and MDMA in February 2007, which nearly resulted in his death. Rodham was put into an [[induced coma]] in an effort to prevent him from dying. He later recovered.<ref>{{cite web | title =Party On? | work = | publisher = TV3 New Zealand | date = 2007-04-09 | url =http://www.tv3.co.nz/Programmes/NewsandCurrentAffairs/60Minutes/tabid/88/ArticleID/24491/Default.aspx | format = | doi = | accessdate = 2007-04-14 }}</ref> After many millions of doses consumed worldwide, two deaths have been officially recorded in correlation with the use of BZP, although no causal relationship has been proven.<ref name="Balmelli">{{cite journal |author=Balmelli C, Kupferschmidt H, Rentsch K, Schneemann M |title= Fatal brain edema after ingestion of ecstasy and benzylpiperazine |journal=Dtsch Med Wochenschr |volume=126 |issue=28-29 |pages=809–11 |year=2001 |pmid=11499262 |doi=10.1055/s-2001-15702}} 11.</ref><ref name="Carter">{{cite web | last = Carter | first = Bridget | title =Coroner probes party pill link in New Year death | publisher = New Zealand Herald | date = 2007-01-07 | url =http://www.nzherald.co.nz/section/1/story.cfm?c_id=1&objectid=10418032 | accessdate = 2007-04-22 }}</ref> In the first case in [[Zurich]] in 2001 a 23-year-old took two BZP tablets as well as ecstasy ([[MDMA]]) and drank more than 10 litres of water in a 15-hour period, subsequently dying of [[cerebral edema]] due to [[hyponatremia]] resulting from [[water intoxication]].<ref name="Balmelli"/> In the second case a 25 year old male ingested a large quantity of alcohol alongside BZP and MDMA.<ref name="Carter"/> The cause of death of this individual has not been released. It is uncertain what role the BZP may have had in these deaths; death from hyponatremia is a well known consequence of drinking too much fluid after consuming MDMA,<ref name="Gee-2005"/><ref>{{cite journal |author=Hall A, Henry J |title=Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management |journal=Br J Anaesth |volume=96 |issue=6 |pages=678–85 |year=2006 |pmid=16595612 |doi=10.1093/bja/ael078}}</ref> it is likely that the additional hyponatremic effects from the BZP may have increased the hyponatremic effects from the MDMA, to the point that death resulted. ===Addictive effects=== One in every 45 (2.2%) last-year users of BZP in New Zealand is classed as dependent upon it, although 97.9% of users said that "it would not be difficult to stop using legal party pills", and 45.2% of people who reported using both BZP and illegal drugs such as [[methamphetamine]] reported that they used BZP so that they did not have to use methamphetamine, which was perceived as more harmful.<ref name="Wilkins">{{cite web | author=Wilkins C, Girling M, Sweetsur P, Huckle T, Huakau J | title =Legal party pill use in New Zealand: Prevalence of use, availability, health harms and ‘gateway effects’ of benzylpiperazine (BZP) and triflourophenylmethylpiperazine (TFMPP) | publisher = Centre for Social and Health Outcomes Research and Evaluation (SHORE) | url =http://www.spiritualhigh.co.uk/spiritualhigh.co.uk/downloads/Legal-party-pills-in-New-Zealand-report.pdf | format = [[PDF]] | accessdate = 2007-04-14}}</ref> Still, most of the people who use BZP, even though they say it is quite easy to stop, do not want to, and continue to use the drug, feeling that it helps them to reach higher levels of mood, sociability, and energy.<ref name="Wilkins" /> Studies undertaken on animals have indicated that BZP can substitute for methamphetamine in addicted rats, although it is ten times less potent and produces correspondingly weaker addictive effects.<ref>{{cite journal |author=Brennan K, Johnstone A, Fitzmaurice P, Lea R, Schenk S |title=Chronic benzylpiperazine (BZP) exposure produces behavioral sensitization and cross-sensitization to methamphetamine (MA) |journal=Drug Alcohol Depend |volume=88 |issue=2-3 |pages=204–13 |year=2007 |pmid=17125936 |doi=10.1016/j.drugalcdep.2006.10.016}}</ref> ==Legal issues== The drug was classified as a Schedule I [[controlled substance]] in the United States in 2002,<ref name="DEA-2006"/> following a report by the [[Drug Enforcement Administration|DEA]] which incorrectly stated that BZP was 10 to 20 times ''more'' potent than amphetamine,<ref>{{cite web | title =BZP: Fast Facts. | publisher = National Drug Intelligence Center |date=September 2004 | url =http://www.usdoj.gov/ndic/pubs11/11052/index.htm | accessdate = 2007-04-22 }}</ref> when in fact BZP is ten times ''less'' potent than dexamphetamine.<ref>{{cite web | title =DEA error on BZP potency | work = | publisher = Stargate International | date = 2004-09-15 | url =http://www.stanz.org.nz/DEA-Error.pdf | format = [[PDF]] | doi = | accessdate = 2007-04-22 }}</ref> The DEA subsequently admitted this mistake, but nevertheless retained the Schedule 1 classification. BZP is banned in all Australian states. Victoria, the last state in which it was legal, changed its classification on September 1 2006.<ref>{{cite web | title =Warning on buying banned drug over web | work = | publisher = [[The Australian]] | date = 2006-10-10 | url =http://www.theaustralian.news.com.au/story/0,20867,20557915-29277,00.html | format = | doi = | accessdate = 2007-04-14}}</ref> This is the date BZP and piperazine analogs become illegal in the federal schedules which are now enacted by all Australian states and territories. BZP is also a banned substance in Japan, along with TFMPP. Both Australia and Japan admit that their scheduling decisions were made primarily in response to the Schedule 1 classification given to BZP in the USA, although some instances of BZP use had been reported by law enforcement authorities in both countries. BZP is also banned in [[Greece]], [[Italy]], [[Malta]], [[Denmark]] and [[Sweden]].<ref name="Gee-2007"/><ref name="Erowid Law"/> [[Piperazine]] and salts of [[piperazine]] are classified as [[Prescription Only Medicines]] in the [[UK]]. Any products containing salts of [[piperazine]] would be licensable under the [[Medicines Act]]<ref>Sect. 8 of Medicines Act 1968 - Schedule 3, SI 3144 The Medicines for Human Use (Marketing Authorisations Etc) Regulations 1994</ref> and consequently anyone manufacturing and supplying it legally must hold the relevant licenses to do so. BZP is not a salt of [[piperazine]], but mislabelling of BZP products as containing "piperazine blend" have resulted in some prosecutions of suppliers in the UK by the Medicines and Healthcare Products Regulatory Agency, though to this date there has not been a successful prosecution in the UK for the sale of BZP, so its legal status remains uncertain.<ref> {{cite web | title =Thousands of 'pep' pills seized in Middlesbrough | work = | publisher = Medicines and Healthcare products Regulatory Agency | date = 2006-08-17 | url =http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2024549&ssTargetNodeId=389 | format = | doi = | accessdate = 2007-04-14}}</ref> Although sale is regulated, possession of BZP is still legal. For now, BZP and other analogous piperazines are legal and uncontrolled in many countries such as [[Canada]] and [[Ireland]].<ref name="Erowid Law">{{cite web | title =Benzylpiperazine Legal Status | author= |publisher = Erowid | date = | url =http://www.erowid.org/chemicals/bzp/bzp_law.shtml | format = | doi = | accessdate = 2008-05-26}}</ref> They are not controlled under any UN convention, so the compounds themselves are legal throughout most of the world, although in most countries their use is restricted to pharmaceutical manufacturing and recreational use is unknown.<ref>{{cite web | title =Benzylpiperazine Legal Status | work = | publisher = Erowid.org | date = 2002-11-17 | url =http://www.erowid.org/chemicals/bzp/bzp_law.shtml | format = | doi = | accessdate = 2007-04-22 }}</ref> Benzylpiperazine is, however, to be the subject of a [[European Monitoring Centre for Drugs and Drug Addiction]] (EMCDDA) risk assessment, the results of which will determine what, if any, control will placed on BZP throughout [[European Union|the European Union]]. The [[risk assessment]] comes about as the result of a joint Europol – EMCDDA report which concluded that BZP needs to be looked at in more detail. The results were published in June 2007.<ref>{{cite web | title =New drug under formal scrutiny: Council asks EMCDDA to assess risks of BZP | work = | publisher = European Monitoring Centre for Drugs and Drug Addiction | date = 2007-03-23 | url =http://www.emcdda.europa.eu/index.cfm?fuseaction=public.AttachmentDownload&nNodeID=27522&slanguageISO=EN | format = [[PDF]] | doi = | accessdate = 2007-04-14}}</ref> The report concluded that the use of BZP can lead to medical problems even if the long effects are still unknown. Taking this concession as a basis, the European Commission has decided to ask the Council to place BZP under control of the UN Convention on Psychotropic Substances.<ref name="EU">{{cite web| url =http://europa.eu/rapid/pressReleasesAction.do?reference=IP/07/1103&format=HTML&aged=0&language=EN&guiLanguage=en |title=New Commission proposal to strengthen control of synthetic drug BZP| author=EUROPA | Publisher = EU New Commission | date = 2007-07-17| accessdate = 2008-02-01}}</ref> On [[4 March]] [[2008]], the EU requested countries to place BZP under control within a year <ref>{{cite web | title =New drug BZP to be placed under control across the EU| work = | author= |publisher = European Monitoring Centre for Drugs and Drug Addiction | date = 2008-03-03 | url=http://www.emcdda.europa.eu/attachements.cfm/att_49695_EN_BZPDecision2008FinalEN.pdf | format = | doi = | accessdate = 2008-05-26}}</ref> and France complied on May 20th.<ref>{{cite web | title=Classment comme stupefient de la BZP | url=http://www.psy-desir.com/leg/spip.php?article1956 }}</ref> Based on the recommendation of the EACD, the New Zealand government has passed legislation which placed BZP, along with the other piperazine derivatives TFMPP, mCPP, pFPP, MeOPP and MBZP, into Class C of the New Zealand Misuse of Drugs Act 1975. A ban was intended to come into effect in New Zealand on December 18th 2007, but the law change did not go through until the following year, and the sale of BZP and the other listed piperazines became illegal in New Zealand as of 1st of April 2008. An amnesty for possession and usage of these drugs will remain until October 2008, at which point they will become completely illegal.<ref>{{cite web | title =Misuse of Drugs (Classification of BZP) Amendment Bill | work = | author= |publisher = New Zealand Parliment | date = 2007-08-20 | url =http://www.parliament.nz/NR/rdonlyres/B369ADAE-770D-4B5D-B51A-9CE612B12984/83028/DBHOH_BILL_8220_531999994.pdf | format = | doi = | accessdate = 2008-05-26}}</ref> ==See also== *[[Benzedrine]] *[[TFMPP]] *[[1-(3-Chlorophenyl)piperazine|mCPP]] *[[MeOPP]] *[[pFPP]] *[[1-methyl-4-benzylpiperazine|MBZP]] *[[Methylenedioxybenzylpiperazine|MDBZP]] *[[2C-B-BZP]] *[[Dibenzylpiperazine|DBZP]] *[[Party pills]] *[[Piperazine]] *[[Drug abuse]] *[[Recreational drugs]] ==Footnotes== {{reflist|2}} ==External links== * [http://www.erowid.org/chemicals/bzp/bzp.shtml Erowid BZP Vault] * [http://www.newscientist.com/channel/being-human/drugs-alcohol/mg19125711.000-mindaltering-drugs-does-legal-mean-safe.html New Scientist Story: Mind-altering drugs: does legal mean safe?] {{stimulants}} [[Category:Serotonin receptor agonists]] [[Category:Stimulants]] [[Category:Piperazines]] [[de:1-Benzylpiperazin]] [[fr:Benzylpipérazine]] [[pl:BZP]] [[fi:Bentsyylipiperatsiini]] [[sv:BZP]]