View source for Benzylpiperazine

{{Short description|Recreational drug}}
{{cs1 config|name-list-style=vanc}}
{{Use dmy dates|date=December 2019}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 413890988
| IUPAC_name = 1-Benzylpiperazine
| image = Benzylpiperazine.svg
| image2 = Benzylpiperazine-3D-balls.png
<!--Clinical data-->
| tradename =
| legal_AU = Schedule 9
| legal_BR = F2
| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-07-25}}</ref>
| legal_CA = Schedule III
| legal_CA_comment = <ref>{{cite web| work = Controlled Drugs and Substances Act: Schedule III | title = Benzylpiperazine [BZP], namely 1-benzylpiperazine and its salts, isomers and salts of isomers | date = 14 January 2023 | publisher = Justice Laws Website, Government of Canada |url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/page-11.html#h-95603 }}</ref><ref>{{cite web|title=Amending Schedule III to the Controlled Drugs and Substances Act (BZP and TFMPP). |work=Canada Gazette|url=http://www.gazette.gc.ca/rp-pr/p2/2012/2012-04-11/html/sor-dors66-eng.html|access-date= 24 November 2012}}</ref>
| legal_DE = Anlage II
| legal_NZ = Class C 
| legal_UK = POM
| legal_US = Schedule I
| legal_status =
| routes_of_administration = Oral, intravenous, [[Insufflation (medicine)|insufflation]]
<!--Pharmacokinetic data-->
| bioavailability = Unknown
| metabolism = [[Liver|Hepatic]]
| elimination_half-life = 5.5 Hours<ref>{{cite journal | vauthors = Antia U, Lee HS, Kydd RR, Tingle MD, Russell BR | title = Pharmacokinetics of 'party pill' drug N-benzylpiperazine (BZP) in healthy human participants | journal = Forensic Science International | volume = 186 | issue = 1–3 | pages = 63–67 | date = April 2009 | pmid = 19261399 | doi = 10.1016/j.forsciint.2009.01.015 }}</ref>
| excretion = [[Kidney|Renal]]
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 2759-28-6
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 3UG152ZU0E
| ATC_prefix = none
| PubChem = 75994
| KEGG = C22780
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 68493
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 83537
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 113600
<!--Chemical data-->
| C=11 | H=16 | N=2
| smiles = C1(CN2CCNCC2)=CC=CC=C1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H16N2/c1-2-4-11(5-3-1)10-13-8-6-12-7-9-13/h1-5,12H,6-10H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IQXXEPZFOOTTBA-UHFFFAOYSA-N
}}

'''Benzylpiperazine''' ('''BZP''') is a substance often used as a [[recreational drug]] and is known to have [[euphoriant]] and [[stimulant]] properties. Several studies conducted between 2000 and 2011 found that the effects of BZP are similar to [[amphetamine]], although BZP's dosage is roughly 10 times higher by weight.<ref>{{cite journal | vauthors = Johnstone AC, Lea RA, Brennan KA, Schenk S, Kennedy MA, Fitzmaurice PS | title = Benzylpiperazine: a drug of abuse? | journal = Journal of Psychopharmacology | volume = 21 | issue = 8 | pages = 888–894 | date = November 2007 | pmid = 17606471 | doi = 10.1177/0269881107077260 | s2cid = 27130853 | url = https://zenodo.org/record/3948898 }}</ref><ref>Update on 1-benzylpiperazine (BZP) party pills. 2013. Arch Toxicol. 87/6, 929-47. M.S. Monteiro, M.D.L. Bastos, P. Guedes De Pinho, M. Carvalho. doi: 10.1007/s00204-013-1057-x.</ref>

Adverse effects have been reported following its use including [[psychosis|acute psychosis]], [[renal]] toxicity and [[seizures]].<ref name="Schep2011">{{cite journal | vauthors = Schep LJ, Slaughter RJ, Vale JA, Beasley DM, Gee P | title = The clinical toxicology of the designer "party pills" benzylpiperazine and trifluoromethylphenylpiperazine | journal = Clinical Toxicology | volume = 49 | issue = 3 | pages = 131–141 | date = March 2011 | pmid = 21495881 | doi = 10.3109/15563650.2011.572076 | s2cid = 42491343 }}</ref> Deaths from [[piperazine]] derivatives are extremely rare, but there has been at least one death apparently due to BZP alone.<ref name=":1">{{cite book| vauthors = Gee P, Schep LJ  |title=Novel Psychoactive Substances|date=2022|publisher=Elsevier|isbn=978-0-12-818788-3| veditors = Dargan P, Wood D |edition= 2nd |pages=301–332 |language=en |chapter=Chapter 12: 1-Benzylpiperazine and other piperazine-based stimulants|doi=10.1016/b978-0-12-818788-3.00009-7|s2cid=239180001}}</ref> Its sale is banned in several countries, including Australia, Canada, New Zealand, the United States, the Republic of Ireland, the United Kingdom, Bulgaria, Romania and other parts of Europe.<ref>{{cite web|title =Legal dance drug faces ban amid fears over side-effects| vauthors = Topping A |work=The Guardian|date = 18 June 2007|url =https://www.theguardian.com/drugs/Story/0,,2105482,00.html|access-date = 26 May 2008}}</ref><ref>{{cite web|title = Harney announces ban on stimulant BZP |publisher = The Irish Examiner|date = 18 June 2007|url = http://www.examiner.ie/breaking/ireland/eyaueyidqlql/|access-date = 28 December 2009|archive-date = 6 April 2009|archive-url = https://web.archive.org/web/20090406201015/http://www.examiner.ie/breaking/ireland/eyaueyidqlql/|url-status = dead}}</ref>

== History ==

=== Development history ===
BZP was first synthesized by [[Burroughs Wellcome & Company]] in 1944.<ref name=":0">{{cite journal| vauthors = Kerr JR, Davis LS |date=March 2011|title=Benzylpiperazine in New Zealand: brief history and current implications|journal=Journal of the Royal Society of New Zealand|language=en|volume=41|issue=1|pages=155–164|doi=10.1080/03036758.2011.557036|issn=0303-6758|doi-access=|bibcode=2011JRSNZ..41..155K |s2cid=128850970 }}</ref> It is often claimed that it was originally synthesized as a potential [[antihelminthic]] (anti-parasitic) agent for use in farm animals,<ref>{{cite web|title = Lay off the party pills|publisher = New Zealand Medical Association| date = 1 November 2006|url =http://www.scoop.co.nz/stories/GE0611/S00001.htm|access-date = 22 April 2007}}</ref> but its synthesis is thought to predate their interest in [[piperazine]]s as antihelminthics.<ref name=":0" /> Even so, the majority of the early work with the piperazines were investigations into their potential use as antihelminthics, 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 | vauthors = White RH, Standen OD | title = Piperazine in the treatment of threadworms in children; report on a clinical trial | journal = British Medical Journal | volume = 2 | issue = 4839 | pages = 755–757 | date = October 1953 | pmid = 13082101 | pmc = 2029560 | doi = 10.1136/bmj.2.4839.755 }}</ref><ref>{{cite journal | vauthors = Standen OD | title = Activity of piperazine, in vitro, against Ascaris lumbricoides | journal = British Medical Journal | volume = 2 | issue = 4930 | pages = 20–22 | date = July 1955 | pmid = 14378628 | pmc = 1980175 | doi = 10.1136/bmj.2.4930.20-a }}</ref> It was discovered that BZP had [[Adverse drug reaction|side effects]] and was largely abandoned as a worm treatment.{{cn|date=June 2023}} It next appears in the literature in the 1970s when it was investigated as a potential [[antidepressant]] medication,<ref name=":0" /> 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 name=Campbell>{{cite journal | vauthors = Campbell H, Cline W, Evans M, Lloyd J, Peck AW | title = Comparison of the effects of dexamphetamine and 1-benzylpiperazine in former addicts | journal = European Journal of Clinical Pharmacology | volume = 6 | issue = 3 | pages = 170–176 | date = October 1973 | pmid = 4586849 | doi = 10.1007/BF00558281 | s2cid = 5648863 }}</ref>

=== Recreational history ===
In 1996, the United States [[Drug Enforcement Administration]] noted that it was being recreationally used in California.<ref name=":0" /> It also reported that BZP was being used as an [[adulterant]] in illicit drugs. In around 2000, its use increased worldwide,<ref name=":0" /> which was soon followed by legislative control in Europe and the United States. In New Zealand, it was initially legal, but was restricted in 2005 and later reclassified as [[Misuse of Drugs Act 1975#Class C|Class C]] due to new evidence in 2008.<ref name=":0" /> It was widely used before its reclassification, and an estimated 5 million pills were sold in New Zealand in 2007.<ref name="Gee-2007">{{cite journal | vauthors = Gee P, Fountain J | title = Party on? BZP party pills in New Zealand | journal = The New Zealand Medical Journal | volume = 120 | issue = 1249 | pages = U2422 | date = February 2007 | pmid = 17308559 | url = http://www.nzma.org.nz/journal/120-1249/2422/content.pdf | url-status = dead | archive-url = https://web.archive.org/web/20071013111558/http://www.nzma.org.nz/journal/120-1249/2422/content.pdf | archive-date = 13 October 2007 }}</ref> BZP, which is often mixed with [[TFMPP]], has been claimed to be a safer alternative to other illicit street drugs.<ref name=":0" /> It is also used as an adulterant of or substitute for [[MDMA]],<ref name="DEA MCG">{{cite web | work = Microgram Bulletin | publisher = Drug Enforcement Administration, U.S. Department of Justice | date = December 2008 | title = Ecstasy Mimic Tablets|url = http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg1208/mg1208.html |url-status = dead|archive-url = https://web.archive.org/web/20090114182026/http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg1208/mg1208.html|archive-date = 14 January 2009|df = dmy-all}}</ref> which has similar effects, and is sometimes marketed as "ecstasy", a colloquial term for MDMA.<ref name=":0" />

BZP has also been used and prohibited in [[horse racing]] and athletics.<ref name=":0" />

== Production and distribution ==
[[File:bzp brands.jpg|thumb|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|publisher = Drug Enforcement Administration, U.S. Department of Justice |date = June 2006|url = http://www.deadiversion.usdoj.gov/drugs_concern/bzp_tmp/bzp_tmp.htm|access-date = 22 April 2007|url-status = dead|archive-url = https://web.archive.org/web/20070407080056/http://www.deadiversion.usdoj.gov/drugs_concern/bzp_tmp/bzp_tmp.htm|archive-date = 7 April 2007|df = dmy-all}}</ref>

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">{{cite web|date=17 June 2005|title=Misuse of Drugs Amendment Act 2005|url=http://www.stanz.org.nz/images/ASSENT81.PDF|url-status=dead|archive-url=https://web.archive.org/web/20070716013803/http://www.stanz.org.nz/images/ASSENT81.PDF|archive-date=16 July 2007|access-date=22 April 2007|publisher=New Zealand Government|df=dmy-all}}</ref> 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 | vauthors = Alansari M, Hamilton D | title = Nephrotoxicity of BZP-based herbal party pills: a New Zealand case report | journal = The New Zealand Medical Journal | volume = 119 | issue = 1233 | pages = U1959 | date = May 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 | vauthors = Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB | title = Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain | journal = Annals of the New York Academy of Sciences | volume = 1025 | issue = 1 | pages = 189–197 | date = October 2004 | pmid = 15542717 | doi = 10.1196/annals.1316.024 | s2cid = 9195383 | bibcode = 2004NYASA1025..189B | url = https://zenodo.org/record/1235872 }}</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 | vauthors = 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 = Polish Journal of Pharmacology and Pharmacy | volume = 39 | issue = 2 | pages = 203–211 | year = 1987 | pmid = 2448760 }}</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 |author=BilZ0r |title=Neuropharmacology of BZP |publisher=Erowid.org |date=November 2003 |url=http://www.erowid.org/chemicals/bzp/bzp_article1.shtml |access-date=22 April 2007}}</ref> Another study<ref>{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | date = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref> lists 1-Benzylpiperazine (BZP)'s Release DAT, NET, and SERT EC<sub>50</sub>s (i.e. a measure of potency for the release of neurotransmitters via BZP's affinity for the dopamine, norepinephrine, and serotonin transporters respectively--whereby those transporter are induced to shuttle neurotransmitters out of neurons and deposit them in the synaptic gap) as 175, 62, and 6050; for comparison, the values listed for d-amphetamine (25, 7, and 1765) and d-methamphetamine (25, 12, and 736) show a similar DAT:NET affinity ratio as well as minor SERT activity which suggests BZP possesses similar activity to the two aforementioned drugs (when dosed ~7x higher due to lower potency) rather than serotonergic substituted amphetamines like MDMA.

BZP also acts as a non-selective [[serotonin receptor]] [[agonist]] on a wide variety of serotonin receptors.<ref name=Tekes/> Binding to 5-HT<sub>2A</sub> receptors may explain its mild hallucinogenic effects at high doses, while partial agonist or antagonist effects at the 5-HT<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 5-HT<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.<ref name="Nikolova & Danchev">{{cite journal| vauthors = Nikolova I, Danchev N |date=2008|title=Piperazine Based Substances of Abuse: A new Party Pills on Bulgarian Drug Market|journal=Biotechnology & Biotechnological Equipment|language=en|volume=22|issue=2|pages=652–655|doi=10.1080/13102818.2008.10817529|s2cid=84913504 |issn=1310-2818}}</ref>{{Rp|page=652}}

== Effects ==
[[File:eye bzp.jpg|thumb|right|Typical pupil dilation]]

The effects of BZP are largely similar to [[amphetamine]]s,<ref name="Schep2011"/><ref>{{cite journal | vauthors = Fantegrossi WE, Winger G, Woods JH, Woolverton WL, Coop A | title = Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys | journal = Drug and Alcohol Dependence | volume = 77 | issue = 2 | pages = 161–168 | date = February 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 name=Campbell /> A 2005 study has shown that mixtures of BZP with other piperazine drugs such as [[Trifluoromethylphenylpiperazine|TFMPP]] share certain [[pharmacodynamic]] traits with [[MDMA]].<ref>{{cite journal | vauthors = Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB | 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 = 550–560 | date = March 2005 | pmid = 15496938 | doi = 10.1038/sj.npp.1300585 | s2cid = 24217984 | doi-access = free }}</ref>

=== Subjective effects ===

Upon ingestion of between 50&nbsp;mg and 200&nbsp;mg of BZP, the user may experience any or all of the following:

Initial Effects:<ref name="Schep2011"/><ref name="Nicholson-2006" /><ref>{{cite web|title =Erowid experience vault: Lazer Light Loving BZP & TFMPP |publisher = Erowid|date = 28 October 2004|url =http://www.erowid.org/experiences/exp.php?ID=23485|access-date = 26 May 2008}}</ref>

{{Div col}}
* Feelings of [[Euphoria (emotion)|euphoria]], wonder, amazement, well-being, energy and elation
* Rapid mood elevation
* Enhanced sociability
* Enhanced appreciation of music
* Increased desire to move, also slight increase in [[stereotypy]]
* Skin tingling
* Decreased [[appetite]]
* Repetitive thought patterns
* Actual and perceived changes in [[Thermoregulation|body temperature]]
* Mild jaw clenching/[[bruxism]]
* [[Tachycardia|Increased heart rate]]
* [[Pupillary dilation|Dilation of pupils]] (see photo)
* [[Nausea]]
* [[Flushing (physiology)|Flushing]]
* Mild [[xerostomia]] (dry mouth)
* Slight [[urinary incontinence]], often described as "leaking" a small amount of [[urine]] after [[urinating]] (not due to loss of [[urinary bladder|bladder]] control)
{{Div col end}}

Later Effects:<ref name="Nicholson-2006">{{cite journal | vauthors = Nicholson TC | title = Prevalence of use, epidemiology and toxicity of 'herbal party pills' among those presenting to the emergency department | journal = Emergency Medicine Australasia | volume = 18 | issue = 2 | pages = 180–184 | date = April 2006 | pmid = 16669944 | doi = 10.1111/j.1742-6723.2006.00826.x | s2cid = 26016419 }}</ref>

{{Div col}}
* Mild headache
* Nausea
* [[Hangover]]-like symptoms (common with high doses)
* [[Fatigue (physical)|Fatigue]]
* [[Indigestion]] (similar to acid indigestion/heartburn)
* Increased hunger (and sometimes thirst)
* [[Insomnia]]
* [[Confusion]]
* Depression (particularly with frequent/heavy use)
{{Div col end}}

=== Tolerance ===

Research into BZP's tolerance is sparse.<ref name=":1" /> [[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.<ref name="Nikolova & Danchev"/>{{rp|653}}

=== Toxic effects ===

[[File:Bzptablet.jpg|right|thumb|An impure '[[MDMA|ecstasy]]' tablet – seized by law enforcement in the United States – containing BZP, [[methamphetamine]], and [[caffeine]]]]
As with most [[sympathomimetic]] [[stimulant]]s, significant side effects are associated with BZP use. It reportedly produces insomnia and a mild to severe [[hangover]] after the drug effect wears off.<ref name="Nicholson-2006" /> The majority of the toxic effects information came from a 2005 study that recorded all presentations associated with party pill use at the [[Emergency Department]] of [[Christchurch]] Hospital, New Zealand. Fourteen toxic [[seizures]] were recorded in two patients with life-threatening [[toxicity]] with [[status epilepticus]] and severe respiratory and [[metabolic acidosis]].<ref name="Gee-2005" /> The results of this study and others like it showed that BZP can cause unpredictable and serious toxicity in some individuals,<ref name="Nicholson-2006" /><ref name="Theron-2007" /> but the data and dosage collection were reliant on self reporting by drug users, which may result in under-reporting (or over-reporting), and there were complicating factors like the frequent presence of alcohol and other drugs.<ref name="Theron-2007" />

The major side effects include dilated pupils, blurred vision, dryness of the mouth, extreme alertness, [[pruritus]], [[confusion]], [[Psychomotor agitation|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="Schep2011"/><ref name="Nicholson-2006" /><ref name="Gee-2008">{{cite journal | vauthors = Gee P, Gilbert M, Richardson S, Moore G, Paterson S, Graham P | title = Toxicity from the recreational use of 1-benzylpiperazine | journal = Clinical Toxicology | volume = 46 | issue = 9 | pages = 802–807 | date = November 2008 | pmid = 18821145 | doi = 10.1080/15563650802307602 | s2cid = 12227038 }}</ref><ref name="Gee-2005">{{cite journal | vauthors = 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 | volume = 118 | issue = 1227 | pages = U1784 | date = December 2005 | pmid = 16372033 | url = http://www.nzma.org.nz/journal/118-1227/1784/content.pdf | url-status = dead | archive-url = https://web.archive.org/web/20081007080620/http://www.nzma.org.nz/journal/118-1227/1784/content.pdf | archive-date = 7 October 2008 }}</ref><ref name="Theron-2007">{{cite journal | vauthors = 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 | volume = 120 | issue = 1249 | pages = U2416 | date = February 2007 | pmid = 17308553 | url = http://www.nzma.org.nz/journal/120-1249/2416/content.pdf | url-status = dead | archive-url = https://web.archive.org/web/20071012221915/http://www.nzma.org.nz/journal/120-1249/2416/content.pdf | archive-date = 12 October 2007 }}</ref> The more severe toxic effects include psychosis or adverse psychiatric events,<ref>{{cite journal |vauthors=Mohandas A, Vecchio D |title=A case report of Benzylpiperazine induced new onset affective symptoms in a patient with schizophrenia |journal=European Psychiatry |volume=23 |pages=S315–S316 |year=2008|doi=10.1016/j.eurpsy.2008.01.1085|s2cid=145659495 }}</ref><ref>{{cite journal | vauthors = Austin H, Monasterio E | title = Acute psychosis following ingestion of 'Rapture' | journal = Australasian Psychiatry | volume = 12 | issue = 4 | pages = 406–408 | date = December 2004 | pmid = 15715818 | doi = 10.1111/j.1440-1665.2004.02137.x }}</ref> renal toxicity,<ref name=" Alansari-2006" /> [[respiratory failure]],<ref name="Schep2011"/> [[hyperthermia]],<ref name="Schep2011"/> [[serotonin syndrome]],<ref name="Schep2011"/> [[rhabdomyolysis]]<ref name="pmid20184432">{{cite journal | vauthors = Gee P, Jerram T, Bowie D | title = Multiorgan failure from 1-benzylpiperazine ingestion--legal high or lethal high? | journal = Clinical Toxicology | volume = 48 | issue = 3 | pages = 230–233 | date = March 2010 | pmid = 20184432 | doi = 10.3109/15563651003592948 | doi-access = free }}</ref> and [[seizure]].<ref name="Nicholson-2006" /><ref name="Gee-2005" /> Blood benzylpiperazine concentrations have been measured either to confirm clinical intoxication or as part of a medicolegal death investigation.<ref>{{cite book| vauthors = Baselt R |title=Disposition of Toxic Drugs and Chemicals in Man |edition=8th |publisher=Biomedical Publications|place=Foster City, CA|year=2008|pages=[https://archive.org/details/dispositionoftoxe2base/page/155 155–156]|isbn=978-0-931890-08-6|url-access=registration|url=https://archive.org/details/dispositionoftoxe2base/page/155}}</ref>

=== Risk of fatality ===
Ingestion of piperazine derivatives alone rarely causes death.<ref name=":1" /> 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" /> One death has been attributed to ingestion of BZP alone; in this case its blood concentration was measured to be 8&nbsp;mg/L.<ref name=":1" />

Combined with alcohol or other illicit drugs, such as TFMPP and MDMA, multiple deaths have been reported.<ref name=":1" /> A combination of BZP and [[MDMA]] ingested by a 23-year-old DJ nearly resulted in death. He was put into an [[induced coma]], and later recovered.<ref>{{cite web|title =Party On?|publisher = TV3 New Zealand|archive-url=https://web.archive.org/web/20071204030030/http://www.tv3.co.nz/Programmes/NewsandCurrentAffairs/60Minutes/tabid/88/articleID/24491/Default.aspx|archive-date=4 December 2007|date = 9 April 2007|url =http://www.tv3.co.nz/Programmes/NewsandCurrentAffairs/60Minutes/tabid/88/ArticleID/24491/Default.aspx|access-date = 14 April 2007}}</ref> In another case in [[Zürich]] in 2001, a 23-year-old who had taken BZP and MDMA died from a massive [[cerebral edema]] 57 hours after hospital admission.<ref>{{cite journal | vauthors = Arbo MD, Bastos ML, Carmo HF | title = Piperazine compounds as drugs of abuse | journal = Drug and Alcohol Dependence | volume = 122 | issue = 3 | pages = 174–185 | date = May 2012 | pmid = 22071119 | doi = 10.1016/j.drugalcdep.2011.10.007 }}</ref>

=== Addictive effects ===
BZP has not been found to be physically addictive in humans.<ref name=":0" /> Most users of BZP say they could stop, but do not want to.<ref name="Wilkins">{{cite web|title=Legal party pill use in New Zealand: Prevalence of use, availability, health harms and 'gateway effects' of benzylpiperazine (BZP) and trifluorophenylmethylpiperazine (TFMPP)|url=http://www.spiritualhigh.co.uk/spiritualhigh.co.uk/downloads/Legal-party-pills-in-New-Zealand-report.pdf|url-status=usurped|archive-url=https://web.archive.org/web/20070318042503/http://www.spiritualhigh.co.uk/spiritualhigh.co.uk/downloads/Legal-party-pills-in-New-Zealand-report.pdf|archive-date=18 March 2007|access-date=14 April 2007|publisher=Centre for Social and Health Outcomes Research and Evaluation (SHORE)|vauthors=Wilkins C, Girling M, Sweetsur P, Huckle T, Huakau J}}</ref> Studies undertaken on animals have indicated that BZP can substitute for methamphetamine in addicted rats, although it is one-tenth as potent and produces correspondingly weaker addictive effects.<ref>{{cite journal | vauthors = 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 and Alcohol Dependence | volume = 88 | issue = 2–3 | pages = 204–213 | date = May 2007 | pmid = 17125936 | doi = 10.1016/j.drugalcdep.2006.10.016 }}</ref>

== Legal status ==

[[File:Benzylpiperazine legality map.svg|thumb|Map of benzylpiperazine legality worldwide<br />Red: Prohibited<br />Pink: European Union, requested prohibition<br />Gray: Unknown]]

BZP is banned in [[Australia]], [[Austria]], [[Canada]], [[Denmark]], [[Estonia]], [[France]], [[Germany]], [[Greece]], [[Republic of Ireland|Ireland]], [[Italy]], [[Japan]], [[Malta]], [[Poland]], [[Sweden]] and the [[United States]].<ref name="Gee-2007" /><ref name="Erowid Law">{{cite web|date=2015-02-10|title=Benzylpiperazine Legal Status|url=http://www.erowid.org/chemicals/bzp/bzp_law.shtml|url-status=live|access-date=2021-10-10|publisher=Erowid|archive-url=https://web.archive.org/web/20021221033910/http://www.erowid.org:80/chemicals/bzp/bzp_law.shtml |archive-date=21 December 2002 }}</ref> BZP is 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 name="Erowid Law" />

=== Australia ===
BZP is banned in all Australian states. Victoria, the last state in which it was legal, changed its classification on 1 September 2006,<ref>{{cite web|title=Warning on buying banned drug over web |work=The Australian |date=10 October 2006 |url=http://www.theaustralian.news.com.au/story/0,20867,20557915-29277,00.html |access-date=14 April 2007 |archive-url=https://web.archive.org/web/20071016193341/http://www.theaustralian.news.com.au/story/0%2C20867%2C20557915-29277%2C00.html |archive-date=16 October 2007 |url-status=dead }}</ref> when BZP and piperazine analogs become illegal in the federal schedules, which are enacted by all Australian states and territories.

=== Canada ===
In Canada, Benzylpiperazine and salts of benzylpiperazine are classified as Schedule III controlled substances under the [[Controlled Drugs and Substances Act]].<ref>{{cite web|title=Controlled Drugs and Substances Act (S.C. 1996, c. 19) |publisher=Canadian Department of Justice |date=7 July 2014 |url=http://laws-lois.justice.gc.ca/eng/acts/c-38.8/page-26.html#h-30 |access-date=17 August 2014 |url-status=dead |archive-url=https://web.archive.org/web/20131215170432/http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-26.html |archive-date=15 December 2013 }}</ref>

=== European Union ===
Benzylpiperazine was the subject of a [[European Monitoring Centre for Drugs and Drug Addiction]] (EMCDDA) risk assessment to determine to determine how to control it throughout the [[European Union]]. The [[risk assessment]] came about as the result of a joint [[Europol]] – EMCDDA report which concluded that BZP needs to be looked at in more detail. The report was published in June 2007,<ref>{{cite web|title =New drug under formal scrutiny: Council asks EMCDDA to assess risks of BZP|publisher = European Monitoring Centre for Drugs and Drug Addiction|date = 23 March 2007|url =http://www.emcdda.europa.eu/index.cfm?fuseaction=public.AttachmentDownload&nNodeID=27522&slanguageISO=EN|access-date = 14 April 2007}}</ref> and 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]] asked the [[Council of the European Union|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 = 17 July 2007| access-date = 1 February 2008}}</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|publisher = European Monitoring Centre for Drugs and Drug Addiction|date = 3 March 2008|url = http://www.emcdda.europa.eu/attachements.cfm/att_49695_EN_BZPDecision2008FinalEN.pdf|access-date = 26 May 2008|archive-date = 23 December 2009|archive-url = https://web.archive.org/web/20091223131855/http://www.emcdda.europa.eu/attachements.cfm/att_49695_EN_BZPDecision2008FinalEN.pdf|url-status = dead}}</ref>

=== Finland ===
Scheduled in "government decree on narcotic substances, preparations and plants" and is hence illegal.<ref>{{cite web|title=Valtioneuvoston asetus huumausaineina pidettävistä aineista, valmisteista ja kasveista|lang=fi|trans-title=Government Decree on substances, preparations and plants regarded as narcotic drugs|date=2024-05-08|publisher=[[Finlex]]|url=https://finlex.fi/fi/lainsaadanto/2008/543|access-date=2024-08-18}}</ref>

=== New Zealand ===
Based on the recommendation of the EACD, the New Zealand government passed legislation which placed BZP, along with other piperazine derivatives (TFMPP, mCPP, pFPP, MeOPP, and MBZP), into Class C of the [[Misuse of Drugs Act 1975]]. A ban was intended to come into effect in New Zealand on 18 December 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 1 April 2008. An amnesty for possession and usage of these drugs was in effect until October 2008, at which point they became completely illegal.<ref>{{cite web|title = Misuse of Drugs (Classification of BZP) Amendment Bill|publisher = New Zealand Parliament|date = 20 August 2007|url = http://www.parliament.nz/NR/rdonlyres/B369ADAE-770D-4B5D-B51A-9CE612B12984/83028/DBHOH_BILL_8220_531999994.pdf|access-date = 26 May 2008|archive-date = 22 May 2011|archive-url = https://web.archive.org/web/20110522182805/http://www.parliament.nz/NR/rdonlyres/B369ADAE-770D-4B5D-B51A-9CE612B12984/83028/DBHOH_BILL_8220_531999994.pdf|url-status = dead}}</ref>

=== United Kingdom ===
[[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" resulted in some prosecutions of suppliers in the UK by the Medicines and Healthcare Products Regulatory Agency, although none were successful.<ref>{{cite web|title = Thousands of 'pep' pills seized in Middlesbrough|publisher = Medicines and Healthcare products Regulatory Agency|date = 17 August 2006|url = http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2024549&ssTargetNodeId=389|access-date = 14 April 2007|url-status = dead|archive-url = https://web.archive.org/web/20070928010717/http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2024549&ssTargetNodeId=389|archive-date = 28 September 2007|df = dmy-all}}</ref> In May 2009, the [[Home Office]] announced plans to ban BZP,<ref>{{cite web|title =Move to outlaw two 'party' drugs|work=BBC News|date = 21 May 2009|url =https://news.bbc.co.uk/2/hi/uk_news/8061693.stm}}</ref> and launched a consultation on the proposal.<ref>{{cite news|publisher=Homeoffice.gov.uk|url=http://www.homeoffice.gov.uk/documents/cons-2009-bzp/|archive-url=https://archive.today/20120805061711/http://www.homeoffice.gov.uk/documents/cons-2009-bzp/|url-status=dead|archive-date=5 August 2012|date=30 October 2009|access-date=1 January 2010|title=Summary of response: consultation on proposed control under the Misuse of Drugs Act 1971 of (1) 1-Benzylpiperazine and a group of substituted piperazines}}</ref> In October 2009, it was announced that from 23 December 2009, BZP and related piperazines would be [[List of controlled drugs in the United Kingdom#Class C drugs|Class C drugs]] under the [[Misuse of Drugs Act 1971|Misuse of Drugs Act]].<ref>{{cite web|title =Misuse of Drugs Act 1971 (Amendment) Order 2009|url =http://www.opsi.gov.uk/si/si2009/draft/ukdsi_9780111486610_en_1 | work = Legislation.gov.uk }}</ref>

=== United States ===
The drug was federally 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|access-date = 22 April 2007}}</ref> when in fact BZP is ten times ''less'' potent than dexamphetamine.<ref>{{cite web|title =DEA error on BZP potency|publisher = Stargate International|date = 15 September 2004|url =http://www.stanz.org.nz/DEA-Error.pdf|access-date = 22 April 2007|archive-url=https://web.archive.org/web/20081014022708/http://www.stanz.org.nz/DEA-Error.pdf|archive-date=14 October 2008 }}</ref> It is also illegal at the state level in Florida, Oklahoma, Vermont, and Virginia.<ref name="Erowid Law" />

== Chemical derivatives ==
{{Main|Substituted piperazine}}

* Pharmaceuticals
** [[Befuraline]] – Antidepressant
** [[Bifeprunox]] – Antipsychotic
** [[Buclizine]] – Antihistamine
** [[Chlorbenzoxamine]] – Gastrointestinal agent
** [[Fipexide]] – Nootropic
** [[Imatinib]] – Anticancer agent
** [[Meclozine]] – Antihistamine
** [[Piberaline]] – Antidepressant
** [[Piribedil]] – Antiparkinsonian agent
** [[Trimetazidine]] – Antianginal
** [[Vesnarinone]] – Cardiotonic
* Designer drugs
** [[3-Methylbenzylpiperazine]]
** [[4-Methyl-1-benzylpiperazine]] (MBZP)
** [[4-Bromo-2,5-dimethoxy-1-benzylpiperazine]] (2C-B-BZP)
** [[1,4-Dibenzylpiperazine]] (DBZP)
** [[3,4-Methylenedioxy-1-benzylpiperazine]] (MDBZP)

[[Diphenylmethylpiperazine]]s are also similar to benzylpiperazines.

== See also ==
* [[Diphenylmethylpiperazine]]
* [[Phenylpiperazine]]
* [[Pyrimidinylpiperazine]]

== References ==
{{Reflist}}

== External links ==
{{Commons category}}
*[http://www.erowid.org/chemicals/bzp/bzp.shtml Erowid BZP Vault]
*{{Cite web | url = https://www.euda.europa.eu/publications/drug-profiles/bzp_en | publisher = European Union Drugs Agency (EUDA) | title = BZP/piperazines}}
*[https://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?]

{{Hallucinogens}}
{{Stimulants}}
{{Adrenergic receptor modulators}}
{{Monoamine releasing agents}}
{{Serotonin receptor modulators}}
{{Piperazines}}
{{Chemical classes of psychoactive drugs}}

{{Good article}}

[[Category:Alpha-2 blockers]]
[[Category:Arylalkylamines]]
[[Category:Benzylpiperazines]]
[[Category:Designer drugs]]
[[Category:Euphoriants]]
[[Category:1-Piperazinyl compounds]]
[[Category:Serotonin receptor agonists]]
[[Category:Serotonin-norepinephrine-dopamine releasing agents]]
[[Category:Stimulants]]