Benzylpiperazine (BZP) is a recreational substance known for its euphoric and stimulant effects. The impact of BZP on the user is often likened to the effects of amphetamine. However, it’s crucial to note that BZP usage has been associated with adverse outcomes, including instances of acute psychosis, renal toxicity, and seizures. While fatalities linked directly to BZP are exceedingly rare, there is documented evidence of at least one death apparently attributed to BZP use alone.
The sale and distribution of BZP are prohibited in numerous countries, which include Australia, Canada, New Zealand, the United States, the Republic of Ireland, the United Kingdom, Bulgaria, Romania, and various other regions within Europe. These legal restrictions are in place due to concerns over its safety and potential risks to public health.
|CompTox Dashboard (EPA)||DTXSID0022197|
|Chemical and physical data|
|Molar mass||176.263 g·mol−1|
The origins of BZP date back to its synthesis by Burroughs Wellcome & Company in 1944. While there is speculation that it was initially created as a potential antihelminthic (anti-parasitic) agent for use in farm animals, it appears that BZP’s synthesis predates the company’s specific interest in piperazines as anthelmintics. However, early research on piperazines primarily focused on their potential as anthelmintics, with the earliest clinical trials related to piperazine use appearing in articles published in the British Medical Journal during the 1950s. Over time, it became evident that BZP had notable side effects and was eventually abandoned as a treatment for worms. BZP reemerged in the scientific literature in the 1970s when researchers explored its potential as an antidepressant medication. This avenue was also discontinued when studies found that BZP produced amphetamine-like effects and was susceptible to abuse. The research suggested that BZP “should be subject to legal regulations akin to those governing amphetamine use.”
In 1996, the United States Drug Enforcement Administration observed recreational BZP use in California. It was also noted that BZP was being employed as an adulterant in illicit drugs. By around 2000, BZP’s recreational use began to rise worldwide, subsequently leading to legislative controls in both Europe and the United States. In New Zealand, BZP was initially legal but was subject to restrictions in 2005 and was later reclassified as a Class C substance due to new evidence in 2008. Before its reclassification, it was widely used, with an estimated 5 million pills sold in New Zealand in 2007. BZP, often combined with TFMPP, was claimed to be a safer alternative to other illicit street drugs. It was also used as an adulterant for or a substitute for MDMA, which shares similar effects. At times, BZP was marketed as “ecstasy,” a colloquial term for MDMA.
Furthermore, BZP has seen use in horse racing and athletics and, in some instances, has been prohibited in these contexts.
Production and distribution
BZP is a piperazine derivative available in either hydrochloride salt or free base form. The hydrochloride salt presents as a white solid, while the base form appears as a slightly yellowish-green liquid. It’s essential to note that BZP base is corrosive and can cause burns.
BZP is frequently marketed under the guise of a “dietary supplement” to circumvent stricter regulations applicable to medicines and drugs, even though BZP lacks any dietary value. However, since late 2005, the Misuse of Drugs Act in New Zealand has explicitly prohibited its classification and marketing as a dietary supplement. Some retailers may falsely claim that BZP is a “natural” product, portraying it as a “pepper extract” or “herbal high.” In reality, this substance is entirely synthetic, and no evidence suggests that it occurs naturally.
BZP exhibits a multifaceted mechanism of action, influencing both the serotonergic and dopaminergic receptor systems, akin to MDMA. Specifically, BZP exerts amphetamine-like actions on the serotonin reuptake transporter, leading to elevated serotonin levels in the extracellular fluid around cells and increased activation of neighbouring serotonin receptors. BZP’s impact on the noradrenaline reuptake transporter and dopamine reuptake transporter is less potent. Notably, BZP demonstrates a strong affinity for the alpha2-adrenoreceptor, acting as an antagonist similar to yohimbine. This antagonistic action inhibits negative feedback, resulting in increased noradrenaline release.
Another study provides EC50 values for 1-Benzylpiperazine (BZP), measuring its potency in releasing neurotransmitters through its affinity for dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT, respectively). These values are 175, 62, and 6050, respectively. For comparison, the listed values for d-amphetamine are 25, 7, and 1765, while d-methamphetamine’s steals are 25, 12, and 736. These ratios indicate that BZP shares similarities with the drugs above, albeit with lower potency (approximately 7 times more down due to lower affinity). Consequently, BZP exhibits activity akin to these drugs rather than serotonergic substituted amphetamines like MDMA.
Additionally, BZP serves as a non-selective serotonin receptor agonist, affecting various serotonin receptors. Binding to 5-HT2A receptors potentially elucidates its mild hallucinogenic effects at higher doses. Meanwhile, its partial agonist or antagonist effects on 5-HT2B receptors may explain some peripheral side effects, as this receptor is highly concentrated in the gastrointestinal tract. Furthermore, interaction with 5-HT3 receptors may be the underlying cause of common side effects such as headaches, given their involvement in migraine development.
Effects of BZP
The effects of BZP closely resemble those of amphetamines, so much so that a study found that former amphetamine addicts were unable to distinguish between dextroamphetamine and intravenously administered BZP. Furthermore, a study from 2005 revealed that mixtures of BZP and other piperazine drugs, such as TFMPP, share specific pharmacodynamic characteristics with MDMA.
Ingesting BZP, typically between 50 mg and 200 mg, may lead to various experiences:
- Feelings of euphoria, wonder, amazement, well-being, energy, and joy.
- Rapid mood elevation.
- Enhanced sociability.
- Greater appreciation of music.
- Increased desire to move, with a slight rise in stereotypy.
- Skin tingling.
- Decreased appetite.
- Repetitive thought patterns.
- Actual and perceived changes in body temperature.
- Mild jaw clenching/bruxism.
- Increased heart rate.
- Pupil dilation.
- Mild xerostomia (dry mouth).
- Slight urinary incontinence, often described as “leaking” a small amount of urine after urinating (not due to loss of bladder control).
- Mild headache.
- Hangover-like symptoms (common with high doses).
- Indigestion (similar to acid indigestion/heartburn).
- Increased hunger (and sometimes thirst).
- Depression (particularly with frequent/heavy use).
Research on BZP’s tolerance is limited, but anecdotal evidence from online sources suggests that tolerance to BZP’s central action may develop rapidly. Given the fatigue associated with the body’s recovery from stimulants like BZP, it is uncommon for users to sustain a week-long intake: 653.
Like most sympathomimetic stimulants, BZP use is linked to significant side effects. It has been reported to cause insomnia and a mild to severe hangover after the drug effect diminishes. A substantial portion of toxic effects data originates from a 2005 study that catalogued presentations associated with party pill usage at the Emergency Department of Christchurch Hospital, New Zealand. This study documented fourteen toxic seizures in two patients, leading to life-threatening toxicity with status epilepticus and severe respiratory and metabolic acidosis. Several similar studies confirm that BZP can induce unpredictable and extreme toxicity in specific individuals. However, it’s essential to note that these findings relied on self-reports from drug users, which may result in under-reporting or over-reporting and were often complicated by the presence of alcohol and other drugs.
The significant side effects encompass dilated pupils, blurred vision, dry mouth, extreme alertness, pruritus, confusion, agitation, tremor, extrapyramidal symptoms (dystonia, akathisia), headache, dizziness, anxiety, insomnia, vomiting, chest pain, hallucinations, paresthesia, tachycardia, hypertension, palpitations, collapse, hyperventilation, sweating, hyperthermia, and difficulties with urine retention. More severe toxic effects include psychosis or adverse psychiatric events, renal toxicity, respiratory failure, hyperthermia, serotonin syndrome, rhabdomyolysis, and seizures. Blood benzylpiperazine concentrations have been measured, either to confirm clinical intoxication or as part of a medicolegal death investigation.
Risk of Fatality
Ingesting piperazine derivatives alone rarely results in death. A retrospective study conducted at an Auckland emergency department found that BZP presentations made only a minor contribution to their overdose database, with most cases not causing significant toxicity. Only one death has been attributed to ingestion of BZP alone, with a measured blood concentration of 8 mg/L
However, when combined with alcohol or other illicit drugs, such as TFMPP and MDMA, multiple deaths have been reported. For example, a combination of BZP and MDMA taken by a 23-year-old DJ nearly resulted in death, leading to an induced coma and subsequent recovery. Another case from Zurich in 2001 involved a 23-year-old individual who had ingested BZP and MDMA and subsequently died from massive cerebral oedema 57 hours after hospital admission.
BZP has not demonstrated physical addictive properties in humans. Most BZP users claim they could stop using the substance but choose not to. Studies on animals have shown that BZP can serve as a substitute for methamphetamine in addicted rats, albeit with one-tenth the potency and correspondingly weaker addictive effects.
BZP is prohibited in several countries, including Australia, Austria, Canada, Denmark, Estonia, France, Germany, Greece, Ireland, Italy, Japan, Malta, Poland, Sweden, and the United States. Interestingly, BZP is not controlled under any UN convention, meaning that the compounds themselves remain legal in most parts of the world, albeit with restrictions on their use that typically encompass pharmaceutical manufacturing.
In Australia, BZP is banned throughout all states. Victoria, the last state where it remained legal, reclassified it on September 1, 2006. This reclassification placed BZP and piperazine analogues under illegal status in the federal schedules, which are enforced by all Australian states and territories.
Benzylpiperazine and its salts are classified as Schedule III controlled substances under Canada’s Controlled Drugs and Substances Act.
Benzylpiperazine underwent a risk assessment by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) to determine its control within the European Union. This assessment followed a joint Europol – EMCDDA report that recommended a closer examination of BZP. The resulting report was published in June 2007 and concluded that BZP’s use could lead to medical issues, even though the long-term effects remained unknown. Building on this, the European Commission requested the Council to place BZP under the control of the UN Convention on Psychotropic Substances. On March 4, 2008, the EU asked countries to subject BZP to control within a year.
The New Zealand government acted on the advice of the EACD, passing legislation that reclassified BZP and other piperazine derivatives (TFMPP, mCPP, pFPP, MeOPP, and MBZP) as Class C substances under the Misuse of Drugs Act 1975. While the ban was initially scheduled for December 18, 2007, it was not implemented until the following year. Consequently, the sale of BZP and the other listed piperazines became illegal in New Zealand starting on April 1, 2008. An amnesty for possession and use of these drugs remained in effect until October 2008, at which point they became entirely illegal.
In the United Kingdom, piperazine and its salts are classified as Prescription Medicines, and any products containing these salts are licensable under the Medicines Act. This means that anyone manufacturing and supplying them legally must hold the relevant licenses. While BZP is not a salt of piperazine, mislabeling of BZP products as containing a “piperazine blend” led to some prosecutions of suppliers in the UK by the Medicines and Healthcare Products Regulatory Agency, although none were successful. In May 2009, the Home Office unveiled plans to ban BZP and initiated a consultation on the proposal. By October 2009, it was confirmed that, as of December 23, 2009, BZP and related piperazines would be classified as Class C drugs under the Misuse of Drugs Act.
BZP was federally classified as a Schedule I controlled substance in the United States in 2002. This decision followed a DEA report that erroneously stated that BZP was 10 to 20 times more potent than amphetamine when, in reality, BZP is 10 times less potent than dexamphetamine. Additionally, at the state level, BZP is illegal in Florida, Oklahoma, Vermont, and Virginia.
1. What is Benzylpiperazine (BZP)?
Benzylpiperazine, often referred to as BZP, is a synthetic compound that belongs to the class of piperazine derivatives. It is known for its stimulant and euphoric effects, which can be similar to those of amphetamines.
2. How is BZP typically consumed?
BZP is usually consumed orally in the form of pills, capsules, or powder. It can be ingested alone or in combination with other substances, although combining drugs can be risky and is generally discouraged.
3. What are the effects of BZP?
BZP can produce effects similar to amphetamines. These effects may include feelings of euphoria, increased energy, enhanced sociability, and heightened appreciation of music. It can also lead to increased heart rate, dilation of pupils, and mild side effects like nausea and dry mouth.
4. Is BZP addictive?
BZP is not found to be physically addictive in humans. However, it may have some potential for psychological dependence, particularly when used repeatedly or in high doses.
5. What are the potential risks and side effects of BZP?
BZP use can lead to various side effects, including insomnia, headaches, confusion, nausea, and anxiety. In some cases, more severe effects like seizures, hyperthermia, and respiratory issues have been reported. It’s essential to use BZP responsibly and be aware of these potential risks.
6. Is BZP legal?
The legal status of BZP varies from one country to another. It is banned in many countries, including Australia, Canada, New Zealand, the United States, and various European nations. However, the regulations and classifications can change, so it’s essential to check your local laws and regulations.
7. Can BZP be used safely?
Like many recreational substances, the safety of using BZP depends on factors like dosage, frequency of use, and individual reactions. It’s crucial to be informed, use it responsibly, and avoid mixing it with other substances, which can increase risks.
8. What precautions should I take if I choose to use BZP?
If you decide to use BZP, consider the following precautions:
- Start with a low dose to gauge your body’s response.
- Avoid frequent or heavy use to prevent tolerance and dependence.
- Do not combine BZP with other substances, as this can be dangerous.
- Stay hydrated and be mindful of your body’s temperature, especially when using it in hot environments.
9. Can BZP cause fatal overdoses?
Ingesting BZP alone rarely leads to fatal overdoses. However, when combined with other drugs, such as MDMA, or consumed in high amounts, it can lead to severe health complications and, in rare cases, death.
10. Is BZP used for any legitimate medical purposes?
BZP is not approved for medical use and does not have legitimate medical applications. It is primarily used for recreational purposes, although its legality for such use varies by country.
Always prioritize your health and well-being, and consult with healthcare professionals if you have any concerns about using substances like BZP. It’s essential to stay informed and make responsible choices regarding drug use.
**1. Anvisa (24 July 2023). “RDC Nº 804 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial” [Collegiate Board Resolution No. 804 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). The Diário Oficial da União (published 25 July 2023). Archived from the original on 27 August 2023. Retrieved 27 August 2023.
**2. “Benzylpiperazine [BZP], namely 1-benzylpiperazine and its salts, isomers, and salts of isomers.” Controlled Drugs and Substances Act: Schedule III. Government of Canada, Justice Laws Website. 14 January 2023.
**3. “Amending Schedule III to the Controlled Drugs and Substances Act (BZP and TFMPP).” Canada Gazette. Retrieved 24 November 2012.
**4. Antia U, Lee HS, Kydd RR, Tingle MD, Russell BR (April 2009). “Pharmacokinetics of the ‘party pill’ drug N-benzylpiperazine (BZP) in healthy human participants.” Forensic Science International. 186 (1–3): 63–67. doi:10.1016/j.forsciint.2009.01.015. PMID 19261399.
**5. Johnstone AC, Lea RA, Brennan KA, Schenk S, Kennedy MA, Fitzmaurice PS (November 2007). “Benzylpiperazine: a drug of abuse?” Journal of Psychopharmacology. 21 (8): 888–894. doi:10.1177/0269881107077260. PMID 17606471.
**6. Schep LJ, Slaughter RJ, Vale JA, Beasley DM, Gee P (March 2011). “The clinical toxicology of the designer ‘party pills’ benzylpiperazine and trifluoromethylphenylpiperazine.” Clinical Toxicology. 49 (3): 131–141. doi:10.3109/15563650.2011.572076. PMID 21495881.
**7. Gee P, Schep LJ (2022). “Chapter 12: 1-Benzylpiperazine and other piperazine-based stimulants.” In Dargan P, Wood D (eds.). Novel Psychoactive Substances (2nd ed.). Elsevier. pp. 301–332. doi:10.1016/b978-0-12-818788-3.00009-7. ISBN 978-0-12-818788-3.
**8. Topping A (18 June 2007). “Legal dance drug faces ban amid fears over side-effects.” The Guardian. Retrieved 26 May 2008.
**9. “Harney announces ban on stimulant BZP.” The Irish Examiner. 18 June 2007. Archived from the original on 6 April 2009. Retrieved 28 December 2009.
**10. Kerr JR, Davis LS (March 2011). “Benzylpiperazine in New Zealand: brief history and current implications.” Journal of the Royal Society of New Zealand. 41 (1): 155–164. doi:10.1080/03036758.2011.557036. ISSN 0303-6758.
**11. “Lay off the party pills.” New Zealand Medical Association. 1 November 2006. Retrieved 22 April 2007.
**12. White RH, Standen OD (October 1953). “Piperazine in the treatment of threadworms in children; report on a clinical trial.” British Medical Journal. 2 (4839): 755–757. doi:10.1136/bmj.2.4839.755. PMC 2029560. PMID 13082101.
**13. Standen OD (July 1955). “Activity of piperazine, in vitro, against Ascaris lumbricoides.” British Medical Journal. 2 (4930): 20–22. doi:10.1136/bmj.2.4930.20-a. PMC 1980175. PMID 14378628.
**14. Campbell H, Cline W, Evans M, Lloyd J, Peck AW (October 1973). “Comparison of the effects of dexamphetamine and 1-benzylpiperazine in former addicts.” European Journal of Clinical Pharmacology. 6 (3): 170–176. doi:10.1007/BF00558281. PMID 4586849.
**15. Gee P, Fountain J (February 2007). “Party on? BZP party pills in New Zealand” (PDF). The New Zealand Medical Journal. 120 (1249): U2422. PMID 17308559. Archived from the original (PDF) on 13 October 2007.
**16. “Ecstasy Mimic Tablets.” Microgram Bulletin. Drug Enforcement Administration, U.S. Department of Justice. December 2008. Archived from the original on 14 January 2009.
**17. “Drugs and Chemicals of Concern: N-Benzylpiperazine.” Drug Enforcement Administration, U.S. Department of Justice. June 2006. Archived from the original on 7 April 2007. Retrieved 22 April 2007.
**18. “Misuse of Drugs Amendment Act 2005” (PDF). New Zealand Government. 17 June 2005. Archived from the original (PDF) on 16 July 2007. Retrieved 22 April 2007.
**19. Alansari M, Hamilton D (May 2006). “Nephrotoxicity of BZP-based herbal party pills: a New Zealand case report.” The New Zealand Medical Journal. 119 (1233): U1959. PMID 16680176.
**20. Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB (October 2004). “Effects of ‘Legal X’ piperazine analogs on dopamine and serotonin release in rat brain.” Annals of the New York Academy of Sciences. 1025 (1): 189–197. Bibcode:2004NYASA1025..189B. doi:10.1196/annals.1316.024. PMID 15542717.