Benzylpiperazine

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Benzylpiperazine chemical structure
Benzylpiperazine (BZP)
IUPAC name:

N-Benzylpiperazine
CAS number
2759-28-6		 ATC code
 ?
Chemical formula C11H16N2
Molecular weight 176.26
Bioavailability  ?
Metabolism Primarily hydroxylation (hepatic?)
Elimination half-life A few hours (estimate)
Excretion Primarily urinary
Pregnancy category Uncategorised
Legal status Varies; DEA Schedule 1 drug; legal in some countries
Routes of administration Oral

Benzylpiperazine (BZP) is a recreational drug with euphoric, stimulant effects. It is banned in a few countries, including the United States, Australia and in parts of Europe. However, its legal status is less restrictive in some other countries such as the United Kingdom and New Zealand and Canada. (see below).

Contents

[edit] History

It is often mistakenly claimed that BZP was originally synthesized in 1944 as a potential anthelmintic (anti-parasitic) agent for use in farm animals. However, a paper received for publication in August 1943 refers to benzylpiperazine and references the removal of benzyl groups from piperazines as early as 1941. References to BZP in the literature predate interest in piperazines as anthelmintics. The earliest clinical trials in the literature relating to piperazine use as an anthelmintic are two articles in the British Medical Journal in 1953.

BZP next crops up in the literature when a few studies examined its stimulant effects in the 1970s and 1980s.

In the 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 illicit drugs. Not long after, there was an explosion in the drug's use worldwide — a situation which was soon followed by legislative control in many countries. Piperazine based stimulants had remained virtually unavailable in places such as Canada until recently. In early 2006 pills containing the active ingredients BZP and TFMPP first began to appear in the city of Vancouver where they quickly gained popularity with late-night partygoers as a safer alternative to the illicit street drugs currently available there. BZP based "Legal Highs" are marketed to Canadians under the name "Lovely" and the pills are often referred to as "Lovelies" by the locals.

[edit] Production

A selection of products containing BZP. Legally available throughout New Zealand.

Where legal, BZP is 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 (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. It is worth noting however that as of late 2005 it can no longer be classified or marketed as a dietary supplement in New Zealand.[1]

Well over 20 million pills containing BZP have been consumed in New Zealand with no available record attributing deaths or lasting injuries to BZP toxicity.

Some retailers claim that BZP is a "natural" product, describing it as a "pepper extract" or "herbal high." In fact, the drug is entirely synthetic, and does not occur naturally.

[edit] Effects

Typical pupil dilation
Typical pupil dilation

The effects of BZP are largely similar to dextroamphetamine.[2] 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.

A recent study has shown that mixtures of BZP with other piperazine drugs such as TFMPP share certain pharmacodynamic traits with MDMA.[3]

As with most sympathomimetic stimulants there appear to be significant side effects associated with BZP use. BZP reportedly produces insomnia and a severe hangover after the drug effect wears off, however some manufacturers in New Zealand have started including recovery pills which contain 5-HTP and vitamins which allegedly ease these hangovers. Other side effects include dilated pupils, dryness of the mouth, reduced appetite, teeth clenching and problems with urine retention.

[edit] 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:

Coming down:

  • Reduced sexual sensation - erectile dysfunction is not uncommon despite urges
  • Mild headache
  • Hangover-like symptoms (common with high doses)
  • Fatigue
  • Insomnia
  • Confusion (with higher doses)
  • Mild memory loss
  • Gradual reduction of effects in the "coming up" phase

[edit] Tolerance

Research into BZP's tolerance is sparse. Anecdotal evidence from online sources claim if 100–200 mg of BZP is taken daily, tolerance to the drug begins on day seven.[citation needed] 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.

[edit] Mechanism of action

BZP has been shown to have a mixed mechanism of action, acting on the serotonergic and dopaminergic receptor systems. BZP has amphetamine-like actions on the serotonin reuptake transporter, which increase serotonin concentrations in the extracellular fluids surrounding the cell and thereby increasing activation of the surrounding serotonin receptors. BZP also has a lower potency effect on the noradrenaline reuptake transporter and the dopamine reuptake transporter. BZP also has a high affinity action at the alpha2-adrenoreceptor. BZP is an antagonist at the receptor, like yohimbine, which inhibits negative feedback, causing an increase in released noradrenaline. BZP also acts as a non-selective serotonin receptor agonist on a wide variety of serotonin receptors; binding to 5HT2A receptors may explain its hallucinogenic effects at high doses, while partial agonist or antagonist effects at the 5HT2B receptors may explain some of BZPs peripheral side effects, as this receptor is expressed very densely in the gut, and binding to 5HT3 receptors may explain the common side effect of headaches, as this receptor is known to be involved in the development of migraine headaches.

[edit] Toxic effects of BZP in humans

From 1 April 2005 to 1 September 2005 all presentations associated with party pill use at the Emergency Department of Christchurch Hospital, New Zealand were captured on a prospective data collection form. The aim was to study the patterns of human toxicity related to the use of 1-benzylpiperazine (BZP)-based 'party pills'. 61 patients presented on 80 occasions.

The results of this study indicate that BZP can cause unpredictable and serious toxicity in some individuals.

However, a recent study in New Zealand cleared BZP as a cause of a variety of adverse effects, stating that it wasn't to be connected with life threatening seizures in neurologically normal subjects.[4]

Two deaths have been officially recorded in connection with the use of BZP.[5][6] In both cases, the individual had consumed a quantity of BZP as well as MDMA, and in the first case she had consumed over 10 litres of water, while in the second case a large quantity of alcohol had been consumed. The first individual subsequently died of cerebral edema due to hyponatremia resulting from water intoxication, while the cause of death of the second individual has not been released. It is uncertain what role the BZP may have had in these deaths; while it should be noted that death from hyponatremia is a well known consequence of drinking too much fluids after consuming MDMA, 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. In both cases the actual cause of death appears likely to be fluid intoxication with the drugs as a secondary exacerbating factor, and so these individuals lives could have been saved if they had been given electrolyte drinks or salt when the first signs of hyponatremia appeared, and even when hyponatremia is quite advanced it can usually be reversed by intravenous saline, so it is unfortunate that these individuals did not receive appropriate medical attention quickly enough to save them.

[edit] Addictive Effects

1 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.[7] 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.[8]

[edit] Legal issues

The drug was classified as a Schedule I controlled substance in the United States in 2002, following a report by the DEA which incorrectly stated that BZP was ten times more potent than dexamphetamine, when in fact BZP is ten times less potent than dexamphetamine. 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. 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.

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[9] and consequently anyone manufacturing and supplying it legally must hold the relevant licences to do so. BZP is not a salt of piperazine, but mislabelling of BZP products as containing "piperazine blend" (perhaps in a poorly judged attempt by marketers to conceal the identity of the active ingredient from competitors) has resulted in some prosecutions of suppliers in the UK by the Medicines and Healthcare Products Regulatory Agency.[10]

In some other places (such as New Zealand), BZP is legal. It is classed in New Zealand as a "Restricted Substance" by the Misuse of Drugs Act and restricted to those over 18 years.[11] Products containing BZP are marketed by manufacturers and sellers as a harm-reduction measure, however the legislation is currently under review pending the findings of a number of research projects into the effects of the drug. Research into the long term effects of BZP use are scarce. To date, the drug has been considered to be of low risk of harm to users, but more information is required, and the New Zealand government is considering introducing tighter restrictions in 2007. BZP and TFMPP are legal and uncontrolled recreational drugs in many countries such as Canada, Ireland, New Zealand and the United Kingdom,[12] and 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. Legality

[edit] See also

[edit] References

  1. ^ Misuse of Drugs Amendment Act 2005PDF (81.3 KiB)
  2. ^ One study found that former amphetamine addicts were unable to distinguish between d-amphetamine and BZP administered intravenously. ("Comparison of the effects of dexamphetamine and 1-benzylpiperazine in former addicts." Eur J Clin Pharmacol. 1973 Oct;6(3):170-6.)
  3. ^ "N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy')." Neuropsychopharmacology. 2005 Mar;30(3):550-60.
  4. ^ Gee P, Richardson S, Woltersdorf W, Moore G. Toxic effects of BZP-based herbal party pills in humans: a prospective study in Christchurch, New Zealand. New Zealand Medical Journal. 2005 Dec 16;118(1227):U1784.
  5. ^ Balmelli C, Kupferschmidt H, Rentsch K, Schneemann M. Fatal brain edema after ingestion of ecstasy and benzylpiperazine. Dtsch Med Wochenschr. 2001 Jul 13;126(28-29):809-11.
  6. ^ http://www.nzherald.co.nz/section/1/story.cfm?c_id=1&objectid=10418032
  7. ^ [1]PDF (230 KiB)
  8. ^ K. Brennan, A. Johnstone, P. Fitzmaurice, R. Lea, S. Schenk. Chronic benzylpiperazine (BZP) exposure produces behavioral sensitization and cross-sensitization to methamphetamine (MA). Drug and Alcohol Dependence (2006), doi:10.1016/j.drugalcdep.2006.10.016
  9. ^ Sect. 8 of Medicines Act 1968 - Schedule 3, SI 3144 The Medicines for Human Use (Marketing Authorisations Etc) Regulations 1994
  10. ^ http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2024549&ssTargetNodeId=389
  11. ^ Misuse of Drugs Amendment Act 2005PDF (81.3 KiB)
  12. ^ Controlled Drugs and Substances Act

[edit] External links

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Stimulants

Adrafinil, Amphetamine (speed), Armodafinil, Caffeine, Cocaine, Ephedrine, Epinephrine (adrenaline), Methylphenidate, Modafinil, Nicotine

See also Sympathomimetic amines

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