Researching the toxicity of party pills: party pill use is on the increase. A research study at Christchurch Hospital's emergency department is tracking the adverse reactions to ingestion of these substances, which in New Zealand are freely availabe to any one aged over 18.

Party pills or "herbal highs" have become widely available and commonly used among New Zealanders in the past 12 months. They have been marketed as "herbal" and "safe" but accumulating evidence is showing they are neither. A growing number of patients are experiencing adverse effects from piperazine-based party pills (PPPs).

Three months ago a 16-year-old female had a life threatening event as a result of 1-Benzyl piperazine (BZP), the main ingredient in most party pills in New Zealand. She was out having a good time at a sporting event with friends. She had drunk no alcohol but had taken three party pills at 7pm and took a further one at 8.30pm. She had no suicidal or self harm intent, merely a desire to enjoy the evening. At 11pm she collapsed in a crowd and had a witnessed tonic clonic seizure. The ambulance arrived when the patient was post ictal. Seizure activity started again and two doses of diazepam were required to stop the seizures. The patient was totally unresponsive and was intubated for airway control and transferred to the hospital. On arrival she had a heart rate of 14g, blood pressure of 70/55 and blood sugar of 5.6. She had three further seizures in the emergency department (ED). Her first blood gas showed a severe mixed metabolic and respiratory acidosis with a pH of 6.87 units/L (7.35-7.45) The patient was transferred to the intensive care unit (ICU). Twelve hours later she was extubated and had a Glasgow Coma Scale reading of 15.

Potentially fatal outcome

A week later she reported she "felt unwell but better" and appeared to have suffered no apparent further significant adverse effects. This patient was lucky and owes her good outcome to early ambulance and hospital care. Her outcome could easily have been fatal.

Party pills are taken for their ability to increase alertness, elevate mood and energy. The main ingredient in most party pills in New Zealand is BZP. It is sometimes mixed with a related compound, trifluormethylphenylpiperazine (TFMPP).

For several years PPPs have been sold free of any legal constraint. As from July 2005 BZP is legally available for sate to anyone over 18 years old in New Zealand. It is available under dozens of brand names including Frenzy, Bliss, Charge and Herbal Ecstasy. It is sold as capsules, powder or liquid from an increasing number of retailers.

One common misconception is that BZP is a naturally occurring substance. It is a purely synthetic compound. Most BZP on the New Zealand market seems to be manufactured and imported from east Asia. The chemical process to manufacture BZP is easy and cheap and it is probably also being manufactured in domestic kitchens.

BZP was originally synthesised by the Wellcome Research Laboratories United Kingdom as a potential livestock de-wormer. (1) It was not used because it caused seizures in mammals. BZP's parent compound, piperazine, is still used as a poultry worming drug. A cluster of human studies was done in the 1970s to investigate BZP as a potential antidepressant. Research was formally stopped after it was found to have psychoactive effects indistinguishable from dexamphetamine. The researchers recommended that BZP be placed in the same legal class as amphetamines. (2) Little active research in the past 20 years has been done. BZP is illegal in the United States, many European Union countries and is controlled in Australia. It is also banned as a performance-enhancing drug under Sports Drug Agency and World Anti-Doping Agency regulations. One New Zealand athlete has already tested positive and run foul of his sporting code's competitive regulations. (3)

Increase in presentations

Patients were presenting to Christchurch Hospital's Emergency Department (ED) with PPP toxicity as early as three years ago but were very infrequent up until six months ago. Every weekend this year, three to five patients are seen with adverse and toxic effects from PPPs. This increase in presentations is consistent with the increase in availability of PPPs--they are available from party pill shops, dairies, garages and mobile "party vans" There is very tittle toxicity research in humans that can help guide management of these cases. Most human experimental research was based on the use of much smatter doses of BZP than currently used in New Zealand. Absence of toxicity data, however, does not necessarily equate to absence of toxicity. In Christchurch we have been collating the presentations of patients to Christchurch Hospital's ED, who report or who have clear signs of PPP toxicity. There has been no other significant research on human BZP toxicity in the international literature. Patients experienced symptoms such as anxiety, nausea, vomiting, palpitations, myoclonus/involuntary muscle twitching and urinary retention.

Most patients with minor toxicity attend ED because of intractable vomiting, tachycardia, anxiety or confusion. Some present because of insomnia or inability to pass urine. There have also been reports of a prolonged "hangover" and of reversible impotence in males. Most of these patients respond to reassurance, a period of observation and very selective use of benzodiazepines. Some patients have intractable vomiting that does not respond to standard anti-emetics.

The number of patients who present to hospital for treatment probably represents a very small fraction of users in any particular weekend. It has been estimated that more than 20 million doses of BZP have been sold in New Zealand to date.

Many patients take multiple doses of PPP, as the initial dose does not produce any immediate subjective effects. The effects of BZP are often not felt for up to two hours after oral ingestion. Slow onset of action and slow abatement of symptoms seem characteristic for this drug, when taken orally. Unfortunately this means that patients may take excessive doses of BZP before they actually begin to feel any effects. Patients may also suffer adverse effects (commonly palpitations and/or vomiting) for up to 24 hours after ingestion. Many users now overcome this "shortcoming "and inject intravenously to get a faster high.

Case reports are accumulating of patients who have developed new onset psychosis or decompensation of an existing psychiatric disorder. One 20-year-old patient developed an acute paranoid psychosis after ingestion of four PPPs and set fire to his house. He was subdued by police and his symptoms abated after 48 hours under psychiatric care. (4)

Of greatest concern are 12 patients in our study who had seizures after the ingestion of party drugs. Two patients required ICU admission because of seizures. One was described above. The other patient had a total of five seizures, despite repeated doses of diazepam and midazolam. She had a recorded plasma pH of 6.64. Subsequent toxicology on both these patients confirmed the presence of BZP with no other toxic agents. Both received intensive supportive treatment and recovered with no apparent long-term effects.

Another patient had a seizure white driving, several hours after PPP use, and narrowly averted a head-on collision. A case was recently reported from the North Island where a young woman took one tablet of a diet pill containing BZP and suffered a seizure.

BZP induces toxic seizures in neurologically normal subjects. It is not clear whether this is a dose related effect as yet--one patient reported taking 12 tablets before a seizure and one reported having only taken one before having a seizure. In animal studies 10mg/kg of BZP is enough to induce seizures in most laboratory rats. BZP is available in Christchurch in dose packages equivalent to 20mg/kg for a human. Our experience with BZP has shown it to have a very similar toxic profile to amphetamines. Other side effects of amphetamines such as cardiac arrhythmia, haemorrhagic stroke and chronic neurological excitotoxicity have yet to be linked conclusively to BZP. We are planning to conduct a larger study of BZP toxicity once ethics committee approval is granted.

The Government has passed legislation to place legal controls on the sale of BZP to minors. It has determined that there is inadequate information about BZP to put stronger controls on its distribution at present and has commissioned research into BZP toxicity. It is planned to review the available evidence in 2006 to make a more informed decision on specific regulation. In the meantime, vigilance is required when dealing with patients with BZP toxicity. The authors strongly recommend that:

* PPPs should be avoided if the potential user has known cardiac disease, a known seizure history or a psychiatric disorder.

* PPPs should not be taken if the potential user is on prescription antidepressants, antipsychotics or is using illicit drugs.

* People should not drive for 12 hours after using PPPs.

* Any cases of BZP toxicity should be directly notified to the National Poisons Centre 0800 POISON or e-mail [e-mail].

References

(1) BZP: General Information http://www.erowid.org/chemicais/bzp/bzp.html

(2) Campbell, H., Cline, W., Evans, M., Lloyd, J. and Peck, A.W. (1973) Comparison of the Effects of Dexamphetamine and 1-Benzyipiperazine in Former Addicts. Eur J Clin Pharmacol; 6: 3,170-6.

(3) Dilemma as athlete tests positive to party drug BZP. The New Zealand Herald, Wednesday, July 13, 2005.12.00pm. http://www.nzherald.co.nz/topic/story.cfm?c_id=500833&objectid=10335623.

(4) Austin H and Monasterio E. (2004) Acute psychosis following ingestion of 'Rapture'. Australas Psychiatry; 12: 4, 406-8.

Paul Gee, MB ChB, BHB, BHB, FACEM, is an emergency consultant in the Emergency Department (ED), Christchurch Hospital, Canterbury Distirct Health Board (CDHB). Sandra Richardson, RN, BA, DipSocSci, PG DipHealthSci, is a nurse researcher in the ED, Christchurch Hospital, Canterbury DHB.