Researching the toxcity of party pills

RESEARCH
Party pill use is on the increase.
A research study ot 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.
By Paul Gee and
Sandra Richardson,
A variety of party pills.
P
arty 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 pariiy piLLs (PPPs).
Three months ago a 15-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 149, bLood pressure of
70/55 and bLood sugar of 5.6. She had three
furiiher seizures in the emergency depari;ment
(EO). 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 fortheir 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).
'BZP was originally synthesised
by the Wellcome Research
Laborotones United Kingdom
as a potential livestock dewormer. It was not used because it caused seizures in
mammals.'
For several years PPPs have been sold free of any
legaL constraint. As from JuLy 2005 BZP is LegaLLy avaiLabLe for saLe to anyone over 18 years
oLd in New ZeaLand. It is avaiLabLe under dozens
of brand names incLuding Erenzy, 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
naturaLiy 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.^ 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.^ 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.^
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 veiy Little toxicity
research in humans that can heLp guide management of these cases. Most human experimentaL research was based on the use of much
smaLLer 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 interna-
KAI n A K I NUR5ING NEW ZEALAND > DECEMBER/JANUARY 2005/2006
tionaL Literature. Patients experienced symptoms
such as anxiety, nausea, vomiting, paLpitations,
myoclon us/in voluntary muscLe twitching and
urinary retention.
'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.'
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
a nti-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 decom-
pensation 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.^
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.
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.
The chemical structure of BZP.
Another patient had a seizure whiLe driving, sev-
• PPPs should not be taken if the potentiaL
eraL hours after PPP use, and narrowLy averted a
user is on p r e s c r i p t i o n
head-on coLLision. A case was recently reported
antipsychotics or is using iLLicit drugs.
antidepressants,
from the North IsLand where a young woman
• PeopLe shouLd not drive for 12 hours after
took one tablet of a diet piLL containing BZP
using PPPs.
and suffered a seizure.
• Any cases of BZP toxicity shouLd be directLy
BZP induces toxic seizures in neurologicaLLy
notified to the NationaL Poisons Centre 0800 POI-
normal subjects. I t is not cLear whether this is a
SON
dose reLated effect as yet — one patient re-
mairead.harnett@stonebow.otago.ac.nz. •
or
e-maiL
ported taking 12 tabLets before a seizure and
one reported having only taken one before having a seizure. In animaL studies lOmg/kg of BZP
Paul Gee, MB ChB, BHB, BHB, FACEM, is
is enough to induce seizures in most Laboratory
an emergency consuLtant in the Emergency
rats. BZP is avaiLabLe in Christchurch in dose pack-
Department (ED), Christchurch HospitaL,
ages equivalent to 20mg/kg for a human.
Canterbury Distirct HeaLth Board (CDHB).
Our experience with BZP has shown i t to have a
Sandra Richardson, RN, BA, DipSocSd, PG
very simiLar toxic profiLe to amphetamines. Other
DipHealthSd, is a nurse researcher in the
side effects of amphetamines such as cardiac
ED, Christchurch Hospital, Canterbury DHB.
arrhythmia, haemorrhagic stroke and chronic
References
1) BZP: General Information
http://www.erowid.org/chemicals/bzp/bip, html
2) Campbell, H., Cline, W., Evans, M,, Lloyd, J. and Peck, A.W. (1973) Comparison of the Effects of Dexamphetamire and l-Benzylpiperazine in Former Addicts. Eur J din Pharmacol; 6: 3,170-6.
3) Dilemma as athlete tests positive lo party drug BZP. The New /eaiand
Herald. Wednesday, July 13, ?0O5.12,O0pm, http://www.nifherald.co.nz/topic/story.cfm?c_i(l-500833&objecti(l-10335623.
i) Austin H and Mona^terio E. (3004) Acute psychosis following irgestion of 'Rapture'. Austratai Piychiatry;
12: 4, 406-8.
KAI nAKI NURSING NEW ZEALAND > DECEMBER/JANUARY 2005/2006