Abstract
‘Rapture’ is one of a number of ‘party pills’ or ‘herbal highs’ that are currently available over the counter throughout New Zealand. They are particularly popular among young people, and, due to their reported ability to produce feelings of euphoria, increased energy and a desire to socialize,[1] they are promoted as ‘rave drugs’. These pills, which also include ‘Frenzy’, ‘Exodus’ and ‘Charge’, are marketed as dietary supplements and are actively promoted by their manufacturers as a safe and legal alternative to the use of amphetamines. The main ingredients of these substances are piperazines, which are reported to have stimulant and hallucinogenic properties. These substances are also known to produce increased heart rate, blood pressure, body temperature and locomotor activity and at high doses have been reported to produce hallucinations, convulsions and respiratory depression.[2]
The piperazine substances are derived from pepper plants and they can also be produced synthetically. Pharmacologically, the piperazine class of compounds is divided into two classes, the benzylpiperazines, which includes N-benzylpiperazine (BZP) and the phenylpiperazines, which includes trifluromethylphenylpiperazine (TFMPP). Rapture contains both these compounds.[1] Piperazines are readily absorbed from the gastrointestinal tract. A portion of the absorbed drug is degraded and the remainder is excreted in urine. There is wide variation in the rates at which piperazines are excreted by different individuals, which adds to the variability of their toxicity. N-benzylpiperazine was first synthesized in 1944 as a potential antiparasitic agent and piperazine derivatives are also widely used in industrial chemicals throughout the world. There is, however, no human therapeutic application for BZP or TFMPP.[2],[3]
Abuse of BZP was first described in the USA in 1996 and its use is reported to have spread rapidly throughout the country, particularly in counter culture venues, such as dance parties. Increasing abuse of BZP and TFMPP in the USA is also evidenced by increasing encounters by law enforcement agencies. On the grounds that they have a high potential for abuse and no currently accepted medical use, the United States Drug Enforcement Administration placed these substances under Schedule 1 of the Controlled Substances Act, ‘to avoid an imminent hazard to public safety’, in September 2002.[4]
In recent months, the New Zealand Customs Department has expressed concern at an increase in the volume of piperazines that are being imported into New Zealand. These substances, which are illegal in some states of Australia, are currently being investigated by the New Zealand Expert Advisory Committee on drugs.[5]
In March 2004 the New Zealand Herald published an article on these substances and reported that five young people were admitted to hospital in Dunedin after overdosing on party pills. They were reported to have experienced tachycardia, hypertension and increased body temperature.[3] However, a review of the psychiatric literature (MEDLINE, Psyc Info and Cinahl databases) failed to find any systematic research or documented case reports related to the use of these substances. Personal correspondence with the Christchurch Drug Information Service confirmed only anecdotal evidence of psychiatric symptoms following the use of these compounds, with no formal case reports available. We wish to report the case of a man who developed an acute and serious psychotic episode 12 h after ingesting Rapture.
CASE REPORT
Mr A, 20 years old, had no family history of psychotic disorders or prior history of significant mental health problems. He had no history of conduct disorder or fire setting and had been very successful in terms of academic and social achievements. Mr A attended a party and ingested four tablets of Rapture (maximum recommended dose three tablets) in addition to the use of nitrous oxide and a very small quantity of cannabis (two puffs). Mr A had on two previous occasions used these substances without any problems. Twelve hours following ingestion, Mr A developed an acute psychotic episode associated with intense persecutory delusional beliefs and auditory and visual hallucinations. He believed that he had been imprisoned in the bedroom of his flat where he was under video surveillance and that he was being poisoned by a toxic gas being pumped into the room. He experienced perceptual disturbances as he heard the sound of his door being screwed shut, could see a video camera in the corner of his room and was able to hear and smell the noxious gas. He felt a sensation of tightness in his chest and noticed that his hands had gone blue, which he interpreted as evidence of poisoning. As he believed that his life was in imminent danger, Mr A attempted to alert the authorities to his plight by setting fire to his room. He then jumped out the window of the second floor room and ran away before phoning the police. Mr A subsequently came to psychiatric attention and was admitted to an acute inpatient psychiatric unit. Routine blood tests (including full blood count, electrolytes, creatinine and liver functions) were normal, and a urinary drug screen was negative for alcohol and cannabinoids, but was positive for an amphetamine class compound, most likely benzylpiperazine. Mr A continued to experience anxiety symptoms associated with ongoing persecutory beliefs. These symptoms completely abated within 48 h, with the only treatment being benzodiazepines on an as-needed basis. At 6 month follow up, Mr A remains free of symptoms of psychosis or other psychiatric syndromes.
DISCUSSION
While Mr A did consume other substances in the 24 h preceding the psychotic episode, we believe that it is most likely to have been induced by Rapture or as a consequence of the unusual combination of substances.
Although cannabis has been extensively reported to induce brief psychotic symptoms such as persecutory delusions or auditory and visual hallucinations, especially in persons with underlying psychiatric disorders, Mr A's reported intake of cannabis was negligible and this was evidenced by the absence of cannabinoids in a urinary drug screen taken on hospital admission.[6] Therefore, it is unlikely that cannabis use precipitated Mr A's psychotic episode.
Mr A also consumed a small quantity of nitrous oxide. A search of the literature failed to find documented cases of psychosis following the inhalation of this substance. Users of nitrous oxide may experience euphoria and a pleasant dreamlike state; however, this drug has a rapid onset and offset of action, mostly being excreted in the breath with little or no biotransformation.[6] Given that Mr A's symptoms did not develop until 12 h after the last ingestion of nitrous oxide, it would seem unlikely that this was a causative factor in his psychotic episode.
With regards to the piperazines, BZP is reported to have amphetamine-like effects. Studies have shown it to have a central serotoninomimetic action, which involves a 5-HT uptake inhibition and 5-HT-1 receptor agonist effect. It is reported that TFMPP has hallucinogen-like effects and is thought to have serotoninergic properties.[1]
Although the action of the piperazines on the serotonergic system is the most studied aspect, there is also some evidence that these compounds may have an additional effect on the noradrenergic and dopaminergic systems.[7] Hence, it is conceivable that by their effect on monoaminergic pathways, these compounds could have played a part in triggering the psychotic episode.
Finally, the effect of the piperazines in combinations with other recreational drugs is not known. There is one reported case of fatal brain oedema after ingestion of ecstasy and benzylpiperazine.[1] Given the increasing use of these substances, we recommend that clinicians are alert to the possibility of psychiatric symptoms following their use and that well documented clinical data are obtained.