Illegal drug-makers have been combining an ultra-potent "zombie" chemical linked to dozens of deaths with another better known from New Zealand's notorious party pill era.
Scientists don't know why the two have been mixed in synthetic cannabis coming into the country – but suspect designers are either trying to make their highs longer and stronger, or less harmful.
The two chemicals are AMB-Fubinaca, reported to be 75 more powerful than the THC in cannabis plants, and pFPP, a piperazine derivative sold as an ingredient in psychedelic party pills here and overseas.
AMB-Fubinaca is particularly infamous for inducing zombie-like behaviour, and fuelling an outbreak in New York in 2016 that gained it worldwide notoriety.
In New Zealand, it's been involved in 80 per cent of 90 synthetic cannabis-related deaths reported between 2017 and September last year - most of them in the upper North Island.
ESR scientists, who regularly carry out forensic examination of suspected drugs seized by police and Customs, have been tracking the worrying rise of AMB-Fubinaca over the past few years.
In 2017, ESR received plant material from nearly 150 seizures that year, most of it contained in unmarked bags and weighing from less than a gram to hundreds of grams.
Of 246 analyses carried out, 157 samples were found to contain AMB-Fubinaca, of which 55 also included pFPP.
In a just-published study describing the results, researchers could only speculate on why the two had been mixed in together.
"We don't know the reason," ESR's forensic chemistry manager Kevan Walsh told the Herald.
"The use of multiple drugs is known as 'polydrug' use. Polydrug use may be employed to maximise desired mind-altering effects or it may be used to balance or counteract undesirable effects of the use of a particular drug."
The study concluded there was "potential harm" to the user, given the variability of dose and the addition of other drugs in the mix.
"As with all drug use, health concerns relate to the unknown constituents and unknown dosage," Walsh said.
"Polydrug use is a cause for increased concern as the cumulative effects can have unintended and dangerous consequences. This may be compounded by the variable and high dosages typically observed."
It happened to be the first time anywhere in the world that a piperazine had been found in plant material with a synthetic cannabinoid.
In Europe, it was common to find pFPP and MDMA in the same tablets.
Walsh said their combined use was reported as being due to the piperazine exhibiting a less potent and intense effect compared to MDMA, which resulted in a gradual return to normality rather than a sharp decrease.
"The combined use of pFPP with AMB- Fubinaca encountered in New Zealand, may be for a similar reason as that observed in Europe."
Back in the early 2000s, New Zealand was a global hot-spot for party pills or "legal highs", and piperazines like pFPP were common ingredients.
Walsh said it may be that using pFPP with newer psychoactive substances like AMB-Fubinaca could "reflect familiarity".
Professor Michelle Glass, head of Otago University's Department of Pharmacology and Toxicology, said piperazines were usually considered to be amphetamine-like in their effects.
But, unlike the well-known BZP, little was understood about the molecular pharmacology or toxicology of pFPP.
Although pFPP was a metabolite of niaprazine - a sedative, hypnotic drug – it was not believed to have any sedative effects.
Rather, Glass said, it was suggested to be what's called a 5HT1a agonist – something that was thought to actually prevent sedation.
"So we speculate that pFPP could be added to the synthetic cannabinoids to modify some of the adverse effects."
Glass and colleagues were exploring the potential interactions in a new study recently awarded funding from the Health Research Council.
Over recent years, synthetic recreational drugs had become such a problem that Wellington's Capital and Coast District Health Board launched a pilot programme to try to pin-point new ones that patients had taken.
It was part of ESR's wider "Border to Grave" drug surveillance activities, which aimed to identify new synthetic drugs as they entered New Zealand and track their real-time use in the community.
A Customs spokesperson said synthetic cannabinoids and psychoactive substances were continuing to be seized, although no spike had been observed recently.
Customs statistics showed nearly 23kg of synthetic cannabinoids had been intercepted over the past decade – with most of the 176 different items coming through the mail centre.