The number of deaths involving legal highs are at their highest level in five years in Yorkshire and the Humber.
There were 18 deaths registered in 2015 in Yorkshire and the Humber where the cause of death was drug-related and a legal high, otherwise known as a new psychoactive substance, was mentioned on the death certificate.
This was 200% higher than the six deaths recorded in 2014 and up from five in 2011.
The list of new psychoactive substances potentially included in the figures includes mephedrone, synthetic cannabinoids, such as Spice, Khat, and 2-DPMP, known as Ivory Wave.
Across England and Wales, there were 114 deaths registered in 2015 where the underlying cause was drug-related and a new psychoactive substance was mentioned on the death certificate.
This was 39% higher than the 82 deaths recorded in 2014, and nearly four times higher than the number in 2011, 31.
London had the highest number of deaths where a new psychoactive substance was mentioned on the death certificate at 21, followed by Yorkshire and the Humber at 18.
The figures from the Office for National Statistics are for deaths registered, rather than deaths occurring in each calendar year.
Meanwhile, nearly 500 people have been arrested since a ban on so-called legal highs came into force six months ago, the Home Office has said.
Just four people have been jailed since psychoactive substances were outlawed at the end of May, but the Government said more are progressing through the courts.
The designer drugs have increasingly become the drugs of choice for prisoners, and have been blamed for contributing to rising levels of violence in Britain’s troubled jails.
Some 492 people were arrested in the six months after the legislation came into force on May 26.
Some 332 shops across the UK have stopped selling the drugs while 31 head shops – which sell drugs paraphernalia – have closed down.
Home Office minister Sarah Newton said: “We banned new psychoactive substances because they are not safe, they can devastate lives and we will not tolerate them in this country.
“I am pleased to see the police making full use of the new powers, arresting dealers and ensuring they are punished with prison sentences which reflect the seriousness of this crime.
“At the same time as supporting law enforcement in tackling the supply of illegal drugs, we are also taking action to prevent the harms caused by their use – from educating young people about the risks to helping dependent individuals through treatment.”