Deaths linked to so-called "legal highs" more than tripled in two years, an official report has found.
Experts said the number has increased over a ten-year period from 2004, with a total of 76 recorded during that time frame in England and Wales.
There was a "marked" rise between 2011 and 2013 when cases jumped from seven to 23.
The analysis by the Office for National Statistics - which comes as the Government prepares to introduce a crackdown on the drugs - found that men in their 20s were most at risk.
Its study said the average age for deaths involving legal highs is 28, ten years younger than the average for illegal drugs.
The youngest person to die after taking a legal high was aged 18, and nine teenagers have died between 2004 and 2013.
Vanessa Fearn, mortality researcher at the ONS, said: "Some people think that because these drugs are or were legal until recently, they are safe.
"Forensic testing has shown that a single tablet or powder can contain a mixture of different substances, and even 'traditional' illegal drugs, which may explain why the majority of deaths involving legal highs involved more than one drug."
The number of deaths involving legal highs remains "very small" compared with those linked to illegal drugs such as heroin and cocaine.
Over the same 10-year period there were more than 100 times as many deaths involving heroin or morphine (7,748) and more than 20 times as many deaths involving cocaine (1,752).
Legal highs - officially referred to as new psychoactive substances - saw an explosion in popularity on the drug scene in around 2008 and 2009. They contain substances which mimic the effects of "traditional" illegal drugs like cocaine, cannabis and ecstasy.
Researchers examined the impact of the controlling of mephedrone - also known as "meow meow" - which was outlawed as a Class B substance in April 2010.
The first death involving mephedrone occurred in 2009, and deaths continued to rise for several years following the ban, peaking at 22 deaths in 2012, before falling to 12 deaths in 2013, according to the report.
It added: "This suggests that banning mephedrone did not immediately reduce the number of mephedrone-related deaths. However, it is possible that mephedrone use would have increased and deaths would have been even higher, had it not been banned."
A blanket ban on the production, distribution, sale and supply of new psychoactive substances is scheduled to be rolled out within weeks, with sellers facing up to seven years in prison.
The measures had been expected to come into force earlier this month but the start date was pushed back.
The ONS analysis focused on substances that were not controlled under the Misuse of Drugs Act 1971 on the day the person died, and analysed drug-related deaths cases in which a death certificate mentioned a legal high.
Other drugs or alcohol may also have been mentioned, so the legal high may not have been the primary cause of death in all 76 cases.