The number of deaths involving so-called legal highs soared by 80% last year.
Deaths linked to new psychoactive substances - also known as legal highs - increased sharply from 29 in 2011 to 52 in 2012, the Office for National Statistics (ONS) said.
The number of deaths caused by the substances, such as mephedrone, was relatively stable between 2008 and 2011, ranging from 22 to 29, but then spiked last year.
In its bulletin on deaths related to drug poisoning in England and Wales in 2012, the ONS also revealed the number of deaths involving painkiller tramadol has more than doubled since 2008 to 175 in 2012.
Within legal highs, deaths involving a substance called cathinone tripled from six in 2011 to 18 in 2012.
The Advisory Council on the Misuse of Drugs (ACMD) advises the Government on whether a drug should be banned or reclassified.
This process led to new synthetic cannabinoids - such as those sold under the name Black Mamba - and methoxetamine, sold as Mexxy, being made Class B drugs last year. And in June this year, NBOMe and 'Benzofury, two groups of legal highs, were banned for 12 months using a temporary class drug order after advice from the ACMD.
Elsewhere, the ONS revealed that there were 1,706 male drug poisoning deaths - involving both legal and illegal drugs - registered in 2012, a 4% decrease since 2011. Female drug poisoning deaths have increased every year since 2009, reaching 891 in 2012, the ONS said.
The number of male drug misuse deaths involving illegal drugs decreased by 9% from 1,192 in 2011 to 1,086 in 2012, while female deaths decreased by 1% from 413 in 2011 to 410 in 2012. The highest mortality rate from drug misuse was in 30 to 39-year-olds, at 97.8 and 28.9 deaths per million population for males and females respectively in 2012. The number of deaths involving heroin or morphine fell slightly in 2012 to 579 deaths, but these remain the substances most commonly involved in drug poisoning deaths, the ONS said.
Regionally, mortality rates from drug misuse were significantly higher in Wales than in England in 2012, at 45.8 and 25.4 deaths per million population respectively. In England, the North West had the highest mortality rate from drug misuse in 2012 at 41.0 deaths per million population.