The number of deaths in England and Wales due to the synthetic opioid fentanyl rose by 29% in 2017, Office for National Statistics data shows.
Forms of the drug - used to treat cancer pain - are often imported illegally from Chinese laboratories and sold to users via the dark web.
Deaths from psychoactive substances like spice or mephedrone halved.
Drug policy campaigners called on the government to fund drug treatment and stop criminalising users.
"The UK government has nowhere left to hide. They are responsible for vulnerable people dying in droves," Martin Powell from Transform Drug Policy Foundation said.
