More than 40 deaths were linked to a group of now-banned legal highs in 2010, eight times as many as the previous year, figures have shown.
The biggest increase related to meow meow, which rose from five deaths in 2009 to 29 the following year, the National Programme on Substance Abuse Deaths report showed.
Methcathinones, which include meow meow and have since been made class B drugs, "tightened their grip on the recreational drug scene in western Europe but especially the British Isles", the report said.
It went on: "The rapidity with which these new substances have emerged appears to be at an increasing rate.
"In the past, the market for new psychoactive substances to explore evolved steadily over much longer periods of time.
"It is now difficult to gauge with any certainty what will be the next 'big thing' that will capture the attention of the experimenter or regular recreational drug user."
Deaths from use of methcathinones - which include mephedrone, commonly known as meow meow - rose to 43 in 2010 from five the previous year, the figures based on information from coroners showed.
Controls on previous legal highs such as ketamine, piperazines, and so-called date-rape drugs GHB and GBL helped reduce their popularity, the report said.
Overall, drug-related deaths in the UK fell by almost 14% to 1,883 in 2010 from 2,182 the previous year.
Professor Hamid Ghodse, director of the International Centre for Drug Policy (ICDP) at St George's Hospital, London, which released the report, warned against complacency.
"There are indications that there is still a general upward trend in fatalities involving emerging drugs such as mephedrone and prescription drugs such as methadone," he said.
"This is a great concern and it is clear that much work is still required in improving access to effective treatment and rehabilitation services, and, most importantly, finding prevention strategies to stop people being at risk in the first place."
A Department of Health spokeswoman said: "Any death related to misuse of drugs is a tragedy for the victim, their families and their friends.
"So-called legal highs are not a safer alternative to illegal drugs. As with any substances, the risks increase if you combine them with alcohol or other drugs."
She went on: "Our drugs strategy aims to get people off drugs and stay off drugs and from next year, local authorities will be given a ring-fenced public health budget to tackle local public health issues.
"This will offer real opportunities to integrate drug treatment and other local services."
The number of drug-related deaths in England fell to 1,358 from 1,524 in 2009, while in Scotland the number of deaths fell to 365 from 479, and in Wales they were down to 81 from 102.
In Northern Ireland, the number of drug-related deaths rose to 72 from 65, the figure showed.
In the UK, around three-quarters of deaths were of men (1,386) and three in five were aged 25-44 (1,135).
The highest rate of drug-related deaths per 100,000 population aged 16 and over in 2010 was in Brighton and Hove (14.8), followed by Manchester (13.4), Blackpool and The Fylde (11.8), Fife (10.3), and Lothian and Borders (10).