The number of people who died from drugs in 2020 was almost 4% higher than in 2019, when there were 4,393 drug-related deaths, according to new ONS figures.
Heroin and morphine were the most common causes of drug deaths over 2020, up 69% from ten years ago.
MDMA caused ten times more deaths than it did in 2010, while cocaine caused five times more over the same period and benzodiazepine-related deaths rose by almost 60%.
The highest rates of drug deaths were in the North East, which recorded 105 drug-related deaths per million people, while London, where the rate was 33 per million, had the lowest.
The highest rate of drug-related deaths was among those aged 45 to 49, and there were more than twice as many deaths among men than women.
The ONS says said around half of the drug-related deaths in 2020 will have actually occurred in 2019, because of delays in registering deaths.
The ONS has said the increase may be down to ageing drug users suffering from the long-term effects of drug use, as well as new trends for taking some drugs, such as gabapentinoids and benzodiazepines, at the same time as taking heroin or morphine.
Experts say the figures aren't surprising when cocaine is now "as easy to order as Deliveroo".
Eytan Alexander, a recovering drug addict and CEO of UK Addiction Treatment Centres, told the Guardian: "We're living in a parallel pandemic: a drug, alcohol, and mental health pandemic that has only worsened due to the virus. Enough is enough … we need to come together as a society and take real action."
Last week the government announced it will launch projects in eight areas in England to "disrupt drug supply and support those in need with treatment and recovery".
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