So-called "legal highs" have been linked to the deaths of at least 39 prisoners in two years, new figures show.
They indicate that the number of fatalities behind bars in which the use of the drugs may have played a part has risen.
The latest figures cover deaths between June 2013 and June 2015, where the prisoner was known or "strongly suspected" to have been using the new psychoactive substances (NPS).
A previous report published last year recorded 19 deaths between April 2012 and September 2014 in which it was suspected the drugs may have been a factor.
The new total included: two with no cause of death; two that were the result of drug toxicity and the drugs included NPS; six were the result of natural causes but NPS "may have played a part"; one was a homicide of a prisoner "involved with NPS by another prisoner suspected of smoking NPS"; and the remaining 28 were self-inflicted, with some involving psychotic episodes probably resulting from NPS, while for others the drugs "appeared to exacerbate vulnerability".
The disclosure was made by prisons and probation ombudsman Nigel Newcomen.
In a speech to the Reform think-tank he said: "The links to the deaths were not necessarily causal, but nor can they be discounted."
He warned that staff and other prisoners may also be at risk from users "reacting violently" to the effects of new psychoactive substances.
"There are even cases of prisoners being given 'spiked' cigarettes by others who wanted to test new batches of NPS, as a way of gauging the effect before taking it themselves," he said.
"In other cases, prisoners have been used as unwitting NPS guinea pigs, just for the amusement of others."
He identified three types of risk associated with the drugs: to physical health, mental health and associated problems of debt and bullying.
The availability and use of legal highs have been linked to rising levels of violence across the prison estate.
Last year, former chief inspector of prisons Nick Hardwick described new psychoactive substances as the most serious threat to the safety and security of jails.
There were also warnings that the rampant use of the drugs in prisons was placing local ambulance services under strain as paramedics are increasingly called out to tend to inmates who have used them.
New laws have been introduced to target smugglers attempting to sneak the substances into prisons, while a new testing regime is being rolled out.
Mr Newcomen commended prison and health care services for beginning to act.
"We must hope that these efforts have an effect," he said. "But there is a long, long way to go."
Prisons Minister Andrew Selous said: "We take a zero tolerance approach to drugs in our prisons and use sniffer dogs, cell searches and mandatory drugs tests to find them.
"We have already legislated to make smuggling new psychoactive substances into prison illegal, and those caught trying to throw packages over prison walls can now face up to two years in jail.
"However we must do more, which is why we are investing £1.3 billion to transform the prison estate, to better support rehabilitation and tackle bullying, violence and drugs."