One in three prisoners said they had taken drugs formerly known as "legal highs" in the last month, a poll found.
Of 625 respondents, 33% of inmates reported having used spice - a synthetic substance which mimics the effects of cannabis - in recent weeks.
This means it is now the most popular drug behind bars, according to a report from charity User Voice.
It said: "The main causes of the thriving spice market in custody were prisoners' desire for 'mind-numbing' experiences, combined with the huge amounts of money which can be made from selling spice inside prison."
Participants cited addiction, debt, violence, bullying and mental health problems among the harmful consequences associated with using spice.
Researchers surveyed prisoners in nine prisons in England between December and March, to examine the phenomenon of legal highs - officially referred to as new psychoactive substances (NPS).
The study - covering a period before new laws aiming to crack down on the drugs were introduced - was carried out on behalf of the NHS.
The findings come as the Government attempts to get a grip on the problem of NPS use behind bars, after it was linked to soaring levels of violence across the prison estate.
Figures show the drugs may have played a part in the deaths of at least 39 inmates between June 2013 and June 2015.
Last week a blanket ban criminalising the production, distribution, sale and supply of the former legal highs came into force. Under the new law it is also an offence to possess a psychoactive substance in a custodial institution.
Kate Davies, of NHS England, said: "The worrying increase in new psychoactive substance use in prisons is a priority for all health care service providers now and in the future.
"The voice and experience of men and women in prisons is vital to provide a thorough understanding of how this can be tackled and will help determine the level of response required with our partners across the National Offender Management Service and prison estate."
A Prison Service spokesman 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."