How fixing one drug problem inadvertently boosted another



CREATED IN THE LATE 19TH CENTURY, HEROIN — an opiate analgesic first formulated to treat severe pain — has had a long and not-so-pristine existence. As other drugs go in and out of fashion, heroin remains a staple of the illegal drug trade, a favorite of users for its easy availability and the euphoric “high” it produces.

The continuing “popularity” of heroin has never been lost on Theodore J. Cicero, PhD, who has been studying the drug and its abuse for the past four decades.

But even he admits surprise at the latest wrinkle in the heroin game: A reformulation of OxyContin — a prescription painkiller widely abused in the 1990s — has made it harder for users to alter that drug for inhalation or injection. As a result, they are switching from OxyContin to other drugs, including heroin.

And although only about 10 percent of former OxyContin users have turned to heroin (the other 90 percent use other opiates, such as Vicodin or fentanyl), that statistic may be misleading.

“It sounds like a small number,” says Cicero, “but it’s a huge number relative to heroin users in this country. What’s more, we’re now seeing a migration of heroin and other dangerous drugs from the inner cities to the suburbs and rural areas.”

Examining samples in the lab: Neuropharmacologist Theodore J. Cicero, PhD, and senior research coordinator Matthew S. Ellis, MPE
Photo Credit: Robert Boston

Theodore J. Cicero, PhD, left, and Matthew S. Ellis, MPE

For the past three years, Cicero and colleagues have collected information from patients entering treatment for drug abuse. More than 2,500 patients from 150 treatment centers in 39 states have answered survey questions about their drug use, with a focus on the reformulation of OxyContin. Results from those surveys were published in the July 12, 2012 issue of the New England Journal of Medicine.

The widely prescribed pain-killing drug originally was thought to be part of the solution to the abuse of opioid drugs because OxyContin (the brand name for the generic drug oxycodone) was designed to be released into the system slowly, thus not contributing to an immediate “high.”

But creative drug abusers quickly figured out how to evade that mechanism by crushing the pills and inhaling the powder, or by dissolving the pills in water and injecting the solution, thereby getting an immediate rush as large amounts of the drug entered the system all at once.

Unlike “street” heroin, which varies in purity and is often laced with dangerous fillers by drug dealers, OxyContin came as advertised: Users knew the exact dosage they were getting and, in its slow-release form, that was a lot — as much as 15 to 20 times more oxycodone than what comprised the normal immediate-release capsules.

In addition, from a psychological standpoint, many OxyContin abusers felt it wasn’t such a bad thing; after all, it was legal with a prescription and carried none of the stigma of heroin usage.

To combat these issues, the drug’s manufacturer introduced a new formulation of OxyContin in 2010. The new pills were much more difficult to crush and dissolved more slowly. The idea, according to Cicero, was to make the drug less attractive to illicit users who wanted to experience an immediate high. And it worked — sort of.

“Our data show that OxyContin use by inhalation or intravenous administration has dropped significantly since the abuse-deterrent formulation came onto the market,” says Cicero, professor of neuropharmacology in psychiatry. “In that sense, the new formulation was very successful.”

However, although many users stopped using OxyContin, they didn’t stop using drugs.

“The most unexpected, and probably detrimental, effect of the new formulation was that it contributed to a huge surge in the use of heroin, which is like OxyContin in that it also is inhaled or injected,” Cicero says. “We’re now seeing reports from across the country of large quantities of heroin appearing in suburbs and rural areas.”

Cicero’s research into heroin began in the 1970s, when he and colleagues were studying the drug’s effects using animal models. They found — and later confirmed in human studies — that morphine (to which heroin converts in the brain), depresses testosterone, the male sex hormone, leading to hypogonadism, a now well-recognized side effect of chronic opioid abuse.

So for 20 years, the investigators dealt mainly with young men from urban minority populations in their study of heroin, which at that time was essentially the only opiate available for purchase on the street. In the 1990s, with the emerging popularity of OxyContin, known as “hillbilly heroin” by its rural and suburban users, heroin suddenly had a director competitor.

Now Oxycontin’s formula change has left users in need of a substitute, and heroin has once again made tremendous inroads.

And although heroin abuse is a complicated issue, Cicero is frustrated by the government’s focus only on shutting down the supply of illegal drugs. Instead, he is more interested in the “why” of drug use, and current studies in his laboratory are examining risk factors for heroin and other opioid abuse to decrease the demand side of the supply-and-demand economic model.

“This trend toward increases in heroin use is important,” says Cicero. “As users switch to heroin, overdoses may become more common. We want to get the word out to physicians, regulatory officials and the public.”