It has been known for years that people formerly dependent on opioids who are coming out of prison are at increased risk for overdose. The seminal article on deaths after release from incarceration was published by Ingrid A. Binswanger and colleagues in The New England Journal of Medicine in 2007; at that time, drug overdoses -- about half from cocaine and half from opioids -- were the leading cause of death after release from incarceration (http://www.nejm.org/doi/full/10.1056/NEJMsa064115).

Today, however, opioids are the epidemic, in terms of use and overdoses. Increasingly, overdoses related to opioids upon release from incarceration have been blamed on people returning to their former doses. Likewise, many patients who go to drug-free treatment are at high risk for overdose upon release, again because it is assumed that they are returning to their former doses. But whether that is true is not clear, as the doses they used do not appear to have been studied.

“In my opinion, it’s a myth, and a dangerous one,” said Sam Snodgrass, Ph.D., a behavioral pharmacologist who works at CATAR, a buprenorphine-methadone clinic in Arkansas. Most experienced opioid users would not go back to their former doses, he said. “We aren’t that stupid,” he said. “We understand the risk of overdose, and we use what we believe is a safe dose — what we think will get us high but won’t kill us.” Unfortunately, this estimate often fails. “Too many times, that safe dose isn’t safe,” said Snodgrass.

“The point is that no one knows what dose can be fatal after a period of abstinence,” said Snodgrass. “So, if we err, then perhaps we should do it on the side of caution and tell people that what they think is a safe dose may, in fact, not be.”

In fact, even returning to a low dose of opioids after a period of abstinence could result in an overdose for a long-term opioid user, he said.

In most cases, no one knows what an overdose victim’s last dose consisted of, said Snodgrass. “But look at how many people have relapsed, used and are still around,” he said. If they had used even close to the same amount when they relapsed as they had at the end of their previous use, they would die, he said. Snodgrass knows patients who started with two hydrocodones a day and ended up using 15 to 20 roxycodones, multiple Dilaudids, or a half-gram of heroin or more in one shot. After treatment, when they relapsed, if they used even a third of what they used at the end, they would have died, he said. “As far as tolerance, they were back to being drug virgins,” he said.

Tolerance

Two top drug researchers agreed with Snodgrass about tolerance but disagreed about whether drug users are “smart” about what dose to pick up after abstinence.

“In terms of use, it is not a matter of being ‘smart,’” said Josiah D. Rich, M.D., professor of medicine and epidemiology at Brown University and director of the Center for Prisoner Health and Human Rights. “There are plenty of ‘smart’ people who develop opioid dependence—if being smart could fix the problem, they wouldn’t stay addicted.” They are “continuing the behavior despite the risk of adverse outcomes, which is the very definition of addiction.”

The two hallmarks of addiction are the development of tolerance and withdrawal, said Rich, adding that tolerance can develop fairly quickly, driving people to escalate their dose to achieve the same effect. But he agreed with the idea that tolerance can disappear quickly, which places people who have been abstinent for even a short time at risk of overdose. “Even though your mind might understand you have lost tolerance—and many people do not even know that—your body believes that you can handle it because you have done so before,” he said.

And Charles O’Brien, M.D., Ph.D., Kenneth Appel Professor at the University of Pennsylvania, said that it’s important to teach patients at discharge about tolerance. “They are smart but still can’t control drug dose,” O’Brien said, noting that naltrexone can prevent overdose. “In our naltrexone parolee study, we had seven overdoses in the control group, but zero in the naltrexone group.” He added that in the United Kingdom, parolees are released with a package of naloxone.

Reducing ‘enough’

“The majority of our clients overdose for several reasons—using too much of an opioid, the drug is stronger than usual, or mixing substances such as opioids and benzodiazepines and alcohol,” said Billy Golden of the Cincinnati Exchange, a harm-reduction organization.

Some people know to reduce the amount of opioids after a break, “but they do not reduce enough,” said Golden. “Others don’t realize that their tolerance can decrease after only a few days of being without an opioid, so they might think that they still have the same tolerance level after a week.” And others may not be able to get drugs from the same source after their break, and the drug may be stronger than what they were used to. “Here in Cincinnati, clients report that dealers often wait outside the courthouse,” he said. If someone is in withdrawal and sick, buying the drug “right then and there is going to make a lot more sense than having to go through the effort of going back to the usual source,” he said.

Hair study

The closest researchers have come to determining the dose of heroin that resulted in an overdose is in a 1998 study published in The Lancet. The researchers looked at the morphine content in the hair of heroin users who had fatal overdoses. The amounts of morphine in the hair of those who died from an overdose after a period of abstinence were significantly lower than the amounts in the hair of current users who had died. Assuming a hair growth rate of 1 centimeter per month, and assuming a positive correlation between mean heroin intake and morphine concentrations in hair, the findings showed that most of the individuals who died from a heroin overdose had abstained from heroin during the four-month period preceding the overdose. “Thus, the results of this hair analysis support a theory of high susceptibility to opioid overdose after periods of intentional or unintentional abstinence,” the study concluded. “The reasons for increased susceptibility to overdose remain unclear, but it is likely that a lower heroin tolerance after a period of abstinence, or a low tolerance owing to light or irregular heroin use, leads to a corresponding decrease in the size of a fatal dose.” (For the article, go to http://www.thelancet.com/pdfs/journals/lancet/PIIS0140673697101015.pdf.)

The bottom line is that without treatment, a period of abstinence does not treat addiction. The biggest problem for people when they get out of jail or drug-free rehab, said Golden, is “what they left behind is still waiting for them.” When the triggers are there, relapse is easy, he said, and no matter how intelligent the person is, “they can overlook the fact that their tolerance is decreased when nothing else has changed.”

Editor’s note: This is the kind of story that often has academic researchers and policymakers on one side and patient advocates on the other. To try to bridge the gap, we asked the New York State Department of Health if we could speak with their new director of drug user health, Allan Clear, formerly head of the Harm Reduction Coalition. When the Health Department press office found out what we wanted to talk about, they declined to make him available for an interview.