As the opioid epidemic evolves, impacts bleed into cocaine overdose

America's opioid epidemic is fueling a startling increase in cocaine-related overdose deaths in recent years, as users mix deadly cocktails involving the stimulant that had otherwise shown encouraging signs of stalling impact, according to a U.S. News analysis of mortality data.

The findings raise serious concerns about the extent to which drug users are mixing cocaine, which can result in overdose on its own, with even more deadly drugs like heroin and fentanyl, a strong synthetic opioid. It also raises questions about whether people are mixing the drugs intentionally or are falling victim to tainted products.

The devastation wrought by the U.S. opioid epidemic has been well-documented in recent years: People were weaned onto the cheap street drug heroin through initiation by prescription painkillers like oxycodone. Now, users are increasingly overdosing on fentanyl, a synthetic opioid.

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Opioid painkillers capitalize on our body's natural pain-relief system. We all have a series of naturally produced keys ("ligands") and keyholes ("receptors") that fit together to switch on our brain's natural reward system — it's the reason we feel good when we eat a good meal or have sex, for example. But opioids mimic the natural keys in our brain — yes, we all have natural opioids! When they click in, we can feel an overwhelming sense of euphoria.

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Opioid painkillers can have effects similar to heroin and morphine, especially when taken in ways other than prescribed by a doctor.

When prescription painkillers act on our brain's pleasure and reward centers, they can make us feel good. More importantly, though, they can work to reinforce behavior, which in some people can trigger a repeated desire to use.

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You may also feel sleepy.

Opioids act on multiple brain regions, but when they go to work in the locus ceruleus, a brain region involved in alertness, they can make us sleepy. Why? The drugs essentially put the brakes on the production of a chemical called norepinephrine, which plays a role in arousal.

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Your skin may feel flushed and warm.

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You'll begin to feel their effects 10 to 90 minutes after use, depending on whether they're taken as directed or used in more dangerous ways.

Some drugmakers design versions of their medications to deter abuse. Extended-release forms of oxycodone, for example, are designed to release slowly when taken as directed. But crushing, snorting, or injecting the drugs can hasten their effects.

It can also be deadly. Between 2000 and 2014, nearly half a million Americans died from overdoses involving opioid painkillers and heroin, a report from the US Centers for Disease Control and Prevention found. The most commonly prescribed painkillers were involved in more overdose deaths than any other type of the drug.

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Your breathing will slow as well.

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Depending on the method used, the effect can last anywhere from four to 12 hours.

For severe pain, doctors typically prescribe opioid painkillers like morphine for a period of four to 12 hours, according to the Mayo Clinic. Because of their risks, it's important to take prescription painkillers only according to your physician's specific instructions.

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Overdosing can stop breathing and cause brain damage, coma, or even death.

2014 report from the American Academy of Neurology estimates that more than 100,000 Americans have died from prescribed opioids since the late 1990s. Those at highest risk include people between 35 and 54, the report found, and deaths for this age group have exceeded deaths from firearms and car crashes.

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Combining them with alcohol or other drugs — even when taken according to the directions — can be especially deadly.

Since they slow breathing, combining opioid painkillers with other drugs with similar effects can drastically raise the chances of accidental overdose and death.

Yet they're often prescribed together anyway, according to the National Institute on Drug Abuse. "Unfortunately, too many patients are still co-prescribed opioid pain relievers and benzodiazepines [tranquilizers]," the institute said. In 2011, 31% of prescription opioid-related overdose deaths involved these drugs.

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Abusing opioid painkillers has been linked with abusing similar drugs, like heroin.

A CDC report found that people who'd abused opioid painkillers were 40 times as likely to abuse heroin compared with people who'd never abused them. The National Institute on Drug Abuse says that close to half of young people surveyed in three recent studies who'd injected heroin said they'd abused prescription painkillers before they started using heroin.

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You may also develop a tolerance for the drugs so that you need more to get the same effect over time.

Tolerance to opioid painkillers happens when the brain cells with opioid receptors — the keyholes where the opioids fit — become less responsive to the opioid stimulation over time. Scientists think that this may play a powerful role in addiction.

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Suddenly stopping the drugs can result in withdrawal symptoms like shakiness, vomiting, and diarrhea.

Taking prescription painkillers for an extended period increases the likelihood that your brain will adapt to them by making less of its own natural opioids. So when you stop taking the drugs, you can feel pretty miserable. For most people, this is uncomfortable but temporary.

But in people who are vulnerable to addiction, it can be dangerous because it can spurn repeated use.

"From a clinical standpoint, opioid withdrawal is one of the most powerful factors driving opioid dependence and addictive behaviors," Yale psychiatrists Thomas Kosten and Tony George write in a 2002 paper in the Journal of Addiction Science & Clinical Practice.

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Less discussed, however, is the effect that the opioid epidemic has on people who use cocaine.

The Centers for Disease Control and Prevention recently reported that cocaine was responsible for the second-most drug-overdose deaths in 2014. In recent years, mortality data show cocaine-related deaths gradually increasing following a steady decline, even as the drug's availability for the most part did not appear to increase significantly.

The CDC's Wide-Ranging Online Data for Epidemiologic Research, or WONDER database, which uses information from death certificates, revealed that mixes with opioids were driving the increase.

The trend hasn't escaped the attention of federal data scientists, who have concluded the increase in cocaine-related deaths is largely attributable to using multiple drugs at the same time and have been working on broader reports to alert the public, the medical community and policymakers.

"When there are no opioids involved in cocaine-overdose deaths you see an overall decline in recent years," says Christopher M. Jones, an acting associate deputy assistant secretary with the Department of Health and Human Services. "But when you look at cocaine and opioids together, we see a more than doubling in the number of overdoses since 2010, with heroin and synthetic opioids increasingly involved in these deaths."

Using CDC's WONDER database, U.S. News calculated the number of cocaine-related deaths and subtracted the number of deaths that also included heroin, prescription painkillers, methadone and fentanyl, or a combination of these. When opioids are removed from the equation, cocaine-related deaths stall.

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For instance, an examination of CDC data show that 6,784 people died of a cocaine-involved overdose in 2015. Of these, 2,565 also had heroin as a contributing cause of death and 1,077 had a prescription pain reliever. In 1,542 cases, fentanyl contributed to the cause of death, and some of these drugs overlapped, meaning that about 63 percent of cases involved an opioid.

"I think what we are seeing play out is a poly-substance issue that's linked to the opioid epidemic ," Jones says.

Is the Drug Cocktail Intentional?

Officials aren't certain whether the trend is occurring more among people who typically use cocaine or opioids. Cocaine can be fatal on its own by causing a heart attack or stroke but hasn't proved as deadly as many opioids. Still, the combination is dangerous. In the CDC mortality database, all drugs listed are specifically determined to be the cause of death and do not merely refer to those detected in a person's system.

"From the death data, we don't know whether these are cocaine users who added opioids or were opioid users who added cocaine," says Dr. Wilson Compton, deputy director of the National Institute on Drug Abuse, part of the National Institutes of Health. "Both are possible. The data shows us that both drugs may have been related to the deaths."

While "speedballing" – a dangerous practice in which people snort or inject the drugs together to feel the relaxing effects of opioids following an intense cocaine high – isn't new, experts fear some people may have used cocaine without knowing it contained opioids their bodies weren't used to.

"Opioids alone can be lethal," Compton says. "Cocaine alone can be lethal. The combination can also be lethal."

Heroin and other opioids, even among long-term users, can lead to overdose and death because they can cause people's breathing to slow or stop. Even in cases where people intentionally take heroin and cocaine together, some might not know that their drugs have been laced with fentanyl, which can be fatal even when taken in small amounts.

About 2 milligrams of the synthetic opioid – the weight of six grains of salt – can kill someone. Dealers have been found to add fentanyl to heroin and other opioids to strengthen their effects and to make a generous profit, as it is inexpensive. The Drug Enforcement Agency also has found cases in which fentanyl has been made to look like prescription painkillers.

Some users do purposefully seek out the cheaper drug because it gives them a more intense, shorter-lasting high compared to heroin, but the DEA says fentanyl has been mixed with other drugs without a user knowing.

"These are about as far from a regulated market as one can imagine," Compton says of fentanyl. "There is no quality control or product specification. You never know what's in these things."

Is a Jump in Cocaine Use Ahead?

A potential reinvigoration of the cocaine market could compound the problem.

A report from the Substance Abuse and Mental Health Services Administration, or SAMHSA, recently showed that cocaine use was up among young adults in 16 states, raising concerns that cocaine may be a re-emerging public health concern.

"It's on our radar for sure," says Art Hughes, a statistician with SAMHSA, about the climb in cocaine-related deaths.

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"We are seeing a higher increase in initiation," he added about young adults.

Some signs show cocaine production is on the rise. The Office of National Drug Control Policy estimates that the potential cocaine production from Colombia in 2015 was at its highest level since 2007 and an increase of more than 100 percent compared with 2013.

The DEA also has noted a bump in cocaine seizures. Cases in which authorities identified the drug reached a high of 640,141 in 2006 – a record year for cocaine-related overdose deaths – then gradually dropped to 213,167 by 2014. Last year, however, the DEA identified cocaine in 216,129 cases.

The DEA reported in its National Drug Threat Assessment report in early December that it projected the cocaine supply was likely to "continue increasing in the near term" and that "we can expect to see increased cocaine seizures, new cocaine users and cocaine-related deaths."

Tracing the Impact

In the drug assessment report, DEA officials noted the emergence of cocaine mixed with fentanyl in some areas, calling it a "potential trend of concern."

They listed a few instances in which this combinations was found. In November 2014, the FBI's Detroit field office seized mixtures that originated from St. Louis. In March 2015 in New York, the Buffalo Police Department seized two cocaine and fentanyl mixtures totaling almost 53 pounds. At the same time, New York's Rochester Police Department reported two separate incidents in which three people died from mixing fentanyl and cocaine. The report states that in this case crack cocaine pipes were present at each scene.

In the CDC's mortality database, cocaine deaths also include crack, but officials don't think it's responsible for the bulk of drug combination data they are seeing because crack use makes up a small proportion of cocaine use. A SAMHSA report on drug use found that 833,000 of 4.8 million cocaine users reported they used crack in 2015.

"We are not seeing the same pattern we are seeing for cocaine in general," Hughes says. "It has been fairly slack over the last few years."

Other localized reports show cases in which cocaine and fentanyl have been mixed. A CDC study on fentanyl deaths in Florida found that the percentage of those who also tested positive for cocaine increased from 17 to 33 percent from 2010 to 2014, and to 42 percent by the first half of 2015. In more than a dozen counties in Ohio, 23 percent of fentanyl-related deadly overdose victims also tested positive for cocaine in 2014.

The DEA has concluded that fentanyl is coming from China, often by way of Mexico. To arrive at this conclusion, they cite state-level data showing increasing seizures and note that doctors haven't increased their prescribing of the drug, often used to treat pain in cancer patients. Barbara Carreno, a DEA spokeswoman, says Chinese officials have been working on the issue with her agency.

Officials caution that mortality data should be read with several caveats. Each year the reporting is different, and some counties are better at reporting deaths than others. The information is based on death certificates, and some use the term "drug overdose" rather than specifying the substance, says Compton from the National Institute on Drug Abuse.

"All the drug-specific deaths are, if anything, underestimates because there is a large number in which a drug overdose is unspecified," he says.

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