The immune infliction of heroin addiction

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The Rise of Opioid Addiction in the US

There's little doubt heroin addiction is a serious problem in the United States. According to the Centers for Disease Control and Prevention, the use of this opioid drug has skyrocketed since 2002. While the major concern is overdose, long term use can also lead to serious health problems including infection and chronic diseases.

The usual suspect in propensity to any disease is the immune system. It's the defense force for our bodies and does its best to protect against troubles on the inside. But this complex network is sensitive to changes in our behavior such as diet, exercise, and exposure to foreign elements. When this happens, we become susceptible to a variety of ailments. This normally happens in the form of infection but other conditions ranging from cardiovascular disease to mental health disorders can also occur.

One of the first signs of heroin's impact on immunity appeared over forty years ago. Researchers discovered a change in the way addicts form antibodies. The impetus came from a rather high rate of multisystem diseases including endocarditis, kidney disease and cancer.

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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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At the time, these conditions were thought to have a microbial origin and as such researchers believed the immune response was simply not working as well as it should. Sure enough, there was a lack of protective antibodies in chronic users. The researchers advised this reduction in proper immune function could lead to even greater health troubles for addicts.

As more advanced techniques for studying immunity became available, research gained a greater appreciation for the effect of the drug on immune function. In the 1990s another branch of the network – cellular immunity – was explored. The results were not good as heroin once again suppressed immunity. Even worse, this effect could be sustained for almost two years. This meant even those kicking the habit were still vulnerable to troubles.

This particular piece of evidence was concerning and led researchers to figure out what might be causing these lasting effects. The most likely suspect was inflammation. This was eventually found in animal studies although this did not necessarily mean the same process was happening in humans. For that to be unveiled, clinical trials were needed. Yet, until recently, the only available subjects were those who had died. While the results from cadavers revealed a high level of inflammation, they could not be solely attributed to heroin use.

But the answers may finally be at hand thanks to a group of American researchers. They have revealed the theories about inflammation are indeed correct. The results provide perspective on the real-time troubles occurring with the immune system as well as the potential for disease later in life.

The team performed a trial with 19 heroin users and an equal number of controls. To be certain the results were reflective of only heroin use, all users were shown to be negative for both human immunodeficiency virus and hepatitis C virus. Blood was taken from both these groups and then analyzed for the presence of a variety of immunological cells, proteins, and other markers.

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When the data crunching was complete, the theories and experiments of the past were confirmed. There was indeed a change in the antibody population and a rise in molecules known to be involved in inflammation. This of course was expected. But there were a few surprises in store.

In some users, the rise in inflammation appeared to be due to the presence of a microbial factor known as lipopolysaccharide, or LPS. This molecule is regarded as a toxin by the immune system and can lead to long-term inflammatory response. The results suggested bacterial infection or a leaky gut contributed to the worsening state of immunity. This could also explain why recovery of proper immune function takes so long after stopping drug use.

The other factor in the development of inflammation was the presence of several types of fat known as ceramides. These molecules can help to keep the immune system in check and ensure a proper response is maintained. But certain ceramide forms can drive inflammation and they were found in much higher concentrations in heroin users than controls.

By the end of the experiments, the team was able to predict heroin use simply by examining the levels of the various markers. This in itself could prove to be useful in terms of identifying users during drug screens. In addition, this could help to identify individuals who may not be able to respond well to vaccination due to drug use.

However, the real goal of this study was to better understand the effect of heroin on immunity in the hopes of developing better medical treatment. For the authors, the way forward appears to be an exploration of the benefit of anti-inflammatory agents. In essence, curbing the inflammatory effect might help to resolve the action of use. In light of the affliction of addiction in America, almost anything at this stage may help to reduce the trend.

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