Opioid abuse disorder

Opioids, sometimes called narcotics, are a type of drug. Opioids include strong prescription pain relievers, such as oxycodone, hydrocodone, fentanyl, and tramadol. The illegal drug heroin is also an opioid. Some opioids are made from the opium plant, and others are synthetic (man-made). Opioid use disorder means using these drugs in a way that keeps you from living the life you want. When your use is out of control, it harms you and your relationships. Opioid abuse and addiction is a major public health crisis.

You may have an opioid use disorder if two or more of the following are true:

• You use larger amounts of the drug than you ever meant to. Or you’ve been using it for a longer time than you ever meant to.
• You can’t cut down or control your use. Or you constantly wish you could cut down.
• You spend a lot of time getting or using the drug, or recovering from the effects.
• You have strong cravings for the drug. You can no longer do your main jobs at work, at school, or at home.
• You keep using even though your drug use hurts your relationships.
• You have stopped doing important activities because of your drug use.
• You use drugs in situations where doing so is dangerous.
• You keep using the drug even though you know it’s causing health problems.
• You need more and more of the drug to get the same effect, or you get less effect from the same amount over time. This is called tolerance.
• You can’t stop using the drug without having uncomfortable symptoms. This is called withdrawal.

An estimated 2.1 million people in the United States had a substance use disorder related to prescription opioid pain medicines in 2016 ¹. However, only a fraction of people with prescription opioid use disorders receive specialty treatment (17.5 percent in 2016) ¹. Overdose deaths linked to these medicines were five times higher in 2016 than 1999 ². There is now also a rise in heroin use and heroin use disorder as some people shift from prescription opioids to their cheaper street relative; 626,000 people had a heroin use disorder in 2016, and more than 15,000 Americans died of a heroin overdose in 2016 ³. Besides overdose, consequences of misusing opioids include a rising incidence of infants born dependent on opioids because their mothers used these substances during pregnancy, this can lead to babies being addicted and going through withdrawal, known as neonatal abstinence syndrome ⁴ and increased spread of infectious diseases, including HIV and hepatitis C (HCV), as was seen in 2015 in southern Indiana ⁵.

Opioid drugs include:

• opium
• codeine
• fentanyl
• heroin
• hydrocodone
• hydromorphone
• methadone
• morphine
• oxycodone
• oxymorphone
• paregoric
• sufentanil
• tramadol

The drastic increase in opioid use disorder is at least partially due to overprescribing of opioid medications. In particular, the 1990s saw an explosion in opioid prescribing due to the pain as fifth vital sign campaign, downplay of the abuse potential of opioids, and aggressive marketing of drugs such as oxycontin and Opana.

Risks of using prescription opioids include dependence and addiction:

• Dependence means feeling withdrawal symptoms when not taking the drug. Drug dependence is when the way your body works changes because you have taken a drug for a long time. These changes cause you to have withdrawal symptoms when you stop using the drug.
• Addiction is a chronic brain disease that affects your brain and your behavior. Addiction causes a person to compulsively seek out drugs, even though they cause harm. At first, you have control over your choice to start using drugs. If you misuse a drug, its pleasurable effect eventually makes you want to keep using it. Over time, your brain actually changes in certain ways so that you develop a powerful urge to use the drug.

The risks of dependence and addiction are higher if you misuse prescription opioids. Misuse can include taking too much prescription opioid, taking someone else’s prescription opioid, taking it in a different way than you are supposed to, or taking the prescription opioid to get high.

Opioid medications bind to opioid receptors in the central and peripheral nervous systems (primarily delta, kappa, mu). These effects allow for effective treatment of pain, cough, and diarrhea. Action on these same receptors leads to intense euphoria which leads individuals to attempt to recreate that first high. Most people who misuse opioids do so chiefly for pain relief. However increasing evidence is dispelling the myth that opioids are effective long-term analgesic medications.

Below are receptors matched to physiologic effects (nociceptin and zeta receptors increasingly being researched):

• Delta: analgesia, antidepressant, convulsant, physical dependence, modulate mu-related respiratory depression
• Kappa: analgesia, anticonvulsant, depression, hallucination, diuresis, dysphoria, miosis, neuroprotection, sedation
• Mu: analgesia, physical dependence, respiratory depression, miosis, euphoria, reduced GI motility, vasodilation

Withdrawal symptoms manifest when opioids are discontinued abruptly, though these can occur with tapered cessation of medications. Withdrawal symptoms can be divided into acute, subacute, and chronic phases. Most healthcare providers are aware of the acute withdrawal symptoms: hot/cold flashes, vomiting, sweating, lacrimation, insomnia, anxiety, dehydration.

Opioid use disorder treatments usually includes medicines, group therapy, one or more types of counseling, and drug education. Sometimes medicines are used to help you quit. They may help control cravings, ease withdrawal symptoms, and prevent relapse. This treatment is called medication-assisted treatment, or MAT. Effective medications exist to treat opioid use disorder include: methadone, buprenorphine, and naltrexone. During medication-assisted treatment (MAT), you take a substitute drug (usually methadone or buprenorphine) in place of the opioid you were using. This can help you focus on getting healthy. Most people take the medicine for months or years as a part of the treatment, along with therapy or counseling. It helps you cope with the anger, frustration, sadness, and disappointment that often happen when a person tries to stop using drugs.

Many people with opioid use disorder, and sometimes their families, feel embarrassed or ashamed. Don’t let these feelings stand in the way of getting treatment. Remember that opioid use disorder can happen to anyone who uses opioids, no matter what the reason.

How do I know if I’m addicted to opioid?

You might be addicted if you crave the drug or if you feel like you can’t control the urge to take the drug. You may also be addicted if you keep using the drug without your doctor’s consent, even if the drug is causing trouble for you. The trouble may be with your health, with money, with work or school, with the law, or with your relationships with family or friends. Your friends and family may be aware of your addiction problem before you are. They notice the changes in your behavior.

If you think you are addicted to opioids, know that there is help for you. The first step in breaking addiction is realizing that you control your own behavior.

The following steps will help you fight your addiction:

• Commit to quitting. Take control of your behavior and commit to fighting your addictions.
• Get help from your doctor. He or she can be your biggest ally, even if you’re trying to quit a drug he or she prescribed. Your doctor may be able to prescribe medicine that will help ease your cravings for the addictive drug. Talking with your doctor or a counselor about your problems and your drug use can be helpful, too.
• Get support. Certain organizations are dedicated to helping people who have addictions. They want you to succeed and will give you the tools and support you need to quit and move on with your life. Ask your family and friends for support, too.

What causes opioid addiction?

Opioid drugs alter your brain by creating artificial endorphins. Besides blocking pain, these endorphins make you feel good. Too much opioid use can cause your brain to rely on these artificial endorphins. Once your brain does this, it can even stop producing its own endorphins. The longer you use opioids, the more likely this is to happen. You also will need more opioids over time because of drug tolerance. Receptor desensitization and down-regulation are molecular processes that cause tolerance.

In people with opioid use disorder, the brain is continually exposed to high levels of opioids as well as dopamine, which is released in the reward circuit following opioid receptor activation. Brain cells respond to this by reducing their response to receptor activation and by removing opioid and dopamine receptors from the cell membrane, resulting in fewer receptors that can be activated by the drug ⁶. These mechanisms result in a lessened response to the drug, so higher doses are required to elicit the same effect. This opioid tolerance is the reason that people with opioid use disorder do not experience euphoric effects from therapeutic doses of buprenorphine or methadone, while people without opioid use disorder do Walsh SL, June HL, Schuh KJ, Preston KL, Bigelow GE, Stitzer ML. Effects of buprenorphine and methadone in methadone-maintained subjects. Psychopharmacology (Berl). 1995;119(3):268-276. It is also the reason why people are at increased risk of overdose when relapsing to opioid use after a period of abstinence: They lose their tolerance to the drug without realizing it, so they no longer know what dose of the drug they can safely tolerate.

Opioid tolerance. Drug tolerance is when your body, over time, gets used to the effects of a drug. As this happens, you may need to take a higher dose of the drug to get the same effect. When you take opioids over time, you need a higher does to get the same pain relief.

If you stop using an opioid for a period of time, your tolerance will begin to fade. If you need to begin taking it again, you most likely will not need your former higher dose. That can be too much for the body to take. If you stop taking a medication, and then resume, talk to your doctor about dosage.

Mechanisms of opioid dependence. The sustained activation of opioid receptors that results from opioid use disorder and causes tolerance also causes withdrawal symptoms when the opioid drugs leave the body. Drug withdrawal symptoms are opposite to the symptoms caused by drug taking. In the case of opioids, they include anxiety, jitters, and diarrhea ⁷. Avoidance of these negative symptoms is one reason that people keep taking opioids, and in the early stages of treatment, medications such as methadone and buprenorphine reduce withdrawal symptoms.

Drug tolerance and dependence are a normal part of taking any opioid drug for a long time. You can be tolerant to or dependent on, an opioid drug and not yet be addicted to it.

Addiction, however, is not normal. It is a disease. You are addicted to a drug when it seems that neither your body nor your mind can function without the drug. Addiction causes you to obsessively seek out the drug, even when the drug use causes behavior, health, or relationship problems.

Opioid use disorder prevention

Many people are able to use opioids safely without becoming addicted to them. But their potential for addiction is high. This is especially true if you use them for long-term pain management.

In general, you are more likely to avoid addiction if you can use opioid drugs no longer than a week. Research shows that using them for more than a month can make you dependent on them.

Opioid use disorder symptoms

The first step toward recovery is recognizing that you have a problem with opioids. The signs and symptoms of substance abuse can be physical, behavioral, and psychological. One clear sign of addiction is not being able to stop using the substance. It is also not being able to stop yourself from using more than the recommended amount.

Other signs and symptoms of opioid abuse include:

• poor coordination
• drowsiness
• shallow or slow breathing rate
• nausea, vomiting
• constipation
• physical agitation
• poor decision making
• abandoning responsibilities
• slurred speech
• sleeping more or less than normal
• mood swings
• euphoria (feeling high)
• irritability
• depression
• lowered motivation
• anxiety attacks

Opioid withdrawal symptoms

Opioid withdrawal symptoms can be mild or severe, and may include:

• sweating
• nausea or vomiting
• chills
• diarrhea
• shaking
• pain
• depression
• insomnia
• fatigue

If you have been taking a prescription opioid for a long time, work with your doctor. Your doctor can help you avoid opioid withdrawal symptoms by gradually lowering your opioid dose over time until you no longer need the opioid medicine.

Opioid overdose symptoms

An overdose of opioids requires immediate emergency medical treatment. If you suspect someone has overdosed on opioids, call your local emergency services number immediately. Naloxone is an opioid antagonist that can reverse an opioid overdose. If you take it or someone gives it to you soon enough after an overdose, it can save your life. Naloxone comes in a take home naloxone kit you can carry with you. Ask your doctor or pharmacist about having a take-home naloxone kit on hand. You can get naloxone without a prescription at most drugstores or through a community Take Home Naloxone program. In some states, a prescription nasal spray called naloxone (Narcan) is available to keep on hand in case of an opioid overdose. Talk to your doctor to see if you might need this medicine.

Symptoms of an opioid overdose include:

• unresponsive (can’t wake)
• slow, erratic (irregular) breathing, or no breathing at all
• slow, erratic pulse, or no pulse
• vomiting
• loss of consciousness (passing out)
• constricted (small) pupils

Opioid use disorder diagnosis

Your doctor or a medical health professional can diagnose opioid addiction. Diagnosis will include a medical assessment. It also often includes testing for mental health disorders.

Eleven criteria define opioid use disorder ⁸.

The diagnosis is made by meeting two or more criteria in a year time period. Key elements are as follows:

• Increasing dose/tolerance
• Wish to cut down on use
• Excessive time spent to obtain or use the medication
• Strong desire to use
• Use interferes with obligations
• Continued use despite life disruption
• Use of opioid in physically hazardous situations
• Reduction or elimination of important activities due to use
• Continued use despite physical or psychological problems
• Need for increased doses of the drug
• Withdrawal when dose is decreased

Opioid abuse treatment

Treatment for opioid addiction is different for each person. The main goal of treatment is to help you stop using the drug. Treatment also can help you avoid using it again in the future.

When you stop using opioids, your body will react. You will have a number of symptoms that may include nausea and vomiting, abdominal pain, and anxiety. This reaction is called withdrawal.

Your doctor can prescribe certain medicines to help relieve your withdrawal symptoms when you stop using opioids. They also will help control your cravings. These medicines include methadone (often used to treat heroin addiction), buprenorphine, and naltrexone.

Methadone and buprenorphine help reduce withdrawal symptoms by targeting the same centers in the brain that opioids target. Only they do not make you feel high. They help restore balance to your brain and allow it to heal. According to National Institutes of Health (NIH), you may safely take the medicines long term, even for a lifetime. You should not quit them without first telling your doctor.

Naltrexone is another medicine your doctor may prescribe. This medicine doesn’t help you stop taking opioids. It is for helping prevent you from relapsing. Relapsing means to start taking opioids again. This medicine is different from methadone and buprenorphine because it does not help with cravings or withdrawal. Instead, it prevents you from feeling the high you would normally feel when you take opioids.

Medicine can help with your physical addition to opioids. But you may also need help with your mental or emotional addition to opioids. Behavioral treatments can help you learn how to manage depression. These treatments also help you avoid opioids, deal with cravings, and heal damaged relationships. Some behavioral treatments include individual counseling, group or family counseling, and cognitive therapy. Ask your doctor for a recommendation.

Opioid use disorder medication

Studies show that people with opioid use disorder who follow detoxification with complete abstinence are very likely to relapse, or return to using the drug ⁹. While relapse is a normal step on the path to recovery, it can also be life threatening, raising the risk for a fatal overdose ¹⁰. Thus, an important way to support recovery from heroin or prescription opioid use disorder is to maintain abstinence from those drugs. Someone in recovery can also use medications that reduce the negative effects of withdrawal and cravings without producing the euphoria that the original drug of abuse caused. For example, the U.S. Food and Drug Administration (FDA) recently approved lofexidine, a non-opioid medicine designed to reduce opioid withdrawal symptoms. Methadone and buprenorphine are other medications approved for this purpose.

Because each medication works differently, your treatment provider should decide on the optimal medication in consultation with you and should consider your unique history and circumstances.

Methadone

Methadone is a synthetic opioid agonist that eliminates withdrawal symptoms and relieves drug cravings by acting on opioid receptors in the brain—the same receptors that other opioids such as heroin, morphine, and opioid pain medications activate. Although it occupies and activates these opioid receptors, it does so more slowly than other opioids and, in an opioid-dependent person, treatment doses do not produce euphoria. It has been used successfully for more than 40 years to treat opioid use disorder and must be dispensed through specialized opioid treatment programs ¹¹.

Buprenorphine

Buprenorphine is a partial opioid agonist, meaning that it binds to those same opioid receptors but activates them less strongly than full agonists do. Like methadone, it can reduce cravings and withdrawal symptoms in a person with an opioid use disorder without producing euphoria, and patients tend to tolerate it well. Research has found buprenorphine to be similarly effective as methadone for treating opioid use disorders, as long as it is given at a sufficient dose and for sufficient duration ¹². The U.S. Food and Drug Administration (FDA) approved buprenorphine in 2002, making it the first medication eligible to be prescribed by certified physicians through the Drug Addiction Treatment Act. This approval eliminates the need to visit specialized treatment clinics, thereby expanding access to treatment for many who need it. Additionally, the Comprehensive Addiction and Recovery Act (CARA), which was signed into law in July 2016, temporarily expands eligibility to prescribe buprenorphine-based drugs for medication-assisted treatment (MAT) to qualifying nurse practitioners and physician assistants through October 1, 2021. Buprenorphine has been available for opioid use disorders since 2002 as a tablet and since 2010 as a sublingual film ¹³. The FDA approved a 6-month subdermal buprenorphine implant in May 2016 and a once-monthly buprenorphine injection in November 2017. These formulations are available to patients stabilized on buprenorphine and will eliminate the treatment barrier of daily dosing for these patients.

Naltrexone

Naltrexone is an opioid antagonist, which means that it works by blocking the activation of opioid receptors. Instead of controlling withdrawal and cravings, it treats opioid use disorder by preventing any opioid drug from producing rewarding effects such as euphoria. Its use for ongoing opioid use disorder treatment has been somewhat limited because of poor adherence and tolerability by patients. However, in 2010, an injectable, long-acting form of naltrexone (Vivitrol®), originally approved for treating alcohol use disorder, was FDA-approved for treating opioid use disorder. Because its effects last for weeks, Vivitrol® is a good option for patients who do not have ready access to health care or who struggle with taking their medications regularly.

How effective are medications to treat opioid use disorder?

Abundant evidence shows that methadone, buprenorphine, and naltrexone all reduce opioid use and opioid use disorder-related symptoms, and they reduce the risk of infectious disease transmission as well as criminal behavior associated with drug use ¹⁴. These medications also increase the likelihood that a person will remain in treatment, which itself is associated with lower risk of overdose mortality, reduced risk of HIV and HCV transmission, reduced criminal justice involvement, and greater likelihood of employment ¹⁴.

Methadone

Methadone is the medication with the longest history of use for opioid use disorder treatment, having been used since 1947. A large number of studies support methadone’s effectiveness at reducing opioid use. A comprehensive Cochrane review in 2009 ¹¹ compared methadone-based treatment (methadone plus psychosocial treatment) to placebo with psychosocial treatment and found that methadone treatment was effective in reducing opioid use, opioid use-associated transmission of infectious disease, and crime. Patients on methadone had 33 percent fewer opioid-positive drug tests and were 4.44 times more likely to stay in treatment compared to controls ¹¹. Methadone treatment significantly improves outcomes, even when provided in the absence of regular counseling services ¹⁵; long-term (beyond 6 months) outcomes are better in groups receiving methadone, regardless of the frequency of counseling received ¹⁶.

Buprenorphine

Buprenorphine, which was first approved in 2002, is currently available in two forms: alone (Probuphine®, Sublocade™, Bunavail®) and in combination with the opioid receptor antagonist naloxone (Suboxone®, Zubsolv®). Both formulations of buprenorphine are effective for the treatment of opioid use disorders, though some studies have shown high relapse rates among patients tapered off of buprenorphine compared to patients maintained on the drug for a longer period of time ¹⁷.

A Swedish study ¹⁸ compared patients maintained on 16 mg of buprenorphine daily to a control group that received buprenorphine for detoxification (6 days) followed by placebo. All patients received psychosocial supports. In this study, the treatment failure rate for placebo was 100 percent vs. 25 percent for buprenorphine ¹⁸. More than two opioid-positive urine tests within 3 months resulted in cessation of treatment, so treatment retention was closely related to relapse. Of patients not retained in treatment, there was a 20 percent mortality rate.

Meta-analysis determined that patients on doses of buprenorphine of 16 mg per day or more were 1.82 times more likely to stay in treatment than placebo-treated patients, and buprenorphine decreased the number of opioid-positive drug tests by 14.2 percent ¹².

To be effective, buprenorphine must be given at a sufficiently high dose (generally, 16 mg per day or more). Some treatment providers wary of using opioids have prescribed lower doses for short treatment durations, leading to failure of buprenorphine treatment and the mistaken conclusion that the medication is ineffective ¹⁹.

Methadone and Buprenorphine compared

Methadone and buprenorphine are equally effective at reducing opioid use. A comprehensive Cochrane review comparing buprenorphine, methadone, and placebo found no differences in opioid-positive drug tests or self-reported heroin use when treating with methadone or buprenorphine at medium-to-high doses ¹².

Notably, flexible dose regimens of buprenorphine and doses of buprenorphine of 6 mg or below are less effective than methadone at keeping patients in treatment, highlighting the need for delivery of evidence-based dosing regimens of these medications ¹².

Naltrexone

Naltrexone was initially approved for the treatment of opioid use disorder in a daily pill form. It does not produce tolerance or withdrawal. Poor treatment adherence has primarily limited the real-world effectiveness of this formulation ²⁰. As a result, there is insufficient evidence that oral naltrexone is an effective treatment for opioid use disorder ²¹. Extended-release injectable naltrexone (XR-NTX) is administered once monthly, which removes the need for daily dosing. While this formulation is the newest form of medication for opioid use disorder, evidence to date suggests that it is effective ²⁰.

The double-blind, placebo-controlled trial that was most influential in getting XR-NTX approved by the FDA in 2010 for opioid use disorder treatment showed that XR-NTX significantly increased opioid abstinence. The XR-NTX group had 90 percent confirmed abstinent weeks compared to 35 percent in the placebo group. Treatment retention was also higher in the XR-NTX group (58 percent vs. 42 percent), while subjective drug craving and relapse were both decreased (0.8 percent vs. 13.7 percent) ²². Improvement in the XR-NTX group was sustained throughout an open label period out to 76 weeks ²³. These data were collected in Russia, and additional studies are required to determine if effectiveness will be similar in the United States ²⁴.

Buprenorphine and Naltrexone compared

A National Institute on Drug Abuse (NIDA) study showed that once treatment is initiated, a buprenorphine/naloxone combination and an extended release naltrexone formulation are similarly effective in treating opioid use disorder. Because naltrexone requires full detoxification, initiating treatment among active opioid users was more difficult with this medication. However, once detoxification was complete, the naltrexone formulation had a similar effectiveness as the buprenorphine/naloxone combination.

What treatment is available for pregnant mothers and their babies?

Opioid use disorder is a treatable disease. When opioid use disorder is managed with medicines and counseling, you can have a healthy pregnancy and a healthy baby. However, during pregnancy, adjustments to your opioid use disorder treatment plan and medicines may be needed.

Untreated opioid use disorder during pregnancy can have devastating effects on the fetus. The fluctuating levels of opioids in the blood of mothers misusing opioids expose the fetus to repeated periods of withdrawal ²⁵, which can also harm the function of the placenta and increase the risk of:

• fetal growth restriction
• placental abruption
• preterm labor
• fetal convulsions
• intrauterine passage of meconium
• fetal death ²⁶

In addition to these direct physical effects, other risks to the fetus include:

• untreated maternal infections such as HIV ²⁷
• malnutrition and poor prenatal care ²⁸
• dangers conferred by drug-seeking lifestyle, including violence and incarceration ²⁶

To lessen the negative effects of opioid dependence on the fetus, treatment with methadone has been used for pregnant women with opioid use disorder since the 1970s and has been recognized as the standard of care since 1998 ²⁶. Recent evidence, however, suggests that buprenorphine may be an even better treatment option ²⁹.

Both methadone and buprenorphine treatment during pregnancy:

• stabilize fetal levels of opioids, reducing repeated prenatal withdrawal ³⁰
• improve neonatal outcomes ²⁸
• increase maternal HIV treatment to reduce the likelihood of transmitting the virus to the fetus ²⁶
• link mothers to better prenatal care ²⁶

A meta-analysis showed that, compared to single-dose methadone treatment, buprenorphine resulted in ²⁹:

• 10 percent lower incidence of neonatal abstinence syndrome
• shorter neonatal treatment time (an average of 8.4 days shorter)
• lower amount of morphine used for neonatal abstinence syndrome treatment (an average of 3.6 mg lower)
• higher gestational age, weight, and head circumference at birth

Data from the National Institute on Drug Abuse (NIDA)-funded Maternal Opioid Treatment: Human Experimental Research study show similar benefits of buprenorphine ³¹. Still, methadone is associated with higher treatment retention than buprenorphine ²⁹. Divided dosing with methadone has been explored as a way to reduce fetal exposure to withdrawal periods, and recent data show low levels of neonatal abstinence syndrome in babies born to mothers treated with divided doses of methadone ³². Larger comparison studies are needed to determine if split methadone dosing for opioid use disorders in pregnancy is associated with better outcomes.

Neonatal abstinence syndrome still occurs in babies whose mothers have received buprenorphine or methadone, but it is less severe than it would be in the absence of treatment ³³. Research does not support reducing maternal methadone dose to avoid neonatal abstinence syndrome, as this may promote increased illicit drug use, resulting in increased risk to the fetus ²⁵.

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