Medication-assisted treatment (MAT) is an evidence-based approach for treating substance use disorders. It involves combining the use of FDA-approved medications with behavioral therapies such as counseling.1 Although MAT has been previously used in the treatment of both alcohol and opioid use disorders, it has received recent attention with the increase in heroin and prescription opioid abuse and overdose deaths in the last several years.2 This paper will provide an overview of one component of MAT, the use of medications to treat craving and withdrawal when an individual stops using opioids. Withdrawal and cravings can be distressing psychologically and physically, and the use of medications can alleviate these symptoms.1 Pharmacotherapy Pharmacological treatment for narcotic addiction began in the 1960s after biological research suggested that addiction was a physiological disease.3 Methadone was the first FDA-approved pharmacotherapy for long-term opioid addiction to provide relief from cravings and block euphoric effects of illegal substances.3 Today, there are many forms of opioid treatment medications that have been developed and approved for use during the withdrawal process and to prevent future cravings. These medications and their mechanisms of action are discussed in more detail in the chart below. MAT medications can be used to ameliorate the withdrawal process, which is often physically and cognitively strenuous, and as a method of alleviating cravings for abused opioid substances. Medications are often given during the initial acute stages of drug cessation, and may continue to be prescribed for withdrawal or craving symptoms.4 The length of time someone is prescribed these medications depends on the severity of addiction, the type of medication and an individual’s treatment plan with their provider.4 Mechanisms of Action Medications for opioid addiction work neurologically to alleviate opioid addiction withdrawals and cravings. They target specific receptors in the brain related to opioids called mu receptors and function in three ways: 1) as agonists to these receptors, by activating them in a way similar to opioid drugs; 2) as partial agonists, which activate the mu receptors at a lower level than opioid drugs; and 3) as antagonists, which block the receptor and interfere with the rewarding effects of opioids.2 Methadone is a type of synthetic opioid that fully binds to and stimulates opioid receptors.5 As an agonist, it has similar neurobiological actions to addictive opioids, stimulating receptors and thereby increasing the release of dopamine. However, methadone’s effects are slower acting on the brain and thus prevent the extreme feelings of opioid-induced highs and lows. Using methadone concurrently with other illicit substances may alter the intended anti-craving effect and cause overdose.5 Buprenorphine is a partial opioid in that it only partially activates mu opioid receptors in the brain. It has a high affinity to these receptors, more so than prescription or illicit opioids.6 The chemical compounds of Buprenorphine supercedes the effects of other prescription or illicit opioids attempting to activate the mu receptors.7 The low intrinsic activity (efficacy) of buprenorphine at the opioid receptor creates a ceiling effect—after hitting a peak level this partial agonist does not allow larger doses of the medication to cause more intoxication.6 Another form of buprenorphine is used in combination with the medication naloxone. Naloxone is generally used to prevent overdose from opioids by blocking opioid receptor sites as an antagonist (not allowing opioid-like effects) and causing the feeling of withdrawal.2 When taken together, buprenorphine will predominate and quickly bind to the opioid receptors, partially activating them while the naloxone lies dormant.7 If the medication is administered by injection (i.e., diversion), the naloxone will predominate, reaching the brain first and causing an immediate feeling of withdrawal.7 Naltrexone is another form of MAT that functions to reduce the reward feelings of opioids. Formulated as an opioid antagonist, naltrexone blocks the opioid mu receptors, preventing the brain from responding to endorphins and the euphoric effects opioids generally produce.10 Naltrexone has a higher affinity (attraction) for the receptors than heroin or prescription painkillers, thus blocking opioid effects and eliminating the ability to produce reward.9 Opioid antagonists have little to no effect on cravings, but are instead used to prevent the feelings of getting high.9 Efficacy Research shows that the medications commonly used in MAT are effective. Buprenorphine and methadone dramatically reduce the severity of physical symptoms such as pain, chills and weakness, and also reduce psychological symptoms of anxiety, irritability and depression.5, 6 In a review of 27 randomized controlled trials on the efficacy of MAT, buprenorphine maintenance treatment produced better outcomes in the withdrawal management of opioid dependence and retention in treatment than did other opioid agonists, other medication-assisted treatments and no medication at all.8, 11 A scientific review of a large body of research on the efficacy of opioid agonist treatments supported the benefits of certain medications provided to opioid addicted individuals as part of MAT. Although the quality of evidence to support the use of opioid agonists was moderate overall, buprenorphine and methadone present similar benefits for treatment of illicit opioids and treatment retention. MAT using buprenorphine and methadone was tested on long-term outcomes for abstinence rates and retention compared to psychological treatments or no treatment (detoxification). In over 600 participants in interventions ranging from 30 days to 24 weeks, buprenorphine and methadone treatment resulted in lower rates of opioid use in self-reported or urine drug tests for opioid use than all other interventions.6 The use of buprenorphine in MAT appeared most effective overall, outperforming methadone, psychological treatments or detoxification alone.6 MAT using naltrexone is generally used later in the stages of opioid addiction treatment as a preventative measure for relapse. Currently there are inconclusive research findings regarding the use of opioid antagonists, such as naltrexone, to treat opioid addiction based on patient outcomes.9 In an analysis of the scientific literature on the use of naltrexone maintenance treatment versus placebo, or other treatments to reach sustained abstinence from opiate drugs, over 1,150 participants over an average of six months were studied for efficacy of the medication. Results based on stringent reliability and validity of each study found no significant difference in preventing relapse using naltrexone versus other psychiatric medication, placebo or no pharmacological treatments,or psychotherapy.9 A few studies found statistical significance among the use of naltrexone and retention in treatment and abstinence, but the quality of research was unclear.9 An adequate evaluation of naltrexone treatment has not yet been identified, and long-term efficacy of naltrexone is inconclusive for opioid-specific dependent individuals.9 Other moodaltering chemicals, such as alcohol, may present greater benefits to naltrexone than opioids.4 Diversion Medications intended for treating opioid addiction have the potential of misuse known as diversion. The most frequent misuses of non-prescribed medications are for treating and preventing withdrawal sickness and as a substitute to get high when other drugs are not available.11 In a study with over 10,000 participants diagnosed with an opioid use disorder, one-third indicated they had diverted buprenorphine and methadone at some time during their use.12 Precautions need to be taken when considering treatment with MAT, especially using opioid agonists such as buprenorphine and methadone. Download The Use of Medications for Treatment of Opioid Use Disorders white paper.