Medications to Treat Opioid Use Disorder Research Report
What are misconceptions about maintenance treatment?

Because maintenance medications (methadone and buprenorphine) are themselves opioids and are able to produce euphoria in people who are not dependent on opioids, many people have assumed that this form of treatment just substitutes a new substance use disorder for an old one. This belief has unfortunately hindered the adoption of these effective treatments. In the past, even some inpatient treatment programs that were otherwise evidence-based did not allow patients to use these medications, in favor of an "abstinence only" philosophy.

Although it is possible for individuals who do not have an opioid use disorder to get high on buprenorphine  or methadone (see "What is the treatment need versus the diversion risk for opioid use disorder treatment?"), these medications affect people who have developed a high tolerance (see "Opioid Tolerance") to opioids differently. At the doses prescribed, and as a result of their pharmacodynamic and pharmacokinetic properties (the way they act at opioid receptor sites and their slower metabolism in the body), these medications do not produce a euphoric high but instead minimize withdrawal symptoms and cravings (see "Mechanisms of Opioid Dependence"). This makes it possible for the patient to function normally, attend school or work, and participate in other forms of treatment or recovery support services to help them become free of their substance use disorder over time.

The ultimate aim can be to wean off the maintenance medication, but the treatment provider should make this decision jointly with the patient and tapering the medication must be done gradually. It may take months or years in some cases. Just as body tissues require prolonged periods to heal after injury and may require external supports (e.g., a cast and crutches or a wheelchair for a broken leg), brain circuits that have been altered by prolonged drug use and substance use disorder take time to recover and benefit from external supports in the form of medication. In cases of serious and long-term opioid use disorder, a patient may need these supports indefinitely.

In 2005, methadone and buprenorphine were added to the World Health Organization's list of essential medicines, defined as medicines that are "intended to be available within the context of functioning health care systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality, and at a price the individual and the community can afford."34,35

Opioid Tolerance

People who take opioids for long periods of time typically develop tolerance, a state in which more of the drug is needed to produce the same effect. Receptor desensitization and downregulation 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.36,37 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.38,39 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.

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.40 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.

Line graph comparing opioid receptor activity for heroin, methadone, buprenorphine, and naltrexone. Refer to image caption for details.
Sources: Cruciani & Knotkova, 2013; Goodman et al., 2006
Opioid receptor activity. Heroin (red line) activates opioid receptors fully and quickly. Methadone (blue) is also a full agonist, but the activation is much slower and longer lasting. Buprenorphine (green) activates the receptors partially, with a similar time course to methadone. Naltrexone (purple) is an opioid receptor antagonist and therefore prevents receptor activation. 41,42