Opioid agonist therapy
Opioid agonist therapy is a treatment in which prescribed opioid agonists are given to patients who live with opioid use disorder. In the case of methadone maintenance treatment , methadone is used to treat dependence on heroin or other opioids, and is administered on an ongoing basis.
The benefits of this treatment include a more manageable withdrawal experience, cognitive improvement, and lower HIV transmission. The length of OAT varies from one individual to another based on their physiology, environmental surroundings, and quality of life.
The term medication for Opioid Use Disorder is used to describe medication including methadone and buprenorphine, which are used to treat patients with OUD.
Terminology
Other terms that appear in the professional and popular literature include opioid replacement therapy, medication-assisted treatment and medications for opioid use disorder.Biological understanding
An opioid is considered a ligand, which is an ion or a molecule. An opioid ligand travels to the brain and attaches itself to an opioid receptor, which begins the effects of opioids. The mesolimbic system, which is the biological system that moderates the feeling of reward generated by dopamine, is the main system that is affected by opioids. Opioids stimulate the mesolimbic system to release a large amount of dopamine in the brain, which increases the effects of opioids: euphoria and numbness. The difference between an opioid and an opioid agonist is that opioids induce more intense effects and stay in the brain for a short amount of time. Conversely, an opioid agonist induces minimal effects and stays in the brain for a long time, which prevents the opioid user from feeling the effects of natural or synthetic opioids. However, the opioid receptors are still being used when an opioid agonist attaches, which prevents the effects of opioid withdrawal and can help prevent relapse. The two most common opioid agonists are methadone and buprenorphine.Methadone
Methadone is an opioid agonist that binds to the same receptors in the brain as heroin and other opioids. Introduced as an analgesic in the US in 1947, methadone has been used in maintenance treatment—also known as substitution treatment, or drug replacement therapy—since 1964. Methadone treatments usually last for multiple years, although they can last for decades. A dose of methadone often minimizes the effects of withdrawal for approximately 24 hours and the lowest optimal dose is 60 mg. Methadone functions via competitive antagonism; while the prescribed agonist is in the opioid user's body, the use of illicit opioids will not produce the effects of illicit opioids. Methadone has a slower onset than illicit opioids and it produces less effects than illicit opioids. Side effects of methadone may include "constipation, weight gain, reduced libido, and irregular menses".Methadone maintenance reduces the cravings for other opioids, and reduces the risk of fatal overdose from street drugs since the purity and strength of methadone is known, whereas substances obtained from the street vary significantly in strength and purity.
Therapeutic dosing is contingent upon individual patient needs, with a dosage range generally between 20 and 200 mg. Doses are unsafe for opioid-naive individuals, and administration of methadone is gradually increased to reach a therapeutic dose under medical supervision to reduce the risk of overdose. The amount of oral methadone a patient will require is dependent on the amount and power of opioids they consumed prior to initiating treatment, with an assessment in the mid-2000s finding that 1 gram of street heroin is roughly equivalent to 50 to 80 mg of methadone. Methadone is taken either orally as a mixture of 1 mg/1ml supplied as a red or clear liquid, or as a mixture containing 10 mg of methadone in 1ml of liquid or 20 mg in 1ml of liquid. The latter is often used when a person is on a large amount of methadone, and is rarely permitted for unsupervised consumption. Since the formulations are not as viscous as the 1 mg/1ml mixture, they are more prone to misuse since they are easier to inject, and due to the high risk of overdose if diverted to an individual not accustomed to such a large dose. Methadone also comes in 40 mg dispersible tablets called "diskettes", as well as 5 and 10 mg pills that are round or "coffin" shaped. These pills are only given in hospital settings. Methadone can also be delivered by either IV or IM injection, as well as ampoules which come in various strengths ranging from 10 mg up to 50 mg. This method is often used for individuals who have a "needle fixation" and who would otherwise revert to using IV heroin.
With the emergence of other medications for the treatment of opioid addiction such as buprenorphine and long-acting naltrexone, MMT is no longer the dominant medically assisted addiction treatment.
Methadone maintenance has been termed "a first step toward social rehabilitation" because it increases the retention of patients in treatment, relieves them from the need to find, buy, and use multiple daily doses of street opioids, and offers a legal medical alternative. Methadone is one of the most researched treatments for opioid use disorder and has significant research support for its efficacy.
Dispensing
Methadone maintenance generally requires patients to visit the dispensing or dosing clinic daily, in accordance with state-controlled substance laws. Methadone, when administered at constant daily milligram doses, will stabilize patients so they feel a "high" from it and will not require additional street opioids. Most clinics will work with patients to get to a dosing level that will take away all cravings for other opiates without feeling too much of a "high" so they can function correctly throughout their day.In the U.S., patients that attend methadone clinics regularly and abstain from the use of street opioids or other controlled substances can be permitted to take home doses known as privileges, though this is at the discretion of the clinic's medical staff. Depending on the state's law, some clinics will allow the use of drugs like cannabis and still permit take home doses. Some states allow methadone clinics to close on Sundays and provide take-home medication the day before. Clinics that offer take-home privileges will usually do so by slowly offering more take-home days over a period of time, as long as their standards of clean drug tests are met. In some states, these take-home privileges can work their way to people getting take-home doses that would last them 2–4 weeks maximum. Another way take-homes are permitted is if the clinic puts the patient on a split dose schedule where they take part of their dose in the morning and take home a dose to take later in the day. This is usually given out to people on higher doses, or to help lengthen effectiveness throughout the day. States may mandate drug testing in clinic drug abuse groups and/or outside Narcotics Anonymous meetings. In other countries, dispensing of methadone maintenance by pharmacies, or via prescription from general practitioners rather than specialized clinics, is permitted.
Travel
In the UK, patients on methadone maintenance who wish to travel overseas are subject to certain legal requirements surrounding the exportation and importation of methadone. The prescriber must be provided with details of travel, after which they will arrange for a Home Office Export License to be provided. This license is only required if the total amount being exported exceeds 500 mg. Granting of the license does not allow for the importation of methadone into any overseas jurisdiction. For importation, the patient should contact the embassy of their destination country and request permission to import methadone onto their shores, although not all countries allow the importation of controlled drugs. The license also allows for the re-importation of any remaining methadone back into the UK. It is normal for patients traveling overseas to be prescribed methadone in a tablet form, as tablets are easier to transport. For patients who expect to be overseas for a prolonged period of time, "courtesy" arrangements can be made at a local clinic which arrange for the prescription of the necessary medication. If traveling throughout the United States, state or city clinics may offer "take home" doses for the period of time patients will be gone. Depending on length of travel or clinic rules, they may opt to have their "courtesy" dose at another clinic that is closer to where they are travelling.Buprenorphine
Buprenorphine was approved by the United States Food and Drug Administration in 2002. The lowest optimal dose of buprenorphine is 8 mg. Buprenorphine has fewer withdrawal symptoms upon discontinuation, lower risk for overdose, and lower potential for abuse; therefore, it is more effective for unsupervised treatment than methadone. Opioid users can take fewer doses per week than methadone. Side effects of buprenorphine may include constipation and disordered sleep.Comparison with related therapies
The manufacturers of naltrexone have marketed it as superior because it is not an opioid. This argument has moved criminal justice officials to prefer the medicine, and has triggered a Congressional investigation about mismarketing. No study has found naltrexone to be superior to methadone or buprenorphine, and a real-world review of patient records suggests that methadone and buprenorphine are superior at reducing overdose risk or the need for acute drug dependence treatment.Opioid withdrawal
When the body goes through withdrawal, the opioid receptors in the brain are not filled with an adequate amount of opioids, which means that the feelings of euphoria associated with opioids are not felt. Withdrawal only happens when the body has become accustomed to having opioids in the receptors, which changes the structure and functioning of the brain. Thus, without opioids, the brain functions differently in comparison to the brain before the user started becoming dependent on opioids. People who have a dependence on opioids are the only people who experience withdrawal symptoms.Opioids are commonly prescribed to alleviate symptoms of chronic pain. However, misuse of this pain-killer impacts millions of people worldwide each year. According to WHO, approximately 115,000 people died of opioid overdose in 2017. Addiction is widespread among users and can typically be seen through symptoms such as intense cravings, rejection of previously enjoyed activities, and struggling to fulfill responsibilities due to opioid use. OAT is one suggested treatment for opioid misuse because it is commonly reported to minimize the likelihood of experiencing psychological and physiological symptoms associated with withdrawal and alleviate the intensity of most withdrawal symptoms.