Methadone mechanism of action is similar to that of morphine, being a mu-agonist and a synthetic opioid analgesic acting upon the nervous system and the organs which are composed of smooth muscle. The primary methadone use is for analgesia, but it is also instrumental in the maintenance or detox in the case of opioid addiction.
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How Methadone Works
Methadone is a strong synthetic analgesic that acts as a µ-opioid receptor agonist and as an N-methyl-d-aspartate receptor antagonist. As a µ-opioid receptor agonist, the drug can reproduce precisely the natural effects of the opioids, enkephalins, and endorphins in the body, by releasing neurotransmitters that are responsible for pain transmission.
Methadone mechanism of action also comes with its characteristics, especially the decreased risk of neuropsychiatric toxicity (because it lacks active metabolites), good bioavailability, long duration of the activity, and minimal accumulation in renal failure.
Although the drug’s mechanism shares similarities with other opioids, including fentanyl, oxycodone, hydromorphone, and morphine, it also has a unique pharmacokinetic profile providing longer half-life and duration of action.
This makes the use of methadone effective, particularly in the management of pain syndromes, which are hard to treat, including cancer and neuropathic pain for which it is needed more frequent and higher doses of shorter-acting opioids. The drug is also useful in the treatment of addiction, preventing opioid withdrawal symptoms.
What is methadone downside? The drug has an unpredictable half-life and interindividual variability. These characteristics can increase the risk of an overdose or respiratory depression when titrating or initiating the therapy.
Methadone Medical Uses
Maintenance therapy addresses patients with opiate addiction and consists of the administration of methadone hydrochloride for an extended period. The purpose of methadone use is to replace the illicit, parenterally administered heroin with a legal, oral opiate that has a long half-life. Maintenance therapy helps patients avoid the dangers and struggle of the procurement and use of heroin, including the high risk of mortality, and improve the individual reintegrate into the society as a functional member.
What methadone maintenance therapy does is to prevent opiate withdrawal symptoms by blocking the high effect of heroin and reducing cravings. The dosage of this drug in this situation usually starts at 10-20 mg, and it is gradually increased to 40 but, in some cases, even 80 mg a day.
Methadone is used to treat addiction to opiates. The detox implies the short-term use of the drug to diminish abstinence symptoms in individuals dealing with dependence on opioids. The dose of the medicine is gradually tapered until the patient achieves a drug-free state.
Unfortunately, this method is not very useful, and it has a high recidivism rate, mainly caused by a physiologic state and the abstinence syndrome, which is still present long after the completion of the detox.
For detox, the methadone dose also starts at 10-20 mg, being increased to 40 mg a day to control withdrawal symptoms. Once the patient is stabilized, the dosage is maintained for 2-3 days and then decreased daily by 10% or 20%. But this depends on each patient, and the tapering schedule can last for weeks or even months.
For more effectiveness, gabapentin and methadone can be used together for lower drug use and relief of withdrawal symptoms.
Methadone For Chronic Pain
Another one of the methadone uses is in chronic pain. The drug is used for its practical analgesic effects and other unique properties. Patients who have severe side effects from other prescribed opioids or the drugs do not prove to be effective, usually have their treatment replaced with methadone.
How long does methadone stay in the system? Although the drug can remain in the system for about 8 hours, it has analgesia duration of 4-6 hours, which is relative to the drug’s half-life. Therefore, the use of this drug as an analgesic implies more frequent dosing compared to the treatment used for detox or maintenance therapy or detox. The dosing is usually done every 3-4 hours (2.5 to 10 mg) or 6-8 ( 5 to 20 mg for terminally ill patients).
Unfortunately, the drug’s long half-life increases the chance of adverse effects and drug accumulation in frequent dosing.
In the use of methadone for pain, the transition to this drug is usually done either rapidly by discontinuing the previous opioid at once or gradually by tapering the previous opioid while including methadone into the treatment.
Use In Pregnancy
Because the drug crosses the placenta, the use of methadone during pregnancy is not recommended, as it might cause fetal dependence. That is why women with established opiate dependence should only use the drug. Also, opiate detox during pregnancy should be avoided due to fetal distress caused by the withdrawal symptoms. Methadone pregnancy maintenance treatment offers as an advantage longer gestational periods and babies with increased body weight, compared to mothers with heroin dependence who are not treated.
Methadone Recreational Use
Does methadone get one high? The answer is yes, and for this reason, the drug can be abused, in many cases leading to an overdose, which can be deadly.
The use of methadone does not offer a potent or quick high, that is why it is considered relatively safe in the addiction and medical setting, and not a candidate for substance abuse.
The drug works more as a sedative than a stimulant, but in high doses, the drug can still offer a euphoric effect. Because getting high on this drug requires large doses of the drug, this increases the risk of the drug’s abuse and overdose.
The methadone overdose treatment is usually done with a drug that counters the effects of the opioid and brings the respiratory system to normal functioning.
One of the long-term effects of methadone is chemical dependency. During prolonged use of methadone, the patient might develop a physical and psychological dependence on the drug. In this situation, the patient should be gradually tapered from drug use to prevent methadone withdrawal symptoms. Many specialized clinics offer successful addiction treatment plans, personalized according to each patient’s needs.
- Grissinger M. Keeping patients safe from methadone overdoses. Physical Therapy. 2011; 36(8): 462–466. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171821/.
- Substance Abuse and Mental Health services Administration. Methadone. 2019. https://www.samhsa.gov/medication-assisted-treatment/treatment/methadone.