Methadone Opioid — Its Synthetic Status and Agonist Properties

Opium poppy plants naturally produce a substance that people mimic or derive to create the class of medications known as opioids, which offer pain relief. You might be wondering, how is methadone an opioid? Methadone is a synthetic medication that acts on the same receptor as natural opioids. Its action helps to create relief from pain in cases of acute or chronic illnesses. However, unlike natural opioids, it does not produce the euphoric effect that makes natural opioids addictive and causes severe withdrawal symptoms. In this article, the classification of opioids and the relationship between methadone and natural opioids will be clearly explained.

Is Methadone an Opioid?

What Is Methadone?

Methadone is a synthetic opioid agonist used to create relief from pain. It activates the opioid receptor to block pain signal reception. A German scientist synthesized methadone during the Second World War when there was a shortage of morphine. The methadone opioid was approved for use as an analgesic in the United States in 1947.

Opioid Classification

Opioids are analgesics used to provide relief from pain. They have a derivative from opium poppy plants. Opioids work by blocking pain signals sent via the spinal cord to the brain via the opioid receptors on nerve cells. Patients have diverse needs for pain relief as a result of one illness or another, as well as surgical procedures that induce inflammatory action, of which pain is a major characteristic. The need for analgesics goes a long way toward helping patients get the relief they need, either for a short-term period or for chronic conditions.

Is Methadone an Opioid Agonist?

Opioids can be classified into opioid agonists, partial agonists, and antagonists based on their action at the opioid receptor, pharmacologically speaking. An opioid agonist binds to the G-protein-coupled receptor to cause hyperpolarization and the resultant blockage of pain signals to elicit pain. An example of this is methadone.

A partial opioid agonist also binds to the opioid receptor but creates a much lesser effect compared to the full agonist. An example is Bisnorphine. An opioid antagonist binds to the same opioid receptor, but this time it does not activate the receptor and also prevents opioid agonists from binding to the receptor. An example is naltrexone. In the treatment of opioid use disorder, there could be a perception that methadone is an opioid antagonist or agonist. However, methadone is a full agonist and not an antagonist. Opioid agonist-antagonist medication includes drugs with mixed effects, such as butorphanol and buprenorphine.

Types of Opioids

All opioids act on the opioid receptor to block the pain signal from the spinal cord to the brain. Three types are typically used for their production methods to be distinguished. This includes natural, synthetic, and semi-synthetic opioids.

  • Naturally occurring opioids: These are opioids produced directly from the opium poppy plants. Examples include morphine, codeine, and papaverine.
  • Semi-synthetic opioids: human-made chemicals and natural derivatives of the opium poppy are used to create opioids. Examples include dimorphine (heroin), oxycodone, and buprenorphine.
  • Synthetic opioids: human-made chemicals completely derive them with no inclusion from the natural opium poppy plant. Examples include methadone, fentanyl, and pethidine.

Is Methadone Considered an Opioid?

Due to the action of methadone and its relationship with opioids, especially regarding opioid use disorder treatment, two major questions that need to be addressed include: Is methadone an opioid? And Is methadone a synthetic opioid?

Methadone is a synthetic opioid, which means it functions like other naturally occurring opioids in the relief of pain. Chemical action is used to produce it instead of deriving it directly from natural sources like morphine. The synthetic opioid methadone activates the opioid receptor by interacting with the protein-coupled receptor, thereby blocking pain signals from reaching the brain. Methadone is quite similar to natural opioids due to its mechanism of action and effect on pain.

Here are some differences between methadone and other naturally occurring opioids:

OpioidMethadoneNatural Opioids
Time of Action6-8 hours2-6 hours
Analgesic Potency5 to 10 times higher than morphineStandard of comparison
Addiction tendencyLess addictive due to the reduced euphoric effectMore addictive due to its high euphoric effect

Methadone as an Opioid Agonist

An opioid agonist works by activating opioid receptors, thereby blocking the pain signal to the brain. As an opioid agonist, methadone works by acting on the same opioid receptors without promoting euphoria, thereby reducing withdrawal symptoms in patients who have previously had opioid use disorder.

Other opioid agonists, besides methadone, perform similarly and can be divided into three groups.:

Full Opioid Agonists

Phenanthrenes: These are naturally occurring plant-based compounds with two or three fused rings. They mostly act at the mu receptor while some others have multiple receptor action to include the k-receptor. Examples include:

  • Morphine
  • Hydromorphone
  • Oxymorphone
  • Codeine
  • Heroin
  • Dihydrocodeine
  • Hydrocodone
  • Oxycodone
  • Nalbuphine

Full Opioid Agonists

Phenylpiperdine: It is a selective agonist that acts on just the mu receptor and is 50 to 100 times more potent than morphine. Examples include fentanyl and meperidine.

Full Opioid Agonists

Diphenylheptanes: These are mostly synthetic groups of opioid agonists with simple molecules and no multiple rings. The major example in this group is methadone. Methadone is greatly different from other groups of opioids in that it has a relatively longer time of action and higher oral dose efficacy.

Clinical Applications

Methadone is one of the major therapeutic options for the treatment of opioid withdrawal. In methadone-assisted treatment, patients with withdrawal symptoms are given methadone as a replacement therapy. Just like other types of opioids, methadone can be addictive, but it is safer for opioid use disorder patients. For more information on methadone-assisted treatment, see here.

Benefits and Risks of Methadone

Helps in the treatment of opioid use disorder.Could result in respiratory depression in cases of misuse.
Less addictive than natural opioidsRisk of QT prolongation, which could result in arrhythmias.
It is safer to use since it is mostly in oral doses compared to heroin, where there could be a risk of blood-transmitted diseases from needle pricks.It is twice as powerful as morphine. To avoid misuse and overdose, more monitoring is needed.
Has a longer duration of action.There is a risk of seizures, coma, and death in cases of misuse or overdose.

Regulatory Status and Legal Considerations

The Food and Drug Administration (FDA) regulates the use of methadone, like other prescription medications. Also, this drug is a narcotic with a tendency for addiction and abuse. The Drug Enforcement Administration (DEA) under the Department of Justice, regulates it. The Narcotic Addiction Treatment Act of 1974 requires annual DEA registration for health professionals to continuously prescribe this medication.


Methadone is an opioid agonist and is synthetic in production. Its use is similar to that of natural opioids, as it activates the same opioid receptors for the process of pain relief. The use of methadone has gained a lot of influence in the treatment of opioid use disorders as it helps to reduce the withdrawal symptoms seen in patients who have opioid addiction. The use of this medication is mainly prescriptive, which means you have to get a prescription from your doctor to enable you to assess this drug. If you need to use methadone, seek help from methadone-based clinics and a rehab center to get a holistic treatment.