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What is Methadone?

Methadone is an opioid (or narcotic) drug and a controlled substance - this drug has a risk of misuse and may cause dependence.

Methadone is also available as the brand-name drug Methadose. It is used as an oral soluble tablet.  

What is Methadone Used For?

Methadone is used to treat moderate to severe pain. 

It is sometimes prescribed in cases where the patient has an addiction to another opioid. Methadone helps prevent withdrawal symptoms. 

Methadone relieves pain by changing the way your brain and the nervous system respond to pain. It does so by working on the pain receptors.

Methadone relieves pain much slower than other painkillers like morphine.

Side Effects of Methadone

Some common side effects of methadone are:

Some serious side effects are:

Drug Interactions

Opioid medication can interact with many other drugs and cause dangerous side effects. Make sure you notify your doctor if you use other:

Gene-Drug Interactions

UGT2B7 And Withdrawal Symptoms In Methadone Maintenance Patients

Methadone maintenance treatment is the use of methadone for a prolonged period of time to treat pain in patients who have faced addiction issues with other opioids like heroin. 

The UGT2B7 gene is located at chromosome 4q13. It contains instructions for the production of UDP-Glucuronosyltransferase-2B7. 

It is associated with withdrawal symptoms, treatment efficacy, and side effects in methadone maintenance treatment. 


rs4292394 is a single nucleotide polymorphism or SNP in the UGT2B7 gene. It is associated with opioid withdrawal when undergoing methadone maintenance treatment. 

GGMay have increased severity of opiate withdrawal symptoms
CGMay have decreased severity of opiate withdrawal symptoms
CCMay have decreased severity of opiate withdrawal symptoms

CYP3A4 and Methadone Toxicity

The CYP3A enzymes are the most abundant of the CYP450 isozymes, comprising ∼40% of the hepatic CYP450 content. 

The CYP3A4 gene contains instructions for the production of the Cytochrome P 450 3A4 enzyme. CYP3A4 plays a role in the metabolism of 40–60% of all drugs ingested. 

A few studies have reported the role of CYP3A4 polymorphisms in methadone toxicity


rs4646437 is an SNP in the CYP3A4 gene. Studies have demonstrated that the CYP3A4 enzyme expression and activity are increased in females carrying the T allele. 

Increased levels of CYP3A4 result in increased conversion of methadone to inactive metabolites (substances that result from the metabolism of methadone). This increases the risk of fatal methadone intoxication in the female population with the T allele.

Recommendations for Safe Methadone Consumption

Pre-existing Medical Conditions

Notify your doctor of any health conditions you may have, like heart, lung, or kidney disease, as methadone may not be safe to consume in these cases.

Current Medications

Make sure your doctor knows all the drugs you are currently on/have had in the recent past in order to avoid drug interactions.

Pregnant or Breastfeeding Women

Women who are pregnant or breastfeeding may take methadone; however, methadone can cross the placenta and can go into the breast milk. So seek the advice of your medical practitioner if you are pregnant or breastfeeding.

The Correct Dosage

The correct dosage varies according to the purpose - whether to treat pain, for detoxification of opioid addiction, or for maintenance of opioid addiction. 

In case you take too much or experience symptoms of overdosing like slow pulse, cold, clammy skin, slowed breathing, or dizziness, immediately call your doctor or local poison control. If the symptoms are severe, call 911. 

Allergic Reaction

Methadone can cause severe allergic reactions. If you have trouble breathing or experience swelling of your tongue and throat, seek medical attention immediately. 


  1. Methadone is an opioid drug used to treat moderate to severe pain. It is also prescribed to people who suffer from other opioid addictions.
  2. The common side effects of methadone include nausea, vomiting, and stomach pain, and the serious ones include chest pain, increased blood pressure, and seizures.
  3. Methadone Maintenance Treatment (MMT) is used with patients who have had opioid addiction issues. 
  4. People with a certain type of the UGT2B7 gene may have an increased risk for severe opioid withdrawal symptoms than others when on MMT. 
  5. The CYP3A4 gene has been associated with methadone toxicity. Females with a particular type of this gene are at increased risk for methadone toxicity.
  6. While taking methadone, it is important to notify your doctor of your existing medical conditions as well as the list of drugs you are on.
  7. Pregnant and breastfeeding women can take methadone only after consulting with the doctor.
  8. In case of overdose or any allergic reaction, reaching out for immediate medical help is crucial.


Pharmacogenomics, sometimes called as pharmacogenetics, is the study of how genes affect a person’s response to drugs. It is a combination of two fields - pharmacology (the science of drugs) and genomics (the study of genes and their functions). 

Just like how genes determine our eye color, height, etc. they also partly influence how our body responds to drugs. Some chemical changes in these genes can elicit unwanted side effects upon drug consumption.

The long-term goal of pharmacogenomic research is to design drugs best suited for each person, in order to avoid these undesirable side effects. 

The Importance of Pharmacogenomics

Genes influence multiple steps involved in your response to drugs. They include:

Drug Receptors: Some drugs require a type of protein called the receptors, to which they bind and get activated. Your genes can influence the number and effectiveness of these receptors.

Example: T-DM1 is a drug used to treat breast cancer. This drug works by attaching to a receptor called the HER-2 receptor. However, not all breast cancer cells express this receptor. So, this drug may not be effective for all individuals with breast cancer. 

Drug Uptake: Certain drugs are activated only after they are taken into the cells and tissues. If your genetic makeup leads to reduced uptake of the drug, it may accumulate in other parts of the body. 

Example: Statins are a class of drugs commonly used to treat high cholesterol levels. For the drug to work, it must be transported to and taken up by the liver efficiently. SLCO1B1 gene influences this process. A change in this gene results in a reduced transport of statins to the liver. This can result in statin buildup in muscles resulting in pain and weakness. 

Drug breakdown/metabolism: If your genetic makeup results in a faster breakdown of drugs, it gets clear from the body faster. This may warrant an increased dosage of the drug or a different drug. On the other hand, if your drug metabolism is slow, it stays in your body for a longer period. In this case, a lower dosage may do the work. 

Example: Amitriptyline is an antidepressant drug. Two genes, namely, CYP2D6 and CYP2C19, are involved in its metabolism. If you carry a change that slows down or boosts the metabolism, you may need to alter the drug dosage accordingly. 

Patients can respond differently to the same medicine. 

Commonly used drugs to treat some medical conditions need not be effective for everyone. Some examples are:

- Antidepressants drugs (SSRIs) are ineffective in as many as 38% of patients who are prescribed these drugs 

- Asthma drugs are ineffective in as many as 40% of patients who are prescribed these drugs 

- Diabetes drugs are ineffective in as many as 43% of patients who are prescribed these drugs 

- Arthritis drugs are ineffective in as many as 50% of patients who are prescribed these drugs 

- Alzheimer’s drugs are ineffective in as many as 70% of patients who are prescribed these drugs

- Cancer drugs are ineffective in as many as 75% of patients who are prescribed these drugs

- Cardiac Arrhythmias drugs are ineffective in as many as 40% of patients who are prescribed these drugs

Source: Brian B Spear, Margo Heath-Chiozzi, Jeffrey Huff, Clinical application of pharmacogenetics, Trends in Molecular Medicine, Volume 7, Issue 5, 2001, Pages 201-204, ISSN 1471-4914,

What Can a Pharmacogenomics Test reveal?

The purpose of pharmacogenomic testing is to find out if a medication is right for you. A pharmacogenomic test will help in knowing:

Efficacy - Whether a medication may be an effective treatment for you. 

Dosage - What is the best dose for you for specific medications. 

Toxicity - Whether you could have serious side effects from a medication.

CYP gene and Drug Responses

CYP enzymes or the Cytochrome P450 enzymes are the major drug-metabolizing enzymes in the body. The P450 enzymes contain a protein called heme (iron-containing compound) and are commonly present in hepatocytes (cells of the liver). This is why drugs are mostly broken down or metabolized in the liver. 

From a clinical perspective, the most commonly tested CYPs are:

- CYP2D6

- CYP2C9

- CYP2C19

- CYP3A5

Changes in CYP enzymes can influence the metabolism and clearance of drugs.
The CYP450 Test categorizes individuals into one of the four known metabolic profiles, called “predicted phenotypes.”

What are the limitations of a CYP test?

- Pharmacogenomic research is still in its infancy. Therefore, tests are available only for certain drugs.

- Any change in medication will require a new CYP test - this is because different enzymes are responsible for metabolizing different drugs

- The test reveals how genes affect the drugs and not what the drug does to the body (for example, we cannot determine how the drugs change certain receptors in the brain to alleviate the symptoms)

- Some drugs are metabolized and cleared by more than one CYP enzyme. For example, antidepressant drugs like the SSRIs (Selective Serotonin Reuptake Inhibitor) are metabolized by serotonin receptor molecules as well. This can limit the predictive value of the test.

Who should take the PGx test ?

If you answer yes to any of the below questions, you are an ideal candidate for a PGx test.

1. Are you currently taking four or more medications monthly?  

2. Have you or anyone in your family ever been hospitalized for taking medication?  

3. Have you or anyone in your family ever felt ill after taking a new medication?  

4. Has your doctor changed your dose of medication due to a lack of response or a reaction to the medication?  

5. Do you take your prescribed medication, and you still aren’t feeling better?

6. Are you taking or is your doctor considering prescribing to you pain medicine, tamoxifen, or Plavix?  

7. Do you take herbal supplements regularly in addition to your medication?  

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  2. Brian B Spear, Margo Heath-Chiozzi, Jeffrey Huff, Clinical application of pharmacogenetics, Trends in Molecular Medicine, Volume 7, Issue 5, 2001, Pages 201-204, ISSN 1471-4914,
  3. Ingelman-Sundberg M. Trends in Pharmacol Sci 2004;25(4):193-200
  4. Mrazek DA.Curr Psych Online 2004;3(9). Retrieved September 17, 2006
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