How Does Tramadol Work?

How Does Tramadol Work?

Tramadol tablets are classified as synthetic opioid painkillers which is also considered an SNRI (serotonin/norepinephrine reuptake inhibitor). Although it is man-made, the medication is anatomically related to morphine and codeine. The excellent tolerability profile and multimodal MOA classify tramadol as a lower-risk opioid painkiller.

The medication is unique compared to traditional opioids, as it does not just act as an opioid agonist, but also inhibits and enhances the effects of neurotransmitters involved in the treatment of pain. These neurotransmitters are norepinephrine and serotonin. Tramadol activates the descending pain inhibitory pathways.

The tablet exists in the body as a racemic mixture, consisting of two active components that contribute to its pain-relieving property. This is done by tramadol's active metabolites. Its primary metabolite (O-desmethyl-tramadol) is responsible for attaching to the mu-opioid receptor and its other metabolite limits serotonin and norepinephrine reuptake.

Experts refer to this as a dual-acting mechanism of action, where both processes are complementary, improving pain control. It has also been shown to affect several pain modulators found in the central nervous systems.

Due to this broad spectrum of targets that tramadol can achieve, it is no surprise that the medication is effective in treating various pain types, such as neuropathic pain, pain associated with childbirth, osteoarthritis, and back pain. Furthermore, due to tramadol's SNRI ability, the tablets also have anti-anxiety, anti-depressant and anti-shivering properties which can treat common comorbidities associated with the occurrence of pain.

How Long Does Tramadol Take to Work?

There are two forms of tramadol tablets, namely the immediate-acting and the slow-release tablets. The immediate-release formulations are created to dissolve instantly when taken, with no delay in the absorption of the substance. Slow-release tablets have a unique design and action which releases small amounts of the active ingredient in the body over an extended time.

Due to these two different forms, the time tramadol takes to work varies:

  • Immediate-release tablets - 30 to 60 minutes after ingestion. These tablets are usually used in the treatment of acute or moderate pain.
  • Slow-release tablets - 12 to 24 hours after ingestion. Due to its longer-lasting formula, it is used to treat chronic pain, as patients do not have to take a number of doses throughout the day.

Tramadol reaches its peak concentration in the body in two or three hours. The medication has a half-life of about 6 hours. If the tramadol tablet has a protective coating, it may take slightly longer to see effects.

Can I Take Two Tramadol Tablets?

When patients are on their tramadol painkiller treatment plan, their doses are usually divergent as different conditions require different doses. The concentration of the pain they are experiencing also impacts the dosage regimen of the medication.

When starting tramadol, experts recommend that patients take no more than 100 mg a day. First-time patients have to keep track of their side effects and how they feel when starting tramadol, so it is best to stick to the lowest dose.

The starting dose of tramadol is with a single 25 mg tablet, taken in the morning. Tramadol can be used on as-needed basis, as it is best to take the medication when pain is felt. This does not apply to chronic pain conditions. According to tolerance and increasing severity of pain, patients can increase it to 50 mg. However, the dose of tramadol cannot go over 400 mg daily.

If the patient takes two 50 mg tramadol tablets, they should not panic. Usually, this is not a call for concern. However, they should skip the dose for that day. They must start the next day again, ensuring they are taking single doses, 4 to 6 hours apart.

The NIH recommends patients not to take a larger dose when it is not necessary nor take tramadol for a longer duration than required. This can increase the risk of side effects and a heightened tolerance, leading to physical dependence.

Never Mix Tramadol and Alcohol

Never Mix Tramadol and Alcohol

Tramadol has a low potential for dependence, compared to other opioids such as morphine. However, it is still classified as a controlled substance by the FDA from 2014. The treatment is a central nervous system depressant, decreasing excitement in the CNS, causing a slowed heartbeat and breathing.

Alcohol is a substance presenting in wine, beer and spirits that cause intoxication. It is classed as a sedative-hypnotic as it depresses the CNS at high doses. Since it is a CNS depressant, it must not be mixed with tramadol tablets.

This combination can be fatal, as it can increase the respiratory depressing and sedative effects of both substances, leading to trouble breathing, deep sleep or a coma. It can cause life-threatening respiratory depression, causing high levels of oxygen deprivation to the brain.

The dangers of mixing tramadol and alcohol:

  • An increased risk of overdosing on either substance.
  • Slowing down of brain functions, leading to decreased alertness.
  • Increased signs of depression.

Is Tramadol Safe During Pregnancy

The National Institute of Health (NIH) has noted several pregnancy risks significantly increased for patients who take tramadol while pregnant. While it is still prescribed to pregnant women, as pain control in pregnancy is important, it has to be done with caution when advised to do so.

According to statistics, about 21.9% of pregnant women took a prescription opioid, such as tramadol at one point of their pregnancies. In some instances, this figure is as high as 41%. In pregnancies, these medications' abuse potential is increased due to the stressors that come with pregnancy.

There are different pregnancy risks of taking tramadol tablets, such as:

  • Low birth weight
  • Premature birth
  • Congenital disabilities
  • Miscarriage or stillbirth
  • Congenital heart defects

The use of tramadol during pregnancy can also lead to a syndrome called neonatal abstinence syndrome (NAS). This can lead to dangers to the baby, such as stunted growth and increased distress. In short, taking tramadol during any stage of pregnancy puts both mother and baby at risk, even in moderate doses.

There are also effects of tramadol abuse on a pregnant mother, such as:

  • Anxiety
  • Headaches
  • Excessive sedation
  • Aching muscles

Additionally, the use of tramadol must also be avoided when breastfeeding. The active ingredient can be passed through breastmilk, to the baby, causing unwanted effects.

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Updated: 27th January 2021
Review Due: January 2022



Fueled with a passion to try and help people less fortunate than himself Steve immersed himself in the medical industry. By researching new and innovative medical advancements and regularly sharing important information on social media Steve intends to make a difference where it matters most, people's health. His wealth of knowledge and keen eye for detail will help keep our readers informed and contribute towards improved health.

Cameron Scott – Mar 16, 2021
Hello Steve, your blog has been a real help on my road to recovery. The info you provided on the slow release version of the medicine made me look at how I was managing my recovery. I have since made some changes and find that the Tramadol SR gives me sustained relief over a 24-hour period that I was unable to achieve before. Thank you Cameron Scott

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