Is tramadol (tramadol hydrochloride) an opioid?

From the Guidelines

Yes, tramadol is an opioid medication, as it works by binding to mu-opioid receptors in the brain and also inhibiting the reuptake of serotonin and norepinephrine, giving it dual mechanisms for pain relief. According to the most recent and highest quality study, tramadol is considered a weak opioid, with a conversion factor of 0.2 for morphine milligram equivalent doses 1. This means that tramadol is less potent than other opioids, but still carries risks of dependence, addiction, and respiratory depression, especially at higher doses.

Key Characteristics of Tramadol

• Tramadol is a synthetic opioid analgesic that works by binding to mu-opioid receptors in the brain and also inhibiting the reuptake of serotonin and norepinephrine, giving it dual mechanisms for pain relief.
• Tramadol is typically prescribed for moderate to moderately severe pain and comes in immediate-release forms (usually 50-100 mg every 4-6 hours as needed, maximum 400 mg daily) and extended-release formulations (100-300 mg once daily) 1.
• Tramadol has additional side effects not typical of other opioids, including seizure risk (particularly at higher doses or in those with seizure disorders) and serotonin syndrome when combined with other serotonergic medications 1.

Important Considerations

• Due to the risks associated with tramadol, it is classified as a controlled substance in many countries, including being a Schedule IV controlled substance in the United States.
• The risk of abuse with tramadol seems considerably less than that with opioid analgesics, but it is still important to use caution when prescribing this medication 1.
• Tramadol should be used with caution or avoided in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications due to the risk of serotonin syndrome 1.

From the FDA Drug Label

Tramadol Hydrochloride contains tramadol, a centrally acting synthetic opioid analgesic.

Yes, tramadol (tramadol hydrochloride) is an opioid. It is described as a centrally acting synthetic opioid analgesic in the drug label 2. Key points include:

• Opioid activity: due to binding of parent and M1 metabolite to μ-opioid receptors
• Analgesia: produced by both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to μ-opioid receptors
• Comparison to other opioids: tramadol has been shown to have effects similar to those of other opioids, such as dizziness, somnolence, nausea, constipation, sweating, and pruritus.

From the Research

Definition and Classification of Tramadol

• Tramadol is a synthetic opioid with a central effect from the aminocyclohexanol group, which has two main mechanisms of action, including as a weak agonist of opioid receptors and as a norepinephrine and serotonin reuptake inhibitor 3.
• Tramadol is a centrally acting synthetic opioid analgesic that has a dual mechanism of action, binding to mu-opioid receptors and weakly inhibiting the neuronal reuptake of norepinephrine and serotonin 4.
• Tramadol is a central analgesic with a low affinity for opioid receptors, and its selectivity for mu receptors has recently been demonstrated 5.
• Tramadol is considered a mixed-mechanism opioid drug, as it is a centrally acting analgesic that exerts its effects via binding mu receptors and blocking the reuptake of monoamines 6.
• Tramadol is an opioid drug that, unlike classic opioids, also modulates the monoaminergic system by inhibiting noradrenergic and serotoninergic reuptake, making it an atypical opioid 7.

Mechanism of Action

• Tramadol's analgesic action is only partially inhibited by the opioid antagonist naloxone, which suggests the existence of another mechanism of action 5.
• The monoaminergic activity of tramadol inhibits noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake, making a significant contribution to the analgesic action by blocking nociceptive impulses at the spinal level 5.
• Tramadol is a selective agonist of mu receptors and preferentially inhibits serotonin reuptake, whereas (-)-tramadol mainly inhibits noradrenaline reuptake 5.
• The combination of monoamine and opioid mechanisms opens new avenues for the design of innovative analgesics 7.

Comparison to Other Opioids

• Tramadol has a lower affinity for opioid receptors compared to other opioids, such as morphine, with an affinity 6000 times lower 5.
• Tramadol is considered to have a reasonable safety profile compared to other opioids, with a lower potential for abuse 3, 4.
• Tramadol has a different pharmacological profile compared to full opioid agonists, such as heroin, morphine, codeine, oxycodone, meperidine, and fentanyl 6.