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What Is Opioid Potentiation?

By S. Berger
Updated May 17, 2024
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The term "potentiation" refers to increasing the effectiveness of a medication through the actions of other compounds. Potentiation can occur when taking other medications, eating certain foods, or using some dietary supplements. Opioid potentiation generally refers to raising the efficacy of opioid therapies, which are usually used to treat pain. Some individuals using opioids for pain use potentiation to receive a greater therapeutic benefit from their medication without having to increase their dosage. Knowledge about potentiation can also help individuals taking opioids avoid boosting the effects of their medication inadvertently.

There are a few different ways by which opioid potentiation can occur. Opioids are broken down, or metabolized, by enzymes in the liver, and some other substances with a better ability to bind to these enzymes will effectively slow the rate that opioids are broken down, causing them to be effective for a longer period of time. Some compounds, like antacids, change the acidity of the stomach, allowing opioids to more easily enter the bloodstream. Potentiation can also take place in the brain, where certain drugs may have synergistic effects with opioids, increasing their potency.

A wide variety of compounds can cause opioid potentiation, and some of these are more common medications, foods, and beverages that patients using pain therapies should be aware of. Meals that are high in fat may also assist some opioids crossing through the stomach lining into the bloodstream, producing a rise in their intensity. Grapefruit juice contains several compounds that inhibit the activity of liver enzymes that normally help to break down these drugs. When consumed 30 minutes to one hour prior to taking opiate analgesics for pain, their effects may be strengthened, and last for a longer time.

Similar effects on liver enzymes can occur with a number of medications. The antacid cimetidine may exert this effect, and so can dextromethorphan, a cough suppressant. Opioid potentiation will not occur with all opiate analgesics in this manner, however. Some drugs, such as codeine, must be metabolized by enzymes into other forms to be effective. Taking these types of drugs with substances that inhibit liver enzymes will actually decrease their efficacy.

Within the brain itself, opioid potentiation can occur in several ways, with various drugs. Antihistamines such as diphenhydramine may increase the sleep-inducing properties of opioids, without necessarily boosting the painkilling effect. Other drugs such as caffeine, or non-steroidal anti-inflammatory compounds like aspirin, may intensify the pain-relieving properties of opioids, however. Individuals taking them should research the possibility of interactions with other medications, dietary supplements, and common foods to be aware of, possibly causing potentiation could occur.

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