Opioid Drugs and Grapefruit Juice

The opioid/opiate class of drugs includes illicit substances like heroin and prescription painkillers such as codeine, hydrocodone, and oxycodone. Many of these drugs have a very strong potential for abuse and addiction, and both tolerance and dependence may build easily in a short period of time. In the midst of the opioid overdose epidemic, it’s easy to see just how addictive and dangerous both illicit and prescription opioids can be.

Abusing Opioids

In 2016, more than 2 million people in the U.S. had an opioid use disorder, and many more (over 11 million) reported misusing prescription opioids. When an individual misuses a drug in a way other than is prescribed—such as by increasing doses or frequency of use—in order to enhance its effects, it is considered substance abuse. Abuse of any kind of opioid can be incredibly perilous. The Centers for Disease Control estimates that 130 people die every day from an opioid overdose.

Individuals who use or misuse opioids will usually begin to develop some degree of tolerance. According to the National Institute on Drug Abuse, tolerance develops as increasingly high doses are needed to achieve the same initial response. Some individuals who have built up a tolerance to opiates begin to compulsively misuse the substances in an effort to experience the desired effects, whether through taking higher doses, trying new methods of use (e.g., crushing them up and snorting them, or injecting them) or by taking more and more doses throughout the day. They may even try potentiating opiates (heightening their effects) with grapefruit juice. Those who have not built a tolerance may also try this method to seek an intense high, while some people may consume grapefruit juice innocently while on medication without knowing the risks.

Interaction Between Grapefruit Juice and Opioids

The liver and gastrointestinal tract contain a cytochrome enzyme called CYP3A4, which helps to metabolize many drugs, including opioids. Some individuals have far more of this enzyme in their system than others; in fact, CYP3A4 can “vary 30-fold in terms of presence and activity in the liver.” Individuals who have high levels of this particular enzyme may be much less affected after ingesting opioids than those with naturally lower enzyme activity.

Grapefruit juice irreversibly inhibits this enzyme, which can alter drug metabolism and could make you feel the effects of opioids more intensely. Consuming this juice regularly, or at some point prior to taking opioids could increase the bioavailability of the drug and also heighten the effects—not only the pleasurable ones but the harmful ones. You may place yourself at an increased risk of overdose by attempting to get a better high in this way. Other fruits that act similarly to potentiate opioids include Seville oranges, limes, and pomelos.

The Dangers of Potentiating Opiates

Attempting to boost the effects of opiates with grapefruit juice can have devastating consequences. Because compounds in grapefruit juice alter opioid metabolism, doses that might be considered safe under normal circumstances may place you at higher risk of overdose. Left unmanaged, a severe opioid overdose can result in respiratory arrest, permanent brain damage, and death. Common signs of an overdose on opioids include:

  • Decreased muscle tone and limp limbs.
  • Loss of consciousness.
  • Unresponsiveness to external stimuli.
  • Markedly constricted, or pinpoint pupils.
  • Pale, cold, or blue skin.
  • Clammy hands.
  • Slow, shallow, or erratic breathing.
  • A slow or stopped pulse.
  • Vomiting or gurgling sounds in the throat.

If a loved one is exhibiting what is referred to as the opioid overdose triad—pinpoint pupils, loss of consciousness, and respiratory depression—they could be experiencing an overdose on opioids, and it is critical to seek medical attention immediately. Drinking grapefruit juice while using opioid drugs is incredibly dangerous because it is difficult to gauge how much of a metabolic impact it will have. Intentionally drinking grapefruit juice before taking opioids to boost the subjective high—even with prescribed doses—is a form of substance abuse.


  1. National Institute on Drug Abuse. (n.d.). Opioids.
  2. U.S. Department of Health and Human Services. (2018). What is the U.S. Opioid Epidemic?
  3. Centers for Disease Control and Prevention. (2017). Understanding the Opioid Epidemic.
  4. National Institute on Drug Abuse. (2007). 6: Definition of tolerance.
  5. Gregory L. Holmquist, PharmD. (2009). Opioid Metabolism and Effects of Cytochrome P450. American Academy of Pain Medicine, 10(1), 1526-2375.
  6. Maria G. Tanzi, PharmD. (2013). Juice interactions: What patients need to know.
  7. U.S. National Library of Medicine. (n.d.). Opioid Overdose.
  8. Centers for Disease Control and Prevention. (n.d.). Preventing an Opioid Overdose.