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Potentiating Opiates (Grapefruit Juice)

Opioids/opiates refer to a class of drugs that include illicit drugs like heroin and prescription painkilling medications such as codeine, hydrocodone, and oxycodone. These drugs have a very strong potential for abuse and addiction, and a tolerance and dependence to them 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 Opiates

According to 2016 and 2017 data, more than 2 million people in the U.S. suffer from an opioid use disorder and that more than 11 million people reported misusing prescription opioids. When an individual takes a drug in some way other than as recommended or prescribed by a doctor 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 also estimates that 115 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 occurs when a higher dose is needed to achieve the same initial response. Individuals who have built up a tolerance to opiates must find ways to get the effects they crave, 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.

Why Grapefruit Juice?

The liver and gastrointestinal tract contain a cytochrome enzyme called CYP3A4, which helps to metabolize certain drugs including opioids like codeine, fentanyl, and hydrocodone. 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 whose enzyme is less present or active in their system.5

Grapefruit juice inhibits this metabolizing enzyme, and so may make you feel the effects of opioids more intensely. Consuming this juice in combination with opioids could increase the concentration of the drug in your blood 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

Potentiating opiates with grapefruit juice can have devastating consequences. Because compounds in grapefruit juice affect how the body absorbs opiates, doses that might be considered safe under normal circumstances run the risk of resulting in an overdose when mixed with grapefruit juice. The worst consequences of overdosing on opiates are permanent brain damage and death. Common signs of an overdose on opioids include:

  • Limp limbs
  • Pinpoint pupils
  • Pale, cold, or blue skjin
  • Clammy hands
  • Slow, shallow, or erratic breathing
  • A slow or stopped pulse
  • Vomiting or gurgling
  • Loss of consciousness
  • Unresponsiveness to external stimuli

If a loved one has any of the above symptoms, it could be a sign of an overdose on opiates, and it is critical to seek medical attention immediately. Mixing opiates with grapefruit juice is incredibly dangerous because there is no way to predict how much more of the drug the body will absorb until it has already happened. Drinking grapefruit juice before taking opiates is a form of substance abuse, even if only the prescribed amount of an opiate was consumed.

Opiates are not the only drug that people can potentiate with grapefruit juice either.  In a 2012 edition of the Canadian Medical Association Journal, a group of doctors report finding that between 2008 and 2012, the number of medications on the market that grapefruit juice can potentiate increased from 17 to 43 as a result of new chemical formulas. According to their study, there are now more than 85 drugs that can result in some kind of reaction when mixed with grapefruit juice.


  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.
  9. David G. Bailey, George Dresser and J. Malcolm O. Arnold. (2013). CMAJ, 185 (4) 309-316.