Hydrocodone & Oxycodone Potentiators & Their Risks

Opiates can be potentiated with grapefruit juice, Benadryl, alcohol, and more. Potentiating opiates can result in serious adverse health effects, such as a fatal overdose.

Opiates and their Potentiators

Opiates are a class of drugs that include illegal heroin, synthetic opioids such as fentanyl, and prescription pain relievers such as oxycodone and hydrocodone. Opioids react with opioid receptors on the nerve cells in the body and brain. When taken as prescribed by a doctor, opioid pain medications are safe. However, they can produce a euphoric feeling along with pain relief. This causes them to be misused.

According to the U.S. Department of Health and Human Services, in 2018, an estimated 10.3 million people aged 12 or over misused opioids in the past year. Of those 10.3 million people who misused opioids, 9.9 million people misused prescription pain relievers. Additionally, more than 760,000 people have died since 1999 from a drug overdose. In 2018, 2 out of 3 drug overdose deaths involve an opioid.

Opiate potentiators are compounds, herbs, or other medications that are used to increase the potency or effectiveness of a drug. Many people combine substances with the goal of getting a more extreme high. According to an article published in the Journal of Alcoholism Drug Abuse & Substance Dependence, 40 percent of users are potentiating their opiates with enhancers. The most commonly used opiate enhancers are grapefruit juice, cimetidine, codeine, diphenhydramine, quinine, vitamin supplements, gabapentin, clonazepam, and more. Attempting to potentiate opiates puts a person at an increased risk of developing an addiction and experiencing a life threatening overdose.

What Potentiates Opiates

How to make opiates stronger? A few different ways to make opiates more potent is to mix them with grapefruit juice, alcohol, benzodiazepines, or over the counter medications such as Benadryl.

Grapefruit Juice and Opiates

According to an article published in Nutrition Reviews, grapefruit juice enhances the effects of some commonly used medications by increasing their bioavailability by slowing down the digestive process of the drug in the small intestine. Grapefruit contains compounds known as furanocoumarins that block the CYP3A3 enzymes. This slows down the rate of metabolism for opiate drugs. The article mentioned that it takes around 150 mL of grapefruit juice to produce opiate enhancement effects. This is important to know because a lot of people drink grapefruit juice in the morning when medications are commonly consumed.

Alcohol and Opiates

Alcohol is a sedative substance that is known to increase the potency of opiates. Mixing opiates with alcohol can increase a person’s chances of experiencing dangerous respiratory complications. Respiratory depression causes a person’s breathing to become extremely shallow or stop altogether. The National Institute on Alcohol Abuse and Alcoholism mentioned that alcohol increases the analgesic, reinforcing, and sedative effects of opiates, which elevates a person’s risk for overdose.

Benzodiazepines and Opiates

The National Institute on Drug Abuse mentioned that more than 30 percent of overdoses involving opioids also involved benzodiazepines. Benzodiazepines are often used to treat anxiety or help with insomnia. These drugs work by calming a person and raising the level of the inhibitory neurotransmitter GABA in the brain. Common benzodiazepines are Valium, Xanax, and Klonopin. Combining opioids and benzodiazepines can be unsafe because both types of drugs sedate the user and suppress breathing, this increases an opiate drug’s potency, which can be fatal.

Benadryl and Opiates

Benadryl also is known as diphenhydramine is a brand-name for over-the-counter medication that’s used to help relieve symptoms of hay fever, allergies, the common cold, as well as itchy skin due to insect bites, hives, and other causes. Benadryl can cause sedative effects when combined with opioids. The dangerous pairing can result in increased dizziness, drowsiness, breathing problems, confusion, and difficulty concentrating. Some people may also experience impaired judgment, thinking, and motor coordination.

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Oxycodone Potentiators

Oxycodone is an opioid prescription medication that is used to relieve moderate to severe pain. This medication works by changing the way the brain and nervous system respond to pain.  Due to the feelings of relaxation, euphoria, and pain relief opioids provide they are known to be highly addictive.

How to intensify oxycodone? One way to potentiate oxycodone is with grapefruit juice. According to a study published in Basic Clinical Pharmacology Toxicology, grapefruit juice is one of the dietary elements that has a lot of food-drug interactions. Grapefruit juice inhibits intestinal CYP3A enzyme or transporter proteins such as P-glycoprotein and organic anion transporter polypeptide, which help metabolize many drugs, including opioids. People have varying levels of this particular enzyme. Therefore, people with higher concentrations of this enzyme will be more affected after ingesting opioids than those who have less. Since grapefruit juice lessens this enzyme making oxycodone metabolizes slower you can feel the effects of the opioid more intensely. The study mentioned above stated that drinking grapefruit juice for 5 days will increase the plasma concentrations of oral oxycodone making it more potent.

According to Pharmacy Today, oxycodone has a high interaction risk with grapefruit. Therefore, drinking grape juice with oxycodone can increase a person’s chances of experiencing a life-threatening overdose. Drinking grapefruit juice while on opiate medications can result in increased respiratory depression.

Hydrocodone Potentiators

Hydrocodone is an opiate prescription medication that is used to relieve severe pain. This medication works just like oxycodone and alters the way the brain and nervous system respond to pain. Hydrocodone depresses the central nervous system which slows breathing. This increases a person’s feelings of relaxation, euphoria, and pain relief making opioids highly addictive.

How to make hydrocodone more potent? Just like with oxycodone, one way to potentiate hydrocodone is with grapefruit juice. Another way to potentiate hydrocodone is with antihistamines, alcohol, barbiturates, or benzodiazepines. Additionally, cold medication, pain medications, muscle relaxants, and medicines for seizures, depression, or anxiety can all potentiate the medications’ effects. Mixing hydrocodone with any of these pretentious can result in extreme drowsiness, coma, and life-threatening respiratory problems.

The Risks

Potentiating opiates can be extremely dangerous as it can increase your chances of experiencing a number of adverse health effects. One of the most serious health consequences is a life-threatening overdose. An opioid overdose affects the part of the brain that regulates breathing. Signs that a person is overdosing on opioids are their face is extremely pale and/or feels clammy to the touch, their body goes limp, their fingernails or lips have a purple or blue hue, they start vomiting or making gurgling noises, they cannot be awakened, they cannot speak, and their breathing or heartbeat slows or completely stops. These are serious symptoms and you should call 911 immediately.

Finding Help

If you or someone you love is using opiates with potentiators, finding a high-quality rehab clinic can mean the difference between life and death. Rehab clinics will provide a person with all the support they need to overcome their addiction. Through trained medical and mental health professionals your loved one will be safe and comfortable as they detox from their addiction and begin their recovery journey.


Medical disclaimer:

Sunshine Behavioral Health strives to help people who are facing substance abuse, addiction, mental health disorders, or a combination of these conditions. It does this by providing compassionate care and evidence-based content that addresses health, treatment, and recovery.

Licensed medical professionals review material we publish on our site. The material is not a substitute for qualified medical diagnoses, treatment, or advice. It should not be used to replace the suggestions of your personal physician or other health care professionals.

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