Opioid use has increased among American adults due to its recreational and analgesic, or pain relieving, effects. Many opioid users report allergic reactions in response to opioid agents. Usually, these allergic reactions are classified into true allergies, pseudo allergies, or adverse effects. It is important to differentiate true opioid allergy from others as it has different treatment modalities and complications.

Experienced healthcare professionals at Confidant Health can differentiate opioid allergies and help you overcome opioid dependence through Medication-assisted treatment (MAT). This article will discuss the symptoms of true opioid allergy and how we can differentiate it from pseudoallergy and adverse effects.

What is an opioid allergic reaction?

Opioid drugs bind to the receptors of opioids in the spinal cord, brain, and some other areas of the body, relieving pain. Sometimes, opioid use can result in allergic reactions. 

Most allergic reactions are immune-mediated, i.e., they start due to the response of the body's immune system against the substance. Similarly, true opioid allergy happens when the body's immune system produces immune-mediated reactions against opioids. Such an opioid allergy is rare and can have life-threatening effects. 

However, opioids can also produce pseudo allergies and adverse effects that are often misdiagnosed as a true opioid allergies.

True Opioid allergy vs. Pseudoallergy vs. Adverse effects

Like any other drugs, opioids can produce many allergic reactions and side effects. The allergies associated with opioids are of two main types i.e., true opioid allergy and pseudoallergy. Although both types present with similar symptoms, there’s a marked difference in the cascade of these allergies. Let’s briefly discuss both of these types along with the general adverse effects of opioids.

True Opioid allergy

Allergies are the response of our immune system to foreign substances to which it becomes hypersensitive. In true opioid allergy, opioids release the special chemical known as “histamine” in the body. Histamine produces many allergic effects such as hypotension, urticaria, and tachycardia. However, previous exposure to opioid is required for true opioid allergy.

Other symptoms that may appear in results of allergy are:





Hypotension which is severe.


Meperidine, Codeine, and Morphine mostly cause allergic reactions.

True allergy to opioids is less.


Pseudoallergies are allergic reactions that are also caused by the histamine release. These allergies can initiate even from the first dose of opioids and doesn’t require prior sensitization (unlike to true opioid allergy). 

Symptoms of this type of allergy may involve itching, sweating, and flushing. Some symptoms associated with true allergy also appear in pseudoallergies, such as elevated heart rate, hives, and low blood pressure. Other common symptoms include angioedema, gastrointestinal symptoms, skin flushing, edema, headache, and shock.

Adverse effects of opioids:

Adverse effects of opioids mainly occur due to the direct binding of opioids to body cells and the release of histamine. These reactions are usually dose-dependent. Common adverse effects related to opioid includes the following:

  • Constipation

  • Nausea

  • Vomiting

  • Dry mouth

  • Drowsiness

  • Confusion

  • Deficiency of androgens in the body

  • Retention of urination

  • And the severe complications such as respiratory depression and addiction. 

How common is an opioid allergy?

The incidence of true allergy to opioids is rare. There is a less than 2% incidence of true allergies in response to opioids. However, there is a relatively higher incidence of pseudo allergies associated with opioids.

Symptoms of opioid allergy

The symptoms of true opioid allergy include the following,

  • Severe hypotension

  • Maculopapular rash

  • Pustular rash

  • Angioedema

  • Hives

  • Erythema multiforme

  • Angioedema

  • Bronchospasm

  • Hypotension

  • Tachycardia

  • Urticaria

  • Pruritus

  • Allergic dermatitis or eczema

The early symptoms include flushing, nasal congestion, hypotension, pruritus, bronchospasm, urinary emergency, diarrhea, vomiting, and death. In addition, anaphylactic reactions can occur in opioid allergy. Anaphylactic reactions are sometimes so severe that they can lead to shock and coma. 

Can you use another opioid if allergic to one opioid?

Opioids are generally classified into three main types:

  • Phenylpiperidine includes fentanyl and meperidine.

  • Phenanthrene includes levorphanol, oxycodone, hydrocodone, pentazocine, morphine, and codeine.

  • Phenylheptane includes propoxyphene and methadone.If you are allergic to an opioid from one class (e.g., morphine from phenanthrene), your physician can prescribe you an opioid from another class.

Which opioid is most likely to cause histamine release?

Morphine is the most likely opioid to release histamine, followed by hydromorphone. The other common opioids that release histamine include meperidine and codeine. The least likely opioid to cause histamine release is fentanyl.

Thus, there is a higher chance of getting opioid allergic reactions with morphine than with fentanyl. That's why morphine use should be used with pre-caution in hypotensive patients. 

Are there other drug options for pain if you are allergic to opioids?

Although opioids are famous for their analgesic effects, your physician will prescribe you some non-opioid pain-relievers if you are allergic to opioids. The exact pain reliever medication depends upon the type, location, and severity of your pain. The drugs to reduce pain may include the following:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) include ibuprofen (Motrin), Excedrin, and Advil.

  • Acetaminophen(Tylenol) or Paracetamol

  • Tricyclic antidepressants for nerve pain.

  • Muscle relaxants for muscular strains and pain.

Moreover, your physician can also prescribe you non-medicated treatments for pain relief, such as ice therapy, local massage, physiotherapy, exercise, and relaxation techniques. Corticosteroids such as prednisone and hydrocortisone  are anti-inflammatory drugs that can also help to treat chronic pain.

Consult with Confidant's Health care Professionals

If you are struggling with opioid use disorder or eager to ask questions about opioid allergies, you can consult with Confidant's health care team. Our experienced physicians can help you overcome opioid use through Medication-assisted treatment. You can download our app from Google Play Store or Apple Store to contact our physicians.