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What is Diphenhydramine? Precautions, Side Effects, Overdose & Interactions

What is Diphenhydramine?

According to the National Center for Biotechnology Information, diphenhydramine, which is available as an over-the-counter medication, is a first-generation antihistamine that is used in a variety of conditions to treat and prevent dystonias, insomnia, pruritus, urticaria, vertigo, and motion sickness. It also possesses local anesthetic properties for patients with allergies to other, more commonly used local anesthetics; however, this is an off-label use of the medication. Additional off-label use is for the treatment of oral mucositis. [1] Medications that contain diphenhydramine can also be used to prevent nausea and vomiting, as well as dizziness caused by motion sickness.

Diphenhydramine is an active ingredient in many over-the-counter medications. However, as of recently, people are using diphenhydramine for recreational purposes. For example, a recent Benadryl trend on TikTok encouraged users to purposely overdose on the medication (which contains diphenhydramine) to experience hallucinations. Any form of substance abuse is dangerous and can have serious repercussions. Our Delaware drug and alcohol treatment center is sharing more information about Diphenhydramine overdose and how it happens.

Diphenhydramine comes as a tablet, a rapidly disintegrating (dissolving) tablet, a capsule, a liquid-filled capsule, a dissolving strip, powder, and a liquid to take by mouth. 

Some common medications that contain diphenhydramine include:

  • Advil
  • Benadryl
  • Nytol
  • Sominex
  • Tylenol PM
  • Unisom
  • Dimetapp
  • Bayer Aspirin
  • Ivarest

It can also be found in certain store-brand medications, like the “Equate” brand from Walmart or CVS’s Health store brand. Diphenhydramine works by blocking a substance that your body produces naturally during an allergic reaction called histamine. Histamine is a chemical released by white blood cells into the bloodstream in an attempt for the immune system to defend itself against an allergen. Pollen, mold, and different foods can cause these allergic reactions. This drug works to alleviate any discomfort caused by these symptoms while also acting as a sleep aid.

Why is this medication prescribed?

According to, Diphenhydramine is used to relieve red, irritated, itchy, watery eyes; sneezing; and runny nose caused by hay fever, allergies, or the common cold. It is also used to relieve cough caused by minor throat or airway irritation and to prevent and treat motion sickness, to treat insomnia (difficulty falling asleep or staying asleep). Diphenhydramine is also used to control abnormal movements in people who have early-stage parkinsonian syndrome (a disorder of the nervous system that causes difficulties with movement, muscle control, and balance) or who are experiencing movement problems as a side effect of a medication. [2]

This medicine is used to relieve red, irritated, itchy, watery eyes; sneezing; and runny nose caused by hay fever, allergies, or the common cold.

This medication will relieve the symptoms of these conditions but will not treat the cause of the symptoms or speed recovery. Diphenhydramine should not be used to cause sleepiness in children. This drug is in a class of medications called antihistamines. It works by blocking the action of histamine, a substance in the body that causes allergic symptoms. [2]

Precautions Before taking this medicine

  • Tell your doctor and pharmacist if you are allergic to diphenhydramine, any other medications, or any of the ingredients in diphenhydramine preparations. Ask your doctor or pharmacist or check the package label for a list of the ingredients.
  • Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: other diphenhydramine products (even those that are used on the skin); other medications for colds, hay fever, or allergies; medications for anxiety, depression, or seizures; muscle relaxants; narcotic medications for pain; sedatives; sleeping pills; and tranquilizers.
  • Tell your doctor if you have or have ever had asthma, emphysema, chronic bronchitis, or other types of lung disease; glaucoma (a condition in which increased pressure in the eye can lead to gradual loss of vision); ulcers; difficulty urinating (due to an enlarged prostate gland); heart disease; high blood pressure; seizures; or an overactive thyroid gland.If you will be using the liquid, tell your doctor if you have been told to follow a low-sodium diet.
  • Tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking diphenhydramine, call your doctor.
  • You should know that generally diphenhydramine should not be used in older adults, except to manage serious allergic reactions, because it is not as safe or effective as other medication(s) to treat your condition. If you are 65 years of age or older, talk to your doctor about the risks and benefits of taking this medication.
  • If you are having surgery, including dental surgery, tell the doctor or dentist that you are taking diphenhydramine.
  • You should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
  • Remember that alcohol can add to the drowsiness caused by this medication. Avoid alcoholic beverages while you are taking this medication.
  • If you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that some brands of chewable tablets and rapidly disintegrating tablets that contain this medicine may be sweetened with aspartame, a source of phenylalanine. [2]

Side effects

This drug may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • Dry mouth, nose, and throat
  • Drowsiness
  • Dizziness
  • Nausea
  • Vomiting
  • Loss of appetite
  • Constipation
  • Increased chest congestion
  • Headache
  • Muscle weakness
  • Excitement (especially in children)
  • Nervousness

Some side effects may be serious. If you experience any of the following symptoms, call your doctor immediately:

  • Vision problems
  • Difficulty urinating or painful urination


An overdose occurs when you take more than the normal or recommended amount of medication. Overdose can occur accidentally or on purpose. In certain cases when diphenhydramine is used recreationally, mixed with other drugs or alcohol, or taken in large doses on purpose, the risk of overdose increases. 

The symptoms of an overdose from this medication can be life-threatening. Many individuals from young kids to adults have suffered diphenhydramine overdose death.

One study, in particular, reviewed a massive diphenhydramine overdose resulting in the death of a 14-year-old girl. She experienced seizures, hemodynamic compromise (abnormal or unstable blood pressure), and problems with cardiac conduction (irregular heartbeats) after ingesting 7.5g of diphenhydramine, the largest overdosage documented.

Many individuals from young kids to adults have suffered diphenhydramine overdose death.

Some common overdose symptoms include:

  • Difficulties urinating
  • Blurred vision
  • Dry mouth
  • Dry eyes
  • Dry skin
  • Enlarged pupils
  • Ringing in the ears
  • Low blood pressure
  • Increased heart rate
  • Agitation
  • Confusion
  • Delirium
  • Drowsiness
  • Depression symptoms
  • Hallucinations
  • Anxiety
  • Sleepiness
  • Tremors
  • Poor balance
  • Seizures

The dosage that can cause overdose depends on the type of medication the person is taking and their age. Certain medications that contain this component aren’t helpful for children under the age of six, so they shouldn’t take them unless directed by a doctor. Medications that have diphenhydramine vary in dosage depending on the age of the individual. The dosage of this component can vary from 12.5 mg to 50 mg. An overdose can occur if a person takes more than the recommended dose. For example, if the recommended dose for a 12-year-old who’s taking Benadryl is 25 to 50 mg every 4 to 6 hours, ingesting a higher dose or ingesting it more frequently can result in an overdose.

An individual can develop a diphenhydramine addiction and tolerance. Many individuals abuse medications that contain this ingredient to experience side effects like sleepiness and hallucinations. Using this drug recreationally can lead to addictive behaviors. At We Level Up California, we have first-hand experiences with addiction and overdose. Engaging in one form of substance abuse often opens a doorway to other avenues of experimentation with drugs and alcohol. If you or someone you know is struggling with addiction, our medical detox can be the first step in recovery.

The dosage that can cause overdose depends on the type of medication the person is taking and their age.

Most frequently checked interactions

  • Aspirin Low Strength (aspirin)
  • CoQ10 (ubiquinone)
  • Cymbalta (duloxetine)
  • Fish Oil (omega-3 polyunsaturated fatty acids)
  • Flonase (fluticasone nasal)
  • Lexapro (escitalopram)
  • Lyrica (pregabalin)
  • Metoprolol Succinate ER (metoprolol)
  • MiraLAX (polyethylene glycol 3350)
  • Norco (acetaminophen / hydrocodone)
  • ProAir HFA (albuterol)
  • Probiotic Formula (bifidobacterium infantis / lactobacillus acidophilus)
  • Singulair (montelukast)
  • Synthroid (levothyroxine)
  • Tylenol (acetaminophen)
  • Vitamin B12 (cyanocobalamin)
  • Vitamin C (ascorbic acid)
  • Vitamin D3 (cholecalciferol)
  • Xanax (alprazolam)
  • Zyrtec (cetirizine)

What other drugs will affect diphenhydramine?

Ask a doctor or pharmacist before using this medicine if you are also using any other drugs, including prescription and over-the-counter medicines, vitamins, and herbal products. Some medicines can cause unwanted or dangerous effects when used together. Not all possible interactions are listed in this medication guide.

Taking this medicine with other drugs that make you sleepy or slow your breathing can worsen these effects. Ask your doctor before taking this component with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Reclaim your life from substance abuse

Diphenhydramine abuse is a serious practice that can cause major health problems that should not be taken lightly. We Level Up Treatment Center can provide you, or someone you love, the tools to recover from this by detoxification with professional and safe treatment. Feel free to call us to speak with one of our counselors. We can give you further information about the abuse of this medication. Our specialists know what you are going through. Please know that each call is private and confidential.