Benadryl & Alcohol (Understanding Polysubstance Abuse)

Having Benadryl and alcohol in your system at the same time even once can put you at risk of severe adverse effects, including overdose. Frequently combining these two substances or mixing alcohol with other drugs can lead to serious long-term problems and may be a sign of addiction.

Bright Future Recovery Center offers a range of treatment options that can help you end your substance use for good and learn how to live a much healthier life in recovery. For additional information or to schedule a free assessment, contact us today.

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Understanding Benadryl

Benadryl is a popular over-the-counter (OTC) medication that is frequently used to treat symptoms associated with allergies and the common cold. Some people also use it to alleviate motion sickness or overcome temporary bouts of insomnia.

Since anyone can purchase Benadryl tablets, gels, and liquids without a prescription, many people mistakenly assume that the medication poses no health risks whatsoever. But people who use it in certain ways, such as taking particularly large doses or combining Benadryl with alcohol, can be exposing themselves to considerable harm.

The primary active ingredient in Benadryl is diphenhydramine , which is a first-generation antihistamine. 

When your body is exposed to an allergen, it releases a naturally produced chemical called histamine. This chemical helps your body fight off the allergen, but it also triggers symptoms such as itching, sneezing, runny nose, and watery eyes. Antihistamines prevent histamine from binding to certain receptors, which offsets some of these unpleasant effects.

The drawbacks of first-generation antihistamines is that they only last for four to six hours and can cause effects such as sedation. Second-gen antihistamines such as loratadine (Claritin) and cetirizine (Zyrtec) last longer and don’t cause users to become sleepy.

Risks of Mixing Benadryl and Alcohol

The many potential risks of combining Benadryl and alcohol include injuries, organ damage, and overdoses.

Accidents & Injuries

Common effects of both Benadryl and alcohol include:

• Drowsiness
• Deficient focus and concentration
• Poor judgement
• Delayed reaction time
• Diminished coordination

The likelihood of experiencing these side effects means that using either Benadryl or alcohol puts you at risk of injury due to slips, falls, automobile accidents, and other causes. 

Having Benadryl and alcohol in your system at the same time can increase the intensity of the effects listed above, which raises your risk of accidentally harming yourself or someone else due to your physical and cognitive impairments.

Overdose & Death

The overuse of either Benadryl or alcohol can be deadly: 

• Benadryl: Though fatal overdoses involving Benadryl alone are rare, they have occurred. As described in an October 2024 case report in the open access journal Cureus, using an excessive amount of diphenhydramine can lead to seizure, abnormal heart rate, respiratory failure, coma, and death. 
• Alcohol: Alcohol poisoning, which is also known as alcohol toxicity or alcohol overdose, is more common. The National Center for Drug Abuse Statistics has reported that alcohol poisoning causes about 2,200 deaths every year in the U.S., which works out to about six deaths per day.

Using both drugs simultaneously can raise your risk of fatal overdose. The combined physical effects of the two drugs can slow your heart rate and suppress your breathing, and the impact on your judgement and memory can prevent you from realizing that you’ve consumed a potentially lethal amount until it’s too late.

Organ Damage

Combining alcohol and Benadryl even once can lead to accidents, injuries, and overdose. Repeatedly using these two drugs together can cause potentially irreversible organ damage.

Heavy use of alcohol and Benadryl can be harmful to several organs, including:

• Kidneys: The National Kidney Foundation has stated that excessive alcohol use can prevent kidneys from functioning at full capacity and worsen existing cases of kidney disease. An August 2013 Pharmacy and Therapeutics article noted that Benadryl use can contribute to acute kidney injury (AKI) in certain at-risk populations, such as older adults.
• Liver: A 2017 article in Alcohol Research: Current Reviews reported that about 35% of problem drinkers develop advanced liver disease. A paper from the same year in the journal Case Reports in Hepatology found that frequent high-dose use of diphenhydramine can also be toxic to the liver. 
• Heart: A June 2025 study in the journal Circulation reported that consuming three or more drinks per day has been “consistently associated with worse outcomes in every cardiovascular disease entity studied.” In 2020, the U.S. Food and Drug Administration (FDA) issued a warning that taking higher-than-recommended doses of Benadryl can lead to “serious heart problems” and other health concerns.

Dangers of Polysubstance Abuse

Polysubstance abuse describes the use of two or more drugs simultaneously or within in brief window of time. 

Having multiple substances in your system at the same time isn’t necessarily problematic. For example, many people need to take several prescription medications to maintain their physical and/or mental health.

The “abuse” part of the term is what differentiates safe and problematic use:

• If you’re taking a blood pressure medication and an antidepressant as directed by your doctor, that’s not polysubstance abuse.
• If you’re drinking beer while using a medication that shouldn’t be mixed with alcohol, or smoking marijuana while also using illicit opioids, either combination would qualify as polysubstance abuse.

The risks associated with polysubstance abuse can depend on many factors, including which substances you are using, how much of each drug you’ve taken, and how often you engage in the behavior. 

Two ways that polysubstance abuse can be dangerous are:

• Intensified effects: These are the types of dangers posed by combining alcohol and Benadryl. Other drug combos, such as alcohol and opioids, pose a similar risk. When drugs have the same types of effects, especially those that can slow heart rate and respiration, using them together can be extremely dangerous and potentially fatal.

• Decreased effects: Some substances counteract the effects of others. For example, opioids slow the functioning of your central nervous system, which leads to drowsiness, while cocaine stimulates the CNS and increases your energy and alertness. This is dangerous because it can put added strain on your system and promote increased drug use. And if one of the drugs you’re using is a necessary prescription medication, taking other substance that offsets its effects can be life-threatening.

Also, using drugs in situations that pose a clear hazard is a sign of addiction. And polysubstance abuse can absolutely be hazardous to your health. 

So if you know that you should stop drinking or using other recreational substances while taking an over-the-counter or prescription medication, but you’re either unwilling or unable to do so, that can be a sign that you’ve developed an addiction.

Find Treatment for Polysubstance Abuse in Northern California

Bright Future Recovery offers a full continuum of personalized services for adults whose lives have been disrupted by compulsive polysubstance use, addiction, and co-occurring mental health concerns.

Treatment options at our luxury rehab in Northern California include detox, residential care, a partial hospitalization program (PHP), an intensive outpatient program (IOP), and virtual (online) outpatient services.

Call 866-442-8331 today to learn more or verify your insurance now.