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Can You Mix Cyclobenzaprine and Benadryl?

Can You Mix Cyclobenzaprine and Benadryl?

Meet Alex, a high-powered executive in the bustling city of New York. Alex thrives in the first-paced environment of Wall Street, where peak performance is non-negotiable. After a demanding day, Alex craves restorative sleep—but like 14.5% of adults in America, he’s been grappling with sleepless nights.

Not many of us rule Wall Street, but a lot of us can relate to Alex’s story. You might have tried different ways to get restful nights, from meditation to aromatherapy and yoga—yet sleep remains elusive.

Rescue may come in the form of cyclobenzaprine, a muscle relaxant that can help treat sleep issues, or Benadryl, an antihistamine that induces a state of drowsiness, promoting sleep. We’ll explain what you need to know about potential cyclobenzaprine and Benadryl mechanisms of action, benefits for sleep disorders, and potential interactions.

How Cyclobenzaprine Works—A Brief Walkthrough

Cyclobenzaprine is used for treating muscle spasms. Its action on the alpha and gamma motor systems in the brain reduces muscle hyperactivity and promotes relaxation. 

Cyclobenzaprine’s structure is similar to that of tricyclic antidepressants (TCAs) such as amitriptyline, which gives the drug anticholinergic properties—including sedative effects. Clinical research shows that patients who took the medication had more nights of restorative sleep than those who took the placebo, leading to its off-label use in treating insomnia.

Cyclobenzaprine is available in five doses:

  1. 5 mg
  2. 7.5 mg
  3. 10 mg
  4. 15 mg
  5. 30 mg

You should take cyclobenzaprine 30 minutes before bedtime, but only if you can set aside at least seven hours for sleep so you don’t feel drowsy the next day. 

Check out the essential information about the drug in the table below:



Active ingredient

Cyclobenzaprine hydrochloride

FDA approval


Controlled Substance



Tablet, extended-release capsule

Available doses

5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg

Average dose

15 mg

Maximum dose

60 mg

Suitable for children

Not approved for patients under 15

Pregnancy risk

Category B (risks can’t be ruled out)

Keep in mind that the drug’s dosing may vary based on the specific sleep issue and your medical history.

Common Side Effects of Cyclobenzaprine 

Cyclobenzaprine carries the risk of side effects, such as:

  • Constipation
  • Dry mouth
  • Dizziness
  • Drowsiness
  • Fatigue
  • Headache
  • Blurred vision
  • Nausea
  • Unpleasant taste 
  • Heartburn

These unwanted reactions are relatively easy to manage. Patients who experience the following severe but rare side effects should inform their doctors immediately:

  • Irregular or fast heartbeat
  • Confusion
  • Poor judgment
  • Clumsiness or unsteadiness
  • Problems urinating
  • Ringing or buzzing in the ears
  • Hallucinations
  • Convulsions
  • Severe drowsiness
  • Troubled breathing
  • Unexplained muscle stiffness
  • Severe, unusual nervousness

These lists aren’t exhaustive. You should consult your healthcare provider for more details on cyclobenzaprine’s potential side effects and how to prevent them.

Source: Ron Lach

How Benadryl Works—Basic Facts

Benadryl (diphenhydramine) is an antihistamine typically used to relieve the symptoms of allergies and the common cold, including:

  • Sneezing
  • Itching
  • Watery eyes
  • Runny nose
  • Hives
  • Rashes

Diphenhydramine, the active ingredient in Benadryl, works by binding to H1 receptors in the body, neutralizing the effects of histamine on capillaries—the smallest blood vessels in the body. 

However, Benadryl’s action also slows down the central nervous system (CNS), inducing a state of relaxation and making it easier to fall asleep.

The medication is available in three doses:

  1. 12.5 mg
  2. 25 mg
  3. 50 mg

When used for sleeplessness, Benadryl should be taken 30 minutes before going to bed. The drug is quickly absorbed after you take it orally, reaching its peak concentration in 1–2 hours. The effects subside in 4–6 hours, so you should only take the medication if you can afford at least seven hours of sleep.

Get familiar with Benadryl’s primary characteristics in the following table:



Active ingredient

Diphenhydramine HCI

FDA approval


Controlled Substance



Tablets, oral liquid-filled capsules, oral liquid solution, topical gel, topical spray, topical cream, topical stick

Available doses

12.5 mg, 25 mg, 50 mg

Average dose

25 mg

Maximum dose

300 mg per day for adult patients

Suitable for children

Not recommended for patients under 12 (You shouldn’t use it for treating children’s insomnia without consulting a pediatrician)

Pregnancy risk

Category B (risks can’t be ruled out)

While Benadryl is available over the counter, you should talk to your doctor before using it for sleep issues. Otherwise, you risk abusing the drug and developing tolerance, which may make it ineffective.

Common Side Effects of Benadryl 

Benadryl carries the risk of side effects, which can be enhanced when taken with other medications. Some of the side effects are:

  • Drowsiness
  • Dry mouth
  • Dizziness
  • Headache
  • Blurred vision
  • Stomach upset
  • Constipation

Although rare, severe adverse reactions may include:

  • Convulsions
  • Fatigue
  • Heart rhythm problems
  • Hallucinations
  • Memory loss or dementia
  • Confusion
  • Rapid heartbeat
  • Allergic reactions

Can You Take Cyclobenzaprine and Benadryl?

You shouldn’t mix cyclobenzaprine and Benadryl unless your doctor recommends it. The medications have moderate interaction, and taking them together increases the risk of side effects such as severe drowsiness, confusion, difficulty urinating, or memory problems. The effects may be more severe in the elderly and patients with other underlying conditions, so they typically take these drugs in lower doses.

To prevent overdosing, you should follow your doctor’s instructions when using these medications. You should also avoid activities that require sharp focus—like driving or operating heavy machinery—if you feel daytime drowsiness.

Does Benadryl Affect Cyclobenzaprine’s Effectiveness and Which Is Better for Sleep?

Benadryl typically doesn’t reduce cyclobenzaprine’s effectiveness in treating sleep issues. Still, you should take the drugs according to your healthcare provider’s guidelines to benefit from their full potential. Keep in mind that cyclobenzaprine may be more effective than Benadryl in treating sleep issues, so your doctor may discontinue the latter if you tell them it’s affecting your treatment.

Sleeplessness is a complex condition and can stem from numerous factors, so medications alone may not provide a viable solution. Combining effective drugs with cognitive behavioral therapy for insomnia (CBT-I) is a better way to overcome sleep disorders.

To get the best treatment, you should visit a sleep doctor. The challenge is that only 1% of healthcare professionals are trained in sleep medicine, so you may wait for months before getting an appointment. 

Fortunately, telemedicine platforms can help you connect with sleep doctors from the comfort of your home almost immediately. One such platform is Kick, an online performance medicine clinic with a groundbreaking sleep program that has earned a host of positive testimonials on Trustpilot.

Source: Karolina Grabowska

Kick—Gentler Sleep Prescriptions

Kick’s sleep program entails an individualized approach to treating your sleep issues. Our doctors analyze your health history and lifestyle to design a holistic treatment plan grounded in scientific research and cognitive behavioral therapy for insomnia (CBT-I) best practices.

Your doctor will prescribe two gentle trial prescriptions and check in regularly. If the initial drugs don’t yield the desired results, they’ll adjust the doses or recommend alternatives. Our medications include:

  1. Cyclobenzaprine
  2. Trazodone
  3. Hydroxyzine
  4. Doxepin
  5. Ramelteon  
  6. Gabapentin

Our sleep specialist will also offer valuable tips on healthy sleep practices, helping you get all-encompassing treatment.

How To Join Kick

Designed by a Stanford sleep specialist, Dr. Alex Dimitriu, Kick’s sleep program only takes 15 minutes to join:

  1. Go to our signup page to start your sleep visit
  2. Fill out the questionnaire to help us understand your sleep issues
  3. Add your delivery address and payment details

You can choose between home delivery and pharmacy pickup, so the process is highly convenient. If your doctor decides our program isn’t the best solution in your case, they’ll refer you to your primary healthcare provider for further evaluation. In that case, you won’t pay for the initial consultation, according to our Doctor Guarantee.

Source: Meruyert Gonullu

How Long After Taking Benadryl Can I Take Cyclobenzaprine?

You may take Benadryl at least six hours after cyclobenzaprine because that’s how long it typically takes for the medication to subside, but the time may vary. For example, patients with liver or kidney problems and the elderly may need to wait longer due to slower metabolism.

Keep in mind that these are general guidelines—you should talk to your doctor for specific information on the most appropriate time to take each medication.

Benadryl for Sleep—Who Should and Shouldn’t Use It?

While Benadryl can be effective in treating sleeplessness, it’s not suitable for everyone. The drug’s sedative property is a side effect of its primary use as an antihistamine, so its application in treating sleep issues is considered off-label.

Here’s who should and shouldn’t use the medication for sleep:

Who Can Use Benadryl for Sleep?

Who Shouldn’t Use Benadryl for Sleep?

  • Adults (18+)

  • People experiencing occasional sleeplessness

  • People experiencing nighttime allergies

  • Children

  • People with chronic or primary insomnia

  • Patients over 65

  • People with dementia or Alzheimer’s disease

This list isn’t exhaustive, and you should consult your doctor for personalized advice.

Generally, you shouldn’t take Benadryl for more than two weeks—inform your healthcare provider if you continue to experience sleepless nights after treatment discontinuation.

Cyclobenzaprine for Sleep—Who Should and Shouldn’t Use It?

Cyclobenzaprine is generally safe for adults with sleep issues, but that doesn’t make it a one-size-fits-all solution. Below is a list of people who should and shouldn’t use this medication:

Who Can Use Cyclobenzaprine for Sleep?

Who Shouldn’t Use Cyclobenzaprine for Sleep?

  • Adults (18+)

  • People experiencing occasional sleeplessness

  • People experiencing nighttime muscle tension or pain

  • Children

  • People with chronic insomnia

  • Elderly people (over 65)

  • People with hyperthyroidism

  • Patients with heart block, heart rhythm disorder, and congestive heart failure

  • Patients who recently had a heart attack

  • People who took MAO inhibitors in the past 14 days

  • Patients with glaucoma

  • People with liver disease 

  • Patients with difficulties passing urine

Keep in mind that cyclobenzaprine should be taken for a maximum of three weeks. While the drug isn’t addictive, patients who use it for a long time may develop psychological dependence or increased tolerance. Inform your doctor if you experience the following withdrawal symptoms after treatment discontinuation:

  • Nausea
  • Malaise
  • Headache

Benadryl vs. Cyclobenzaprine—Potential Interactions With Other Drugs

Source: cottonbro studio

Cyclobenzaprine and Benadryl may interact with other drugs as explained in the table below:


Interaction With Benadryl

Interaction With Cyclobenzaprine

Opioids and CNS depressants (e.g., tramadol)

Can enhance side effects like drowsiness and difficulty breathing

Can contribute to the risk of severe drowsiness and accidental falls

Heart medications 

Can increase the risk of side effects when taken with beta-blockers and calcium channel blockers. Generally considered safe when taken with diuretics and ACE inhibitors

Can enhance the risk of irregular heart rhythm 

Blood pressure medication

Generally considered safe, but Benadryl can lower blood pressure

Can contribute to the risk of increased heartbeat

Anti-seizure medication (e.g., gabapentin)

Can increase the risk of seizures

Can contribute to drowsiness and confusion

Anti-HIV drugs

Generally considered safe

Consult your doctor for specific guidelines

Infection medications

Consult your doctor for personalized advice

The potential for interaction is low but can’t be ruled out

Sleep or anxiety medications

Can contribute to drowsiness and dizziness

Can increase the risk of side effects like dizziness and headaches

Muscle relaxants (e.g., baclofen)

Can enhance the risk of drowsiness and confusion

Can contribute to the sedative effects

Antihistamines (e.g., hydroxyzine)

Can increase the risk of overdose

Can contribute to the risk of drowsiness and blurred vision

Dietary supplements (e.g., melatonin)

Can enhance the side effects

Can enhance the sedative effects

Non-steroidal anti-inflammatory drugs (e.g., ibuprofen)

No interactions were found, but that doesn’t mean they don’t exist

No interactions were found, but the risks can’t be ruled out

You should tell your doctor about any medications or substances you’re using to help them design the best treatment. If they decide you’re not the best candidate for Benadryl and cyclobenzaprine, they may suggest the following alternatives:

Benadryl vs. Cyclobenzaprine—Potential Interactions With Food and Alcohol

Cyclobenzaprine and Benadryl may also interact with food and alcohol as explained in the table below:


Interaction With Benadryl

Interaction With Cyclobenzaprine


Can enhance the risk of drowsiness and difficulty with cognitive tasks

Can enhance the sedative effects

Grapefruit juice

Can interfere with the metabolism of Benadryl, potentially leading to increased drug levels in the blood and side effects

Can block the action of intestinal CYP3A4, an enzyme that metabolizes cyclobenzaprine, potentially leading to high drug concentration and enhanced side effects

If you experience interactions with other types of food, make sure to consult your healthcare provider for advice.

Featured image source: cottonbro studio