Reviewing Sleep Supplement Ingredients: Diphenhydramine

Reviewing Sleep Supplement Ingredients: Diphenhydramine

Welcome to the fifth blog post in our series on supplement ingredients for sleep! Today, we're going to dive into the world of diphenhydramine, a common ingredient found in many over-the-counter sleep aids. We'll explore what it is, how it affects the brain and body, its potential benefits and drawbacks for sleep, and why we didn't include it in our Knocked formula.

What is Diphenhydramine?
Diphenhydramine, also known by its brand name Benadryl, is an antihistamine medication that is often used to treat allergies and cold symptoms. However, it is also commonly used as a sleep aid due to its sedative effects. It works by blocking histamine, a neurotransmitter in the brain that is responsible for causing wakefulness and alertness.

How does Diphenhydramine affect the brain and body?
When taken as a sleep aid, diphenhydramine enters the brain and binds to histamine receptors, which decreases the activity of the histamine neurotransmitter. This leads to drowsiness and a decreased ability to stay awake. Diphenhydramine also has some effects on other neurotransmitters, including acetylcholine, which can cause side effects such as dry mouth and constipation.

Benefits of Diphenhydramine for Sleep
The main benefit of diphenhydramine for sleep is its ability to induce drowsiness and help people fall asleep more easily. It is also readily available over-the-counter, making it easy to obtain without a prescription.

Potential Side Effects of Diphenhydramine
While diphenhydramine can be effective for sleep, it also has several potential side effects. These include dizziness, confusion, dry mouth, constipation, and urinary retention. In some cases, it can also cause allergic reactions or exacerbate pre-existing medical conditions. Long-term use of diphenhydramine has also been associated with an increased risk of cognitive decline and dementia in older adults.

Why we don't include Diphenhydramine in our Knocked formula
Although diphenhydramine can be effective for sleep, we chose not to include it in our Knocked formula for several reasons. Firstly, it can cause significant side effects, especially with long-term use. We wanted to create a sleep supplement that is safe and well-tolerated for daily use, without the risk of harmful side effects. Additionally, some people may not respond well to diphenhydramine or may have medical conditions that make it unsafe for them to take. Instead, we chose to use natural ingredients that have been shown to promote relaxation and improve sleep quality without the risk of harmful side effects.

Diphenhydramine is a common ingredient in many over-the-counter sleep aids, but it comes with the risk of significant side effects and long-term health risks. While it can be effective for some people, we chose to avoid it in our Knocked formula in favor of natural ingredients that are safe and well-tolerated. As always, it's important to speak with your healthcare provider before starting any new sleep supplement or medication.



  1. Simons, F. E., & Simons, K. J. (2004). Histamine and H1-antihistamines: celebrating a century of progress. Journal of Allergy and Clinical Immunology, 114(6), 1339-1349. []

  2. Kay, G. G., & Berman, B. (2002). The clinical effects of antihistamines on the central nervous system. In Allergy and Asthma Proceedings (Vol. 23, No. 1, pp. 35-39). []

  3. Richardson, G. S., Roehrs, T. A., Rosenthal, L., Koshorek, G., & Roth, T. (2002). Tolerance to daytime sedative effects of H1 antihistamines. Journal of Clinical Psychopharmacology, 22(5), 511-515. []

  4. Lader, M. (2016). Sleep disorders and their treatment. In Handbook of Experimental Pharmacology (pp. 1-18). Springer, Berlin, Heidelberg. []

  5. Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., ... & Larson, E. B. (2015). Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Internal Medicine, 175(3), 401-407. []

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Learn More About Knocked

Knocked Sleep Support is a natural, non-habit forming, melatonin-free sleep aid that relies on simple, mineral and herb based ingredients to help you fall and stay asleep without feeling groggy the next morning. 

No Melatonin. Just Science.

Science-Backed Ingredients, Safe for Daily Use

Knocked is safe to use every day. We’ve done the research, so you don’t have to. We use natural mineral and herb based ingredients that have high safety margins and are non-habit forming.

Supports Your Circadian Rhythm

Knocked is naturally effective. Our ingredients and behavioral sleep tools are proven to support your body's natural sleep processes by easing your nervous system and promoting a state of relaxation.

No More Groggy Mornings

Knocked is melatonin-free. Studies show long-term melatonin use results in hormone imbalances that make it more difficult for you to achieve natural, high-quality sleep.