Benadryl Box With Text Overlay - Interaction With Phenibut


Since Phenibut isn't an approved drug product in the United States, there is a general lack of information regarding it available. This means that it can be difficult to find out drug it may potentially interact with.

Nevertheless, based on what is known about it, there is a chance that taking it with Benadryl can increase the risk of certain side effects, like sedation.

What Is Phenibut?

Based on published information for Phenibut (β-Phenyl-γ-aminobutyric Acid), it appears to work mainly as a 'GABA' agonist, which often produces CNS (central nervous system) depressant effects.[1]

It is structurally similar to the muscle relaxant baclofen and studies show that it works on a variety of GABA receptors (e.g. GABAA and GABAB etc...). This can cause muscle relaxation, and anxiolytic effects (among other things).[2][3]

Interestingly, it also appears to produce mild stimulation in some individuals by increasing levels of dopamine in the brain, which is why it is often used as a nootropic supplement.[4]

Based on what we about Phenibut, there is a chance that it could interact with Benadryl by increasing the severity of certain side effects, like dizziness and drowsiness.

What Is Benadryl?

Benadryl (diphenhydramine) is a sedating first-generation antihistamine, often used to treat and prevent allergies, but can also be used as a sleep aid.[5]

In fact, the active ingredient in Benadryl, (diphenhydramine), is commonly added to over the counter sleep products to induce drowsiness (e.g. Tylenol PM, ZzzQuil).

The duration of action of Benadryl is relatively short (around for to six hours) when compared to newer antihistamines, like Claritin, which last for 24 hours.

For this reason (and the fact that it can cause significant sedation), it is most commonly used as a sleep aid and to aid in reducing the severity of allergic reactions.[6]

The Interaction

A known side effect of Phenibut is sedation, which could be pronounced if taken with Benadryl.

There haven't been any studies evaluating their combined use, but based on their known pharmacology, it appears likely that they will cause additive sedation.

There is no evidence, however, that they affect each other in terms of absorption or medicinal effect.

Final Words

As there isn't much information available regarding Phenibut, it can be hard to discern potential drug interactions for it.

Nevertheless, based on the known pharmacology of it and Benadryl, they likely will have some additive effects in terms of the sedation they cause.

There is no known interaction between ibuprofen and Phenibut.


The use of Phenibut with Benadryl could potentially increase the severity of certain side effects, such as sedation and dizziness.

  1. ^ Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug. PubMed
  2. ^ Dissociative intoxication and prolonged withdrawal associated with phenibut: a case report. PubMed
  3. ^ The effects of agonists of ionotropic GABA(A) and metabotropic GABA(B) receptors on learning. PubMed
  4. ^ Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity. PubMed
  5. ^ Elsevier ClinicalKey: Diphenhydramine Monograph. ClinicalKey
  6. ^ Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: a literature review. PubMed