Drug & supplement interaction

Bacopa + Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.

Moderate Interaction
The bottom line Moderate

Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 drug categories that Bacopa can interact with; the most serious is rated moderate. Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Bacopa and Diphenhydramine Hydrochloride, Naproxen Sodium

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Bacopa interacts with whole categories of medication. Diphenhydramine Hydrochloride, Naproxen Sodium falls into 3 of those categories, so it can interact with Bacopa in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Bacopa interacts with.

Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Aleve PM combines naproxen (a pain reliever) with diphenhydramine (the sedating antihistamine that makes you sleepy). The concern here is mostly theoretical: in lab dishes, bacopa may slow down a liver enzyme called CYP1A2, which helps break down certain drugs. If that happened in the body, these medicines could clear a bit slower and their effects could feel stronger.

In practical terms, you might notice more grogginess, dry mouth, dizziness, or constipation from the diphenhydramine side. That said, the evidence is weak and conflicting, so a real-world problem is far from certain. Still, since both already cause drowsiness, it's worth mentioning bacopa to your pharmacist or doctor before pairing them, especially if you're older.

References
  1. Kar A, Pandit S, Mukherjee K, Bahadur S, Mukherjee PK. Safety assessment of selected medicinal food plants used in Ayurveda through CYP450 enzyme inhibition study. J Sci Food Agric 2017;97(1):333-40. doi: 10.1002/jsfa.7739. PubMed
  2. Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules 2014;19(2):2588-601. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Aleve PM combines naproxen (an anti-inflammatory pain reliever) with diphenhydramine (a sedating antihistamine for sleep). The naproxen half is partly cleared by a liver enzyme called CYP2C9. In lab dishes, bacopa has shown a mild ability to slow that enzyme down, though other lab studies found no meaningful effect. So the theory is that bacopa could let naproxen build up a bit, which might mean more stomach upset, heartburn, or, with heavier use, a higher chance of stomach irritation or bleeding.

Honestly, this is a weak, theoretical concern based only on test-tube data, not on real people. Naproxen is not a prodrug, so this would nudge its levels up, not down. For most folks taking the occasional Aleve PM, this isn't alarming. If you take it often, just mention the bacopa to your pharmacist.

References
  1. Kar A, Pandit S, Mukherjee K, Bahadur S, Mukherjee PK. Safety assessment of selected medicinal food plants used in Ayurveda through CYP450 enzyme inhibition study. J Sci Food Agric 2017;97(1):333-40. doi: 10.1002/jsfa.7739. PubMed
  2. Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules 2014;19(2):2588-601. PubMed
Moderate

ANTICHOLINERGIC DRUGS

3 of 3

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under ANTICHOLINERGIC DRUGS.

Theoretically, concurrent use might decrease the effectiveness of both agents.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs. Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

The piece of Aleve PM I want to focus on here is the diphenhydramine, which is the sleep aid part (the same ingredient as Benadryl). Diphenhydramine works partly by blocking acetylcholine, a brain messenger. Bacopa may gently nudge things the other way by raising acetylcholine levels. So in theory, the two could tug against each other: bacopa might slightly blunt the drowsy, calming effect you take Aleve PM for, and the diphenhydramine could in turn dampen any benefit you hope to get from bacopa.

I want to be honest that this is a theoretical concern based on how these work, not something proven in real patients, so I would not panic over it. The naproxen (pain reliever) side isn't really involved. If you take both regularly, just mention it to your pharmacist or doctor so they can keep an eye on how well each is working for you.

References
  1. Morgan A, Stevens J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med 2010;16:753-9.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Bacopa Also Interacts With Other Medications

Bacopa has 916 moderate, 13 minor known drug interactions in our database — the Diphenhydramine Hydrochloride, Naproxen Sodium one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Bacopa

Covers the 2,830 medications we’ve checked against Bacopa. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium

This page covers Bacopa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine Hydrochloride, Naproxen Sodium page lists 378 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 13 major · 320 moderate · 45 minor.

From our pharmacist’s overview on the Diphenhydramine Hydrochloride, Naproxen Sodium page

“Aleve PM combines naproxen, an NSAID, with the sedating antihistamine diphenhydramine, and its supplement list earns genuine care rather than a quick skim. Thirteen of the 378 ingredients on file rate major, and the two largest themes track the pill's two halves.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine Hydrochloride, Naproxen Sodium interaction page

One more smart check

Taking Bacopa as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,420 real supplement products containing Bacopa, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bacopa. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Bacopa — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Bacopa and Diphenhydramine Hydrochloride, Naproxen Sodium Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Bacopa
Top 10%

#134 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Diphenhydramine Hydrochloride, Naproxen Sodium
Top 10%

#222 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Bacopa

What is Bacopa?

Bacopa
  • Memory and cognitive support
  • Anxiety and stress
  • ADHD symptoms
  • Age-related memory decline
  • General brain health

Bacopa is an Ayurvedic herb most often used for memory and thinking. Some small studies suggest it may modestly help memory when taken regularly for several weeks, but the evidence is limited and quality varies. It is generally well tolerated but can cause stomach upset, and it should be avoided in pregnancy and breastfeeding due to a lack of safety data.

Read the full Bacopa monograph & all interactions
Keep checking

Other Drugs & Bacopa

Browse every other medication we’ve checked against Bacopa — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
916Moderate
13Minor
1,900No known interaction
Moderate

916 interactions

Showing 60 of 916 moderate interactions — see all 916 on the Bacopa page.

Minor

13 interactions

No interaction 1,900 drugs checked — show the list

We also checked Bacopa against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,900 medications checked with no known interaction — see the full Bacopa list.

Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Bacopa and Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions

Can you take Bacopa with Diphenhydramine Hydrochloride, Naproxen Sodium?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Bacopa and Diphenhydramine Hydrochloride, Naproxen Sodium?
Diphenhydramine Hydrochloride, Naproxen Sodium belongs to more than one drug category, and Bacopa interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Bacopa and Diphenhydramine Hydrochloride, Naproxen Sodium interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.