Drug & supplement interaction

Phosphatidylserine + Doxylamine Succinate

Doxylamine Succinate brand name: Unisom.

Moderate Interaction
The bottom line Moderate

Phosphatidylserine has a moderate interaction with Doxylamine Succinate. Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.

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

Phosphatidylserine and Doxylamine Succinate

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ANTICHOLINERGIC DRUGS

Why this applies to Doxylamine Succinate

Doxylamine Succinate falls under ANTICHOLINERGIC DRUGS — the group Phosphatidylserine interacts with.

Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically interfere with the activity of anticholinergic agents.
Severity Moderate Likelihood Possible Evidence B

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

Here's the simple version: doxylamine (Unisom) works by blocking acetylcholine, a chemical messenger in your body. That blocking action is what makes it dry up a runny nose and make you drowsy enough to sleep. Phosphatidylserine, on the other hand, is thought to nudge acetylcholine up a little. So in theory, the two could work against each other, and you might notice your doxylamine doesn't help you sleep quite as well.

I want to be honest about how shaky this is. It's a theoretical concern based on weak evidence, not something we see causing real problems day to day. Most people won't notice a thing. Still, if your sleep aid seems less effective after adding phosphatidylserine, mention it to your pharmacist or doctor so they can help you sort it out.

References
  1. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull 1992;28:61-6.
  2. Kim HY, Akbar M, Lau A, et al. Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 2000;275:35215-23.. PubMed
  3. Zanotti A, Valzelli L, Toffano G. Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacology (Berl) 1989;99:316-21.. PubMed

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

Phosphatidylserine Also Interacts With Other Medications

Phosphatidylserine has 218 moderate known drug interactions in our database — the Doxylamine Succinate one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Phosphatidylserine

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

From our Q&A

Questions About Phosphatidylserine or Doxylamine Succinate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Phosphatidylserine or Doxylamine Succinate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Doxylamine Succinate

This page covers Phosphatidylserine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Doxylamine Succinate page lists 52 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Scopolia (major), Angel's Trumpet (moderate) and Bacopa (moderate).

By severity: 3 major · 38 moderate · 11 minor.

From our pharmacist’s overview on the Doxylamine Succinate page

“Someone reaching for doxylamine succinate (Unisom) to fall asleep is often the same person browsing the supplement aisle, and that pairing deserves genuine care here. Doxylamine is a strongly anticholinergic antihistamine, meaning it dries you out, fogs thinking, and slows digestion, and 30 of the 52 flagged ingredients pile more of th…”

Reviewed by 2 · Jul 18, 2026

Open the Doxylamine Succinate interaction page

One more smart check

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

We hold 1,754 real supplement products containing Phosphatidylserine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phosphatidylserine. Your product may carry other ingredients that interact with Doxylamine Succinate too, on top of Phosphatidylserine — 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 Phosphatidylserine and Doxylamine Succinate 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 Phosphatidylserine
Top 10%

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

29 days ago today
Medication Doxylamine Succinate
Steady interest

#1,697 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 Phosphatidylserine

What is Phosphatidylserine?

Phosphatidylserine
  • Memory and cognitive support
  • Age-related cognitive decline
  • Attention and focus (ADHD)
  • Mental performance under stress
  • Exercise recovery

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinking. Some research suggests possible benefits for age-related memory problems, but the evidence is limited and far from conclusive. It is generally well tolerated, but check with your pharmacist or doctor before using it, especially during pregnancy or breastfeeding.

Read the full Phosphatidylserine monograph & all interactions
Medication

About Diphenhydramine

What Is Diphenhydramine Used For?

Brand name: Unisom

Diphenhydramine temporarily relieves symptoms of hay fever, other upper respiratory allergies, and the common cold — including runny nose, sneezing, itchy or watery eyes, and itching of the nose or throat.

After Bite Xtra gel is formulated for topical use and is approved to temporarily relieve pain and itching from minor burns, minor cuts and scrapes, insect bites, minor skin irritations, and rashes from poison ivy, poison oak, and poison sumac.

See full Diphenhydramine drug information
Keep checking

Other Drugs & Phosphatidylserine

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

0Major
218Moderate
0Minor
2,611No known interaction
Moderate

218 interactions

Showing 60 of 218 moderate interactions — see all 218 on the Phosphatidylserine page.

No interaction 2,611 drugs checked — show the 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 Phosphatidylserine and Doxylamine Succinate Together: Common Questions

Can you take Phosphatidylserine with Doxylamine Succinate?
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.
How serious is the Phosphatidylserine and Doxylamine Succinate 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

Still Have a Question About Doxylamine Succinate and Phosphatidylserine?

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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.