Drug & supplement interaction

Griffonia Simplicifolia + Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine brand name: Actifed Allergy.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Griffonia Simplicifolia has a moderate interaction with Diphenhydramine, Pseudoephedrine. Theoretically, taking Griffonia simplicifolia seed extract with CNS depressants might increase the risk of additive CNS depression.

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

Griffonia Simplicifolia and Diphenhydramine, Pseudoephedrine

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

Moderate

CNS DEPRESSANTS

Why this applies to Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine falls under CNS DEPRESSANTS — the group Griffonia Simplicifolia interacts with.

Theoretically, taking Griffonia simplicifolia seed extract with CNS depressants might increase the risk of additive CNS depression.
Griffonia simplicifolia seed extract contains 5-HTP. In clinical trials, 5-HTP has been associated with drowsiness and somnolence.
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

Here's the thing to know about Actifed Allergy: it's a combination of diphenhydramine (a sedating antihistamine) and pseudoephedrine (a decongestant). The diphenhydramine half is well known for making people sleepy, foggy, and slow to react. Griffonia seed extract supplies 5-HTP, which can also cause drowsiness on its own.

So the concern is simple addition: take them together and you may feel extra drowsy, groggy, or dizzy. To be fair, this is a theoretical caution based on how each one behaves, not strong proof, and pseudoephedrine is actually a stimulant that may offset some sleepiness. Still, don't drive or do anything risky until you know how you react, and check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Cangiano C, Ceci F, Cancino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992;56:863-7. PubMed
  2. den Boer JA, Westenberg HG. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res 1990;31:267-78. PubMed
  3. Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol 1986;25:327-9. PubMed
  4. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci 1985;29:239-48.
  5. Lemaire PA, Adosraku RK. An HPLC method for the direct assay of the serotonin precursor, 5-hydroxytrophan, in seeds of Griffonia simplicifolia. Phytochem Anal 2002;13(6):333-7.

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

Griffonia Simplicifolia Also Interacts With Other Medications

Griffonia Simplicifolia has 316 moderate known drug interactions in our database — the Diphenhydramine, Pseudoephedrine one above is one of them. If you take anything else, check it against the full list below.

Moderate 316 No known interaction 2,514 (incl. Diphenhydramine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Griffonia Simplicifolia

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine, Pseudoephedrine

This page covers Griffonia Simplicifolia only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine, Pseudoephedrine page lists 185 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), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 13 major · 150 moderate · 22 minor.

From our pharmacist’s overview on the Diphenhydramine, Pseudoephedrine page

“This medicine pulls in two directions at once, which is exactly why the supplement list for diphenhydramine and pseudoephedrine (Actifed Allergy) is not one to skim. The antihistamine half is sedating, so anything else that slows the brain deepens drowsiness; beer, wine, and kava all carry major ratings, with alcohol the best documented.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine, Pseudoephedrine interaction page

One more smart check

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

We hold 3 real supplement products containing Griffonia Simplicifolia, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Griffonia Simplicifolia. Your product may carry other ingredients that interact with Diphenhydramine, Pseudoephedrine too, on top of Griffonia Simplicifolia — 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 Griffonia Simplicifolia and Diphenhydramine, Pseudoephedrine 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 Griffonia Simplicifolia
Steady interest

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

29 days ago today
Medication Diphenhydramine, Pseudoephedrine
Top half

#1,161 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 Griffonia Simplicifolia

What is Griffonia Simplicifolia?

Griffonia Simplicifolia
  • Low mood
  • Sleep problems
  • Anxiety
  • Appetite control
  • Headaches

Griffonia simplicifolia is a West African shrub whose seeds are a natural source of 5-HTP, a building block of the brain chemical serotonin. Some people use it for mood, sleep, and appetite, but high-quality human evidence is limited, and it should not replace prescribed treatment. Talk with your pharmacist or doctor before using it, especially if you take medicines that affect serotonin.

Read the full Griffonia Simplicifolia monograph & all interactions
Keep checking

Other Drugs & Griffonia Simplicifolia

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

0Major
316Moderate
0Minor
2,513No known interaction
316 Moderate 2,513 No interaction
Moderate

316 interactions

Showing 60 of 316 moderate interactions — see all 316 on the Griffonia Simplicifolia page.

No interaction 2,513 drugs checked — show the list

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

Showing the 60 most looked-up of 2,513 medications checked with no known interaction — see the full Griffonia Simplicifolia list.

See the full Griffonia Simplicifolia interactions page
See every supplement checked against Diphenhydramine, Pseudoephedrine, ranked by severity
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

Keep exploring
Griffonia Simplicifolia monograph › Uses, safety, and every drug interaction in one place Diphenhydramine, Pseudoephedrine supplement interactions › Every supplement checked against Diphenhydramine, Pseudoephedrine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Griffonia Simplicifolia and Diphenhydramine, Pseudoephedrine Together: Common Questions

Can you take Griffonia Simplicifolia with Diphenhydramine, Pseudoephedrine?
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 Griffonia Simplicifolia and Diphenhydramine, Pseudoephedrine 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 Diphenhydramine, Pseudoephedrine and Griffonia Simplicifolia?

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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.