Drug & supplement interaction

Cannabis + Acetaminophen, Diphenhydramine, Pseudoephedrine

Acetaminophen, Diphenhydramine, Pseudoephedrine brand names: Contac Night Allergy Relief, Children's Tylenol Allergy, Cold Control.

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

Acetaminophen, Diphenhydramine, Pseudoephedrine falls into 2 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, cannabis might have additive effects if used with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabis and Acetaminophen, Diphenhydramine, Pseudoephedrine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Cannabis interacts with whole categories of medication. Acetaminophen, Diphenhydramine, Pseudoephedrine falls into 2 of those categories, so it can interact with Cannabis in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 2

Why this applies to Acetaminophen, Diphenhydramine, Pseudoephedrine

Acetaminophen, Diphenhydramine, Pseudoephedrine falls under CNS DEPRESSANTS — the group Cannabis interacts with.

Theoretically, cannabis might have additive effects if used with other CNS depressants.
Cannabis can have CNS depressant effects. Combining cannabis with other CNS depressants might result in additive or synergistic effects. A small clinical trial in healthy adults shows that inhaling a high-grade cannabis (Bedrocan International B.V., Veendam, The Netherlands) 100 mg, containing delta-9-tetrahydrocannabinol 21.8% and cannabinol 0.1%, modestly increases subjective feelings of sedation when compared with cannabis alone.
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 part to watch with these combination cold and allergy tablets: the diphenhydramine (the antihistamine, the same ingredient in Benadryl) can already make you feel drowsy, foggy, and slow to react. Cannabis, especially products with THC, can add its own sedating, mellowing effect on top of that. Put them together and you may feel more tired, dizzy, or out of it than you'd expect from either one alone. That matters most if you plan to drive or do anything that needs focus.

This is a theoretical concern based on how both act on the brain, not a dangerous chemical reaction, and the acetaminophen and pseudoephedrine pieces aren't the issue here. Still, go easy and check with your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Marinol Prescribing Information. Solvay Pharmaceuticals, Rev March 2008. Available at: http://www.solvaypharmaceuticals-us.com/static/wma/pdf/1/3/2/5/0/004InsertText500012RevMar2008.pdf (Accessed 2 July 2009).
  2. Hollister, L. E. Interactions of cannabis with other drugs in man. NIDA Res.Monogr 1986;68:110-116. DOI
  3. van Dam CJ, van der Schrier R, van Velzen M, et al. Inhaled Delta(9)-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers. Br J Anaesth 2023;130(4):485-493.
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

2 of 2

Acetaminophen, Diphenhydramine, Pseudoephedrine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, cannabis might decrease the levels and clinical effects of CYP2E1 substrates.
In vitro research shows that cannabis can induce the activity of CYP2E1, which might increase the metabolism of CYP2E1 substrates.
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

This combo product pairs a pain reliever (acetaminophen) with an antihistamine (diphenhydramine) and a decongestant (pseudoephedrine). The piece that ties into cannabis here is the acetaminophen, which is partly handled by a liver enzyme called CYP2E1. The lab research suggests cannabis might speed that enzyme up. In theory, that could clear acetaminophen a little faster, which mostly just means your pain or fever relief might not last quite as long.

I want to be honest: this is based only on test-tube data, so it's a weak, theoretical concern, not something most people will notice. The bigger real-world issue is overlap in side effects, since both cannabis and diphenhydramine can cause drowsiness and foggy thinking. Please run it by your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sheweita, S. A. Narcotic drugs change the expression of cytochrome P450 2E1 and 2C6 and other activities of carcinogen-metabolizing enzymes in the liver of male mice. Toxicology 9-30-2003;191(2-3):133-142. 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

Cannabis Also Interacts With Other Medications

Cannabis has 2 major, 1,108 moderate, 25 minor known drug interactions in our database — the Acetaminophen, Diphenhydramine, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

Major 2 Moderate 1,108 Minor 25 No known interaction 1,695 (incl. Acetaminophen, Diphenhydramine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Cannabis

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

From our Q&A

Questions About Cannabis or Acetaminophen, Diphenhydramine, Pseudoephedrine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabis or Acetaminophen, Diphenhydramine, Pseudoephedrine, 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 Acetaminophen, Diphenhydramine, Pseudoephedrine

This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine, Pseudoephedrine page lists 292 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 Ephedra (major).

By severity: 15 major · 234 moderate · 43 minor.

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

“A drink with this medicine is the risk I would flag first. Beer and wine both carry major ratings, well documented in humans, because alcohol deepens the sedation that diphenhydramine already causes.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Diphenhydramine, Pseudoephedrine interaction page

One more smart check

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

We hold 21 real supplement products containing Cannabis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cannabis. Your product may carry other ingredients that interact with Acetaminophen, Diphenhydramine, Pseudoephedrine too, on top of Cannabis — 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 Cannabis and Acetaminophen, 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 Cannabis
Top 25%

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

29 days ago today
Medication Acetaminophen, Diphenhydramine, Pseudoephedrine
Top 25%

#632 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 Cannabis

What is Cannabis?

Cannabis
  • Chronic pain
  • Nausea and vomiting from chemotherapy
  • Muscle spasticity (e.g., multiple sclerosis)
  • Anxiety and stress
  • Sleep problems
  • Appetite stimulation

Cannabis contains many active compounds, mainly THC (which causes a 'high') and CBD (which does not). Some uses, such as chemotherapy-related nausea, certain seizure disorders, and muscle spasticity, have meaningful evidence, while many other popular uses are not well proven. It can cause real side effects and impairment, so talk to your doctor or pharmacist and follow your local laws before using it.

Read the full Cannabis monograph & all interactions
Keep checking

Other Drugs & Cannabis

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

2Major
1,108Moderate
25Minor
1,694No known interaction
2 Major 1,108 Moderate 25 Minor 1,694 No interaction
Major

2 interactions

Moderate

1,108 interactions

Showing 60 of 1,108 moderate interactions — see all 1,108 on the Cannabis page.

Minor

25 interactions

No interaction 1,694 drugs checked — show the list

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

Showing the 60 most looked-up of 1,694 medications checked with no known interaction — see the full Cannabis list.

See the full Cannabis interactions page
See every supplement checked against Acetaminophen, 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
Cannabis monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Diphenhydramine, Pseudoephedrine supplement interactions › Every supplement checked against Acetaminophen, 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 Cannabis and Acetaminophen, Diphenhydramine, Pseudoephedrine Together: Common Questions

Can you take Cannabis with Acetaminophen, 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.
Why are there 2 interactions listed for Cannabis and Acetaminophen, Diphenhydramine, Pseudoephedrine?
Acetaminophen, Diphenhydramine, Pseudoephedrine belongs to more than one drug category, and Cannabis 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 Cannabis and Acetaminophen, 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

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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.