Drug & supplement interaction

Cannabidiol (cbd) + Acetaminophen, Pseudoephedrine, Triprolidine

Acetaminophen, Pseudoephedrine, Triprolidine brand name: Actifed Plus ES.

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

Acetaminophen, Pseudoephedrine, Triprolidine falls into 3 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Cannabidiol may increase levels of drugs metabolized by CYP1A2.

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

Cannabidiol (cbd) and Acetaminophen, Pseudoephedrine, Triprolidine

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

Why Are There 3 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Acetaminophen, Pseudoephedrine, Triprolidine falls into 3 of those categories, so it can interact with Cannabidiol (cbd) 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 Acetaminophen, Pseudoephedrine, Triprolidine

Acetaminophen, Pseudoephedrine, Triprolidine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Cannabidiol (cbd) interacts with.

Cannabidiol may increase levels of drugs metabolized by CYP1A2.
In vitro research shows that cannabidiol inhibits CYP1A2. Furthermore, clinical studies show that cannabidiol may inhibit the metabolism of caffeine, a CYP1A2 substrate. Two pharmacokinetic studies in healthy adults show that taking cannabidiol dosed 640 mg once up to 750 twice daily increases the area under the curve of caffeine. However, results are mixed over whether cannabidiol impacts peak serum levels of caffeine.
Severity Moderate Likelihood Probable Evidence A

Interaction 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..

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

Here's the thing about this combo product (Actifed Plus ES). It contains three ingredients: acetaminophen for pain and fever, pseudoephedrine as a decongestant, and triprolidine, an older antihistamine. CBD can block a liver enzyme called CYP1A2, which can slow the breakdown of certain medicines and let them build up a bit. That said, none of these three are mainly cleared by CYP1A2, so for this specific product the practical effect is usually small.

If anything, you'd watch for a little more of what these drugs already do: drowsiness or dry mouth from the antihistamine, or jitteriness from the decongestant. The bigger picture is just being careful with how much total acetaminophen you take in a day. To be safe, run it by your pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective potent inhibitors of human CYP1 enzymes. Biochem Pharmacol 2010;79(11):1691-8.
  2. Thai C, Tayo B, Critchley D. A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects. Clin Pharmacol Drug Dev. 2021. PubMed
  3. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  4. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

GLUCURONIDATED DRUGS

2 of 3

Acetaminophen, Pseudoephedrine, Triprolidine also falls under GLUCURONIDATED DRUGS.

Cannabidiol might increase levels of certain glucuronidated drugs.
In vitro research shows that cannabidiol inhibits uridine diphosphoglucuronosyl transferase (UGT) 1A9 and UGT2B7, enzymes responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs.
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 gist for Actifed Plus ES, which combines acetaminophen (Tylenol), pseudoephedrine, and triprolidine. The acetaminophen part is cleared partly through a process called glucuronidation. In lab dish studies, CBD has been shown to slow the enzymes that handle that step (UGT1A9 and UGT2B7). In theory, that could let acetaminophen linger a bit longer in your body.

I want to be honest about how weak this is. It's only test-tube research, not proven in real people, so for most folks taking this cold-and-allergy combo as directed it's unlikely to cause trouble. The bigger thing I'd watch is simply not doubling up on acetaminophen from other products, since too much strains the liver. If you use CBD regularly, just give your pharmacist a heads-up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

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

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2E1.
In vitro research shows that cannabidiol inhibits CYP2E1. So far, this interaction has not been reported in humans.
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 combination product contains three things, but the part that matters here is the acetaminophen (the Tylenol ingredient). Your liver uses an enzyme called CYP2E1 to break down a small slice of acetaminophen, and that pathway happens to create a byproduct that can be hard on the liver. CBD has been shown in lab dishes to slow CYP2E1 down. In theory, that could shift how acetaminophen is processed.

Here's the honest part: this has only been seen in test-tube and animal studies, never in real people, so I wouldn't lose sleep over it with normal, occasional doses. The bigger practical caution is just not stacking extra acetaminophen products on top. If you use CBD regularly and reach for this cold medicine often, check in with your pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. 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

Cannabidiol (cbd) Also Interacts With Other Medications

Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Acetaminophen, Pseudoephedrine, Triprolidine one above is among them. If you take anything else, check it against the full list below.

Moderate 1,050 No known interaction 1,780 (incl. Acetaminophen, Pseudoephedrine, Triprolidine)
Taking anything else?

Check Another of Your Medications Against Cannabidiol (cbd)

Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Pseudoephedrine, Triprolidine

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Pseudoephedrine, Triprolidine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Ephedra (major) and Peyote (major).

By severity: 9 major · 149 moderate · 39 minor.

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

“Actifed Plus ES combines acetaminophen, pseudoephedrine, and triprolidine, and the pseudoephedrine is why I would check this page carefully before adding any supplement. Stimulation dominates the list: 44 ingredients, from ephedra to the everyday caffeine in coffee, tea, and cocoa, can stack on the decongestant and push blood pressure…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Pseudoephedrine, Triprolidine interaction page

How much people look this up

Where Cannabidiol (cbd) and Acetaminophen, Pseudoephedrine, Triprolidine 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 Cannabidiol (cbd)
Top half

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

29 days ago today
Medication Acetaminophen, Pseudoephedrine, Triprolidine
Top half

#852 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 Cannabidiol (cbd)

What is Cannabidiol (cbd)?

  • Anxiety and stress
  • Sleep problems
  • Chronic pain
  • Certain seizure disorders
  • Inflammation

CBD is a compound from the cannabis (hemp) plant that does not cause a 'high.' It has strong evidence only for certain rare seizure disorders (as a prescription drug), while most other popular uses are still backed by limited or early research. Product quality varies a lot, so talk with your pharmacist or doctor before using it, especially if you take other medicines.

Read the full Cannabidiol (cbd) monograph & all interactions
Keep checking

Other Drugs & Cannabidiol (cbd)

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

0Major
1,050Moderate
0Minor
1,779No known interaction
1,050 Moderate 1,779 No interaction
Moderate

1,050 interactions

Showing 60 of 1,050 moderate interactions — see all 1,050 on the Cannabidiol (cbd) page.

No interaction 1,779 drugs checked — show the list

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

Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) list.

See the full Cannabidiol (cbd) interactions page
See every supplement checked against Acetaminophen, Pseudoephedrine, Triprolidine, 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
Cannabidiol (cbd) monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Pseudoephedrine, Triprolidine supplement interactions › Every supplement checked against Acetaminophen, Pseudoephedrine, Triprolidine, 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 Cannabidiol (cbd) and Acetaminophen, Pseudoephedrine, Triprolidine Together: Common Questions

Can you take Cannabidiol (cbd) with Acetaminophen, Pseudoephedrine, Triprolidine?
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 Cannabidiol (cbd) and Acetaminophen, Pseudoephedrine, Triprolidine?
Acetaminophen, Pseudoephedrine, Triprolidine belongs to more than one drug category, and Cannabidiol (cbd) 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 Cannabidiol (cbd) and Acetaminophen, Pseudoephedrine, Triprolidine 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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