Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine

Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine brand name: Conar-A.

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

Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine falls into 2 drug categories that Delta-9-tetrahydrocannabinol (thc) can interact with; the most serious is rated moderate. Theoretically, THC might decrease the levels and clinical effects of CYP2E1 substrates.

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

Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine

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

Why Are There 2 Interactions?

Delta-9-tetrahydrocannabinol (thc) interacts with whole categories of medication. Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine falls into 2 of those categories, so it can interact with Delta-9-tetrahydrocannabinol (thc) in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine

Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES — the group Delta-9-tetrahydrocannabinol (thc) interacts with.

Theoretically, THC might decrease the levels and clinical effects of CYP2E1 substrates.
In vitro research shows that cannabis containing THC can induce the activity of CYP2E1, which might increase the metabolism of CYP2E1 substrates. It is unclear if this effect is due to THC, other constituents, or the combination.
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 piece worth knowing about this cold-and-cough combo (Conar-A). One of its ingredients, acetaminophen, is partly handled by a liver enzyme called CYP2E1. Some lab studies suggest THC may speed that enzyme up a bit. In theory, that could shift acetaminophen toward more of a byproduct that's harder on the liver, especially at higher acetaminophen doses or with regular alcohol use.

That said, this is only test-tube and animal data, not real patient evidence, so for occasional, recommended doses I wouldn't lose sleep over it. The bigger everyday tip is simply not to stack multiple acetaminophen products at once. If you use cannabis regularly and take this often, it's worth a quick chat with your pharmacist so you stay under the daily acetaminophen limit.

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
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, THC may increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that cannabis containing THC might modestly inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. It is unclear if this effect is due to THC, other constituents, or the combination. In vitro research also shows that cannabis extracts containing THC modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids cannabidiol (CBD) or cannabigerol (CBG) alone had stronger inhibitory effects than extracts containing both THC and CBD. Conversely, a crossover clinical study in healthy adults shows that oral THC does not inhibit CYP3A4.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the gist with your Conar-A combo (acetaminophen, dextromethorphan, guaifenesin, and phenylephrine). In a test tube, THC seems to mildly slow down a liver enzyme called CYP3A4, which helps clear certain medicines. The dextromethorphan piece (the cough suppressant) is partly handled by that enzyme, so in theory its levels could nudge up a bit. That might mean more drowsiness, dizziness, or feeling foggy.

Honestly, though, I wouldn't lose sleep over this one. The evidence is only from lab studies, and a human study found oral THC didn't actually block CYP3A4. This is rated minor and unlikely. Just be a little cautious about extra sleepiness, and check with your pharmacist or doctor if you use THC regularly.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pellinen, P., Honkakoski, P., Stenback, F., Niemitz, M., Alhava, E., Pelkonen, O., Lang, M. A., and Pasanen, M. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur.J Pharmacol 1-3-1994;2 PubMed
  2. Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. PubMed
  3. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.

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

Delta-9-tetrahydrocannabinol (thc) Also Interacts With Other Medications

Delta-9-tetrahydrocannabinol (thc) has 762 moderate, 336 minor known drug interactions in our database — the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Moderate 762 Minor 336 No known interaction 1,732 (incl. Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Delta-9-tetrahydrocannabinol (thc)

Covers the 2,830 medications we’ve checked against Delta-9-tetrahydrocannabinol (thc). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine page lists 261 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 Grapefruit (major).

By severity: 12 major · 206 moderate · 43 minor.

From our pharmacist’s overview on the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine page

“Picture the week someone takes Conar-A (acetaminophen, dextromethorphan, guaifenesin, phenylephrine): a miserable cold, coffee to push through, maybe wine at night or an herbal remedy on top. Those habits are exactly where this list turns serious.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine 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 Delta-9-tetrahydrocannabinol (thc)
Top half

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

29 days ago today
Medication Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine
Top 25%

#481 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 Delta-9-tetrahydrocannabinol (thc)

What is Delta-9-tetrahydrocannabinol (thc)?

Delta-9-tetrahydrocannabinol (thc)
  • Chronic or nerve pain
  • Nausea and vomiting from chemotherapy
  • Appetite loss and weight loss
  • Muscle spasticity
  • Sleep problems
  • Anxiety and stress

THC is the main mind-altering compound in cannabis and is best known for causing a 'high.' A prescription form (dronabinol) is approved for chemotherapy-related nausea and appetite loss, but for most other uses the evidence is mixed or limited, and THC can impair thinking and driving. It should be avoided in pregnancy and breastfeeding and used only with medical guidance.

Read the full Delta-9-tetrahydrocannabinol (thc) monograph & all interactions
Keep checking

Other Drugs & Delta-9-tetrahydrocannabinol (thc)

Browse every other medication we’ve checked against Delta-9-tetrahydrocannabinol (thc) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
762Moderate
336Minor
1,731No known interaction
762 Moderate 336 Minor 1,731 No interaction
Moderate

762 interactions

Showing 60 of 762 moderate interactions — see all 762 on the Delta-9-tetrahydrocannabinol (thc) page.

Minor

336 interactions

Showing 60 of 336 minor interactions — see all 336 on the Delta-9-tetrahydrocannabinol (thc) page.

No interaction 1,731 drugs checked — show the list

We also checked Delta-9-tetrahydrocannabinol (thc) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,731 medications checked with no known interaction — see the full Delta-9-tetrahydrocannabinol (thc) list.

See the full Delta-9-tetrahydrocannabinol (thc) interactions page
See every supplement checked against Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine, 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
Delta-9-tetrahydrocannabinol (thc) monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine, 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 Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine?
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 Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine?
Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine belongs to more than one drug category, and Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Dextromethorphan, Guaifenesin, Phenylephrine 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.