Cannabis + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 3 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 reportCannabis and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Cannabis interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 3 of those categories, so it can interact with Cannabis in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 3Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CNS DEPRESSANTS — the group Cannabis interacts with.
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.
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.
This combination product (sold as Hycomine Compound) packs in two ingredients that can make you drowsy: hydrocodone, an opioid, and chlorpheniramine, a sedating antihistamine. Cannabis can also calm down your central nervous system. So the worry here is simple addition: stack a sedating cough-and-cold medicine on top of cannabis and the sleepiness, foggy thinking, slowed breathing, and clumsiness can all add up.
To be fair, this is a theoretical concern based on how these things work, not strong proof, and one small study only showed a modest bump in feeling sedated. Still, it's worth respecting. You may feel more dizzy or out of it than expected, so don't drive, and check with your pharmacist or doctor before pairing them.
- 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).
- Hollister, L. E. Interactions of cannabis with other drugs in man. NIDA Res.Monogr 1986;68:110-116. DOI
- 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.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 3Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that cannabis can inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. In vitro research also shows that cannabis extracts modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids CBD and cannabigerol (CBG) had stronger inhibitory effects than extracts containing THC and CBD.
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.
This combo product is a mouthful, but the piece that matters here is the hydrocodone, the narcotic cough and pain ingredient. Your liver uses an enzyme called CYP3A4 to help break it down. Lab studies suggest cannabis can mildly slow that same enzyme, so in theory hydrocodone could hang around a little longer and feel a bit stronger.
If that happened, you might notice more drowsiness, dizziness, slowed breathing, or constipation. Keep in mind this is based only on test-tube research, not real patient data, so the effect (if any) is likely modest. Still, both cannabis and this product can make you sleepy on their own, so the bigger everyday concern is added sedation. Please check with your pharmacist or doctor before combining them.
- 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
- 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
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
3 of 3Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
In vitro research shows that cannabis can induce the activity of CYP2E1, which might increase the metabolism of CYP2E1 substrates.
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.
Here's the thing about this combo product (Hycomine Compound): the piece that touches the CYP2E1 enzyme is mostly the acetaminophen (Tylenol) part. The concern on file is theoretical, coming from lab studies only, where cannabis seemed to speed up that enzyme. In real life this is a low-strength signal, so I wouldn't lose sleep over it.
If anything, faster acetaminophen breakdown could nudge a bit more of it down a pathway that stresses the liver, especially with regular or higher doses. The bigger, more practical worry is overlap in drowsiness: hydrocodone, chlorpheniramine, and cannabis can each make you sleepy and foggy, and together that adds up. Please run this past your pharmacist or doctor before combining them.
- 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.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Cannabis Also Interacts With Other Medications
Cannabis has 2 major, 1,108 moderate, 25 minor known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Cannabis
We haven’t checked that one against Cannabis yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Cannabis. Pick one to open its full report.
Questions About Cannabis or Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine, 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.
See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page
“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page
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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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:
Where Cannabis and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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.
#224 of 1,452 supplements looked up here in the last 7 days
#831 of 2,830 medications looked up here in the last 7 days
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.
About Cannabis
What is 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.
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.
No drugs match “”.
2 interactions
1,108 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Metronidazole ›
- Diphenhydramine ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Fenofibrate ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Acetaminophen ›
- Buprenorphine ›
- Conjugated Estrogens ›
Showing 60 of 1,108 moderate interactions — see all 1,108 on the Cannabis page.
25 interactions
- Fluphenazine ›
- Asenapine ›
- Clozapine ›
- Prochlorperazine ›
- Acetophenazine ›
- Butaperazine ›
- Carphenazine ›
- Chlorprothixene ›
- Isopropamide Iodide ›
- Mesoridazine Besylate ›
- Methotrimeprazine Maleate ›
- Molindone ›
- Olanzapine ›
- Paliperidone ›
- Paliperidone Palmitate ›
- Pericyazine ›
- Perphenazine ›
- Piperacetazine ›
- Promazine ›
- Sertindole ›
- Thiothixene ›
- Trifluoperazine ›
- Triflupromazine ›
- Isopropamide, Trifluoperazine ›
- Isopropamide, Prochlorperazine ›
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.
- Levothyroxine ›
- Methylphenidate ›
- Metoprolol ›
- Rosuvastatin ›
- Escitalopram ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Methamphetamine ›
- Tirzepatide ›
- Semaglutide ›
- Sumatriptan ›
- Lisdexamfetamine ›
- Metformin ›
- Lisinopril ›
- Amoxicillin ›
- Bupropion ›
- Bendamustine ›
- Acyclovir ›
- Methotrexate ›
- Amphetamine ›
- Azithromycin ›
- Dextroamphetamine ›
- Isotretinoin ›
- Methylene Blue ›
- Duloxetine ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Cyclopentolate ›
- Mannitol ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Levothyroxine Sodium ›
- Ezetimibe ›
- Dexmethylphenidate ›
- Spironolactone ›
- Amoxicillin, Clavulanate Potassium ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Factor 7a ›
- Levodopa ›
- Lenvatinib ›
- Mitomycin ›
- Hethylphenidate Hcl ›
- Minoxidil ›
- Cefaclor ›
- Venlafaxine ›
- Azelaic Acid ›
- Phenylephrine ›
- Nortriptyline ›
- Hydroxychloroquine ›
- Vancomycin ›
- Bentoquatam ›
- Pizotifen ›
- Triptorelin ›
- Dirithromycin ›
- Procainamide ›
- Dextrothyroxine ›
Showing the 60 most looked-up of 1,694 medications checked with no known interaction — see the full Cannabis list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine as a medicine that can lower these. This is not an interaction with Cannabis — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Cannabis and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Cannabis with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 3 interactions listed for Cannabis and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Cannabis and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction?
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.