Cannabidiol (cbd) + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine brand name: Colrex.
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls into 6 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Theoretically, cannabidiol might have additive effects if used with other CNS depressants.
Read the full interaction reportCannabidiol (cbd) and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
These two interact in 6 distinct ways. Each one is explained separately below.
Why Are There 6 Interactions?
Cannabidiol (cbd) interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls into 6 of those categories, so it can interact with Cannabidiol (cbd) in 6 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 6Why this applies to Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls under CNS DEPRESSANTS — the group Cannabidiol (cbd) interacts with.
Preliminary clinical research, case reports, and animal studies suggest that high dose cannabidiol has sedative and hypnotic effects. Theoretically, concomitant use of cannabidiol with drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.
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 (Colrex) already has two ingredients that can make you sleepy: codeine (a narcotic cough and pain reliever) and chlorpheniramine (a sedating antihistamine). When you add CBD on top, the main concern is simply additive drowsiness. CBD has its own mild sedative side, so the two together could leave you more tired, foggy, dizzy, or slow to react than either alone. That matters most if you're driving or operating machinery.
To be fair, this caution is mostly theoretical, built on how these things work rather than solid studies, and it's more likely with higher CBD doses. Still, since codeine is a true CNS depressant, I'd run the combo by your pharmacist or doctor first and go easy until you know how you feel.
- Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol 1981;21(8-9 Suppl):417S-27S. PubMed
- Monti JM. Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology (Berl) 1977;55(3):263-5. PubMed
- Pickens JT. Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content. Br J Pharmacol 1981;72(4):649-56.
- Perez-Vilar S, Karami S, Long K, Leishear K. Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021. Clin Toxicol (Phila) 2022. PubMed
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
2 of 6Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
In vitro research shows that cannabidiol inhibits CYP2D6. Theoretically, concomitant use of cannabidiol with CYP2D6 substrates might increase the risk for adverse effects from these substrates. However, a clinical crossover trial in healthy adults shows that cannabidiol does not inhibit dextromethorphan, a substrate of CYP2D6.
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 wrinkle with this combo product: one of its ingredients, codeine, is a prodrug. Your body uses an enzyme called CYP2D6 to turn codeine into morphine, which is what actually relieves pain and quiets a cough. CBD may block that enzyme a bit (this is mostly lab-based, theoretical evidence, not proven in people). If it does, you could turn less codeine into its active form, meaning weaker pain or cough relief rather than more side effects.
Honestly, the real-world effect here is uncertain, and a study with a similar CYP2D6 drug showed no meaningful change. The other ingredients (acetaminophen, chlorpheniramine, phenylephrine) aren't a big concern through this pathway. Still, run it by your pharmacist or doctor before pairing them.
- Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 2011;39(11):2049-56. PubMed
- 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
- Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
3 of 6Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.
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.
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..
This is a combination cold and cough product, and the piece that the CBD interaction touches on is the CYP1A2 enzyme. CBD can slow that enzyme down, which means certain medicines cleared through it may build up a bit. In real life, the main ingredients here (codeine, acetaminophen, chlorpheniramine, and phenylephrine) are not strongly handled by CYP1A2, so for this specific product the practical effect is usually small.
That said, it's worth knowing that codeine and chlorpheniramine can already make you drowsy, and pairing them with CBD may leave you feeling more tired or foggy. If you plan to use both, check in with your pharmacist or doctor first, especially about sleepiness and your acetaminophen total for the day.
- 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.
- 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
- 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
- Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
4 of 6Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro and animal research shows that cannabidiol inhibits CYP3A4. In human studies and case reports, cannabidiol has been associated with an increase in plasma levels of the CYP3A4 substrates zonisamide, tacrolimus, everolimus, citalopram, midazolam, and methadone.
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..
This Colrex product is a combination, and the piece that matters most here is the codeine. Codeine is a prodrug, meaning your body has to convert it (mainly through CYP2D6) into morphine before it relieves pain or cough. CBD's biggest effect is on a different enzyme, CYP3A4, which handles a smaller, secondary breakdown path for codeine. By slowing CYP3A4, CBD could shift a little more codeine toward the active route, so you might feel more drowsiness, dizziness, constipation, or slowed breathing.
Honestly, this is a modest concern rather than an alarm, but the combo already piles on sedation (codeine plus the antihistamine chlorpheniramine plus CBD). Please check with your pharmacist or doctor before pairing these, especially if you'll be driving.
- Yamaori S, Ebisawa J, Okushima Y, et al. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci 2011;88(15-16):730-6. PubMed
- Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
- Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
- Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
- Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transplant. 2019;19(10):2944-2948. PubMed
- Wiemer-Kruel A, Stiller B, Bast T. Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex. Neuropediatrics. 2019. PubMed
- Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
- Anderson LL, Doohan PT, Oldfield L, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. J Clin Psychopharmacol. 2021. PubMed
- 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
- 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
- Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
GLUCURONIDATED DRUGS
5 of 6Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine also falls under 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.
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 Colrex combo has a few moving parts, but the one that lines up with this interaction is the acetaminophen (Tylenol). Your liver clears acetaminophen partly through a process called glucuronidation, and lab studies suggest CBD can slow those particular enzymes. In theory, that could let acetaminophen build up a bit higher than usual.
The key word is theoretical. This concern comes only from test-tube research, not from people, so it's far from proven. Still, since acetaminophen is hard on the liver in large or stacked-up amounts, it's worth being careful not to take extra Tylenol-containing products on top of this. The codeine piece can already cause drowsiness, and CBD may add to that sleepy feeling too. Before pairing CBD with Colrex, just check with your pharmacist or doctor.
- 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)
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
6 of 6Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
In vitro research shows that cannabidiol inhibits CYP2E1. So far, this interaction has not been reported in humans.
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 (Colrex) contains several ingredients, but the one to watch with CBD is the acetaminophen (Tylenol) piece. Your liver uses an enzyme called CYP2E1 to handle a small portion of acetaminophen. In test-tube studies, CBD appears to block that enzyme. In theory, blocking it could shift how acetaminophen is processed, and that's the interaction flagged here.
Here's the honest part: this has only been seen in lab studies, never reported in real people, so I wouldn't lose sleep over it. Still, since acetaminophen can stress the liver in high amounts, it's smart to stay within the recommended dose and avoid stacking other acetaminophen products. If you use CBD regularly and take Colrex often, just give your pharmacist or doctor a quick heads-up.
- 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.
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.
Cannabidiol (cbd) Also Interacts With Other Medications
Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Cannabidiol (cbd)
We haven’t checked that one against Cannabidiol (cbd) yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page lists 338 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: 18 major · 275 moderate · 45 minor.
From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page
“Someone taking Colrex is usually fighting a miserable cold, and cold season is also when people reach for herbal sleep aids and energy boosters, which is exactly where this list bites hardest. Colrex combines acetaminophen, chlorpheniramine, codeine, and phenylephrine, and 18 of its 338 supplement interactions rate major, enough to war…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction page
Where Cannabidiol (cbd) and Acetaminophen, Chlorpheniramine, Codeine, 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.
#375 of 1,452 supplements looked up here in the last 7 days
#305 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 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.
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.
No drugs match “”.
1,050 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Metronidazole ›
- Diphenhydramine ›
- Hydrocortisone ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Bupropion ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Isotretinoin ›
- Orphenadrine ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Griseofulvin ›
- Ivabradine ›
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.
- Levothyroxine ›
- Methylphenidate ›
- Ivermectin ›
- Aspirin ›
- Rosuvastatin ›
- Tirzepatide ›
- Docusate ›
- Sumatriptan ›
- Valacyclovir ›
- Hydroxyurea ›
- Metformin ›
- Semaglutide ›
- Amoxicillin ›
- Methotrexate ›
- Lisinopril ›
- Levothyroxine, Liothyronine ›
- Azithromycin ›
- Doxycycline ›
- Acyclovir ›
- Methylene Blue ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Acetylsalicylic Acid ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Insulin Degludec, Liraglutide ›
- Ezetimibe ›
- Cyclopentolate ›
- Cephalexin ›
- Thyroid Hormone ›
- Mannitol ›
- Carbidopa, Levodopa ›
- Levodopa ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Atenolol, Chlorthalidone ›
- Avatrombopag Maleate ›
- Magnesium Hydroxide (otc Drug) ›
- Spironolactone ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Mitomycin ›
- Alginic Acid, Aluminum Hydroxide ›
- Atenolol ›
- Flutemetamol F-18 ›
- Canagliflozin, Metformin ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Enalapril Maleate ›
- Levothyroxine Sodium ›
- Aspirin, Butalbital ›
- Charcoal (otc Drug) ›
- Minoxidil ›
- Acarbose ›
- Dexmethylphenidate ›
- Articaine, Epinephrine ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Peginterferon Alfa-2a, Ribavirin ›
- Atropine Methyl Nitrate, Digestive Enzymes ›
- Cefaclor ›
- Alpha-1 Proteinase Inhibitor ›
- Daunorubicin, Cytarabine ›
- Insulin Human, Sodium Chloride ›
- Daptomycin ›
Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) 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, Chlorpheniramine, Codeine, Phenylephrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine as a medicine that can lower these. This is not an interaction with Cannabidiol (cbd) — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine nutrient depletion report ›
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 Cannabidiol (cbd) and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine Together: Common Questions
Can you take Cannabidiol (cbd) with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
Why are there 6 interactions listed for Cannabidiol (cbd) and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
How serious is the Cannabidiol (cbd) and Acetaminophen, Chlorpheniramine, Codeine, 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.