Drug & supplement interaction

Cannabidiol (cbd) + Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, Phenobarbital brand name: Phenaphen.

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

Aspirin, Codeine Phosphate, Phenobarbital falls into 5 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 report
SeverityModerate
LikelihoodPossible
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Aspirin, Codeine Phosphate, Phenobarbital

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Aspirin, Codeine Phosphate, Phenobarbital falls into 5 of those categories, so it can interact with Cannabidiol (cbd) in 5 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 5

Why this applies to Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, Phenobarbital falls under CNS DEPRESSANTS — the group Cannabidiol (cbd) interacts with.

Theoretically, cannabidiol might have additive effects if used with other CNS depressants.
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.
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 pill pairs aspirin with two ingredients that calm the brain: codeine (an opioid) and phenobarbital (a barbiturate). CBD's main concern here is the codeine and phenobarbital pieces. Both already slow down the nervous system, and early research suggests CBD can add a sedating, drowsy effect of its own. Stacking them together could deepen sleepiness, dizziness, foggy thinking, or slowed breathing, especially at higher CBD doses.

To be fair, this is a theoretical caution based on how these drugs work, not strong human studies, so it may not be a big deal for everyone. Still, since phenobarbital is potent and breathing-related effects are no joke, I'd run it by your pharmacist or doctor before combining them, and don't drive until you know how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol 1981;21(8-9 Suppl):417S-27S. PubMed
  2. Monti JM. Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology (Berl) 1977;55(3):263-5. PubMed
  3. Pickens JT. Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content. Br J Pharmacol 1981;72(4):649-56.
  4. 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
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 5

Aspirin, Codeine Phosphate, Phenobarbital also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2D6.
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.
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 contains codeine, and codeine is a bit different from most drugs. Your body has to convert codeine into morphine using an enzyme called CYP2D6 before it can really relieve pain. In the lab, CBD looks like it might block that same enzyme. If that happened in real life, you'd expect less pain relief from the codeine, not more, because less of it gets turned into the active form.

Here's the reassuring part: this is only a theory from test-tube research. A human study showed CBD did not actually block a similar CYP2D6 medicine. So a real-world problem is unlikely, but since this product also carries aspirin and phenobarbital, it's worth a quick chat with your pharmacist before mixing in CBD.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. 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
  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.
Moderate

CYTOCHROME P450 2C19 (CYP2C19) INDUCERS

3 of 5

Aspirin, Codeine Phosphate, Phenobarbital also falls under CYTOCHROME P450 2C19 (CYP2C19) INDUCERS.

Theoretically, CYP2C19 inducers might decrease cannabidiol levels.
Cannabidiol is a substrate of CYP2C19 enzymes. Theoretically, drugs that induce CYP2C19 enzymes might decrease the levels and effects of cannabidiol.
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 key thing to understand: with this combo, it's the medicine affecting the CBD, not the other way around. This product contains phenobarbital, which is a known enzyme booster (it speeds up an enzyme called CYP2C19). Since your body uses that same enzyme to break down CBD, taking them together could clear the CBD out faster and leave you with less of it on board. In plain terms, your CBD may simply not work as well.

The good news is this is a theoretical concern based on how the drugs behave in the body, not something proven in studies, so don't be alarmed. Your aspirin and codeine effects shouldn't change from this. If you rely on CBD for a real reason, just mention it to your pharmacist so they can help you watch for reduced benefit.

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 3A4 (CYP3A4) INDUCERS

4 of 5

Aspirin, Codeine Phosphate, Phenobarbital also falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS.

Theoretically, CYP3A4 inducers might decrease cannabidiol levels.
Cannabidiol is a substrate of CYP3A4 enzymes. Theoretically, drugs that induce CYP3A4 enzymes might reduce the levels and effects of cannabidiol.
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 thing to know about this combination product (aspirin, codeine, and phenobarbital): it's the phenobarbital piece that matters for CBD. Phenobarbital is a well-known booster, or 'inducer,' of a liver enzyme called CYP3A4, which is one of the pathways your body uses to break down CBD. So when these are taken together, your body may clear the CBD faster, leaving less of it in your system and making it work less well.

This one is theoretical, based on how the drugs behave rather than solid human studies, so I don't want you to be alarmed. The aspirin and codeine parts aren't the concern here. If you use a CBD product regularly, just mention it to your pharmacist or doctor so they can keep an eye on whether your CBD seems to be doing its job.

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 2B6 (CYP2B6) SUBSTRATES

5 of 5

Aspirin, Codeine Phosphate, Phenobarbital also falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES.

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2B6.
In vitro research shows that cannabidiol inhibits CYP2B6. However, this interaction has yet to be reported in humans. Until more is known, use with caution. Theoretically, concomitant use of cannabidiol with CYP2B6 substrates might increase the risk for adverse effects from these 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 pill includes phenobarbital, which your body partly clears using an enzyme called CYP2B6. In test tube studies, CBD appears to slow that enzyme down. The thinking is that if phenobarbital is broken down more slowly, it could build up in your system. That might mean more sedation than usual, so think extra drowsiness, dizziness, slowed breathing, or feeling groggy. The codeine piece can add to that sleepiness too.

Here's the honest part: this is only a theoretical concern from lab work, and it hasn't actually been seen in real people yet. Phenobarbital is a medicine where even small changes matter, though, so I wouldn't wing it. Please check with your pharmacist or doctor before pairing these, rather than starting or stopping anything yourself.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Maeda C, Yamamoto I, Watanabe K. Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids. Forensic Toxicol 2011;29:117-24. DOI
  2. 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 Aspirin, Codeine Phosphate, Phenobarbital 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. Aspirin, Codeine Phosphate, Phenobarbital)
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 Aspirin, Codeine Phosphate, Phenobarbital

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Codeine Phosphate, Phenobarbital page lists 352 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 Danshen (major).

By severity: 12 major · 304 moderate · 36 minor.

From our pharmacist’s overview on the Aspirin, Codeine Phosphate, Phenobarbital page

“Alcohol is the entry I would flag first with Phenaphen (aspirin, codeine phosphate, phenobarbital): beer or wine layered onto codeine and phenobarbital can deepen sedation and, at worst, slow breathing. This medication deserves real caution with supplements.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Codeine Phosphate, Phenobarbital interaction page

How much people look this up

Where Cannabidiol (cbd) and Aspirin, Codeine Phosphate, Phenobarbital 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

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

29 days ago today
Medication Aspirin, Codeine Phosphate, Phenobarbital
Top 25%

#332 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 Aspirin, Codeine Phosphate, Phenobarbital, 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 Aspirin, Codeine Phosphate, Phenobarbital supplement interactions › Every supplement checked against Aspirin, Codeine Phosphate, Phenobarbital, 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 Aspirin, Codeine Phosphate, Phenobarbital Together: Common Questions

Can you take Cannabidiol (cbd) with Aspirin, Codeine Phosphate, Phenobarbital?
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 5 interactions listed for Cannabidiol (cbd) and Aspirin, Codeine Phosphate, Phenobarbital?
Aspirin, Codeine Phosphate, Phenobarbital 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 Aspirin, Codeine Phosphate, Phenobarbital 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.