Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + 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 Delta-9-tetrahydrocannabinol (thc) can interact with; the most serious is rated moderate. Theoretically, THC 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

Delta-9-tetrahydrocannabinol (thc) and Aspirin, Codeine Phosphate, Phenobarbital

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

Why Are There 5 Interactions?

Delta-9-tetrahydrocannabinol (thc) interacts with whole categories of medication. Aspirin, Codeine Phosphate, Phenobarbital falls into 5 of those categories, so it can interact with Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) interacts with.

Theoretically, THC might have additive effects if used with other CNS depressants.
Cannabis containing THC can have CNS depressant effects. Combining THC with other CNS depressants might result in additive or synergistic 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 contains two ingredients that already slow down your brain and nervous system: codeine (an opioid pain reliever) and phenobarbital (a barbiturate sedative). THC works on receptors in your brain too, so stacking it on top can add up. The concern here is mostly theoretical, based on how these substances behave rather than firm studies, but it makes sense to take it seriously.

Together they could leave you feeling extra drowsy, foggy, dizzy, or slowed in your breathing. That's a real worry with opioids and barbiturates already on board. Driving or operating machinery would be especially risky. Please don't change anything on your own. Check in with your pharmacist or doctor first so they can guide you safely.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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).
  2. Hollister, L. E. Interactions of cannabis with other drugs in man. NIDA Res.Monogr 1986;68:110-116. DOI
  3. 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.
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 5

Aspirin, Codeine Phosphate, Phenobarbital also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, THC might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.
In vitro research shows that THC inhibits platelet aggregation.
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 (Phenaphen) contains aspirin, which is the piece that matters most here. Aspirin already works as a blood thinner by keeping your platelets from clumping together. Lab studies suggest THC may also nudge platelets in that same direction, so in theory the two together could make it a little easier to bruise or bleed, like nosebleeds, gum bleeding, or a cut that takes longer to stop.

I want to be honest about the strength of this: it is based only on test-tube research, not on real people, so it is more of a caution than a proven problem. The codeine and phenobarbital parts are not the concern for bleeding. Still, if you use THC regularly with this medicine, mention it to your pharmacist or doctor so they can keep an eye on it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Levy, R., Schurr, A., Nathan, I., Dvilanski, A., and Livne, A. Impairment of ADP-induced platelet aggregation by hashish components. Thromb.Haemost. 12-31-1976;36(3):634-640. DOI
  2. Formukong, E. A., Evans, A. T., and Evans, F. J. The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation. J.Pharm.Pharmacol. 1989;41(10):705-709.
Moderate

BARBITURATES

3 of 5

Aspirin, Codeine Phosphate, Phenobarbital also falls under BARBITURATES.

Theoretically, THC might increase the levels and adverse effects of barbiturates.
Some research shows that synthetic THC (dronabinol) increases the elimination half-life of pentobarbital by 4 hours when dosed concomitantly. Also, in animal research, THC potentiated pentobarbital-induced sleep by more than three-fold.
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 contains phenobarbital, a barbiturate, which is the piece that matters here. The concern is that THC may slow how your body clears phenobarbital and add to its sedating effect. In practice that could mean more drowsiness, dizziness, slowed breathing, or feeling foggy and uncoordinated. Keep in mind the codeine in this product is also a sedative, so layering THC on top could pile on the sleepiness.

That said, the evidence here is weak. It comes mainly from animal studies and a small finding that THC lengthened a related drug's half-life. We don't have strong human data. Still, since both phenobarbital and codeine slow you down, it's worth checking with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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).
  2. Kimura T, Takaya M, Usami N, Watanabe K, Yamamoto I. ?9-Tetrahydrocannabinol, a major marijuana component, enhances the anesthetic effect of pentobarbital through the CB1 receptor. Forensic Toxicol. 2019;37(1):207-214. DOI
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 reduce the levels and clinical effects of THC.
THC is a substrate of CYP3A4 enzymes.
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 the part of this combo pill that matters is the phenobarbital. It's a barbiturate that revs up a liver enzyme called CYP3A4, which is one of the enzymes your body uses to break down THC. By speeding that cleanup process up, phenobarbital could lower your THC levels, so you might feel less of its effect than you expect. The codeine and aspirin pieces aren't the players in this particular interaction.

Keep in mind this is a theoretical concern based on how these drugs behave, not something proven in real-world studies, so don't panic. Also worth noting: mixing THC with codeine and phenobarbital can stack up drowsiness and slowed thinking. Please loop in your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Product information for Marinol. AbbVie. North Chicago, IL 60064. August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) INDUCERS

5 of 5

Aspirin, Codeine Phosphate, Phenobarbital also falls under CYTOCHROME P450 2C9 (CYP2C9) INDUCERS.

Theoretically, drugs that are CYP2C9 inducers might decrease the levels and clinical effects of THC.
THC is a substrate of CYP2C9 enzymes.
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 with this combination product: the ingredient that matters for THC is phenobarbital. Phenobarbital is a classic enzyme booster (an inducer), and it can speed up the liver pathway (CYP2C9) that breaks down THC. In plain terms, your body may clear THC faster, so you could feel less of its effect than expected.

I want to be honest that this is a theoretical concern based on how these compounds behave in the lab, not something proven in real patients, so don't be alarmed. The bigger practical point is that phenobarbital itself is sedating, and so is THC, so the two together can stack up drowsiness, dizziness, and slowed thinking. Please loop in your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Product information for Marinol. AbbVie. North Chicago, IL 60064. August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf.

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 761 moderate, 336 minor 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 761 Minor 336 No known interaction 1,733 (incl. Aspirin, Codeine Phosphate, Phenobarbital)
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 Aspirin, Codeine Phosphate, Phenobarbital

This page covers Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc)
Top half

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

29 days ago today
Medication Aspirin, Codeine Phosphate, Phenobarbital
Top half

#1,166 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
761Moderate
336Minor
1,732No known interaction
761 Moderate 336 Minor 1,732 No interaction
Moderate

761 interactions

Showing 60 of 761 moderate interactions — see all 761 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 1,732 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 1,732 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 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
Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) and Aspirin, Codeine Phosphate, Phenobarbital Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) and Aspirin, Codeine Phosphate, Phenobarbital?
Aspirin, Codeine Phosphate, Phenobarbital 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 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.