Cannabis and Acetaminophen And Codeine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Cannabis
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Your medicine acetaminophen with codeine contains an opioid pain reliever (codeine). Opioids calm down your brain and nervous system, which can make you feel sleepy, slow your breathing, and cloud your thinking. Cannabis can do many of the same things.
When you use both together, those calming effects can add up. You might feel more drowsy, dizzy, or foggy than expected, and in a big way this could slow your breathing. This concern is based on how these substances work rather than on strong studies, so the real-world risk varies a lot depending on the cannabis product. The good news is your care team can manage this by tailoring your doses and keeping a closer eye on you. Please talk with your pharmacist or doctor before combining them.
Effect: Additive CNS depression when cannabis (especially high-THC products) is combined with the codeine component of acetaminophen/codeine.
- Mechanism: Pharmacodynamic, additive CNS and respiratory depression. No specific enzyme/prodrug issue drives this interaction (though codeine is a CYP2D6-activated prodrug, the concern here is additive PD sedation).
- Direction/magnitude: Potentiated sedation, psychomotor impairment, and respiratory depression risk; magnitude highly variable given cannabis product variability (THC:CBD ratio, potency, route).
- Onset: Unspecified. Evidence: Theoretical.
- Management: Avoid high-THC cannabis with psychoactive drugs. If co-use is necessary, adjust CNS depressant dosage, individualize, and monitor for sedation/respiratory status.
What happens
An increased risk of CNS depression
Interaction Deep Dive
Concomitant use of cannabis with other CNS depressants (eg, opioids, alcohol, or sedative/hypnotics) may lead to potentiated CNS depressant effects. Avoid use of cannabis containing primarily delta-9-tetrahydrocannabinol (THC), especially in high levels, in patients receiving concomitant psychoactive drugs. Expect the clinical significance of cannabis drug interactions to vary due to the wide variability of cannabis products (eg, potencies, THC and cannabidiol [CBD] ratios, dosage ranges, and administration routes) and populations using cannabinoids1. If concomitant use is necessary, adjust dosage of CNS depressant and, if possible, monitor drug levels 2.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking your prescribed acetaminophen with codeine as directed, and do not stop it on your own. The main step is to bring up any cannabis use with your pharmacist or prescriber so it can be managed safely.
- Your care team may adjust and individualize your opioid dose and monitor you more closely if both are used.
- Higher-THC products carry more of this additive sedation risk, so this is worth discussing.
- Watch for excess drowsiness, confusion, dizziness, or slowed breathing, and seek help promptly if these occur.
- Avoid adding alcohol or other sedatives on top.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Cannabis and Acetaminophen And Codeine together?
Combining cannabis with acetaminophen/codeine can add up to more drowsiness and slowed breathing, so tell your pharmacist or doctor so they can adjust your dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cannabis and Acetaminophen And Codeine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Cannabis and Acetaminophen And Codeine interaction managed?
Keep taking your prescribed acetaminophen with codeine as directed, and do not stop it on your own. The main step is to bring up any cannabis use with your pharmacist or prescriber so it can be managed safely. Your care team may adjust and individualize your opioid dose and monitor you more closely if both are used. Higher-THC products carry more of this additive sedation risk, so this is worth di… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Cannabis or Acetaminophen And Codeine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Page RL II, Allen LA, Kloner RA, et al: Medical marijuana, recreational cannabis, and cardiovascular health: a scientific statement from the American Heart Association. Circulation 2020; 142(10):e131-e152. PubMed
- Caicedo DA, Perez-Mana C, Farre M, et al: An overview of the potential for pharmacokinetic interactions between drugs and cannabis products in humans. Pharmaceutics 2025; 17(3):319. PubMed
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