Delta-9-tetrahydrocannabinol (thc) - Acetaminophen, Butalbital, Caffeine, Codeine Interaction
Herbal: Delta-9-tetrahydrocannabinol (thc)
Also Known As: BHO, Black Glass, Budder, Butane Hash Oil, Butane Honey Oil, Butter, Dabs, Delta-9 Tetrahydrocannabinol, Delta-9 THC, Delta-9-THC, Dronabinol, Honeycomb
Drug: Acetaminophen, Butalbital, Caffeine, Codeine
Brand names:
Esgic with Codeine, Fioricet w/ Codeine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 04, 2025
Interaction Details
Acetaminophen, Butalbital, Caffeine, Codeine is classified as belonging to the following category: Cns Depressants
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.
Interaction Rating
Likelihood of Occurrence
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
References
- 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.
- 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.
Interaction Details
Acetaminophen, Butalbital, Caffeine, Codeine is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates
Theoretically, THC may increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that cannabis containing THC might modestly inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. It is unclear if this effect is due to THC, other constituents, or the combination. In vitro research also shows that cannabis extracts containing THC modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids cannabidiol (CBD) or cannabigerol (CBG) alone had stronger inhibitory effects than extracts containing both THC and CBD. Conversely, a crossover clinical study in healthy adults shows that oral THC does not inhibit CYP3A4.
Interaction Rating
Likelihood of Occurrence
UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
References
- 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
- 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.
- Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Interaction Details
Acetaminophen, Butalbital, Caffeine, Codeine is classified as belonging to the following category: Cytochrome P450 2E1 (Cyp2E1) Substrates
Theoretically, THC might decrease the levels and clinical effects of CYP2E1 substrates.
In vitro research shows that cannabis containing THC can induce the activity of CYP2E1, which might increase the metabolism of CYP2E1 substrates. It is unclear if this effect is due to THC, other constituents, or the combination.
Interaction Rating
Likelihood of Occurrence
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
References
- 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.
Interaction Details
Acetaminophen, Butalbital, Caffeine, Codeine is classified as belonging to the following category: 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.
Interaction Rating
Likelihood of Occurrence
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
References
- 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).
- 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.
Delta-9-tetrahydrocannabinol (thc) Overview

Delta-9-tetrahydrocannabinol (thc) - More Interactions
Delta-9-tetrahydrocannabinol (thc) interacts with 1070 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
Unknown | No interactions have been reported or no interaction data is currently available. |
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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.
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Drug descriptions are provided by MedlinePlus.