Daily Dose Q&A
2026-01-23
What cytochrome p450 isoenzymes are induced by the polyaromatic hydrocarbons found in cannabis smoke?
Polyaromatic hydrocarbons present in cannabis smoke, as well as in tobacco smoke, have been shown to induce CYP1A2 activity. This enzyme induction can increase the clearance of drugs metabolized by CYP1A2, potentially leading to reduced plasma concentrations and reduced therapeutic efficacy. For example, chlorpromazine and other typical antipsychotics are metabolized by CYP1A2. In one study, cannabis smokers exhibited a 50% increase in chlorpromazine clearance, while individuals who smoked both cannabis and tobacco experienced an even greater increase of 107%. Similarly, patients who reported smoking cannabis demonstrated greater clearance of theophylline, (also a CYP1A2 substrate), compared with those who did not smoke cannabis. There is no evidence that orally consumed cannabis induces CYP1A2 activity. Jusko, W. J., Schentag, J. J., Clark, J. H., Gardner, M., & Yurchak, A. M. (1978). Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clinical Pharmacology & Therapeutics, 24(4), 406-410. https://doi.org/10.1002/cpt1978244406
Lopera, N. C., Ruiz, J. A., Rojas, C. A., & Manrique-Abril, F. G. (2023). Cannabinoids and the endocannabinoid system: An overview of their potential role in clinical practice. Frontiers in Pharmacology, 14, 1123457. https://doi.org/10.3389/fphar.2023.1123457
Stout SM, Cimino NM. (2014) Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: A systematic review. Drug Metab Rev Feb;46(1):86-95.
2026-01-22
Are there any risks associated with the co-administration of CBD and amitriptyline?
When CBD is administered with amitriptyline, the risk of adverse effects such as anticholinergic syndrome, sedation, and QT interval prolongation may increase. Balachandran, P., Elsohly, M., & Hill, K. P. (2021). Cannabidiol interactions with medications, illicit substances, and alcohol: A comprehensive review. Journal of General Internal Medicine. https://doi.org/10.1007/s11606-020-06504-8
2026-01-21
Does chronic cannabis smoking impact Theophylline levels?
Yes. Chronic cannabis smoking induces CYP1A2. As a result, the clearance of theophylline (and of aminophylline) is increased. Keep in mind that theophylline and aminophylline have a narrow therapeutic index. Huestis, M. A. (2007). Human cannabinoid pharmacokinetics. Chemistry & Biodiversity, 4(8), 1770-1804. https://doi.org/10.1002/cbdv.200790152.
2026-01-20
CBD may inhibit the cytochrome P450 enzyme CYP2C19. Does that pose an issue for patients who take CBD along with methadone?
Yes. Methadone is metabolized by CYP2C19. If CYP2C19 activity is inhibited, the concentration of methadone will increase, and the combination of CBD and methadone may lead to an increase in sedation. Madden, K., Tanco, K., & Bruera, E. (2020). Clinically significant drug-drug interaction between methadone and cannabidiol. Pediatrics, 145(5), e20194001. https://doi.org/10.1542/peds.2019-4001
2026-01-16
CBD may inhibit the cytochrome P450 enzyme CYP2C19. Does that pose an issue for patients who take CBD along with warfarin?
Yes. Warfarin has a narrow therapeutic window, and the inhibition of CYP2C19 by CBD can increase levels of warfarin. Multiple reports have indicated that the pharmacokinetic interaction between warfarin and CBD results in a greatly increased risk of bleeding.Treese, N. M., & Flowers, M. (2020). Pharmacist's guide to CBD oil. U.S. Pharmacist, 45(3), 20-23.