Daily Dose Q&A

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.

2026-01-15

THC inhibits the cytochrome P450 enzyme CYP2C9. What commonly used drugs are substrates of CYP2C9? What's the potential clinical impact?

Some of the commonly used medications metabolized by CYP2C9 include: antidepressants, antiepileptics, proton pump inhibitors and warfarin. THC's inhibition of CYP2C9 may increase bioavailability and increase adverse effects of these substrates.

Brown, J. D. (2020). Potential adverse drug events with tetrahydrocannabinol (THC) due to drug-drug interactions. Journal of Clinical Medicine, 9(4), 919. https://doi.org/10.3390/jcm9040919

2026-01-14

What are the risks and limitations of oral administration?

While oral administration offers a smoke-free delivery route, there are several limitations associated with the oral administration of cannabinoids. Delayed onset of action can lead to dose stacking (repeated dosing before the initial dose has taken effect). Dose stacking may result in unanticipated intoxication and adverse reactions. Slow and erratic absorption, first-pass metabolism (which results in psychoactive metabolites), and variable gut bioavailability complicate dosing predictability Oral intake may be unsuitable for patients who are experiencing nausea and vomiting or have difficulty in swallowing

Grotenhermen, F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics, 42(4), 327-360. https://doi.org/10.2165/00003088-200342040-00003 Slawek, D. E., Curtis, S. A., Arnsten, J. H., & Cunningham, C. O. (2022). Clinical approaches to cannabis: A narrative review. Medical Clinics of North America, 106(1), 131-152. https://doi.org/10.1016/j.mcna.2021.08.004

2026-01-13

How does tolerance to cannabis develop?

Tolerance arises from repeated exposure causing physiologic adaptations such as CB1 receptor desensitization, downregulation, and altered signaling within the endocannabinoid system.

Huestis, M. A. (2007). Human cannabinoid pharmacokinetics. Chemistry & Biodiversity, 4(8), 1770-1804. https://doi.org/10.1002/cbdv.200790152. Zamarripa, C. A., Vandrey, R., & Spindle, T. R. (2022). Factors that impact the pharmacokinetic and pharmacodynamic effects of cannabis: A review of human laboratory studies. Current Addiction Reports, 9(4), 608-621. https://doi.org/10.1007/s40429-022-00429-4

2026-01-12

Compare the bioavailability of rectal administration of THC to that of oral THC.

THC administered via rectal suppository avoids first-pass metabolism through the liver, making it more bioavailable than orally administered THC. In fact, in human studies, Brenneisen et al. found that the bioavailability of the rectal route was approximately twice that of the oral route due to a higher degree of absorption and less first-pass metabolism.

Brenneisen, R., Egli, A., ElSohly, M. A., Henn, V., & Spiess, Y. (1996). The effect of orally and rectally administered delta-9-tetrahydrocannabinol on spasticity: A pilot study with two patients. International Journal of Clinical Pharmacology and Therapeutics, 34(10), 446-452. ElSohly, M. A., Little, T. L., Jr., Hikal, A., Harland, E., Stanford, D. F., & Walker, L. (1991). Rectal bioavailability of delta-9-tetrahydrocannabinol from various esters. Pharmacology Biochemistry and Behavior, 40(3), 497-502. https://doi.org/10.1016/0091-3057(91)90356-4