Concerns Over Cannabis-Medication Interactions

Emerging Acceptance and Legalization

As cannabis use becomes increasingly accepted and gains international legalization, concerns have arisen regarding its interactions with commonly prescribed medications. These interactions, known as contraindications, have prompted further investigation into how cannabis derivatives impact the body.

Study on Cannabis and Prescription Drugs

Researchers at Washington State University have conducted the first study to demonstrate that cannabis can significantly interfere with prescription medications. The findings were published in the journal Drug Metabolism and Disposition.

Effects of Cannabinoid Metabolites

Interaction with P450 Enzymes

The study focused on the interactions between cannabinoid metabolites and hepatic (liver) P450 enzymes, which are crucial for metabolizing drugs and preventing toxic accumulation. The primary cannabinoids examined include (-)-trans-∆9-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD). During metabolic breakdown, these cannabinoids are converted into metabolites, with THC metabolites remaining in the bloodstream at higher concentrations for extended periods. This prolonged presence increases the likelihood of interference with other medications taken days after cannabis consumption.

Inhibition of Enzyme Activity

Using enzyme kinetic methods, researchers analyzed how cannabinoid metabolites affect P450 enzyme activity. All three cannabinoids—THC, CBN, and CBD—demonstrated competitive inhibition patterns on select P450 enzymes. Competitive inhibition occurs when metabolites block the active site of enzymes, preventing them from metabolizing other drugs. This can lead to drug accumulation and potential toxicity, particularly for medications such as anti-cancer drugs metabolized by these enzymes.

THC was found to competitively inhibit CYP1A2, CYP2B6, CYP2C9, and CYP2D6, reducing their activity by approximately 50% with 10 micromolar of THC. Similarly, CBN inhibited CYP2B6, CYP2C9, and CYP2E1, reducing their activity to 75%, 55%, and 80%, respectively. CBD also showed competitive inhibition, decreasing the activity of CYP3A4, CYP2B6, CYP2C9, CYP2D6, and CYP2E1 by more than 50% with 10 micromolar.

Risks for Patients with Kidney Disease

Impact on Kidney Function

CBD was noted to block three enzymes responsible for 95% of kidney UGT metabolism. According to Philip Lazarus, the study’s senior author, patients with kidney disease who consume cannabis may inhibit normal kidney function, potentially resulting in long-term health effects.

Lazarus emphasized the need for physicians to recognize the potential for toxicity or diminished therapeutic effects when patients use cannabinoids. He remarked, “It’s one thing if you’re young and healthy and smoke cannabis once in a while, but for older individuals using medications, taking CBD or medicinal marijuana may negatively impact their treatment.”

Need for Further Research

Additional research is necessary to fully understand the mechanisms underlying cannabis drug-drug interactions in the body.

References

Nasrin, S. et al. Cannabinoid metabolites as inhibitors of major hepatic CYP450 enzymes, with implications for cannabis-drug interactions. Drug Metabolism and Disposition; 49(12): 1070-1080. Doi: 10.1124/dmd.121.000442.
Van Dongen, J. (2021). Cannabis use could cause harmful drug interactions. EurekAlert! Accessed 16 Dec. 2021. Retrieved from https://www.eurekalert.org/news-releases/937642.