Medicinal Cannabis and Drug-Drug Interactions
Like a wide variety of medications, medicinal cannabis (also known as marijuana), is broken down by the cytochrome p450 (CYP450) enzymes in the liver. The two major cannabinoids, THC and CBD are reported to be broken down by CYP3A4 and CYP2C9, while CBD, but not THC, is also metabolised by CYP2C19 (2). Certain medications that inhibit or induce these enzymes may therefore lead to unwanted side effects when taken in combination with medicinal cannabis.
- Substances that inhibit CYP3A4 and CYP2C9 can increase the bioavailability of THC: eg. macrolides, antimycotics, calcium antagonists, HIV protease inhibitors, amiodarone and isoniazid (2).
- Drugs that induce CYP3A4 and CYP2C9 may decrease the bioavailability of THC: eg. rifampicin, carbamazepine, phenobarbital, phenytoin, primidone, rifabutin, and troglitazone (2).
- THC, CBD, and CBN inhibit CYP1A1, CYP1A2 and CYP1B1 and may increase bioavaliabilty of amitryptiline, phenacetin, theophylline, granisetron, dacarbazine, and flutamide (3).
In a study investigating the interaction between cannabinoids and opioids, no statistically significant changes in the AUC for morphine or oxycodone were reported. A decrease in the Cmax of morphine sulfate was observed, however, cannabis was still reported to have an average pain reduction of 27% (4). CBD, believed to be efficacious in the treatment of seizures, has also been reported to interact with antiepileptic drug (AEDs) through CYP metabolism. In an abstract presented by the American Epilepsy Society Annual Meeting, serum AED levels were measured during active titration of CBD in refractive epilepsy patients enrolled in an open label study. Increase in the serum levels of rufinamide (p < 0.01), topiramate (p < 0.01), and desmethyclobazam (p < 0.01, active metabolite of clobazam), and a decrease in the levels of clobazam (p < 0.01) was seen with increasing CBD dose in the combined pediatric and adult arms. Furthermore, a significant increase in serum levels of zonisamide (p=0.02) and eslicarbazepine (p=0.04) with increasing CBD dose was seen in the adult arm only. No significant interactions were observed between CBD and the other AEDs investigated, which included valproate, levetiracetam, lacosamide, and perampanel (5).
More information about medical cannabis products can be viewed by healthcare professionals on the CannabisAcess portal.
- Lemberger L, Axelrod J, Kopin IJ. Metabolism and disposition of delta-9-tetrahydrocannabinol in man. Pharmacol Rev. 1971;23:371–380.
- Office of Medicinal Cannabis. Medicinal Cannabis, Information for Health Care Professionals. The Netherlands; Ministry of Health, Welfare and Sports, 2008.
- Yamaori, S., Kushihara, M., Yamamoto, I., and Watanabe, K. (2010). Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem.Pharmacol. 79: 1691-1698.
- Abrams, Couey, Shade, Kelly and Benowitz. Cannabinoid–Opioid Interaction in chronic Pain. Nature. Vol. 90 N0. 6
- Gaston, T, Liu, Y, Cutter, G, Bebin, E, & Szaflarski, J. (2016). Drug interactions between pharmaceutical grade cannabidiol (CBD) oil and commonly used anti-epileptic drugs (AEDs). Presented at the 2016 American Epilepsy Society Annual Meeting, Abstract 2.208. https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2421615