CBD and Drug Interactions

Cannabidiol (CBD) is the major non-intoxicating and non-psychotropic phytocannabinoid found in cannabis plants. It has many potential therapeutic effects for a broad range of disorders, including anxiety, depression, chronic pain, epilepsy and inflammation among others. [1] Like other molecules, CBD has been found to potentially interact with pharmaceuticals like anti-epileptics, antidepressants, opioid analgesics, and also other common medications such as paracetamol or substances such as alcohol. [1] It’s important to note that drug-drug interactions are often dose dependent, so only high compound concentrations and combinations may cause any negative effects.

CBD is mainly metabolized in the liver by the cytochrome (CYP) P450 family and in particular by the isozymes CYP3A4 and CYP2C19. [2] Because this class of enzymes is involved in the uptake of many medications, CBD administration can have an influence on other drugs absorption. The inhibition of CYP3A4 enzymes by drugs like ketoconazole, ritonavir, itraconazole and clarithromycin can lead to increased levels of CBD in the body for a long period of time, slower CBD metabolism and a higher chance of adverse effects. On the other hand, drugs like phenobarbital, carbamazepine, rifampicin, and phenytoin nduce CYP3A4 activity leading to reduced CBD bioavailability thus lower perceived CBD beneficial effects. A similar and often more worrying effect can be on the drug levels: CBD may inhibit the enzymes, leading to higher rates of medications in the body, for a longer time.

[1] Other possible drug-drug interactions are linked to CBD targets that can be modulated also by other medicaments. Among CBD targets there are cannabinoid receptors type 1 and 2 (CB1, CB2), serotonin 1A (5-HT1A) receptors, transient receptor potential cation channel subfamily V member 1 (TRPV1) and more. [3] Every drug that shares the same CBD mechanism of action or that is an agonist, antagonist, modulator or blocker of these targets can lead to an interaction.

So far, most findings on this important issue come from in vitro studies or preclinical animal data, and more research should be done in order to translate the results into clinical trials, ultimately leading to a better understanding of the actual mechanisms of CBD-drug interactions.
As with most treatments involving cannabis, its good practice to start with low CBD dosages and increase progressively the amount, in order to monitor our body sensitivity to the compound, and also the possible effects from the interactions with other medicaments. The safety profile of CBD in relation to other commonly taken medicines is very high, and usually, even if there could be a possible CBD-drug interaction, simply taking them two or three hours apart can solve the problem.

Bottom line: there may be an interaction between the CBD and other medications you’re taking, usually this can be taken care of relatively easily, but always consult your physician about possible drug-drug or drug-cannabis interactions.

 

References:

[1] Balachandran P, Elsohly M, Hill KP. Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review. J Gen Intern Med. 2021 Jul;36(7):2074-2084. doi: 10.1007/s11606-020-06504-8.

[2] Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K. Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci. 2011;89(5-6):165–170.

[3] https://go.drugbank.com/drugs/DB09061/biointeractions#target-tab