The Potential Clinical Implications and Importance of Drug Interactions Between Anticancer Agents and Cannabidiol in Patients With Cancer

Abstract

<jats:p> The objective of this review was to identify and examine the pharmacokinetic and pharmacodynamic interactions between cannabidiol (CBD)-only products, such as CBD oil, and anticancer agents. A literature search of PubMed (1980 to September 2018) and the Cochrane Collection (1980 to September 2018) was performed using the following search terms: “cannabidiol,” “cancer,” “cannabis,” “marijuana,” and “interaction,” as well as any combination of these terms. Literature was excluded if it did not appear in the search when limited to the “full text” filter on PubMed, if it was not published in the English language, or if it did not explore potential pharmacodynamic or pharmacokinetic interactions of CBD and anticancer agents. There were 10 studies that met these inclusion criteria. The majority of the facts regarding the interactions with CBD were found using in vitro studies and the true in vivo implications are not well-known. Minimal data were available regarding the interactions between CBD and anticancer agents. However, pharmacists should always consider the possibility of interactions and their consequences whenever they are aware of a patient using CBD products. </jats:p>

Adverse events following cannabis for medical use in Tuscany: An analysis of the Italian Phytovigilance database

“…Moreover, CBD inhibits P‐glycoprotein mediated transports in a dose‐dependent manner . Established cannabis‐related DDIs involve THC and psychotropic agents, CBD and anticancer agents, CBD and gabapentin, and cannabinoids and warfarin . In general, clinicians should always take into account that medical cannabis could bidirectionally interact with concomitant administered agents by affecting membrane transporters and/or metabolising enzymes …”

Reduction in Tamoxifen Metabolites Endoxifen and N-desmethyltamoxifen With Chronic Administration of Low Dose Cannabidiol: A CYP3A4 and CYP2D6 Drug Interaction

“…As CBD is being utilized more commonly as a therapeutic agent to treat cancer pain, the potential for drug interactions with other anticancer agents is highly probable. 4 In the case of this patient, the significance of this interaction was not clinically relevant, as the patient possessed an ultra-rapid metabolic profile (CYP 2D6 *1/*1 copy number variation—3 N), which resulted in therapeutic endoxifen levels despite the presence of CBD inhibition of CYP2D6 and 3A4/5. However, the potential for a CYP2D6 interaction with CBD may be particularly meaningful if a patient possesses an intermediate or poor CYP2D6 metabolic profile.…”

“…[1][2][3] It has been theorized that tetrahydrocannabinol (THC) and cannabidiol (CBD) have the potential for significant drug interactions, complicating drug therapy in conditions such as cancer. 4 Unlike THC, CBD interacts more extensively with the cytochrome P450 system. As noted in several in vitro studies, CBD acts as an inhibitor of enzymes 2C9, 2C19, 2D6, 3A4 and also potentially inhibits or induces CYP 1A2 and 2B6 respectively.…”

“…1-3 It has been theorized that tetrahydrocannabinol (THC) and cannabidiol (CBD) have the potential for significant drug interactions, complicating drug therapy in conditions such as cancer. 4…”

Potential Pharmacokinetic Drug-Drug Interactions between Cannabinoids and Drugs Used for Chronic Pain

“…CBD is not only a substrate but also an inhibitor of CYP450 enzymes and UGTs. In addition, some isoenzymes of the cytochrome P450 system or UGTs are also subjected to inhibition by THC and CBN [11,[15][16][17][18][19][20][21][22][23][24][25].…”