Cannabis-Derived Lignanamides: Potential Candidates for the Treatment of Multidrug-Resistant Cancers

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A key mechanism weaponized by cancer cells to evade chemotherapeutic treatments in patients with multidrug-resistant cancer is the overexpression of P-glycoprotein (P-gp) on their cell surfaces. In 2000, Anticancer Research published a study demonstrating a role for cannabis-derived compounds in mediating cytotoxic drug accumulation in multidrug-resistant mouse lymphoma cells. This notion was revived in a study recently published in In Silico Pharmacology. In the study, researchers looked to hemp (Cannabis sativa L.) for novel candidate compounds that inhibit the P-gp transport system. These analyses revealed that two lignanamides (also known as ‘cannabisins’) in particular – cannabisin M and cannabisin N – are likely to bind the drug-binding pocket of P-gp with higher affinity (– 10.2 kcal/mol for both compounds) than either tariquidar and zosuquidar (binding affinities of –10.1 and – 9.6 kcal/mol, respectively).

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