In VitroScreening of Three Commercial Cannabis-Based Products on ATP-Binding Cassette and Solute-Carrier Transporter Function

Introduction:Legalization of medicinal cannabis around the world has led to an increase in the use of commercial cannabis-based products in the community. These cannabis-based products are being used in combination with conventional drugs to treat a variety of health conditions. Moreover, recreational cannabis-based products may be used in combination with other drugs. In this setting, there is increased potential for drug-drug interactions (DDIs) involving commercial cannabis-based products. Since DDIs can lead to serious adverse events, drug regulatory bodies require that every investigational drug be evaluated for DDI potential at metabolic enzymes and transporters. However, this seldom occurs for cannabis-based products due to legislation in many jurisdictions allowing a direct pathway to market. This study aimed to examine the inhibitory potential of three commercially available cannabis-based products at human ATP-binding cassette (ABC) and solute-carrier (SLC) transporters. Materials and Methods:Three commercial cannabis-based products (Spectrum Yellow (TM), Tweed Argyle, and Spectrum Red (TM)) that contain differing concentrations of cannabidiol (CBD) and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) were evaluated for DDI potential at 12 drug transporters. HEK293 cells or vesicles expressing human ABC transporters (ABCB1, ABCC2, ABCG2, or ABCB11) and SLC transporters (SLC22A1, SLC22A2, SLC22A6, SLC22A8, SLCO1B1, SLCO1B3, SLC47A1, and SLC47A2) were used to measure transporter function. Results:Spectrum Yellow and Tweed Argyle inhibited ABCG2 transporter function. The IC(50)value of Spectrum Yellow based on CBD and Delta(9)-THC content was 4.5 mu M for CBD and 0.20 mu M for Delta(9)-THC, and the IC(50)value of Tweed Argyle was 9.3 mu M for CBD and 6.0 mu M for Delta(9)-THC. Tweed Argyle also inhibited ABCB11 transporter function with an IC(50)value of 11.9 mu M for CBD and 7.7 mu M for Delta(9)-THC. SLC22A6, SLC22A1, SLC22A2, SLCO1B1, and SLCO1B3 transporter functions were modestly inhibited by high concentrations of the cannabis-based products. The three cannabis-based products did not inhibit ABCB1, ABCC2, SLC47A1, SLC47A2, or SLC22A8 transporters. Discussion:Novel findings were that the cannabis-based products inhibited ABCB11, SLC22A6, SLC22A1, SLC22A2, SLCO1B1, and SLCO1B3 (although modestly in most instances). Spectrum Yellow and Tweed Argyle potently inhibited ABCG2, and futurein vivoDDI studies could be conducted to assess whether cannabis products affect the pharmacokinetics of medications that are ABCG2 substrates.

Automated summary

The legalization of medicinal cannabis has led to increased use of commercial cannabis-based products, which can potentially interact with other drugs. This study evaluated the inhibitory potential of three commercially available cannabis-based products on human transporters and found that some of these products can inhibit transporter function.