Lyndsey L Anderson1,2,3, Maia G Etchart1,2, Laura MacNair4, M Hunter Land4, Irina A Mosesova4, Marcel O Bonn-Miller4, Jonathon C Arnold1,2,3. 1. Brain and Mind Centre, The University of Sydney, Sydney, Australia. 2. Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, Australia. 3. Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. 4. Canopy Growth Corporation, Smiths Falls, Ontario, Canada.
Abstract
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™, Tweed Argyle, and Spectrum Red™) that contain differing concentrations of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-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 IC50 value of Spectrum Yellow based on CBD and Δ9-THC content was 4.5 μM for CBD and 0.20 μM for Δ9-THC, and the IC50 value of Tweed Argyle was 9.3 μM for CBD and 6.0 μM for Δ9-THC. Tweed Argyle also inhibited ABCB11 transporter function with an IC50 value of 11.9 μM for CBD and 7.7 μM for Δ9-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 future in vivo DDI studies could be conducted to assess whether cannabis products affect the pharmacokinetics of medications that are ABCG2 substrates.
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™, Tweed Argyle, and Spectrum Red™) that contain differing concentrations of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-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 IC50 value of Spectrum Yellow based on CBD and Δ9-THC content was 4.5 μM for CBD and 0.20 μM for Δ9-THC, and the IC50 value of Tweed Argyle was 9.3 μM for CBD and 6.0 μM for Δ9-THC. Tweed Argyle also inhibited ABCB11 transporter function with an IC50 value of 11.9 μM for CBD and 7.7 μM for Δ9-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 future in vivo DDI studies could be conducted to assess whether cannabis products affect the pharmacokinetics of medications that are ABCG2 substrates.
Authors: J Molnár; D Szabó; R Pusztai; I Mucsi; L Berek; I Ocsovszki; E Kawata; Y Shoyama Journal: Anticancer Res Date: 2000 Mar-Apr Impact factor: 2.480
Authors: Lyndsey L Anderson; Maia G Etchart; Dilara Bahceci; Taliesin A Golembiewski; Jonathon C Arnold Journal: Sci Rep Date: 2021-07-22 Impact factor: 4.379