Open AccessIn Vitro Screening of Three Commercial Cannabis-Based Products on ATP-Binding Cassette and Solute-Carrier Transporter Function
Author(s) -
Lyndsey L. Anderson,
Maia G. Etchart,
Laura MacNair,
M Hunter Land,
Irina Mosesova,
Marcel O. BonnMiller,
Jonathon C. Arnold
Publication year - 2022
Publication title -
cannabis and cannabinoid research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.156
H-Index - 17
eISSN - 2578-5125
pISSN - 2378-8763
DOI - 10.1089/can.2020.0053
Subject(s) - cannabis , pharmacology , atp binding cassette transporter , transporter , drug , cannabidiol , chemistry , biology , biochemistry , medicine , psychiatry , gene
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 Δ 9 -tetrahydrocannabinol (Δ 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 Δ 9 -THC content was 4.5 μM for CBD and 0.20 μM for Δ 9 -THC, and the IC 50 value of Tweed Argyle was 9.3 μM for CBD and 6.0 μM for Δ 9 -THC. Tweed Argyle also inhibited ABCB11 transporter function with an IC 50 value of 11.9 μM for CBD and 7.7 μM for Δ 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 future in vivo DDI studies could be conducted to assess whether cannabis products affect the pharmacokinetics of medications that are ABCG2 substrates.