In-silico ADME Toxicity Analysis of Impurities in Commercially Marketed Δ8-THC Products for Potential Bio-medical Applications

Abstract

Background: Δ8-Tetrahydrocannabinol (Δ8-THC) is a psychoactive cannabinoid compound naturally occurring in the Cannabis sativa plant. The commercial Δ8-THC products are typically synthesized from cannabidiol (CBD), which may lead to the formation of various impurities. These impurities may contribute to unintended pharmacological or toxicological effects, highlighting the need for comprehensive safety assessment.

Purpose: This study aims to assess the pharmacokinetic and toxicity profiles of Δ8-THC and its structurally related impurities using in silico methods, thereby providing preliminary safety insights before in vitro or in vivo experimentation.

Method: In silico ADMET predictions were performed using the pkCSM web server.

Results: All analyzed compounds possess good membrane permeability and showed favorable values for intestinal absorption. The skin permeability values were within acceptable limits, with the exception of compound 10 (log Kp value -2.443). This suggests that compound 10 may have significantly reduced dermal permeability. All compounds were also predicted to exhibit high Caco-2 cell permeability. Compounds 3, 6, 7, 8, 9 (0.704, 0.542, 0.531, 0.531, 0.648), and 11 (0.227) showed relatively low VDss values. This could influence their duration of action and tissue-specific effects. All the compounds are unlikely to penetrate the blood-brain barrier (BBB), based on predicted log BB and CNS permeability indices. Our predictions indicate that impurities 6, 7, 8, 10, and 12 have the potential to inhibit the hERG channel, flagging them as possible cardiotoxic agents.

Conclusion: Δ8-THC and its structurally related impurities exhibited favorable absorption and distribution characteristics; variations in volume of distribution and dermal permeability, particularly for compound 10, may influence their pharmacological behavior. The predicted hERG inhibition by impurities 6, 7, 8, 10, and 12 raises potential cardiotoxicity concerns. Future work should include in vitro and in vivo validation of these predictions, as well as expansion to include additional impurities formed under various synthetic and storage conditions.

  • Page Number : 1-9

  • Published Date : 2025-09-30

  • Keywords
    Δ8-THC, ADMET, Cannabinoid impurities, In-silico

  • DOI Number
    10.15415/jmrh.2025.112001

  • Authors
    Munagala Alivelu and Natte Kavitha

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