Journal of Molecular and Pharmaceutical Sciences
Volume 4, Numéro 2, Pages 1-13
2025-12-25
Molecular Mechanistic Evaluation Of Spermatotoxic And Mutagenic Effects Of δ⁹-tetrahydrocannabinol (thc) On The Male Reproductive System And Genomic Integrity
Authors : Edu N. Enyogor . Pius O. Adah . Bethel .c. Ateb . Henry .b. Kogbara . Elizabeth .u. Ateb . Gabriel .i. Abu . Nsude .l. Odinakachukwu . Akwagiobe .p. Abuh . Adamu Muhammed .
Abstract
Δ⁹-tetrahydrocannabinol (THC), currently reported as the major psychoactive compound in Cannabis sativa, has become increasingly consumed by young adults and adolescents globally. Despite its recreational and medicinal potential, the molecular mechanism by which THC exerts its toxic effect on male fertility and genomic stability remains partially understood. This study seeks to address this gap by investigating the biochemical and genetic pathways affected by THC in male reproductive cells using an in-silico approach. The major target protein genes responsible for spermatogenesis and mutagenic genes were identified using Gene Card, and Network pharmacology was employed to reveal the main critical pathways affected. The docking result demonstrates high binding affinities with the spermatogenic and mutagenic-related genes, ranging from -6.2 to 8.2 kcal/mol. ADMET/Tox prediction of THC shows high intestinal absorption, high blood-brain barrier penetration, and active mitochondrial toxicity, revealing its adverse effect on male fertility and genomic stability when it comes into contact with genes responsible for regulating sperm development and DNA repair. These findings profile computational evidence revealing the toxic effect of THC on the male reproductive system and therefore underscore the need for further experimental validation and future awareness to save our male counterparts
Keywords
spermatotoxicity ; mutagenicity ; Δ⁹-tetrahydrocannabinol ; molecular docking ; network pharmacology. ; Cannabis sativa ; ADMET
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