Structural changes of tubulin by interacting with Δ9-tetrahydrocannabinol: in-vitro and theoretical studies

Abstract Background There is growing evidence of the contribution of microtubule dynamics to dendritic spine changes, synaptic plasticity, axonal transportation, and cell polarity. Besides, one of the well-studied effects of Cannabis on human behavior is memory disability. As Δ9-tetrahydrocannabinol (Δ9-THC) is the most pivotal chemical of Cannabis, we investigated the effect of Δ9-THC on microtubule dynamicity and the structural study of tubulin (microtubule monomer). Results Our results show that Δ9-THC changes microtubule dynamicity compared to the control group. The turbidity assay results demonstrated that Δ9-THC reduces microtubule polymerization in a concentration-dependent manner. Circular Dichroism spectroscopy also studied the structural changes of the purified tubulin, which revealed significant changes in the secondary structure of the tubulin. Furthermore, Silico studies predicted one binding site for Δ9-THC on β-tubulin. Conclusions We concluded that Δ9-THC could reduce the microtubule’s stability, which may conversely affect brain function by microtubule dynamic changes caused by secondary structural changes of tubulin and preventing tubulin-tubulin interaction.