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

## TL;DR

This study shows that Δ9-THC, a compound in cannabis, affects microtubule structure and stability, which could impact brain function.

## Contribution

The study combines in-vitro and computational methods to reveal how Δ9-THC alters tubulin structure and microtubule dynamics.

## Key findings

- Δ9-THC reduces microtubule polymerization in a concentration-dependent manner.
- Circular Dichroism shows Δ9-THC induces secondary structural changes in tubulin.
- Computational modeling identifies a potential binding site for Δ9-THC on β-tubulin.

## Abstract

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).

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.

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.

The online version contains supplementary material available at 10.1186/s12868-025-00957-5.

The online version contains supplementary material available at 10.1186/s12868-025-00957-5.