Cyclodextrins (CDs) are well-known carriers for encapsulating hydrophobic molecules, while among cannabinoids, cannabidiol (CBD) has attracted considerable attention due to its therapeutic capability. In this framework, we employed molecular dynamics and docking techniques for investigating the interaction energy and thermodynamical issues between different CDs (α, β, and γ type) and CBD immersed in water and a solution mimicking a physiological environment. We quantified the energetic aspects, for different thermal conditions, in which both aqueous solutions interact with CBDs and CDs and the CBD-CDs complex itself. In order to approximate the physiological conditions, our simulations also included the mammalian temperature. The calculations revealed significant interaction energy between lactate and the CD surface and a movement of lactate toward CD as well. We observed an almost constant number of lactate molecules forming clusters without exhibiting a temperature dependence. Next, the degree of CBD-CDs complexation at four different temperatures was analyzed. The results showed that the complexation depends on the medium, becoming weaker with the temperature increment. Our findings highlighted that the entropy contribution is relevant for CBD-α-CD and CBD-β-CD, while CBD-γ-CD is practically insensitive to temperature changes for both solutions. In both water and artificial physiological solutions, the γ-CD appears more stable than the other complexes. Overall, CBD achieved partial encapsulation considering α-CD and β-CD, showing a temperature dependence, while γ-CD remained fully immersed no matter the thermal level assumed. We also discuss the pharmacological relevance and physiological implications of these findings.

环糊精（CD）是众所周知的包裹疏水性分子的载体，而在大麻素中，大麻二酚（CBD）因其治疗能力而备受关注。在此框架中，我们采用分子动力学和对接技术来研究浸入水中的不同 CD（α、β 和 γ 型）和 CBD 以及模拟生理环境的溶液之间的相互作用能和热力学问题。我们量化了不同热条件下的能量方面，其中两种水溶液与 CBD 和 CD 以及 CBD-CD 复合物本身相互作用。为了近似生理条件，我们的模拟还包括哺乳动物的温度。计算揭示了乳酸和 CD 表面之间的显着相互作用能以及乳酸向 CD 的运动。我们观察到几乎恒定数量的乳酸分子形成簇，而没有表现出温度依赖性。接下来，分析了四种不同温度下 CBD-CDs 的复合程度。结果表明，络合依赖于介质，随着温度的升高而减弱。我们的研究结果强调，熵贡献与 CBD-α-CD 和 CBD-β-CD 相关，而 CBD-γ-CD 实际上对两种解决方案的温度变化都不敏感。在水和人工生理溶液中，γ-CD 似乎比其他复合物更稳定。总体而言，考虑到 α-CD 和 β-CD，CBD 实现了部分封装，表现出温度依赖性，而无论假设的热水平如何，γ-CD 都保持完全浸没。我们还讨论了这些发现的药理学相关性和生理意义。