Cannabidiol (CBD) Induces Lipid Microdomain Disruption or Budding in Ternary Mixtures

CBD, one of the main phytocannabinoids present in <i>Cannabis sativa</i>, is a singular and promising molecule in medicine, as it is increasingly being used to alleviate diseases derived from inflammation. However, until now, the molecular targets through which it produces its therapeutic effects remain unclear. In fact, since at least 65 physiological targets related to its biological action have been described, it seems that we are far from fully understanding the correct underlying effect. Could it be that the mechanism of action lies elsewhere? To explore the influence of CBD on membranes, we here study its effect on lipid domains in giant and small vesicles. In our experiments, we used fluorescence microscopy, differential scanning calorimetry, isothermal titration calorimetry, and dynamic light scattering to show that in the presence of CBD, lipid domains are disrupted and sometimes lift off. The fission event occurs only near the phase separation temperature, where biological membranes normally function. In addition, we propose a phase field model to theoretically describe the observed budding effect. In the context of recent results showing that degradation of lipid domains can have an impact on analgesia, our findings could provide key elements to consider that the action of CBD on biological cells could be driven by a soft matter phenomenon.