Recently, we published a paper that suggested that FKBP5 single‐nucleotide polymorphisms may play a role in functional seizures (psychogenic nonepileptic seizures/attacks). ¹ We also published another paper entitled “FKBP5 blockade may provide a new horizon for the treatment of stress‐associated disorders: An in‐silico study” providing a list of the currently available and approved drugs (e.g., fluticasone propionate, prednisolone, dexamethasone, mirtazapine, sertraline, fluoxetine, and citalopram) that could potentially be used for this purpose. ²

More recently, I read an article entitled: “Cannabidiol alleviates neuroinflammation and attenuates neuropathic pain via targeting FKBP5.” ³ In this study, cannabidiol (CBD) was identified as an antagonist of FKBP5 and FKBP5 was an endogenous target of CBD. ³ This is a very interesting study that opens a very intriguing avenue for future research.

FK506‐binding protein 51 (FKBP5/FKBP51) is a gene that encodes FKBP51 protein and contributes to the regulation of glucocorticoid receptor sensitivity. Mutant variants of FKBP5 have been associated with reduced glucocorticoid receptor sensitivity, which can lead to decreased hypothalamus–pituitary–adrenal (HPA) axis negative feedback and subsequent maintenance of glucocorticoids in the absence of threats and stress. ⁴ Accordingly, FKBP5 polymorphisms have been associated with various stress‐associated disorders such as major depression and post‐traumatic stress disorder (PTSD), and potentially with functional seizures (psychogenic nonepileptic seizures/attacks). ¹ , ⁵ Therefore, FKBP5 blockade may hold promise as a treatment option for stress‐associated disorders, including potentially functional seizures (psychogenic nonepileptic seizures/attacks). ²

At the moment, psychotherapy is considered the best treatment option for patients with functional seizures (psychogenic nonepileptic seizures/attacks). But a large clinical trial failed to demonstrate that cognitive behavioral therapy (CBT) has a statistically significant advantage compared with standardized medical care alone for the reduction of monthly seizures in these patients. ⁶ Functional seizures (psychogenic nonepileptic seizures/attacks) have devastating effects on patients' lives ⁷ and therefore, the scientific community should try to discover efficacious therapeutic options (e.g., a drug) for the treatment of this condition.

In conclusion, the suggestion that CBD is an antagonist of FKBP5 and FKBP5 is an endogenous target of CBD could open a new horizon for future research in discovering a treatment option for patients with functional seizures (psychogenic nonepileptic seizures/attacks).