Unravelling Mechanisms for Novel Fast-Acting Antidepressant Drugs with Cannabidiol

BACKGROUND: All known antidepressants promote mood improving effects only after several weeks of treatment and are ineffective in about 40% of patients. Identification of novel molecular and cellular targets for more efficient antidepressants represent a significant unmet medical need. Although several targets for antidepressant drugs have been identified, it is not clear how these targets are translated into mechanisms that trigger their clinical effect. In the search for new drug targets that may help point the way to developing more effective medication for mood disorders, we will explore the molecular signature underlying the actions of cannabidiol (CBD), which triggers fast and sustained antidepressant effects. The mechanisms behind this remarkable action OBJECTIVES. The overall objectives are to investigate and clarify the molecular and morphological landscape of two new promising antidepressant strategies, ketamine and CBD, in disease models of depression, as well as to identify potential biomarkers for depression and response to treatment. METHODS: Methylomic, transcriptomic (RNAseq), proteomic (LC/MS) and neuroplastic data will be obtained from advanced animal models of depression and treatment-resistant depression. The data from the brain and peripheral tissue will be subjected to an advanced pathway analysis in order to understand common molecular and morphological signatures, which will later be compared to clinical samples. SCIENTIFIC, SCHOLARY & SOCIETAL RELEVANCE: By unbiased identification of the common molecular signatures of CBD and ketamine, the project will clarify the molecular mechanisms involved in the antidepressant effect. The project will also contribute with the identification of potential biological markers associated with response/resistance to treatment. The success of the research program could benefit society in several aspects, from the patient to universities and the pharmaceutical industry.