New drugs for alcohol use disorder to focus on combination therapy

When searching for effective therapeutic options for patients with alcohol use disorder (AUD), research should combine several compounds rather than focusing on a single compound [1].

According to Dr Hamid Noori (Max Planck Institute for Biological Cybernetics, Germany), AUD is characterised by multiscale complexity, which not only shows in the multitarget molecular action of ethanol but also in the diversity of neurochemical and functional response patterns, as well as the different patterns of alcohol abuse and its behavioural consequences.

Neurochemistry has been used for decades by in vivo microdialysis to screen acute and chronic drug effects on brain chemistry. However, the effects are very local and do not necessarily relate to the complete system. “We need to realise that there is a large amount of data available; around 215,000 studies have used this technique. If we were able to use this data and convert it properly for each brain region (which would be valid for the whole brain), it could provide us with all-brain fingerprints for psychiatric drugs.”

Dr Noori and his team took a different approach and focused on big data. After data screening and the application of several inclusion criteria, they selected approximately 4,000 studies. This resulted in an open-access database with data on 200,000 rats and 258 drugs (antidepressants, anxiolytics, antipsychotics, and psychostimulants). The drugs are either clinically approved or experimental compounds.

Regarding the rats, 96% were male and 80% adult. By applying big-data analyses, they found that traditional classes of drugs like antidepressants do not necessarily relate to their neurobiology. When assessing the effect of an antidepressant on a systematic level, it could not be distinguished from an anxiolytic drug, Dr Noori stated. “We also saw a major overemphasis on specific neurochemical systems, such as the dopamine system. This is not necessarily the best target to select because it is not a biomarker for particular drugs, for it reacts to everything,” Dr Noori said. “These findings only emphasise that there is a mismatch between indications of neuropsychiatric drugs and their effects, which also affects their use in AUD. Therefore, a broader look into the therapeutic use of various drugs and compounds seems feasible.”

1. Noori HR. Systemic neurochemical fingerprinting of clinically approved and experimental neuropsychiatric drugs: implications for pharmacotherapy of AUD. S.02.03. ECNP Congress 2020.

Posted on 2 November 20205 August 2021