– IBRAA

Alcohol addiction is a common psychiatric disorder with largely unmet treatment needs. While low to moderate levels of consumption already exert detrimental health effects, there is a large variability of responses to alcohol drinking in the population. We argue that a large proportion of the variable vulnerability to the effects of alcohol lies in the interaction between the immune system and the brain.
The proposal focuses on vulnerability studies during early abstinence in alcohol use disorders (AUD).
In addition to the well-documented alcohol-induced peripheral inflammation, such as that induced by the liver and the gut, we hypothesise that cessation of alcohol consumption itself, in these chronic drinkers, is a stimulus that triggers a rebound proinflammatory response in the brain. The prediction is that individuals with a higher immune reactivity would develop an exacerbated neuroinflammatory response during early abstinence, with higher risk of brain damage, deficits in executive functions and relapse to excessive alcohol consumption. Conversely, less reactive immunotypes in the population would be protected. Accordingly, interventions that can attenuate the rebound neuroinflammation after alcohol withdrawal will be neuroprotective.
The study aims to (1) identify vulnerability and resiliency factors in AUD, with spatial and temporal signatures transformed into biomarkers, and (2) to explore interventions that can attenuate the rebound neuroinflammation after alcohol withdrawal and therefore be neuroprotective and therapeutic.
We will perform human studies using novel non-invasive diagnostic tools developed by the research team to look for associations between neuroinflammation and vulnerability, in parallel with translationally validated animal models to investigate cellular and molecular mechanisms. Interventions will include omega-3 fatty acids and psilocybin, a psychedelic drug with anti-inflammatory activity and demonstrated efficacy for AUD treatment.
This proposal brings together complementary skills from internationally renowned research groups interested in understanding vulnerability and resiliency factors in AUD, proven expertise in the study of the immune-brain axis, and technical capabilities beyond the state of the art. A strong validation of our hypotheses would lead to modifications in clinical practice, including the use of nutritional supplements and pharmacological anti-inflammatory interventions as potential treatments to enhance resiliency in AUD patients.