A translational investigation of the anti-inflammatory and antidepressant effects of Psychedelics in Depression

There has been a renewed interest in the therapeutic potential of psychedelics. These substances (e.g. psilocybin, D-lysergic acid diethylamide, dimethyltryptamine) when given under psychiatric supervision and with psychological support have been shown to have therapeutic benefits for a range of disorders with restricted or maladaptive patterns of thought and behaviour. Psilocybin therapy is on course to be approved as a treatment for depression in the coming years.

It is thought that psychedelic compounds primarily work by activating the brain’s serotonin system which is vital for the regulation of mood and anxiety. However, psychedelic compounds may also reduce inflammation. Dysregulation of the immune system is a major contributor to poor physical and mental health.

Depression is associated with low grade inflammation. A theory has developed that at least some types of depression result from an ‘inflammed brain’. While some types of drugs targeting the immune system have been developed and tested, none have reached the clinic for the benefit of patients. The majority of the currently available antidepressant drugs target neurotransmitters like serotonin and/or noradrenaline, but they don’t work for everybody. There is an increasing need for better treatments in depression and a greater understanding of the biological processes involved.

Very little is known about how psychedelics affect the immune system in depression. This study will explore the anti-inflammatory action of psychedelics by adding a range of psychedelics to blood samples taken from people who are depressed and comparing them to people without depression. The underlying anti-inflammatory and anti-depressant mechanisms will be further explored using rodent models. This study will advance our understanding of psychedelics by providing valuable evidence of how psychedelics affect the immune system. We hope this will pave the way for additional effective treatment options not only for people with depression, but potentially a range of other disorders.

Award Date
01 July 2022
Award Value
Principal Investigator
Dr John Kelly
Host Institution
Trinity College Dublin
Investigator Led Projects