Abstract

Growing evidence on classic serotonergic psychedelics suggests that these substances may induce transdiagnostic health benefits. With regard to mental health, it can be assumed that various psychiatric disorders such as depression, anxiety in life-threatening diseases, and substance use disorders may benefit from psychedelic therapy. And with regard to somatic diseases, there is initial evidence that psychedelics induce positive effects across a wide range of cardiovascular, metabolic, neurodegenerative and immunological pathologies.

Interestingly, mitochondrial dysregulations are a common denominator across all these mental and somatic disorders.
Based on preliminary evidence suggesting positive effects of 5-HT2A receptor agonists on mitochondria (e.g., increased mitochondrial biogenesis and efficiency of ATP production), we point out that these effects of psychedelics on mitochondria may substantially explain their transdiagnostic benefits. To substantiate this relationship with experimental data, in this poster, wie provide preliminary results of psychedelic-induced changes in frontal brain mitochondrial activity in treatment-resistant depressed in-patients.

The ongoing study in the Psychiatric Hospital Münsterlingen, Switzerland, compares, in a naturalistic group-comparison design, three groups of treatment interventions in treatment-resistant depression: 1) psychedelic-assisted psychodynamic psychotherapy (PAP); 2) electroconvulsive therapy (ECT); and psychodynamic psychotherapy as treatment as usual (TAU). The primary outcome measure is a mitochondrial activity marker: frontal brain cytochrome c oxidase (CCO) activity in the frontal brain. CCO is the last enzyme in the respiratory electron transport chain and is measured by a novel technique of broadband near-infrared spectroscopy (NIRS), which has the advantage over older techniques that it allows monitoring of both brain haemodynamics (oxygenated and deoxygenated haemoglobin) and metabolism (changes in the redox state of CCO).

Increases in CCO activity along the treatment period may constitute preliminary evidence for the effects of psychedelics on mitochondria in humans. This study will also allow us to compare the magnitude of these changes with other treatment forms, and to examine the relation of CCO activity with measures of psychopathology and cognitive functioning.