Psychedelics are a paradigm-shifting therapy for a wide range of mental health disorders. We are leveraging their transdiagnostic potential to treat obesity and diabetes in individuals with comorbid depression. Inflammation is a key factor in this pathophysiological nexus. Most research and development of psychedelic therapy is targeted at the central nervous system. We are taking a more tractable approach by targeting the gut and the microbiota-gut-brain axis with the tangible endpoint of improving human health.
A great challenge in treating depression is addressing clinical heterogeneity and selecting the appropriate treatment for an individual. Depressed individuals have a greater risk of developing numerous chronic diseases, such as obesity and type 2 diabetes.
Inflammatory and metabolic markers associated with obesity and diabetes can be used to stratify depressed individuals in a precision medicine approach. Psychedelics, such as psilocybin, have been shown to modulate the immune system and exhibit anti-inflammatory effects, thus have great promise as a novel targeted therapy for these difficult to treat individuals.
DEPRESSION AFFECTS MORE THAN
264 MILLION PEOPLE WORLDWIDE
Over 60% of patients with major depressive disorder will experience some form of treatment resistance throughout pharmacological and clinical management. The global antidepressant drug market is projected to grow to $15.9 billion by 2023.
425M PEOPLE GLOBALLY LIVE WITH DIABETES.
Approximately 30% of the global population, or 2.1 billion, are overweight or obese. There is a bidirectional association between depression and obesity — having one increases the risk of having the other. One meta-analysis found obese individuals had a 55% increased risk of developing depression, and depressed individuals had a 58% increased risk of developing obesity.
WE NEED NOVEL THERAPIES TO ADDRESS
THESE GROWING EPIDEMICS.
There are direct and indirect pathways connecting the central nervous system, the enteric nervous system, and our digestive tract, collectively known as the microbiota-gut-brain axis.
Psilocybin has the strong potential to address physiological and psychological factors in obesity, through modulation of inflammation and the gut-brain axis.
Obesity-associated neuroinflammation affects multiple brain structures influencing mood, energy balance, and eating behaviour. We have identified a pathway that is known to be important in the communication between the gut and the brain, and is dysregulated in inflammation-related depression, as well as chronic inflammatory metabolic disorders such as obesity and diabetes.
We believe a targeted treatment of very low, sub-behavioural doses of psilocybin can modulate both systemic and tissue inflammation through this pathway, providing a clear path to progress to developing a sustainable treatment.
Chronic, low-grade systemic inflammation is associated with obesity and secondary disorders such as insulin resistance and diabetes.
Translocation of bacterial ligands from the gut into circulation due to intestinal permeability drives systemic inflammation leading to downstream signaling alterations in tissue and insulin resistance.
BY EXAMINING THE EFFECT OF A VERY LOW DOSE OF PSILOCYBIN ON THE MICROBIOME IN THIS IMMUNOMETABOLIC CONTEXT, WE HOPE TO ELUCIDATE ITS THERAPEUTIC EFFECTS IN OUR INDICATIONS.