Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics.
Antonella Campanale, Antonio Inserra, Stefano Comai
Progress in Neuro-Psychopharmacology and Biological Psychiatry August 30, 2024 DOI: 10.1016/j.pnpbp.2024.111058 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Gut-brain axis Kynurenine pathway Serotonergic psychedelics Severe mental illness |
| Citations | 18 |
| Key findings | Serotonergic psychedelics may therapeutically modulate the kynurenine pathway in the altered gut-brain axis underlying severe mental illness and its cardiometabolic comorbidities, though mechanisms and outcomes remain largely unknown. |
Abstract
Mounting evidence points towards a crucial role of the kynurenine pathway (KP) in the altered gut-brain axis (GBA) balance in severe mental illness (SMI, namely depression, bipolar disorder, and schizophrenia) and cardiometabolic comorbidities. Preliminary evidence shows that serotonergic psychedelics and their analogues may hold therapeutic potential in addressing the altered KP in the dysregulated GBA in SMI and comorbidities. In fact, aside from their effects on mood, psychedelics elicit therapeutic improvement in preclinical models of obesity, metabolic syndrome, and vascular inflammation, which are highly comorbid with SMI. Here, we review the literature on the therapeutic modulation of the KP in the dysregulated GBA in SMI and comorbidities, and the potential application of psychedelics to address the altered KP in the brain and systemic dysfunction underlying SMI and comorbidities. Psychedelics might therapeutically modulate the KP in the altered GBA in SMI and comorbidities either directly, via altering the metabolic pathway by influencing the rate-limiting enzymes of the KP and affecting the levels of available tryptophan, or indirectly, by affecting the gut microbiome, gut metabolome, metabolism, and the immune system. Despite promising preliminary evidence, the mechanisms and outcomes of the KP modulation with psychedelics in SMI and systemic comorbidities remain largely unknown and require further investigation. Several concerns are discussed surrounding the potential side effects of this approach in specific cohorts of individuals with SMI and systemic comorbidities.
Comparable studies
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Citations in the library
Cited by 6
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- Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia. International Journal of Molecular Sciences September 14, 2025
- The compulsive eating paradigm: can psychedelics help in treating obesity? Journal of Eating Disorders April 7, 2025
- Psilocybin in Older Adults: Therapeutic Opportunities in Inflammation-Driven Disorders of Aging-From Depression to Neurodegeneration. International Journal of Molecular Sciences May 9, 2026
and 1 more in the library
Cites 71
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and 66 more in the library