Neurobiological mechanisms of antidepressant properties of psilocybin: A systematic review of blood biomarkers.
Juliana Lima Constantino, Jens H van Dalfsen, Sara Massetti, Jeanine Kamphuis, Robert A Schoevers
Progress in neuro-psychopharmacology & biological psychiatry January 10, 2025 DOI: 10.1016/j.pnpbp.2025.111251 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 9 |
| Population | Healthy participants in studies investigating blood-based biomarkers after psilocybin administration |
| Intervention | Psilocybin |
| Topics | Depression Psilocybin |
| Keywords | Systematic review Psychedelic medicine Clinical depression Biomarkers biological markers Blood markers Biochem |
| Citations | 6 |
| Key findings | Psilocybin administration in healthy participants is consistently associated with decreased interleukin-6, C-reactive protein, and eosinophils, and increased cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids. |
Abstract
Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials. A systematic search was performed in MEDLINE, Embase, and Web of Science to retrieve studies investigating changes in serum and plasma levels of neurotrophic, immunologic, neuroendocrine, and metabolic markers. Nine studies were included, describing findings on 15 biomarkers, exclusively in healthy participants. Studies consistently reported a decrease in interleukin-6, C-reactive protein, and eosinophils, and an increase in cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids following psilocybin administration. Less consistent effects were observed on interleukin-1β, interleukin-8, tumour necrosis factor-alpha, soluble urokinase plasminogen activator receptor, and growth hormone. The results are in line with preclinical studies and provide initial support from human studies that psilocybin potentially leads to beneficial effects on biomarkers of MDD. However, given the limited number of studies, findings should be approached with caution prior to replication. Further research should include larger samples, clinical populations, longer-term assessment, rigorous experimental designs, and account for the potential confounding of psychological stress related to the psychedelic experience.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders | 2016 | Systematic review | n = 423 |
| Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... | 2023 | Systematic review with meta-analysis | n = 14 |
| Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression | 2018 | Systematic review | n = 445 |