# The Use of Psilocybin in the Treatment of Depressive Disorders: A Narrative Review

**Authors:** Lukasz Siwek, Marta Nowocien, Barbara Balajewicz, Angelika Samborska, Sara Szukalska, Marta Karczewska, Karolina Lichwala, Kamil Wróblewski, Paulina Wróblewska

PMC · DOI: 10.7759/cureus.102694 · Cureus · 2026-01-31

## TL;DR

This paper reviews recent research on using psilocybin, a psychoactive compound, as a potential treatment for depression, highlighting its promising therapeutic effects.

## Contribution

The paper provides a narrative review of recent studies on psilocybin's potential as a novel treatment for depressive disorders.

## Key findings

- Psilocybin shows high therapeutic efficacy compared to conventional depression treatments.
- Research suggests psilocybin-assisted therapy may have a more sustained effect with minimal adverse effects.
- Interest in psilocybin is growing due to the rising global burden of depression.

## Abstract

Psilocybin is a psychoactive chemical compound that exerts its effects through the activation of serotonergic receptors. It occurs naturally in mushrooms of the genus Psilocybe. Despite its potential medical applications, this substance is regarded as a drug with no recognized medical use. Depression constitutes a psychiatric disorder of substantial global burden, affecting millions of individuals worldwide, with epidemiological data indicating a continuing upward trend in its prevalence. It is a complex disease entity that, despite years of research, remains not fully understood and constitutes a significant therapeutic challenge. Its pathogenesis is based on the interaction of biological, environmental, and social factors. It is estimated that by the year 2030, depression will become the leading cause of disability. The concern associated with this projection, together with human curiosity, has formed the foundation of numerous scientific studies conducted in recent years, aimed at identifying a breakthrough therapeutic approach that would expand the range of treatment options available to psychiatrists. The aim of this paper is to present the most recent reports on attempts to use the controversial substance psilocybin in the treatment of depression. Owing to promising research results demonstrating high therapeutic efficacy in comparison with conventional, currently recommended treatments, psilocybin-assisted therapy offers hope for the development of a modern therapeutic approach that provides the expected clinical outcomes, with a proven and more sustained therapeutic effect in treated patients, as well as a minimal number or complete absence of adverse effects.

## Linked entities

- **Chemicals:** psilocybin (PubChem CID 10624)
- **Diseases:** depression (MONDO:0002050)

## Full-text entities

- **Genes:** SLC6A4 (solute carrier family 6 member 4) [NCBI Gene 6532] {aka 5-HTT, 5-HTTLPR, 5HTT, HTT, OCD1, SERT}, CYP2D6 (cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene)) [NCBI Gene 1565] {aka CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2}, MAOA (monoamine oxidase A) [NCBI Gene 4128] {aka BRNRS, MAO-A}, HTR2A (5-hydroxytryptamine receptor 2A) [NCBI Gene 3356] {aka 5-HT2A, HTR2}, HTR2C (5-hydroxytryptamine receptor 2C) [NCBI Gene 3358] {aka 5-HT1C, 5-HT2C, 5-HTR2C, 5HTR2C, HTR1C}, SLC6A2 (solute carrier family 6 member 2) [NCBI Gene 6530] {aka NAT1, NET, NET1, SLC6A5}
- **Diseases:** Anxiety (MESH:D001007), sexual dysfunction (MESH:D012735), Huntington's disease (MESH:D006816), cancer (MESH:D009369), Alzheimer's disease (MESH:D000544), mental disorders (MESH:D001523), substance abuse (MESH:D019966), insomnia (MESH:D007319), Parkinson's disease (MESH:D010300), addiction to alcohol (MESH:D000437), sleep disorders (MESH:D012893), anhedonia (MESH:D059445), serotonin syndrome (MESH:D020230), trauma (MESH:D014947), headaches (MESH:D006261), vomiting (MESH:D014839), anxiety disorders (MESH:D001008), hyperthermia (MESH:D005334), hyperactivity (MESH:D006948), hypotension (MESH:D007022), MDD (MESH:D003865), seizures (MESH:D012640), Confusion (MESH:D003221), Fatigue (MESH:D005221), nausea (MESH:D009325), tachycardia (MESH:D013610), Suicidal ideation (MESH:D001072), Mood Disturbance (MESH:D019964), HAM-D (MESH:D015493), dizziness (MESH:D004244), impotence (MESH:D007172), visual distortions (MESH:D006311), gastrointestinal disturbances (MESH:D005767), psychotic (MESH:D011618), agitation (MESH:D011595), cardiovascular (MESH:D002318), urinary disturbances (MESH:D014548), hypertension (MESH:D006973), abnormalities in brain function (MESH:D001927), GAD (MESH:C000726808), visual hallucinations (MESH:D006212), metastasis (MESH:D009362), Adaptive disorders (MESH:D018489), BDI (MESH:D057767), QT interval prolongation (MESH:D008133), oncological (MESH:D000072716), decreased appetite (MESH:D001068), constipation (MESH:D003248), dysthymic disorder (MESH:D019263), depressed mood (MESH:D003866), adjustment (MESH:D000275), thyroid disorders (MESH:D013959), dry mouth (MESH:D014987)
- **Chemicals:** Bupropion (MESH:D016642), citalopram (MESH:D015283), escitalopram (MESH:D000089983), duloxetine (MESH:D000068736), histamine (MESH:D006632), NE (MESH:D009638), acetylcholine (MESH:D000109), trazodone (MESH:D014196), Reboxetine (MESH:D000077593), venlafaxine (MESH:D000069470), water (MESH:D014867), sertraline (MESH:D020280), corn-starch (MESH:D013213), fluvoxamine (MESH:D016666), Mirtazapine (MESH:D000078785), niacin (MESH:D009525), NASSAs (-), 5-HT (MESH:D012701), 4-phosphoryloxy-N,N-dimethyltryptamine (MESH:D011562), dopamine (MESH:D004298), fluoxetine (MESH:D005473)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC12951688/full.md

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Source: https://tomesphere.com/paper/PMC12951688