{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:10:44Z","timestamp":1788779444924,"version":"build-2803163510"},"reference-count":132,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Standard pharmacotherapy for mental disorders, including depression and anxiety, is supported by extensive clinical validation and international treatment guidelines. However, it is frequently associated with limitations such as adverse side effects, low patient adherence, and the risk of relapse. Conventional approaches rely primarily on antidepressants, anxiolytics, mood stabilizers, neuroleptics, and stimulants, which modulate monoaminergic, GABAergic, and dopaminergic neurotransmission. Recently, preclinical and emerging clinical studies have suggested that selected natural substances\u2014specifically mushroom-derived compounds and well-established medicinal plants\u2014may offer complementary therapeutic pathways. This narrative review critically evaluates the pharmacological efficacy, mechanisms of action, and safety profiles of selected natural compounds, including psilocybin-related tryptamines, Hericium erinaceus, ibotenic acid\/muscimol from Amanita muscaria, ergothioneine, as well as notable botanical agents (e.g., Hypericum perforatum, Valeriana officinalis). We systematically distinguish between robust human clinical data (e.g., psilocybin-assisted therapy) and preliminary in vitro\/in vivo findings. Particular attention is paid to their neurotrophic, anti-inflammatory, and neuromodulatory properties, while emphasizing substantial safety concerns, including intoxication risks associated with isoxazole derivatives, and potentially severe cytochrome P450-mediated drug\u2013drug interactions. Ultimately, while certain natural compounds show promise as adjunctive interventions, most remain strictly investigational and cannot replace evidence-based conventional pharmacotherapy without further long-term, large-scale randomized controlled trials.<\/jats:p>","DOI":"10.3390\/molecules31173130","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:30:46Z","timestamp":1788777046000},"page":"3130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Efficacy of Natural and Conventional Psychiatric Treatments: A Comparative Review of Mushroom-Derived Compounds and Medicinal Plants in the Management of Mental Disorders"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1183-7872","authenticated-orcid":false,"given":"Katarzyna","family":"Gaw\u0142owska","sequence":"first","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna Kaja","family":"Nowakowska","sequence":"additional","affiliation":[{"name":"The Faculty of Medicine and Health Sciences, Collegium Medicum of the University of Zielona Gora, Zyty 28, 65-046 Zielona Gora, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Wiktoria","family":"Mak\u00f3wka","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3444-9627","authenticated-orcid":false,"given":"Wojciech","family":"Bajurny","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena Patrycja","family":"G\u00f3ral","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Boche\u0144ska","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon Dariusz","family":"Kopecki","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7246-3946","authenticated-orcid":false,"given":"Weronika Marta","family":"Grodzi\u0144ska","sequence":"additional","affiliation":[{"name":"Scientific Society for Neurotoxicology, Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4J, 50-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-8114","authenticated-orcid":false,"given":"Agnieszka","family":"Ch\u0142opa\u015b-Konowa\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Division of Molecular Techniques, Wroclaw Medical University, Sklodowskiej-Curie 52, 50-369 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","first-page":"479","article-title":"DSM-5","volume":"18","author":"Messent","year":"2013","journal-title":"Clin. Child Psychol. Psychiatry"},{"key":"ref_2","unstructured":"(2026, June 26). International Classification of Diseases (ICD). 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