Psilocybin and Chronic Pain: A New Perspective for Future Pain Therapists? Article Swipe
Silvia Natoli
,
Arturo Cuomo
,
Maurizio Marchesini
,
Livio Luongo
,
Giuliano Lo Bianco
,
Vittorio Andrea Guardamagna
,
Shigeki Yamaguchi
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/medsci13040277
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/medsci13040277
Background: Chronic pain affects nearly one in five adults worldwide and remains a major healthcare burden due to its persistence, multidimensional impact, and resistance to conventional therapies. The opioid crisis has further highlighted the urgent need for safer and more effective alternatives. Psilocybin, a serotonergic psychedelic compound, has re-emerged as a potential therapeutic option for chronic pain given its effects on neuroplasticity, neuroinflammation, and emotional regulation. Methods: This narrative review synthesized evidence from published preclinical and clinical studies. The focus was on the mechanisms of action of psilocybin, animal models of neuropathic and inflammatory pain, and early human trials exploring its effects on pain, mood, and quality of life. Results: Preclinical studies demonstrated that psilocybin promotes synaptogenesis via BDNF-TrkB signalling, modulates 5-HT2A receptor activity, and reduces neuroinflammatory processes, leading to persistent analgesic and anxiolytic effects. Animal models of chemotherapy-induced neuropathy and inflammatory pain showed long-lasting antinociceptive responses. Clinical studies, though limited, reported improvements in depression, anxiety, resilience, and quality of life in patients with advanced cancer and chronic conditions, with preliminary evidence of analgesic benefit. Conclusions: Psilocybin shows promise as a multidimensional therapy for chronic pain, addressing both sensory and affective components. However, ethical issues, safety concerns, and regulatory barriers necessitate careful management, and robust randomized controlled trials are essential to confirm efficacy and guide clinical translation.
Related Topics
Concepts
Medicine
Chronic pain
Analgesic
Clinical trial
Psilocybin
Serotonergic
Quality of life (healthcare)
Neuropathic pain
Intensive care medicine
Narrative review
Psychiatry
Nociception
Anxiety
Opioid
Perspective (graphical)
Anxiolytic
Psychotherapist
Human studies
Randomized controlled trial
Fibromyalgia
Pharmacology
Hallucinogen
Animal studies
Neuralgia
Intervention (counseling)
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/medsci13040277
- https://www.mdpi.com/2076-3271/13/4/277/pdf?version=1763631043
- OA Status
- gold
- References
- 63
- OpenAlex ID
- https://openalex.org/W7106128606
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W7106128606Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/medsci13040277Digital Object Identifier
- Title
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Psilocybin and Chronic Pain: A New Perspective for Future Pain Therapists?Work title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-11-20Full publication date if available
- Authors
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Silvia Natoli, Arturo Cuomo, Maurizio Marchesini, Livio Luongo, Giuliano Lo Bianco, Vittorio Andrea Guardamagna, Shigeki YamaguchiList of authors in order
- Landing page
-
https://doi.org/10.3390/medsci13040277Publisher landing page
- PDF URL
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https://www.mdpi.com/2076-3271/13/4/277/pdf?version=1763631043Direct link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.mdpi.com/2076-3271/13/4/277/pdf?version=1763631043Direct OA link when available
- Concepts
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Medicine, Chronic pain, Analgesic, Clinical trial, Psilocybin, Serotonergic, Quality of life (healthcare), Neuropathic pain, Intensive care medicine, Narrative review, Psychiatry, Nociception, Anxiety, Opioid, Perspective (graphical), Anxiolytic, Psychotherapist, Human studies, Randomized controlled trial, Fibromyalgia, Pharmacology, Hallucinogen, Animal studies, Neuralgia, Intervention (counseling)Top concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
-
63Number of works referenced by this work
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