Advancing cancer neuroscience through stress modulation: Interdisciplinary potential of psilocybin and ketamine
Alan C. Courtes, Blake Myers, Noah Daly, Greg Jones, Jair C Soares, Carlos A. Zarate, Rodrigo Machado‐Vieira
General Hospital Psychiatry February 25, 2026 DOI: 10.1016/j.genhosppsych.2026.02.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Psilocybin Ketamine |
| Topics | Esketamine Ketamine Psilocybin |
| Citations | 1 |
| Key findings | Psilocybin and ketamine may reduce cancer progression by normalizing HPA axis function and reducing adrenergic tone, interrupting stress-driven tumor-neuron signaling. |
Abstract
Psychological stress not only undermines quality of life for people with cancer but also fuels tumor growth. Emerging evidence from the nascent field of cancer neuroscience suggests that adrenergic signaling from direct tumor-neuron interactions drives cancer progression, resistance to treatment, and worse outcomes. Cancer neuroscientists are increasingly seeking to repurpose psychoactive medications (e.g., β-blockers and others) to augment primary cancer therapies. Preclinical models reveal that psychological stress can be a key activator of the sympathetic pathways that promote pathological tumor-neuron crosstalk. However, conventional antidepressants/anxiolytics used to address psychological distress are often less effective in this population. Conversely, while sample sizes are limited, psilocybin has achieved 60-80% long-term remission of cancer-related depression and anxiety and peri-palliative ketamine studies demonstrate rapid but short-lived symptom control. In preclinical models these agents appear to normalize hypothalamic-pituitary-adrenal (HPA) axis function while upregulating neurotrophic factors, mechanisms which putatively promote stress reductions and resilience. In this review, we propose that this neuroplastic recalibration may reduce sustained adrenergic tone, thereby interrupting the stress-driven tumor-neuron signaling that accelerates cancer progression. Integrating these rapid agents into oncology practice could thus disrupt maladaptive adrenergic signaling, enhance treatment adherence, and ultimately improve survival. Hospital-based psychiatrists are uniquely positioned to lead this effort by collaborating with oncologists, embedding biomarker-rich clinical trials, and monitoring both psychiatric and tumor-neuron interaction metrics. Advancing interdisciplinary research with ketamine and psilocybin will clarify whether targeting systemic stress indices represents a cancer-relevant endpoint beyond psychological symptom relief itself, while advancing research in cancer neuroscience mechanisms to improve oncologic outcomes.
Comparable studies
Other narrative reviews on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The pharmacology of psilocybin | 2002 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| Psychedelics, Meditation, and Self-Consciousness | 2018 | Review | |
| The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act | 2018 | Review |
Citations in the library
Cites 70
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 65 more in the library