---
title: "Cannabidiol (CBD) reduces chemotherapy-induced cognitive decline in a mouse model"
id: "pubmed-42202974"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42202974"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42202974/"
doi: "10.1016/j.canlet.2026.218612"
published_at: "2026-09-28T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Cannabidiol (CBD) reduces chemotherapy-induced cognitive decline in a mouse model
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42202974
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42202974/)
- **DOI:** [10.1016/j.canlet.2026.218612](https://doi.org/10.1016%2Fj.canlet.2026.218612)
- **Published At:** 2026-09-28T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Chemotherapy with doxorubicin (Adriamycin®, ADR) and cyclophosphamide (CYP) is associated with long-term cognitive impairments in cancer survivors and shows neurodegenerative and neuroinflammatory signatures in clinical studies. - Existing mitigation strategies for cancer therapy-related cognitive impairments (CRCI) remain limited, prompting evaluation of new approaches. - Cannabidiol (CBD), a non-psychoactive cannabis component with recognized **neuroprotective** and **anti-inflammatory** properties, and an FDA-approved 99% pure formulation (Epidiolex®) for pediatric epilepsy, was evaluated preclinically for CRCI. - Using a mouse model of adjuvant chemotherapy (ADR + CYP), the investigators administered oral 99% pure CBD at 20 mg/kg in sesame oil for one month to chemotherapy-treated mice. - CBD-treated chemotherapy mice showed significant improvements in learning and memory, executive function, and memory consolidation tasks that are commonly impaired in cancer survivors. - Treatment with CBD restored brain **endocannabinoid (ECB)** levels and reduced expression of ECB-metabolizing enzymes in vivo. - CBD mitigated several neuropathological changes induced by chemotherapy, including loss of **neurogenesis**, reduced neuronal plasticity and synaptic density, and increased **gliosis**. - The study presents preclinical evidence supporting a translationally feasible approach to alleviate CRCI, addressing an unmet medical need. - The abstract does not report detailed experimental parameters (sample sizes, specific behavioral tests, statistical outcomes) in this summary; those details were not reported in the provided source text. - The authors declared no competing financial interests or personal relationships influencing the work.
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Epub 2026 May 26. # Cannabidiol alleviates chemotherapy-induced cognitive decline and neuropathology [Shreya Madan](https://pubmed.ncbi.nlm.nih.gov/?term=Madan+S&cauthor_id=42202974)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-1 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smadan2@uci.edu."), [Sanad M El-Khatib](https://pubmed.ncbi.nlm.nih.gov/?term=El-Khatib+SM&cauthor_id=42202974)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-2 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smelkhat@uci.edu."), [Asrita Prathigudupu](https://pubmed.ncbi.nlm.nih.gov/?term=Prathigudupu+A&cauthor_id=42202974)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-3 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: aprathig@uci.edu."), [Heidi C Avalos](https://pubmed.ncbi.nlm.nih.gov/?term=Avalos+HC&cauthor_id=42202974)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-4 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: hcavalos@hs.uci.edu."), [Faizy Ahmed](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmed+F&cauthor_id=42202974)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-5 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: fahmed@uci.edu."), [Daniele Piomelli](https://pubmed.ncbi.nlm.nih.gov/?term=Piomelli+D&cauthor_id=42202974)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-6 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: piomelli@hs.uci.edu."), [Alexandre Chan](https://pubmed.ncbi.nlm.nih.gov/?term=Chan+A&cauthor_id=42202974)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-7 "Department of Clinical Pharmacy Practice, University of California, Irvine, United States. Electronic address: a.chan@uci.edu."), [Kalpna Gupta](https://pubmed.ncbi.nlm.nih.gov/?term=Gupta+K&cauthor_id=42202974)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-8 "Department of Medicine, University of California, Irvine, United States. Electronic address: kalpnag@hs.uci.edu."), [Kwang Mook Jung](https://pubmed.ncbi.nlm.nih.gov/?term=Jung+KM&cauthor_id=42202974)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-9 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: kmjung@hs.uci.edu."), [Munjal M Acharya](https://pubmed.ncbi.nlm.nih.gov/?term=Acharya+MM&cauthor_id=42202974)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#full-view-affiliation-10 "Department of Anatomy and Neurobiology, University of California, Irvine, United States; Department of Radiation, Oncology, University of California, Irvine, United States. Electronic address: macharya@uci.edu.") Affiliations Expand ### Affiliations * 1 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smadan2@uci.edu. * 2 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smelkhat@uci.edu. * 3 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: aprathig@uci.edu. * 4 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: hcavalos@hs.uci.edu. * 5 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: fahmed@uci.edu. * 6 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: piomelli@hs.uci.edu. * 7 Department of Clinical Pharmacy Practice, University of California, Irvine, United States. Electronic address: a.chan@uci.edu. * 8 Department of Medicine, University of California, Irvine, United States. Electronic address: kalpnag@hs.uci.edu. * 9 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: kmjung@hs.uci.edu. * 10 Department of Anatomy and Neurobiology, University of California, Irvine, United States; Department of Radiation, Oncology, University of California, Irvine, United States. Electronic address: macharya@uci.edu. * PMID: **42202974** * DOI: [ 10.1016/j.canlet.2026.218612 ](https://doi.org/10.1016/j.canlet.2026.218612) Free article Item in Clipboard # Cannabidiol alleviates chemotherapy-induced cognitive decline and neuropathology Shreya Madan et al. Cancer Lett. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Cancer Lett Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cancer+Lett%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Lett%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42202974/) . 2026 Sep 28:656:218612. doi: 10.1016/j.canlet.2026.218612. Epub 2026 May 26. ### Authors [Shreya Madan](https://pubmed.ncbi.nlm.nih.gov/?term=Madan+S&cauthor_id=42202974)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-1 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smadan2@uci.edu."), [Sanad M El-Khatib](https://pubmed.ncbi.nlm.nih.gov/?term=El-Khatib+SM&cauthor_id=42202974)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-2 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smelkhat@uci.edu."), [Asrita Prathigudupu](https://pubmed.ncbi.nlm.nih.gov/?term=Prathigudupu+A&cauthor_id=42202974)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-3 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: aprathig@uci.edu."), [Heidi C Avalos](https://pubmed.ncbi.nlm.nih.gov/?term=Avalos+HC&cauthor_id=42202974)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-4 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: hcavalos@hs.uci.edu."), [Faizy Ahmed](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmed+F&cauthor_id=42202974)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-5 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: fahmed@uci.edu."), [Daniele Piomelli](https://pubmed.ncbi.nlm.nih.gov/?term=Piomelli+D&cauthor_id=42202974)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-6 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: piomelli@hs.uci.edu."), [Alexandre Chan](https://pubmed.ncbi.nlm.nih.gov/?term=Chan+A&cauthor_id=42202974)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-7 "Department of Clinical Pharmacy Practice, University of California, Irvine, United States. Electronic address: a.chan@uci.edu."), [Kalpna Gupta](https://pubmed.ncbi.nlm.nih.gov/?term=Gupta+K&cauthor_id=42202974)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-8 "Department of Medicine, University of California, Irvine, United States. Electronic address: kalpnag@hs.uci.edu."), [Kwang Mook Jung](https://pubmed.ncbi.nlm.nih.gov/?term=Jung+KM&cauthor_id=42202974)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-9 "Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: kmjung@hs.uci.edu."), [Munjal M Acharya](https://pubmed.ncbi.nlm.nih.gov/?term=Acharya+MM&cauthor_id=42202974)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42202974/#short-view-affiliation-10 "Department of Anatomy and Neurobiology, University of California, Irvine, United States; Department of Radiation, Oncology, University of California, Irvine, United States. Electronic address: macharya@uci.edu.") ### Affiliations * 1 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smadan2@uci.edu. * 2 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: smelkhat@uci.edu. * 3 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: aprathig@uci.edu. * 4 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: hcavalos@hs.uci.edu. * 5 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: fahmed@uci.edu. * 6 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: piomelli@hs.uci.edu. * 7 Department of Clinical Pharmacy Practice, University of California, Irvine, United States. Electronic address: a.chan@uci.edu. * 8 Department of Medicine, University of California, Irvine, United States. Electronic address: kalpnag@hs.uci.edu. * 9 Department of Anatomy and Neurobiology, University of California, Irvine, United States. Electronic address: kmjung@hs.uci.edu. * 10 Department of Anatomy and Neurobiology, University of California, Irvine, United States; Department of Radiation, Oncology, University of California, Irvine, United States. Electronic address: macharya@uci.edu. * PMID: **42202974** * DOI: [ 10.1016/j.canlet.2026.218612 ](https://doi.org/10.1016/j.canlet.2026.218612) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Chemotherapy is frequently associated with long-term cognitive impairments in cancer survivors that negatively impact their quality of life. Effective mitigation strategies for cancer therapy-related cognitive impairments (CRCI) are still underdeveloped. Our clinical studies on breast cancer patients treated with doxorubicin (Adriamycin®, ADR) and cyclophosphamide (CYP) found significant CRCI associated with neurodegenerative and neuroinflammatory signatures. Current preclinical and clinical studies highlight the potential of cannabidiol (CBD) for alleviating cognitive deficits in neurodegenerative conditions. For example, Epidiolex® is an FDA-approved 99% pure formulation of CBD for treating pediatric epilepsy. CBD, a non-psychoactive component of cannabis, is recognized for its neuroprotective and anti-inflammatory effects. This study, using a mouse model of adjuvant chemotherapy (ADR and CYP)-induced cognitive decline, tested the efficacy of oral administration of 99% pure CBD (20 mg/kg) in sesame oil. ADR + CYP-treated mice receiving CBD for one month showed significant neurocognitive improvements in learning and memory, executive function, and memory consolidation tasks often impaired in cancer survivors. CBD treatment also restored brain endocannabinoid (ECB) levels and reduced ECB-metabolizing enzymes in vivo. Notably, CBD mitigated chemotherapy-induced loss of neurogenesis, neuronal plasticity, synaptic density, and elevated gliosis. In summary, this data provides preclinical evidence for a translationally feasible approach to alleviate CRCI, an unmet medical need. **Keywords:** CB2 receptor; CBD; Cannabinoids; Chemobrain; Chemotherapy; Cognitive function; Epidiolex; Neurogenesis; Neuroinflammation. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ FDA-approved cannabidiol [Epidiolex®] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis. ](https://pubmed.ncbi.nlm.nih.gov/39169440/) Kodali M, Madhu LN, Kolla VSV, Attaluri S, Huard C, Somayaji Y, Shuai B, Jordan C, Rao X, Shetty S, Shetty AK.Kodali M, et al.Mil Med Res. 2024 Aug 22;11(1):61. doi: 10.1186/s40779-024-00563-2.Mil Med Res. 2024.PMID: 39169440Free PMC article. * [ BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences. ](https://pubmed.ncbi.nlm.nih.gov/39696694/) El-Khatib SM, Vagadia AR, Le ACD, Baulch JE, Ng DQ, Du M, Johnston KG, Tan Z, Xu X, Chan A, Acharya MM.El-Khatib SM, et al.Acta Neuropathol Commun. 2024 Dec 18;12(1):190. doi: 10.1186/s40478-024-01906-9.Acta Neuropathol Commun. 2024.PMID: 39696694Free PMC article. * [ Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice. ](https://pubmed.ncbi.nlm.nih.gov/38759736/) Xie G, Gao X, Guo Q, Liang H, Yao L, Li W, Ma B, Wu N, Han X, Li J.Xie G, et al.Brain Behav Immun. 2024 Jul;119
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