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. 2025 Aug 6;13(8):1921.
doi: 10.3390/biomedicines13081921.

Comparative Effects of THC and CBD on Chemotherapy-Induced Peripheral Neuropathy: Insights from a Large Real-World Self-Reported Dataset

Ravit Geva  1 , Tali Hana Bar-Lev  1 , Lee Ahuva Lavi Kutchuk  1 , Tali Schaffer  1 , Dan Mirelman  1 , Sharon Pelles-Avraham  1 , Ido Wolf  1 , Lihi Bar-Lev Schleider  2
Affiliations

Comparative Effects of THC and CBD on Chemotherapy-Induced Peripheral Neuropathy: Insights from a Large Real-World Self-Reported Dataset

Ravit Geva et al. Biomedicines. .

Abstract

Background/Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting adverse effect of various chemotherapeutic agents. Previous work demonstrated that cannabis alleviates symptoms of oxaliplatin-induced CIPN. To evaluate the effects of cannabis components, cannabidiol (CBD) and tetrahydrocannabinol (THC), on CIPN-related symptoms. Methods: We reviewed a patient-reported outcomes dataset from "Tikun Olam," a major medical cannabis provider. Of 1493 patients, 802 reported at least one CIPN symptom at baseline, including a burning sensation, cold sensation, paresthesia (prickling) and numbness, and 751 of them met the study inclusion criteria. Patients were categorized into THC-high/CBD-low and CBD-high/THC-low groups. Symptom changes after six months of cannabis use were analyzed using K-means clustering and logistic regression, incorporating interactions between baseline symptoms and THC and CBD doses. Linear regression assessed changes in activities of daily living (ADL) and quality of life (QOL). Results: Both groups reported symptom improvement. The THC-high group showed significantly greater improvement in burning sensation and cold sensation (p = 0.024 and p = 0.008). Improvements in ADL and QOL were also significantly higher in the THC group (p = 0.029 and p = 0.006). A significant interaction between THC and CBD was observed for symptom improvement (p < 0.0001). Conclusions: Cannabis effectively reduces CIPN symptoms and improves QOL and ADL. Higher THC doses were more effective than lower doses, with combined CBD and THC doses yielding greater symptom relief.

Keywords: cannabidiol (CBD); cannabinoid; cannabis; chemotherapy; neuropathy; quality of life; side effects.

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Conflict of interest statement

L.B.-L.S., T.H.B.-L., L.A.L.K., T.S., D.M., S.P.-A., and I.W. declare no conflicts of interest. R.G declares Honoria (self) from Roche, MSD, Merck, Medison, Janssen, Pfizer, AstraZeneca, Amgen, Takeda, Novartis, Gilead advisory and Consultancy; Astrazeneca, Roche, Bayer, MSD, Oncotest, Pfizer, Neopharm Group astellas, Eisai, J&J Innovative Medicine. Leadership Role in Pyxis as medical lead Shareholder/Stockholder/Stock options in Pyxis (options). The companies had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
CIPN pathology and potential therapeutic targets of THC and CBD via CB1/CB2 receptors.
Figure 2
Figure 2
Study methodology flowchart outlining data selection, patient clustering, and statistical analysis.
Figure 3
Figure 3
Patient enrollment flowchart.
Figure 4
Figure 4
Cancer type distribution within the study cohort.
Figure 5
Figure 5
Proportions of patients per number of symptoms pre-treatment and number of symptoms that improved after six months.
Figure 6
Figure 6
(A) Optimal number of clusters based upon THC and CBD doses (mg/day). (B) Proportions of patients per pre-treatment symptoms and symptoms that improved after six months. (C) Changes in QOL and ADL scores after six months of cannabis treatment.
Figure 7
Figure 7
(A) Range of CBD and THC doses in the study population. (B) Of patients, 56% contained THC alone while 44% contained both THC and CBD. (C) Improvement in CIPN-related symptoms by cluster (THC-high vs. CBD-high). Burning sensation and cold sensation improvements are presented with statistical annotations (p = 0.02 and p = 0.008, respectively). The THC × CBD interaction was determined to be additive based on logistic regression modeling.
See this image and copyright information in PMC

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