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Oral cannabidiol for prevention of acute and transient chemotherapy-induced peripheral neuropathy

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Abstract

Purpose

To assess the safety, dosing, and preventive effects of cannabidiol (CBD) on chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving oxaliplatin- or paclitaxel-based chemotherapy.

Methods

Patients with cancer scheduled to undergo treatment with carboplatin and paclitaxel (Carbo-Tax) or capecitabine and oxaliplatin (CAPOX) received 150 mg CBD oil twice daily (300 mg/daily) for 8 days beginning 1 day before initiation of chemotherapy. Ten CIPN-specific patient-reported outcome (PRO) measures were captured at baseline and each day after the first cycle of chemotherapy for 8 days. Multi-frequency vibrometry (MF-V) was captured at baseline and day 4 ± 1 after initiation of chemotherapy. Controls were obtained from a similar patient cohort that did not receive CBD. Adverse events were captured using the CTCAE ver. 4.03.

Results

From March to December 2021, 54 patients were recruited. CBD-treated patients were significantly older (p = 0.013/0.037, CAPOX/Carbo-Tax) compared to controls. Patients receiving CBD and CAPOX or Carbo-Tax showed significantly lower (better) change in Z-scores in high-frequency MF-V (125 and 250 Hz) compared to controls. This difference was most pronounced for patients receiving Carbo-Tax (− 1.76, CI-95 = [− 2.52; − 1.02] at 250 Hz). CAPOX patients treated with CBD had significantly lower peak baseline-adjusted difference in three PRO items on cold sensitivity to touch, discomfort swallowing cold liquids, and throat discomfort (− 2.08, − 2.06, and − 1.81, CI-95 = [− 3.89; − 0.12], NRS 0–10). No significant differences in PRO items were found for patients receiving Carbo-Tax. Possible side effects included stomach pain (grades 1–2) for patients receiving CAPOX.

Conclusion

CBD attenuated early symptoms of CIPN with no major safety concerns. Long-term follow-up is ongoing. Results should be confirmed in a larger, randomized study.

Trial registration number

NCT 04,167,319 (U.S National Library of Medicine; ClinicalTrials.gov). Date of registration: November 18, 2019.

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Data availability

Data can be shared for transparency purposes if requested.

Code availability

All statistical operations were done in R-Studio (ver.1.3.1093).

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Acknowledgements

The authors would like to thank Glostrup Pharmacy and Nordic Cannabis Research for their support in partial funding of cannabidiol and the NEYE Foundation for funding the CINCAN-1 and -2 studies. In addition, we would like to thank the biostatisticians of OPEN, University of Southern Denmark, Inge Petersen, and Anna Mejldal for statistical consultation. Lastly, we would like to thank the patients for their time and for opening their homes to research visits.

Funding

The NEYE Foundation provided funding for salary in the CINCAN-1 and -2 studies. Glostrup Pharmacy and Nordic Cannabis Research partially funded cannabidiol.

Author information

Authors and Affiliations

  1. Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Vestermarksvej 9, 4000, Roskilde, Denmark

    Sebastian W. Nielsen, Simone Dyring Hasselsteen, Helena Sylow Heilmann Dominiak, Dejan Labudovic, Lars Reiter, Susanne Oksbjerg Dalton & Jørn Herrstedt

  2. Survivorship & Inequality in Cancer, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark

    Susanne Oksbjerg Dalton

  3. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1165, Copenhagen, Denmark

    Susanne Oksbjerg Dalton & Jørn Herrstedt

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  1. Sebastian W. Nielsen
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Contributions

S.W.N. and J.H. contributed to the study conception and design. Data collection were performed by S.W.N., S.D.H., and H.S.H.D. Data analysis was performed by S.W.N. The first draft of the manuscript was written by S.W.N. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sebastian W. Nielsen.

Ethics declarations

Ethics approval

The trial adhered to the Declaration of Helsinki and standards of Good Clinical Practice (GCP). The Danish Medicines Agency and the Ethical Committee approved the trial (EudraCT: 2020–002681-14, Protocol ID: SJ-846). GCP monitoring was conducted by the Danish GCP Units, Copenhagen Department. Data was handled in compliance with EU General Data Protection Regulation and the Danish Data Protection Act.

Consent to participate

All patients provided written consent.

Consent for publication

N/A.

Competing interests

The authors declare no competing interests.

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Nielsen, S.W., Hasselsteen, S.D., Dominiak, H.S.H. et al. Oral cannabidiol for prevention of acute and transient chemotherapy-induced peripheral neuropathy. Support Care Cancer 30, 9441–9451 (2022). https://doi.org/10.1007/s00520-022-07312-y

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