1 Division of Experimental Medicine, Faculty of Medicine and Health Sciences, Graduate Program in Clinical and Translational Research, McGill University, Montreal, Quebec, Canada.
2 Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
3 Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
4 McGill Nutrition and Performance Laboratory, Research Institute-McGill University Health Centre, Montreal, QC, Canada.
5 Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, QC, Canada.
6 School of Human Nutrition, McGill University, Macdonald Campus, Sainte-Anne-de-Bellevue, QC, Canada.
7 Division of Palliative Care, Jewish General Hospital, Montreal, Canada.
8 Department of Family Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
9 Department of Microbiology,

Purpose: This study explored the effectiveness of cannabidiol (CBD) alone and in combination with multi-modal exercise (MME) to improve signs and symptoms of chemotherapy-induced peripheral neuropathy (CIPN), quality of life (QoL), and functional capacity in cancer survivors.

Methods: Cancer survivors (n = 27) with CIPN were enrolled in a 4-month interventional open-label study. Participants underwent two consecutive 2-month interventions: CBD (up to 300 mg/day) and CBD combined with MME. They were assessed using the painDETECT questionnaire for CIPN-related neuropathic pain and the Functional Assessment of Cancer Treatment/Gynecological Oncology-Neurotoxicity-13 (FACT-GOG-Ntx-13) questionnaire for CIPN neurotoxic symptoms (Ntx), perceived physical function (PPF) and overall QoL. Their functional status was examined through gait speed and timed up and go for mobility, the 9-hole peg test for manual dexterity, a hand-held hydraulic dynamometer for hand grip strength, and five repetitions sit-to-stand for dynamic balance, upper/lower extremity and overall strength.

Results: Positive effect sizes were measured by Cohen's d or Cohen's r with 95% confidence intervals (CI) from mean scores, and were d 0.62, CI 0.03-1.20 for Ntx; d 0.62, CI 0.09-1.26 for PPF; and r 0.401, CI 0.13-0.61 for hand grip strength after 2 months of CBD alone. After adding MME to CBD for another 2 months, the effect sizes were d 0.526, CI -0.15-1.19 for painDETECT; d 0.862, CI 0.67-1.55 for CIPN neurotoxic symptoms; d 1.03, CI 0.30-1.74 for perceived physical function; r 0.447, CI 0.15-0.67 for overall QoL; r 0.339, CI 0.03-0.59 for gait speed; and r 0.389, CI 0.08-0.63 for manual dexterity.

Conclusions: The study provides a proof of concept for the therapeutic effect of CBD alone and in combination with MME to improve symptoms' burden, QoL and functional impairments related to CIPN in patients who are cured from cancer. Future randomized studies are needed to confirm the causal effects of CBD and exercise on CIPN, and to replicate our findings.