Cannabinoids in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Randomized Double Blind Controlled Trial

Marisa Carey Weiss^1,2*Muath Giaddui¹Stephanie Kjelstrom¹Joseph Gary³Sara Jane Ward⁴Jessica Burrell¹Katherine Diguilio¹Gabrielle Bidas⁵Ebuwa Erebor¹Sam Meske^1,2Lisa Saeed¹Sarah Windawi¹Katherine Aliano Ruiz¹Arezoo Ghaneie¹Julianne Hibbs⁵John H Marks¹David Holtz¹Zonera Ali⁵Aarti Shevade⁵Jennifer Sabol⁵Robin Ciocca⁵Erik Zeger⁵PAUL B GILMAN¹Sharon Larson^1,6Shoichi Shimamoto⁵Diana Martinez³

• ¹Lankenau Institute for Medical Research, Wynnewood, United States
• ²Breastcancer.org, Ardmore, Pennsylvania, United States
• ³Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, United States
• ⁴Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
• ⁵Lankenau Medical Center, Wynnewood, Pennsylvania, United States
• ⁶Center for Population Health Research, Wynnewood, Pennsylvania, United States

Chemotherapy-induced peripheral neuropathy (CIPN) can greatly impair function, leading to disability or truncated treatment in cancer patients. Previous animal studies show that cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) can ameliorate CIPN. This study assessed the effect of combined CBD and THC on CIPN symptoms amongst cancer patients treated with taxane-or platinum-based agents.This 12-week randomized, double-blind, placebo-controlled trial included participants with nonmetastatic breast, colorectal, endometrial, or ovarian cancer experiencing grade 2-3 CIPN. The active group received CBD (125.3-135.9 mg) combined with THC (6.1-10.8 mg) in gelcaps. The Quality-of-Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20) sensory subscale was used as the primary outcome. Additional outcomes assessed pain, sleep, and function. Neurologic exams evaluated touch, pressure, and vibration sense. Following the randomized controlled trial, participants were invited to enroll in a 12-week open-label observational study.Of 230 participants identified, 124 met eligibility, 54 were enrolled, 46 were randomized, and 43 completed 12 weeks of treatment. The mean age was 60 +/-9 years, 88% were female, 63% had breast cancer. All participants had completed chemotherapy. The primary analysis showed no differences in outcome measures between active and placebo groups. However, a secondary analysis (of the 46 randomized, adjusted for time in study and baseline CIPN severity) showed that the active group experienced greater improvement in the QLQ-CIPN20 measures of sensory impairment relative to placebo (-10.4 (95% -20.5, -0.3), p = 0.044) and symptoms of numbness and tingling (-10.5 (95% CI -20.9, -0.1), p = 0.048). There was also improvement in light touch and vibration sensation of the feet on neurological exam that approached significance. There was no effect on other measures, including pain, and no between-group differences in side effects. The observational study showed similar results.Although the primary analysis showed no between-group difference, our secondary analysis indicated that CBD with THC could improve self-reported sensory impairment and might increase touch and vibration sense. Given that CIPN is prevalent, but difficult to treat, cannabinoids should be further investigated as a potential treatment.