title: An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain.
abstract: Cannabinoids are emerging as potential options for neuropathic pain treatment. This study evaluated an oral cannabinoid, nabilone, in the treatment of refractory human diabetic peripheral neuropathic pain (DPN). We performed a single-center, randomized, double-blind, placebo-controlled, flexible-dose study with an enriched enrollment randomized withdrawal design. DPN subjects with a pain score ≥ 4 (0-10 scale) continued regular pain medications and were administered single-blinded adjuvant nabilone for 4 weeks. Subjects achieving ≥ 30% pain relief (26/37) were then randomized and treated with either flexible-dose nabilone 1-4 mg/day (n=13) or placebo (n=13) in a further 5-week double-blind treatment period, with 30% (11/37) of subjects deemed run-in-phase nabilone nonresponders. For nabilone run-in-phase responders, there was an improvement in the change in mean end-point neuropathic pain vs placebo (mean treatment reduction of 1.27; 95% confidence interval 2.29-0.25, P=0.02), with an average nabilone dose at end point of 2.9 ± 1.1mg/day, and improvements from baseline for the anxiety subscale of the Hospital Anxiety and Depression Scale, the Medical Outcomes Study sleep scale problems index, and the European Quality of Life-5-Domains index score (each P<0.05). Nabilone run-in-phase responders reported greater global end-point improvement with nabilone than with placebo (100% vs 31%; P<0.05). Medication-related confusion led to discontinuation in 2/37 subjects during single-blind nabilone treatment. Potential unmasking occurred in 62% of both groups. Flexible-dose nabilone 1-4 mg/day was effective in relieving DPN symptoms, improving disturbed sleep, quality of life, and overall patient status. Nabilone was well tolerated and successful as adjuvant in patients with DPN.
authors.affiliation: The Department of Clinical Neurosciences, the Hotchkiss Brain Institute, and the University of Calgary, Calgary, Alberta, Canada.
authors.forename: Cory
authors.initials: C
authors.lastname: Toth
authors.forename: Shefina
authors.initials: S
authors.lastname: Mawani
authors.forename: Shauna
authors.initials: S
authors.lastname: Brady
authors.forename: Cynthia
authors.initials: C
authors.lastname: Chan
authors.forename: CaiXia
authors.initials: C
authors.lastname: Liu
authors.forename: Essie
authors.initials: E
authors.lastname: Mehina
authors.forename: Alexandra
authors.initials: A
authors.lastname: Garven
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bestard
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korngut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000175:diagnosis / Q000188:drug therapy*; D015990:Placebo Effect; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; C011941:nabilone; D013759:Dronabinol