Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial

BackgroundPreclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine. MethodsIn this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% {Delta}9-tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was [≥]1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization. ResultsNinety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events. ConclusionsAcute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours. Trial Registration NumberNCT04360044 DisclosuresNMS has received research funding from Migraine Research Foundation, Novaremed, UCSD Academic Senate, UCSD Department of Anesthesiology RAG, and NIH CTSA Grant UL1TR000100 and has consulted for Eli Lilly & Co., Averitas, Syneos, Schedule 1 Therapeutics, Vectura Fertin, and ShiraTronics. He serves on the editorial board of Pain Medicine (Oxford University Press). DCB has been a consultant for Abbvie, Amgen, Biohaven, Lilly, Lundbeck, Teva, Theranica. She has received grant support from the US Food and Drug Association and National Headache Foundation. She is an editor for Current Pain and Headache Reports. MSW, TM, EL, LL and MS have no disclosures to report.