Background: After traumatic brachial plexus injuries, despite treatment with appropriate medications, some patients experience uncontrollable pain, which can be devastating. Cannabis-based medicine is considered to have pain-relieving benefits in this situation, but the evidence is limited., Questions/purposes: Is cannabis-based medicine effective compared with the placebo in (1) reducing pain (measured by the VAS for pain) and neuropathic pain (measured by the DN4 questionnaire), and (2) improving sleep quality (measured by the VAS for sleep quality) in patients with traumatic brachial plexus injury?, Methods: This prospective, triple-blinded (the researcher administering the substance, the patients, and the evaluator were all blinded to the substance used), two-period crossover, placebo-controlled, randomized controlled trial was conducted at a single center. Between January 2020 and January 2022, we treated 147 patients for neuropathic pain related to a traumatic brachial plexus injury. Our inclusion criteria were age between 20 and 60 years and moderate-to-severe pain (VAS for pain equal to or greater than 4 of 10 for more than 6 months), even with the use of appropriate medications. Based on these criteria, 20% (30) of patients were eligible. They were randomly allocated to receive either cannabis-based medicine followed by the placebo or vice versa. Fifteen patients received cannabis-based medicine first, and 15 patients received the placebo first. The groups did not differ at baseline in terms of demographic parameters. Participants received both the cannabis-based medicine and the placebo; they started with 10 days of the initial intervention, followed by a 14-day washout period, and then a 10-day period with the second intervention. The dosage regimen adhered strictly to the protocol. The outcomes were the (1) VAS for pain, which ranges from 0 to 10 and where 0 represents no pain and 10 signifies the worst pain; (2) the DN4 questionnaire which ranges from 1 to 10 and where a score of 4 or higher indicates a positive result for neuropathic pain; and (3) VAS for sleep quality, from 0 (worst) to 10 (best). The minimum clinically important difference of VAS for pain was defined as a 2-point improvement. After enrollment, 7% (2 of 30) of patients (one patient received the cannabis-based medicine first and another received the placebo first) were lost before the minimum study follow-up, leaving 93% (28 of 30) for analysis. With 28 patients in each group, the study was powered a priori at 90% to detect a clinically important difference of 2 points in the VAS for pain. No carryover or period effects were observed in the study. Four patients experienced mild dizziness during the cannabis-based medicine period but were able to continue the intervention., Results: When comparing the use of cannabis-based medicine alongside pain control medications with the combination of placebo and pain control medications, the reduction in pain VAS from the preintervention resulted in a mean difference of 1 (99% CI -0.03 to 2.1; p = 0.01). Neuropathic pain was reported by 75% (21 of 28) of patients in both interventions (OR 1 [99% CI 0.07 to 14.1]; p > 0.99). The VAS for sleep quality favored cannabis-based medicine with a mean difference of 1.5 (99% CI 0.7 to 2.4; p < 0.001)., Conclusion: Our study findings indicate that cannabis-based medicine did not improve pain by a clinically important margin. Consequently, our study advises against the addition of cannabis-based medicine to the standard medication treatment for pain in patients with traumatic brachial plexus injury., Level of Evidence: Level 1, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)