Review finds cannabinoid effects vary by pain condition and formulation

INTRODUCTION: Low back pain, migraine, and other headache disorders are major contributors to disability, and interest in cannabinoid-based interventions has increased despite uncertainty regarding their indication-specific therapeutic value. This systematic review evaluated the efficacy and safety of isolated cannabinoids, synthetic cannabinoids, vaporized Cannabis products, and standardized Cannabis extracts for low back pain, migraine, and medication-overuse headache. METHODS: Electronic databases, trial registries, and supplementary sources were searched for double-blind randomized clinical trials in adults. Eligible studies were assessed using Risk of Bias 2, synthesized narratively according to synthesis without meta-analysis guidance, and rated for certainty using Grading of Recommendations Assessment, Development, and Evaluation (PROSPERO registration: 582772). RESULTS: Five randomized controlled trials involving 1,072 participants met the inclusion criteria. In acute low back pain, a single 400-mg oral dose of isolated cannabidiol was not superior to placebo. In acute migraine, vaporized tetrahydrocannabinol (THC) plus cannabidiol (CBD) improved 2-h pain relief, pain freedom, and freedom from the most bothersome symptom, with sustained benefits observed for selected outcomes through 24-48 h, compared with placebo, whereas a CBD-dominant formulation showed no clear benefit. In medication-overuse headache and chronic musculoskeletal pain, nabilone showed favorable but very uncertain signals for pain-related outcomes and analgesic consumption. In chronic low back pain, a phase III trial showed that the standardized full-spectrum Cannabis extract VER-01 improved pain intensity, disability, sleep quality, and patient-reported outcomes compared with placebo. THC-containing inhaled formulations were associated with more psychoactive adverse effects and possible functional unblinding. CONCLUSION: Current randomized evidence does not support a class-wide effect of cannabinoid-based therapies for low back pain or headache disorders. Efficacy appears to depend on indication, formulation, route of administration, and cannabinoid composition. Moderate-certainty evidence supports vaporized THC + CBD for acute migraine outcomes, including 2-h efficacy and sustained response for selected outcomes through 24-48 h and VER-01 for chronic low back pain; evidence for single-dose oral cannabidiol and nabilone remains very uncertain. Larger independently replicated trials using analytically standardized formulations, harmonized outcomes, active-placebo strategies when THC is present, and additional studies evaluating repeated use across multiple migraine attacks and longer-term safety are needed.