First RCT: vaporized THC+CBD was superior to placebo for acute migraine, with effects lasting 48 hours

THC+CBD (6% THC + 11% CBD) was superior to placebo for pain relief (67.2% vs 46.6%, OR 2.85), pain freedom (34.5% vs 15.5%, OR 3.30), and most bothersome symptom freedom (60.3% vs 34.5%, OR 3.32) at 2 hours, with sustained benefits at 24 and 48 hours. THC-dominant was superior for pain relief only (68.9% vs 46.6%, OR 3.14). CBD-dominant was not superior to placebo for any primary outcome. No serious adverse events.

Randomized, double-blind, placebo-controlled, crossover trial. 92 adults with migraine treated up to four attacks, one each with: (1) 6% THC, (2) 11% CBD, (3) 6% THC + 11% CBD, or (4) placebo cannabis flower. Minimum 1-week washout between attacks. 247 migraine attacks treated total. Primary endpoint: pain relief at 2 hours.

This is the first ever randomized controlled trial of cannabis for acute migraine. Migraine affects over 1 billion people globally, and current treatments fail for many patients. The finding that THC+CBD achieved 67% pain relief at 2 hours (comparable to triptans) with sustained 48-hour benefits and no serious adverse events is a landmark result.

The finding that CBD alone did not work for migraine while THC+CBD did suggests THC is the primary analgesic component, with CBD potentially contributing to the combination effect. This has practical implications for patients in jurisdictions where THC is restricted. The sustained benefits at 24 and 48 hours suggest cannabinoids may address mechanisms beyond acute pain, possibly including neuroinflammation.

Vaporization limits generalizability to patients willing and able to inhale. The placebo response was substantial (47%). Crossover design with up to four attacks per person means some variability in migraine characteristics. Sample size of 92 was modest. Only acute treatment was studied, not preventive use.