Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of Δ9-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat. Microinjection of the TRPA1 agonist allyl isothiocyanate (AITC) onto the dura mater produced migraine-like pain for 3 h as measured by depression of home cage wheel running. Concurrent systemic administration of 0.32 but not 0.1 mg/kg of THC prevented AITC-induced depression of wheel running. However, 0.32 mg/kg was ineffective when administered 90 min after AITC. Administration of a higher dose of THC (1.0 mg/kg) depressed wheel running whether rats were injected with AITC or not. Administration of a CB1, but not a CB2, receptor antagonist attenuated the anti-migraine effect of THC. These data suggest that: 1) THC reduces migraine-like pain when administered at the right dose (0.32 mg/kg) and time (immediately after AITC); 2) THC's anti-migraine effect is mediated by CB1 receptors; and 3) Wheel running is an effective method to assess migraine treatments because only treatments producing antinociception without disruptive side effects will restore normal activity. These findings support anecdotal evidence for the use of cannabinoids as a treatment for migraine in humans and implicate the CB1 receptor as a therapeutic target for migraine.