Graduate Program in Neuroscience, Washington State University, Pullman, WA, USA.
Department of Psychology, Washington State University Vancouver, Vancouver, WA, USA.
Eur J Pharmacol. 2018 Jan 5;818:271-277. doi: 10.1016/j.ejphar.2017.10.054. Epub 2017 Oct 28.
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 ∆-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 3h as measured by depression of home cage wheel running. Concurrent systemic administration of 0.32 but not 0.1mg/kg of THC prevented AITC-induced depression of wheel running. However, 0.32mg/kg was ineffective when administered 90min after AITC. Administration of a higher dose of THC (1.0mg/kg) depressed wheel running whether rats were injected with AITC or not. Administration of a CB, but not a CB, 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 (0.32mg/kg) and time (immediately after AITC); 2) THC's anti-migraine effect is mediated by CB 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 CB receptor as a therapeutic target for migraine.
目前的偏头痛治疗方法疗效有限，且有许多副作用。虽然有传闻证据表明大麻对偏头痛有效，但这一假说尚未在对照实验中得到验证。因此，本研究测试了给予 ∆-四氢大麻酚（THC）是否会在雌性大鼠中产生抗偏头痛作用。将 TRPA1 激动剂丙烯基异硫氰酸酯（AITC）微注射到硬脑膜上，可通过抑制家笼轮跑来测量 3 小时的偏头痛样疼痛。同时给予 0.32 但不是 0.1mg/kg 的 THC 可预防 AITC 诱导的轮跑抑制。然而，当在 AITC 后 90 分钟给予 0.32mg/kg 时，其无效。给予较高剂量的 THC（1.0mg/kg），无论大鼠是否注射 AITC，都会抑制轮跑。给予 CB1 但不是 CB2 受体拮抗剂可减弱 THC 的抗偏头痛作用。这些数据表明：1）当给予正确剂量（0.32mg/kg）和时间（在 AITC 后立即）时，THC 可减轻偏头痛样疼痛；2）THC 的抗偏头痛作用是通过 CB 受体介导的；3）轮跑是评估偏头痛治疗方法的有效方法，因为只有产生镇痛作用而没有破坏性副作用的治疗方法才能恢复正常活动。这些发现支持了大麻素作为人类偏头痛治疗方法的传闻证据，并暗示 CB 受体是偏头痛的治疗靶点。
