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The Anti‐migraine Effects of Delta‐9‐tetrahydrocannabinol in Female Rats are Mediated by CB 1 Receptors
Author(s) -
Kandasamy Ram,
Dawson Cole T,
Lee Andrea T,
Morgan Michael M
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.811.6
Subject(s) - migraine , antagonist , agonist , zolmitriptan , pharmacology , medicine , sumatriptan , migraine treatment , receptor antagonist , rizatriptan , cannabinoid receptor , microinjection , population , anesthesia , receptor , environmental health
Migraine affects 15% of the world's population, yet treatment options are limited by poor efficacy and adverse effects such as medication overuse headache. Anecdotal data suggest that marijuana may be an effective treatment for migraine. We tested this hypothesis by measuring whether administration of delta‐9‐tetrahydrocannabinol (THC), the psychoactive constituent of marijuana, has anti‐migraine effects in female rats. In addition, we administered cannabinoid receptor antagonists to determine whether these anti‐migraine effects are mediated by CB 1 or CB 2 receptors. Migraine pain was induced in female rats by microinjection of the TRPA1 agonist allyl isothiocyanate (AITC, 10%) onto the dura via a cannula implanted through the skull one week earlier. Migraine‐like pain was assessed by measuring changes in home cage wheel running. Rats were injected with either vehicle, the CB1 receptor antagonist SR141716 (1 mg/kg), or the CB2 receptor antagonist SR144528 (3.2 mg/kg) 30 min prior to simultaneous administration of AITC and vehicle or THC (0.32 mg/kg, i.p.). Microinjection of AITC caused a reduction in wheel running that lasted approximately 3 hours. Administration of THC attenuated the depression of wheel running caused by AITC administration. Administration of the CB 1 , but not the CB 2, receptor antagonist attenuated the anti‐migraine effects of THC. Neither antagonist depressed wheel running in control animals. Taken together, these data indicate that the anti‐migraine effects of THC are mediated by CB 1 receptors. Support or Funding Information This study was supported in part by State of Washington Initiative Measure No. 502 and NIH grant NS095097 (to MMM).