“Aim: To investigate the effect of different cannabinoid compounds on the periorbital mechanical allodynia and photosensitivity in acute and chronic migraine models.
Methods: Female Wistar rats were treated systemically with different cannabinoid compounds (cannabidiol, CBD, 30 mg/kg; CBD and cannabigerol, CBD/CBG – 2:1; CBD and 0.3% tetrahydrocannabinol (CBD/THC); or CBD/CBG/THC) followed by injection of calcitonin-gene-related peptide (CGRP) or pituitary adenylate cyclase-activating polypeptide (PACAP) into the trigeminal ganglion to induced immediate periorbital mechanical allodynia and late photosensitivity. The effect of CBD and CBD/THC was also assessed on periorbital mechanical allodynia and photosensitivity in the chronic migraine model induced by repeated nitroglycerin (NTG) injections.
Results: Periorbital mechanical allodynia induced by CGRP was significantly reduced by CBD alone and combined with THC or CBG. CBD/THC was the most effective treatment in this condition since it presented the longer effect (up to three hours) and was the only treatment capable of reducing late photosensitivity associated with CGRP. All four compounds presented antinociceptive effect on acute migraine-like responses induced by PACAP, with CBD alone presenting the longer effect (from 30 minutes up to two hours). Except for CBD/CBG, all compounds also reduced (up to two hours) late photosensitivity associated with PACAP. In the chronic migraine model induced by NTG, CBD reduced periorbital mechanical allodynia on days 5, 7 and 11, while CBD/THC suppressed the development of periorbital allodynia up to day 13 and significantly reduced photosensitivity up to three hours.
Conclusion: Altogether, these results suggest that cannabinoid compounds may represent effective alternatives for the treatment of episodic and chronic migraine.”
https://pubmed.ncbi.nlm.nih.gov/41129688/
“The present findings highlight the potential of specific cannabinoid formulations, particularly the low-THC and CBD/THC combination, as candidates for migraine management.
This compound consistently attenuated periorbital allodynia and photosensitivity across acute (CGRP- and PACAP-induced) and chronic (nitroglycerin-induced) migraine models, without producing locomotor or anxiety-like effects. CBD alone demonstrated moderate efficacy, with shorter duration of action and limited effects on light-induced sensitization, while CBG-containing combinations showed variable results depending on the trigger, suggesting distinct interactions with CGRP- and PACAP-mediated pathways.
These data support further controlled clinical studies to evaluate CBD- and CBD/THC-based therapies as potential preventive or adjunctive options for patients with episodic or chronic migraine, particularly those with suboptimal responses to current targeted treatments.”