A 100:1 ratio of CBD to THC pretreatment rescued light sensitivity and partially reduced pain caused by the migraine-triggering peptide CGRP when administered directly into the brains of mice.
100:1 CBD:THC rescued CGRP-induced light aversionA CBD-dominant cannabinoid pretreatment fully reversed one of the hallmark migraine symptoms — light sensitivity — triggered by direct CGRP administration to the brain in mice.
What the researchers found
Pretreatment with a 100:1 CBD:THC ratio (100 mg/kg CBD, 1 mg/kg THC) administered intraperitoneally rescued CGRP-induced light aversion in CD1 mice. The cannabinoid combination also rescued increased resting time in darkness, decreased zone transitions, and partially rescued decreased rearing behavior caused by centrally administered CGRP.
Importantly, the automated squint assay showed that CBD:THC pretreatment partially rescued CGRP-induced spontaneous pain. An open field assay confirmed that the CGRP effects were migraine-specific (light aversion) rather than general anxiety, strengthening the specificity of both the migraine model and the cannabinoid rescue effect.
Why it matters
CGRP is the primary peptide target of modern migraine drugs (gepants and anti-CGRP antibodies), but not all patients respond to these treatments. If cannabinoids can independently counteract CGRP-driven migraine symptoms through the endocannabinoid system, this could open an entirely new therapeutic pathway — potentially helping patients who don't respond to direct CGRP blockade.
How the study worked
Researchers administered a 100:1 CBD:THC mixture intraperitoneally to CD1 mice 60 minutes before testing. CGRP was then injected intracerebroventricularly (directly into the brain) 30 minutes before behavioral assays. Three behavioral tests were used: a light/dark assay measuring light aversion and motility, an automated squint assay measuring spontaneous pain, and an open field assay to rule out general anxiety as a confound.
What this study cannot tell us
This is a mouse study using direct brain injection of CGRP, which is a more extreme model than how migraines develop naturally in humans. The CBD:THC doses used (100 mg/kg CBD) are very high relative to typical human dosing and may not translate directly. Only one CBD:THC ratio was tested. The study used pretreatment rather than acute treatment, so it's unclear whether cannabinoids would help once migraine symptoms are already present.
How to read the evidence
This is a preclinical animal study using a direct brain injection model of migraine. While the controlled experimental design and multiple behavioral assays strengthen the findings, animal models of migraine are imperfect proxies for the human condition, and the results require clinical validation.
When this study was published
Published in 2025, this is a very recent study at the frontier of CGRP-cannabinoid interaction research. It represents an emerging area of investigation that is likely to generate significant follow-up studies.
The bigger picture
This study bridges two major areas of neuroscience research: the CGRP-migraine pathway and the endocannabinoid system. While CGRP-targeting drugs have transformed migraine treatment, and anecdotal reports of cannabis helping migraines are widespread, this is among the first studies to demonstrate a direct interaction between cannabinoids and CGRP-induced migraine symptoms in a controlled preclinical model. It provides mechanistic support for investigating cannabinoid-based migraine therapies.
Questions still open
- Would cannabinoid treatment be effective when administered after CGRP-induced symptoms are already present, or only as a preventive pretreatment?
- What is the optimal CBD:THC ratio for migraine relief, and would pure CBD alone be sufficient?
- Through which specific receptor pathways (CB1, CB2, or others) do cannabinoids counteract CGRP's migraine-triggering effects?
Common questions
What is CGRP and why is it important in migraines?
Could this study lead to cannabinoid-based migraine treatments?
Read the original research
Cannabinoids rescue migraine symptoms caused by central CGRP administration in mice.
Cephalalgia : an international journal of headache, 45(11), 3331024251392103
Citation
Zorrilla, Erik; Duong, Thomas L; Piña, Cassandra L; Russo, Andrew F. (2025). Cannabinoids rescue migraine symptoms caused by central CGRP administration in mice.. Cephalalgia : an international journal of headache, 45(11), 3331024251392103. https://doi.org/10.1177/03331024251392103