CBD and THC Together Rescue Migraine Symptoms in a Mouse Model

A 100:1 CBD-to-THC ratio pretreatment reversed CGRP-induced migraine symptoms in mice, including light aversion and spontaneous pain, supporting cannabis-based approaches for migraine.

Zorrilla, Erik et al.·Cephalalgia : an international journal of headache·2025·Preliminary Evidencepreclinical
RTHC-08054PreclinicalPreliminary Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
preclinical
Evidence
Preliminary Evidence
Sample
Not reported

What This Study Found

Pretreatment with 100 mg/kg CBD + 1 mg/kg THC rescued CGRP-induced light aversion, reduced resting time in darkness, increased light/dark transitions, and partially rescued spontaneous pain (squint assay) in mice. The effects were specific to migraine (CGRP-induced) rather than general anxiety.

Key Numbers

100:1 CBD:THC ratio (100 mg/kg CBD, 1 mg/kg THC). Rescued light aversion, resting time in darkness, zone transitions. Partially rescued squint (spontaneous pain). Open field confirmed no anxiety confound.

How They Did This

Preclinical study administering 100:1 CBD:THC ratio intraperitoneally 60 minutes before intracerebroventricular CGRP injection in CD1 mice, measuring photophobia (light/dark assay), motility, and spontaneous pain (automated squint assay).

Why This Research Matters

CGRP is the validated target in current migraine medications. Showing that cannabinoids can counteract CGRP-induced migraine symptoms provides mechanistic support for cannabis-based migraine treatment and clarifies the optimal CBD:THC ratio.

The Bigger Picture

Migraine affects over 1 billion people worldwide. Many patients report cannabis helps, but clinical evidence is sparse. This mechanistic study supports the biological plausibility of cannabinoid-based migraine treatment by targeting the CGRP pathway.

What This Study Doesn't Tell Us

Mouse migraine model using direct CGRP injection doesn't replicate human migraine triggers. 100:1 ratio at these doses may not translate to human dosing. Only pretreatment, not acute treatment, was tested.

Questions This Raises

  • ?Would this CBD:THC ratio be effective as an acute migraine treatment in humans?
  • ?How does the cannabinoid mechanism interact with CGRP-targeted antibody medications?

Trust & Context

Key Stat:
Evidence Grade:
Well-designed preclinical study with multiple behavioral endpoints and appropriate controls, but mouse model and pretreatment-only design limit clinical translation.
Study Age:
Recent study providing mechanistic support for cannabinoid-based migraine treatment at a specific CBD:THC ratio.
Original Title:
Cannabinoids rescue migraine symptoms caused by central CGRP administration in mice.
Published In:
Cephalalgia : an international journal of headache, 45(11), 3331024251392103 (2025)
Database ID:
RTHC-08054

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Can cannabis help with migraines?

This mouse study shows a 100:1 CBD:THC combination reversed migraine symptoms triggered by CGRP (the same molecule targeted by newer migraine drugs). Human clinical trials are needed to confirm.

Why a 100:1 CBD to THC ratio?

This ratio provides primarily CBD effects with minimal THC, avoiding the psychoactive high while potentially retaining therapeutic benefit. The small amount of THC may enhance CBD's effects through the entourage effect.

Read More on RethinkTHC

Cite This Study

RTHC-08054·https://rethinkthc.com/research/RTHC-08054

APA

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

MLA

Zorrilla, Erik, et al. "Cannabinoids rescue migraine symptoms caused by central CGRP administration in mice.." Cephalalgia : an international journal of headache, 2025. https://doi.org/10.1177/03331024251392103

RethinkTHC

RethinkTHC Research Database. "Cannabinoids rescue migraine symptoms caused by central CGRP..." RTHC-08054. Retrieved from https://rethinkthc.com/research/zorrilla-2025-cannabinoids-rescue-migraine-symptoms

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.