Cannabinoids and migraine

Editor’s note: The research described below comes from a recipient of a 2024 MSC Travel Grant supporting travel to the 66th Annual Scientific Meeting of the American Headache Society. These grants reimburse travel expenses for those who have had their abstract for a presentation or poster accepted at a meeting.

By Erik Zorrilla, PhD student, University of Iowa, US.

What is the research gap that your study addresses?

Currently, there are medications such as CGRP monoclonal antibodies designed to help treat migraine. Approximately 30% of individuals taking these medications see a 75% reduction, and 10-20% of individuals see a complete reduction in migraine symptoms. These medications are at best effective at treating about 50% of individuals that suffer from migraine. As a result, there is a huge demand to seek out alternative therapies given the large percentage of migraine patients that do not see any therapeutic benefit from these medications.

This study aimed to address this gap by investigating whether cannabinoids can alleviate migraine symptoms in mice.

What is your research hypothesis?

There were 2 hypotheses in this experiment:

1) Can CBD and THC reduce migraine symptoms (central and peripheral)?

2) Will a combination of the two be more effective while limiting any adverse effects?

What methodology did you use to address your research hypothesis?

We have examined the efficacy and adverse effects of cannabinoids CBD and THC in a preclinical model of migraine using both peripherally (CGRP and SNP) and centrally (CGRP) administered migraine triggers.

To determine the ability of CBD:THC to reduce migraine-like phenotypes caused by peripheral (CGRP and SNP) and central (CGRP) triggers, we measured light aversion in the dark using the light-dark assay.

Light Aversion (Peripheral administration of CGRP and SNP): Using the light-dark assay, we measured the efficacy of various cannabinoid ratios on light aversion. The cannabinoids were peripherally injected 30 minutes prior to peripherally administering either the known migraine triggers CGRP (0.1 mg/kg) or SNP (2.5 mg/kg).

Light Aversion (Central Administration of CGRP): In this experiment, CBD:THC 100:1 was injected (i.p) 60 minutes before testing and CGRP was injected (i.c.v) 30 minutes before placing mice in the testing chamber in dim light.

The potential adverse effects of the different combinations of CBD:THC in mice were determined using the following assays: anxiety (light dark and open field), motor function (rotarod), spatial memory (Y-maze), depression (tail suspension).

What are the main results of your study?

Data from our lab indicate that a 100:1 ratio of CBD:THC is effective for treating light aversion (photophobia) from peripheral administration of CGRP and the nitric oxide donor SNP. We also report similar findings where pretreatment with the 100:1 ratio alleviates light aversion caused by central administration of CGRP while minimizing adverse effects.

This early research suggests the potential of cannabis-based treatments for peripheral and central mechanisms of migraine pathogenesis.

What conclusions did you reach based on your results?

We reached the following conclusions:

1) 100:1 rescued light aversion caused by peripheral administration of CGRP and SNP.

2) 100:1 rescued light aversion caused by central administration of CGRP.

3) None of the doses tested produced any adverse effects.

What are the limitations of your study?

Limitations to the study are the following:

1) The work is done on mice which has a valid concern of translatability.

2) There are hundreds of cannabinoids, and this study just focuses on THC and CBD.

Future studies either incorporating other cannabinoids or human studies would help address these two concerns.

What is the relevance of your study to migraine?

Migraine has a peripheral component because CGRP acts peripherally on the trigeminal ganglia, vasculature, and immune cells in the meninges. The CNS also contributes to migraine pathogenesis, since sensory abnormalities are present during a migraine, and CGRP receptors are distributed throughout the brain.

Triptans act on the CNS but have a list of serious side effects. CGRP monoclonal antibodies don’t easily cross over into the brain and are acting in the PNS.

Cannabinoids cross the BBB and act on receptors in the CNS and PNS. Our results show that cannabinoids are treating migraine symptoms cause by central and peripheral mechanisms.