Evidence map›Paper›PMID 41549028›Full record

ReviewNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2026

Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.

Adriana Della Pietra, Andrew F Russo

Abstract readReview
In one paragraph

Review in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. The evolving landscape of primary headache therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Adriana Della PietraDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA. Electronic address: adellapietra@uiowa.edu.
Andrew F RussoDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA; Department of Neurology, University of Iowa, Iowa City, IA, USA; Veterans Affairs Healthcare System, Iowa City, IA, USA.

Funding

Role of Sleep Disruption after mTBI as a Driver of Chronic Post-traumatic HeadacheR01NS129573 · NINDS · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI Jeffrey J Iliff, Andrew F Russo · 2023 to 2026
$2.4M
NINDS NIH HHS R01 NS129573
6 · The paper itself

Abstract

Migraine is a disabling neurovascular disorder with limited therapeutic options, especially for patients unresponsive to current treatments targeting calcitonin gene-related peptide (CGRP) signaling. The endocannabinoid system (ECS) has emerged as a promising alternative for migraine modulation, offering analgesic, anti-inflammatory, and neuroimmune-regulatory effects through its main ligands, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their degrading enzymes. This review provides an updated map of endocannabinoid components in central and peripheral migraine-relevant regions, highlighting their spatial distribution and functional regulation in animal models. We summarize the available preclinical evidence supporting the anti-nociceptive effects of endocannabinoid-degrading enzyme inhibitors and cannabinoid receptor agonists/antagonists, with particular emphasis on the therapeutic potential of multi-target compounds. Moreover, we explore non-canonical ECS pathways, including TRPV1, D2 dopamine receptors, serotonergic and ion channel interactions, and their roles in modulating CGRP release and trigeminovascular signaling to treat migraine pathophysiology. Finally, we propose two sleep-related directions for treatments involving ECS modulation of circadian rhythms and glymphatic clearance. Although human translational data are limited, the ECS offers a multifaceted framework for developing next-generation therapeutics targeting migraine pathophysiology.

Indexed as

EndocannabinoidsMigraine DisordersSignal TransductionAnimalsHumansEndocannabinoids2-AGAnalgesicAnandamideCircadian rhythmGlymphatic clearance

Identifiers

PMID41549028
PMCPMC12996789

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.