Headaches

In the landmark Ze 440 RCT (n=170), headache was one of the premenstrual symptoms in the responder definition, and the responder rate (≥50% reduction in symptoms including headache) was 52% on the extract vs 24% on placebo over three cycles ^{1Reference 1Schellenberg R et al. · 7279RCTSchellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract (Ze 440): prospective, randomised, placebo controlled study. BMJ. 2001;322(7279):134–137. https://pubmed.ncbi.nlm.nih.gov/11159568/View study →}.

Headache was a component of the PMS symptom cluster rather than a standalone endpoint, and the data are for a proprietary standardized extract, so the result applies to cyclical, premenstrual headache rather than headache generally.

Migraine is feverfew’s one indication with a real body of human evidence, and that evidence is mixed. Six placebo-controlled RCTs (561 patients), of which the pivotal one — a stable supercritical-CO₂ extract (MIG-99, parthenolide-standardised, 6.25 mg t.i.d., n=170) — cut migraine frequency by ~0.6 attacks/month versus placebo, with no benefit on intensity or duration ^{3,4Reference 3Diener et al. · 2005RCTEfficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention — randomized, double-blind, placebo-controlled studyView study →Reference 4Pfaffenrath et al. · 2002RCTThe efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis — a double-blind, multicentre, randomized placebo-controlled dose-response studyView study →}. A 2015 Cochrane review calls this “some positive evidence” but low quality needing confirmation, echoed by a 2025 meta-analysis ^{5,6Reference 5Wider et al. · 2015Systematic reviewFeverfew for preventing migraine — systematic reviewView study →Reference 6Systematic review et al. · 2025Meta-analysisSystematic review and meta-analysis of Tanacetum parthenium: evaluating its efficacy in migraine relief. (2025) — meta-analysis. Natural Product Research. https://pubmed.ncbi.nlm.nih.gov/41422534/View study →}.

The effect is small, extract-specific, and does not transfer to teas, whole-leaf powder or other extracts. The mechanism runs through serotonin/granule release and vascular smooth-muscle contractility ^{7,8Reference 7Heptinstall et al. · 1985In vitroExtracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes — in vitroView study →Reference 8Barsby et al. · 1992In vitroFeverfew extracts and parthenolide irreversibly inhibit vascular responses of the rabbit aorta — in vitroView study →}. The evidence covers migraine prophylaxis only: prophylactic, not abortive, and null for tension-type headache.

A Clusterbusters medication-use survey reported that indoleamine hallucinogens including psilocybin aborted or prevented cluster-headache attacks, sometimes at sub-hallucinogenic doses ^{9Reference 9Schindler et al. · 2015Indoleamine hallucinogens in cluster headache: results of the Clusterbusters medication use survey}. The source is a single retrospective self-report survey, not a controlled trial.

A 10% peppermint-oil-in-ethanol solution dabbed on the forehead and temples eased tension-type headache in small double-blind trials from the Göbel group, with relief reported comparable to paracetamol at 15–30 minutes ^{10,11Reference 10Göbel et al. · 1996RCTEffectiveness of Oleum menthae piperitae and paracetamol in therapy of headache of the tension type — randomised controlled trialView study →Reference 11Göbel et al. · 2016ReviewPeppermint oil in the acute treatment of tension-type headache — reviewView study →}; the proposed mechanism is menthol activating cold-sensitive TRPM8 receptors in the skin rather than any systemic action ^{11Reference 11Göbel et al. · 2016ReviewPeppermint oil in the acute treatment of tension-type headache — reviewView study →}.

The evidence is a handful of older trials from essentially one research group, no large independent replication, and the effect is for topical oil — not oral use or tea.

Willow’s salicin is metabolised to salicylic acid — aspirin’s active principle — and the standardized extract suppresses COX-2 and inflammatory cytokines about as strongly as aspirin on a weight basis ^{12,13Reference 12European Medicines Agency · 2017ReviewAssessment report on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →Reference 13Khayyal et al. · 2005AnimalMechanisms involved in the anti-inflammatory effect of a standardized willow bark extract — animal model (rat)View study →}, with RCT- and Cochrane-backed analgesia for low back pain ^{14,15Reference 14Chrubasik et al. · 2000RCTTreatment of low back pain exacerbations with willow bark extract: a randomized double-blind study — RCTView study →Reference 15Oltean et al. · 2014Systematic reviewHerbal medicine for low-back pain — Cochrane systematic reviewView study →}.

No trial has tested willow for headache specifically. Its use for fever and headache is traditional, and rests on the same salicylate analgesia, which acts more slowly and weakly than aspirin.

The essential oil of Chrysanthemi Flos eased nitroglycerin-induced migraine in mice by regulating CGRP and substance P ^{2Reference 2Meng et al et al. · 2025AnimalEssential oil of Chrysanthemi Flos alleviates nitroglycerin-induced migraine via CGRP and substance P (mouse model)View study →}. It is the herb’s one direct headache signal, and it aligns with the traditional use of ju hua to “ease headaches.” The finding is in animals only and specific to the essential oil, not the water-extract tea; there are no human data, and it concerns migraine rather than tension or other headache types.

A traditional North American relaxing bitter nervine for nervous-tension headaches; the research is preclinical sedative/nervine only, with no headache data.

Traditionally used for digestion-related (bilious/constipation) headache as a laxative bitter; no research supports a headache indication.

Modern/traditional use for migraine rests on the herb’s anti-inflammatory / anti-allergic (sinus) reputation; no headache-specific research exists.

A traditional Western folk nervine for headaches; the research is preclinical anxiolytic/analgesic only, with no headache data.

The sedative/antispasmodic ‘dark leaves’ are traditionally used for tension headaches and muscle aches; evidence is thin preclinical sedative, and chronic use is limited by annonacin neurotoxicity.

A traditional hepatic bitter for ‘bilious migraine’ / liver-associated headache; no research support, and internal use is weighed against a documented idiosyncratic hepatotoxicity risk.

Traditional Amazonian use for migraine; two-edged, as guarana is the richest natural caffeine source and caffeine both relieves and (via overuse/withdrawal) triggers headaches — no headache-specific research.

A traditional sedative nervine for headaches and neuralgia; the research is sedative/estrogenic with no headache data.

A documented 19th-century North American sedative for headaches, neuralgia and pain; the human research supports situational anxiety and sleep, not headache.

A traditional circulatory nervine ‘for headaches and faintness’; no headache trial exists, and the aroma raised tension-anxiety in one study, so it is not uniformly calming.

A folk/aromatherapy remedy (topical and inhaled) for headaches; the evidence is preclinical (essentially concentrated linalool) and external.

A traditional Peruvian/Amazonian use of the root for headaches; the modern research (anti-hyperuricemic, anti-inflammatory, all preclinical) has no headache data.

A traditional TCM remedy for headache; two-edged, as tea is caffeine-bearing and caffeine both relieves and (via overuse/withdrawal) triggers headaches — no headache-specific research.

A well-established traditional sedative/antispasmodic nervine for tension and stress-associated headaches; no headache-specific trial (and mild headache is itself a listed adverse effect).

The classic European ‘herb for the head’ — a traditional relaxing nervine for tension/anxiety headaches with essentially no direct modern pharmacological validation.

A traditional Western remedy (Gerard) for headaches; the research covers antispasmodic and anti-inflammatory actions but includes no headache-specific data.