Migraine, Natural Treatment and Supplements: What Was Measured, and What About Imitrex and Topamax

In brief5 points · 1-minute read

• No human, animal or laboratory study has ever tested reishi, lion's mane, cordyceps or turkey tail in migraine or headache.
• Lion's mane and headache share a single PubMed record: a 2025 systematic review that names headache as a possible side effect, not a treatment.
• Zolmitriptan (Zomig) is cleared almost entirely by CYP1A2, an enzyme reishi inhibited in rat liver microsomes; nobody has measured the combination in people.
• Vitamin B2 at 400 mg daily reduced migraine days across 673 subjects; magnesium and CoQ10 meta-analyses disagree. We sell none of these.
• Among 1,374 reishi users surveyed, 9.1% reported side effects and vertigo in 3%; headache was not on the list.

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Migraine is a condition where “natural treatment” is searched after “treatment” — and the mushrooms offered are lion’s mane (Hericium erinaceus), reishi (Ganoderma lucidum, the lingzhi of Chinese medicine) and cordyceps. The honest answer: no study, in humans, animals or a dish, has tested a medicinal mushroom in migraine or headache. The one record linking lion’s mane to headache lists it as a side effect. Magnesium, B2 and CoQ10 were measured; we sell none. Imitrex, Zomig, Inderal — below.

The kinds of evidence that do exist, from closest to a person to furthest away: on migraine itself — meta-analyses of supplements we do not sell, a Cochrane review of one plant, and a review of 19 herbal trials without a single mushroom among them; on the drugs — pharmacokinetic reviews that explain how each drug is broken down, and two human trials that show what a real interaction looks like when it is actually measured; on the mushrooms — enzyme inhibition in a dish with rat liver tissue, mouse experiments on thermal pain and on inflammation in a Parkinson’s model, and small human cognition trials in which headache was not measured. On the combination “mushroom × migraine” there is nothing at all. This page is written around what you are actually asking, and says of every item what it is — and what it is not.

Do medicinal mushrooms help with migraine — what was actually tested?

Nothing. Neither reishi, lion’s mane, cordyceps nor turkey tail has been tested in migraine or headache, in any human trial, animal or laboratory model. PubMed returns 2, 1, 2 and 9 records respectively — none a study of the mushroom in migraine. That is not evidence of no effect — it is a total absence of measurement.

To understand how unusual that is, it helps to know the scale of the condition. According to the Global Burden of Disease study for 2021, 1.2 billion people live with migraine, and the burden is highest in women aged 30–44; the previous study in the same series is titled “Migraine remains second among the world’s causes of disability, and first among young women”. For a condition on that scale, with a supplement market that knows how to say “magnesium riboflavin cocktail”, you might have expected someone to test a mushroom. Nobody did. Migraine science has also moved in an entirely different direction: the new generation of drugs — antibodies against CGRP and its receptor — is “the first designed specifically to act on the trigeminal pain system”, as a 2018 review in Nature Reviews Neurology summarizes. Studies on any mushroom and CGRP: 0 records.

And so this page is not built around the mushrooms. It is built around what you type: can a mushroom be combined with the drug you already take, can lion’s mane actually cause headaches, what has been measured in supplements (which we do not sell), and what was found in ocular, vestibular, hormonal or cervicogenic migraine — on those subtypes, incidentally, the answer is identical: zero mushroom studies in each of them, and each of them is a matter for a neurologist.

What was measured, in which system — and what came out?

The table sorts your questions by what was measured and in which organism. The first four rows — the mushrooms — are empty. The drug rows hold the drug’s pharmacology and the mushroom’s test tube, not a measurement of the combination. Only the rows for supplements we do not sell contain randomized human trials in migraine.

Does reishi help with migraine or headaches?

Not measured. Searching reishi with “migraine” or “headache” returns two PubMed records: a 2023 case report of a 47-year-old man who presented with headache and abdominal pain, diagnosed with liver injury after reishi powder with alcohol, and a Nigerian folk-medicine survey where headache is attributed to a different mushroom. No trial, no animal, no dish.

What the market claims. “Reishi calms the nervous system”, “reishi for sleep — and good sleep keeps migraine away”, “reishi is anti-inflammatory”. The second sentence rests on a correct premise (broken sleep is a recognized trigger) and on a claim that was never measured: there is not one controlled trial of reishi on sleep in humans, and we laid that out on the reishi for sleep page. The third sentence comes from cells and mice.

What exactly was measured. The two records. The first is a case report: the headache was a symptom of acute hepatitis, which resolved fully within two weeks after supportive care, and the authors emphasize the concurrent alcohol use. That is a liver finding, not a headache finding, and it joins reishi’s D score in the LiverTox database, which we have written about before. The second is a 2011 ethnobotanical survey: in Nigeria, headache is traditionally attributed to Pleurotus tuber-regium, while reishi is attributed to arthritis and tumors. In other words, even in folk medicine reishi was not linked to headache.

Why it does not carry over automatically to a person. There is nothing to carry over. Even the mechanisms that were measured in reishi — immune-cell stimulation, liver-enzyme inhibition, platelet inhibition — have never been tested against the trigeminal ganglion or against CGRP, and have no known route to get there.

What can be known today. That anyone taking reishi should know what it does to liver enzymes in a dish (the triptan chapter), and which of its side effects were actually measured (the side-effects chapter). What to ask the doctor. Not “does reishi help migraine” — but “which of my drugs go through CYP1A2”.

Does lion’s mane help with migraine — or cause headaches?

On “helps” — zero studies, in any organism. On “causes” — the only PubMed record linking lion’s mane to headache is a 2025 systematic review which writes: “although generally not reported, possible side effects include stomach discomfort, headache and allergic reactions”. In none of the studies in that review was headache measured as an outcome.

This is the mushroom that comes up in the English search — and half of Google’s completions for “lions mane migraine” are actually the opposite question: “can lion’s mane give you headaches”, “lions mane cause migraine”, “mushroom causing headache”. A question born on forums, which lands here because no sales site answers it. So we will.

What was measured, in humans. The 2025 systematic review gathered 5 randomized trials, 3 pilots, one cohort and one case report — all on cognition and mood, not on pain. The most-cited trial: 30 Japanese adults aged 50–80 with mild cognitive impairment, 4 tablets of 250 mg three times a day, 16 weeks; the cognitive score rose at weeks 8, 12 and 16, and fell 4 weeks after stopping; “laboratory tests showed no adverse effect”. The first author works at Hokuto, a mushroom producer. The longest trial: 49 weeks with an erinacine A-enriched mycelium, in which four subjects dropped out because of abdominal discomfort, nausea and skin rash — and “no other adverse events were reported”. First author and corporation: Grape King Bio, a manufacturer. In 41 healthy young adults, 1.8 grams for 28 days — side effects not reported in the abstract. In 30 women who ate lion’s mane cookies for 4 weeks — a complaints questionnaire in which headache did not appear as a reported item. And one case of anaphylaxis after eating fresh lion’s mane, cited in a 2024 clinical review in an ALS journal.

What this means. Three different things, which must not be mixed: “not measured” — headache was not an endpoint in any trial; “not reported” — in the trials that did record side effects, headache was not among them; and “possible” — the review lists it as an effect that is generally not reported. Whoever writes “lion’s mane causes headaches” is relying on one sentence; whoever writes “lion’s mane does not cause headaches” is relying on an absence of measurement. Neither of them has read it. What can be known: if you started a supplement and a new headache appeared — that is a data point you are measuring on yourself, and it is worth more than all the literature; stop, and tell your doctor. And if lion’s mane interests you because of brain fog rather than pain — the lion’s mane and brain fog page lays out what was measured there, and who shouldn’t take lion’s mane lays out who should not.

“Lion’s mane raises NGF and calms neuroinflammation” — what does that mean for migraine?

Nothing that was measured. NGF rose in human astrocytoma cells in a dish and in the hippocampus of mice fed 5% powder for 7 days. “Neuroinflammation” fell in microglial cells and in rats injected with LPS into the substantia nigra — a Parkinson’s model. A migraine model — trigeminal, dural, nitroglycerin — with any mushroom: 0 studies.

This is the mechanism every sales page quotes, so we will go through it slowly. NGF. In 2008, out of extracts of four edible mushrooms, only lion’s mane raised NGF expression and secretion in human 1321N1 astrocytoma cells, through the JNK pathway; hericenones C, D and E — the compounds the market credits with the effect — did not. In mice, 5% dry powder in the feed for 7 days raised NGF in the hippocampus. In 2013, a Malaysian aqueous extract induced NGF secretion in NG108-15 cells and increased neurite outgrowth by 60.6% — and failed to protect against oxidative stress: “neurotrophic but not neuroprotective”, in the authors’ words. Neuroinflammation. Erinacine A from mycelium, in BV-2 microglial cells and astrocytes with LPS, prevented NO and TNF-α production; in rats injected with LPS into the substantia nigra, early administration improved motor tests and lowered TNF-α and IL-1β in the midbrain. Erinacine C, in BV2 cells only, lowered NO, IL-6 and TNF-α through NF-κB and Nrf2. Both of these studies have authors from the supplement industry.

Why it does not carry over to migraine. Migraine, as far as science knows today, begins in the trigeminal system and the neuropeptide CGRP — which is why the new generation of drugs is aimed precisely there. Astrocytoma in a dish, mouse hippocampus and rat substantia nigra with LPS are three other places in the nervous system, in three models of other conditions. The only study of lion’s mane and pain in a whole animal tested a mycelium extract on thermal pain — tail-flick and hot-plate tests in mice — and its authors, from Grape King Bio, themselves write that “further studies are needed to validate the relationship”. Thermal pain in a mouse’s paw is not migraine. And in the absence of a single trigeminal model with a mushroom, even the most beautiful mechanism stays where it is: in the dish.

And what about cordyceps and turkey tail?

Zero. Cordyceps with “migraine” or “headache” — two records: an ethnography of the Sherpa people of Tibet, where headache is treated with seven substances and cordyceps is not among them, and a side-effect review in which the headache belongs to a different plant. Turkey tail — 9 records, all noise: vaccines, brain tumors, acronyms of other preparations.

Cordyceps is sold worldwide as the energy mushroom, and headache is nowhere in its file. In 78 interviews with Sherpa people in Chentang, 824 use reports covered 51 plants and one fungus — cordyceps; headache was among the five most common complaints, with 63 use reports across 7 substances, and none of them was cordyceps. In the retrospective review of 1,816 adverse-event reports in Kraków, “headache and dizziness” appear with a combination of eleuthero and agomelatine — a plant, not a mushroom; cordyceps in that same review appears in one report of gastrointestinal bleeding with sertraline, which we wrote about on the cordyceps safety page. On turkey tail there is not even that. The question “do mushrooms affect serotonin” — relevant, because triptans are 5-HT1B/1D receptor agonists — also returns 0 human studies on the three mushrooms. A full data void, in both directions.

Taking Imitrex, Zomig or Relpax (triptans) — can you combine them with mushrooms?

Not measured — a question for the pharmacist, with one fact: zolmitriptan (Zomig) is broken down in human hepatocytes almost exclusively by CYP1A2, and sumatriptan (Imitrex) partly. Reishi inhibited CYP1A2 — in rat liver microsomes. The combination was never measured in humans. Eletriptan (Relpax) goes through CYP3A4, where reishi was weak in human microsomes.

What is known about the drugs. The 2006 review of headache-drug interactions lists the combinations to avoid: sumatriptan, rizatriptan or zolmitriptan with MAO inhibitors; and drugs that go through CYP2D6 and CYP3A4 — ergot derivatives and eletriptan. In 1999, in fresh human hepatocytes, furafylline — a selective CYP1A2 inhibitor — almost completely abolished zolmitriptan metabolism, while inhibitors of 2C9, 2C19, 2D6 and 3A4 did nothing; CYP1A2 was the only enzyme that formed the active metabolite, and the authors — from the pharmaceutical company that makes it — write that “interactions with drugs that induce or inhibit CYP1A2 can be expected”. In 2023, a re-examination of sumatriptan in recombinant human enzymes found that CYP1A2, CYP2C19 and CYP2D6 also break it down, and that sumatriptan itself is “only a weak substrate” for MAO-A. Eletriptan: in human microsomes, metabolite formation correlates with CYP3A4 (r²=0.932), and erythromycin and miconazole inhibited it markedly.

What is known about reishi. In 2007, a reishi polysaccharide inhibited, in rat liver microsomes and dose-dependently, three enzymes: CYP2E1, CYP1A2 and CYP3A; the authors write that drug pharmacokinetics “may be altered in herb–drug interaction”. And in 2022, in human microsomes, a reishi extract was weak on CYP3A — an IC50 value above 10 micrograms per milliliter, a “lesser effect” compared with other plants in the same assay. On human CYP1A2 — no data at all. On lion’s mane and cordyceps and CYP enzymes — 0 studies.

What a measured interaction looks like. For the word “interaction” to mean something, you need a number. Here are two: in 12 healthy volunteers, four days of moclobemide (an MAO-A inhibitor) before rizatriptan 10 mg raised the area under the curve of rizatriptan 2.2-fold and that of the active metabolite 5.3-fold, and the authors write that the combination “is not recommended”. And in 51 volunteers, seven days of propranolol — a preventive drug many of you take — raised rizatriptan by about 67% and its peak concentration by about 75%, hence the recommendation of 5 mg rizatriptan under propranolol. That is the bar. Mushrooms have no such number — not because it is zero, but because nobody has measured. 0 studies of mushrooms with any triptan.

The wording we can stand behind: reishi inhibited, in a test tube, in rat liver, the enzyme that breaks down Zomig almost alone and takes part in breaking down Imitrex and Inderal; in humans that was not tested — so it is a question for the pharmacist, not a decision to make alone. Not “reishi raises Imitrex levels”, not “dangerous to combine”, not “safe to combine”. What to bring to the pharmacist: the name of the triptan, the name of the supplement, and whatever else you take that goes through CYP1A2. The wider list of what has and has not been measured — on the drug interactions page.

And with Topamax, Inderal (propranolol) or Elavil (amitriptyline)?

Three drugs, three answers — all “not measured”. Topiramate (Topamax) is mostly renally excreted, about 20% metabolized, and “is not subject to drug interaction through enzyme inhibition” — the calmer side. Propranolol (Inderal) is a CYP1A2 substrate — the previous chapter’s enzyme. Amitriptyline (Elavil) goes through CYP2D6 and CYP2C19, which reishi did not inhibit in the dish.

Topamax. The 2004 pharmacokinetics review — co-written by a professor at the Hebrew University of Jerusalem — describes a drug with mostly renal clearance, about 20% metabolism in monotherapy, a half-life of 19–25 hours, and very few interactions: at 200 mg a day, no meaningful effect on amitriptyline, sumatriptan or propranolol. The sentence that matters to you: “not subject to drug interaction due to enzyme inhibition”, because of the renal excretion. In other words, the pathway through which a supplement could change the drug’s blood level barely exists — as with pregabalin, which we wrote about on the fibromyalgia page. The caveat, as always: “not expected” is not “measured”. Mushrooms with topiramate — 0 studies.

Inderal. A 2020 review of 83 clinical trials of propranolol describes dose-dependent bioavailability and a substrate of three enzymes — CYP2D6, CYP1A2 and CYP2C19 — “with potential for pharmacokinetic interactions”. CYP1A2 again, so the triptan chapter applies here too: inhibition in a dish, in a rat, not in a human. And what propranolol itself does to a triptan — 67% more rizatriptan — is the proof that migraine drugs talk to each other even without any supplement. Elavil. The 2016 CPIC consortium guideline establishes that amitriptyline is affected by CYP2D6 and CYP2C19 genotype, to the point of genetic dose adjustment. Reishi in a dish inhibited CYP1A2, CYP3A and CYP2E1 — not those two. In other words, there is not even a direct theoretical link; what exists is one human trial of a mushroom with a drug from the same broad family — cordyceps alongside duloxetine in 59 patients with depression, 6 weeks — in which side effects did not differ from placebo. Not amitriptyline, not migraine, and without blood-level measurement.

And with Ajovy, Emgality or Botox injections?

Here, not even a theoretical axis. CGRP antibodies — fremanezumab (Ajovy), galcanezumab (Emgality), erenumab (Aimovig) — are injected proteins, absorbed through the lymph, and “most of their clearance occurs by intracellular catabolism into peptides and amino acids” — not liver, not kidney, not CYP. Botox acts locally. A pharmacodynamic interaction of a mushroom with CGRP: 0 studies.

The 2019 pharmacokinetics review — by researchers from Eli Lilly, maker of one of the drugs — explains why a monoclonal antibody can barely be affected by a supplement: it is broken down in the gut if swallowed, and so it is injected; it is cleared like any protein in the body; and its efficacy is measured by the size and duration of the drop in free CGRP. Erenumab, the first approved (2018), is an antibody against the CGRP receptor. What could have been relevant — whether a mushroom changes CGRP itself — has never been tested, in any organism. One small note: Ajovy is a migraine drug; Wegovy is a weight-loss drug — do not confuse them.

What was actually measured in migraine that we do not sell — magnesium, vitamin B2 and CoQ10?

Three supplements, dozens of randomized trials, contradictory results. Vitamin B2: 673 subjects, 400 mg a day for 3 months — fewer migraine days (p=.005) and attacks (p=.001). Magnesium: OR 0.20 for frequency in one meta-analysis, “unknown whether effective” in another. CoQ10: −1.87 attacks a month in one, −0.44 and not significant in another. We sell none.

In Hebrew nobody types “riboflavin” or “coenzyme” next to migraine — the completions are empty — while in English “migraine supplement” returns “cocktail”, “protocol”, “magnesium riboflavin”. That gap is why this chapter exists: these are the only supplements measured in randomized trials in people with migraine, and you should know their names before you buy a mushroom that was not measured. Magnesium. A 2016 meta-analysis of 21 trials — 11 of intravenous magnesium in acute attacks (948 participants) and 10 of oral magnesium for prevention (789) — found that oral magnesium reduced frequency and intensity (OR 0.20 and 0.27), with the authors’ caveat that some trials were not properly randomized. A 2019 meta-analysis of vitamins and minerals, which included 3 magnesium trials in 226 participants, found a reduction in severity that did not reach significance, and concluded: “it is unknown whether CoQ10 and magnesium are effective”. And a 2026 network meta-analysis of 14 trials in 791 participants found that magnesium did not significantly reduce frequency (−0.82) — but was the only one to reduce severity, by 3.56 points on a 0–10 scale. Three meta-analyses, three answers. As for the claim “migraine is magnesium deficiency” — there is no meta-analysis of blood levels behind it; the search returns 0.

Vitamin B2 (riboflavin). The most consistent evidence of the three: a 2022 meta-analysis of 8 randomized trials and one controlled study, 673 subjects, found a significant reduction in migraine days, duration, frequency and pain score, at 400 mg a day for 3 months — with high heterogeneity on some measures. A 2017 review of 11 trials wrote “mixed effect”: 5 consistently positive trials in adults, mixed results in children, and side effects “generally mild”. CoQ10. −1.87 attacks a month across 4 trials (221 participants) in a 2020 meta-analysis, with severity and duration not reaching significance; −1.52 attacks across 6 trials (371) in 2021, with no reduction in severity; and −0.44, not significant, across 2 trials (97) in 2019. A 2025 dose-response meta-analysis of 22 trials summed up magnesium −2.51 attacks, CoQ10 −1.73, riboflavin −1.34, vitamin D −1.69, probiotics −1.16 — and omega-3 zero on every measure; and the 2026 network meta-analysis ranked probiotics first (−2.60 attacks a month) — on the basis of one trial against placebo. There is no mushroom in any of these papers. We write these numbers because they are what was measured, not to recommend; the dose and the choice belong with a neurologist.

And what about herbs — and why “mushrooms for migraine” in English is something else entirely?

Feverfew is the most studied plant: a 2015 Cochrane review of 6 trials in 561 patients; largest trial: 0.6 fewer attacks a month than placebo; evidence quality “low”. A review of 19 herbal trials — feverfew, butterbur, curcumin, ginger, peppermint — includes no mushroom. “Mushrooms for cluster headache” means psilocybin — not a medicinal mushroom, not our product.

The plants show what “a plant that was tested” looks like: in the large feverfew trial (218 participants), attacks fell from 4.8 to 2.9 a month on the plant and from 4.8 to 3.5 on placebo — a difference of 0.6; intensity, duration and nausea did not differ; three small trials were positive and the two more rigorous ones — zero. Six randomized trials, and still “low-quality evidence”. Medicinal mushrooms: 0 randomized trials in migraine. The 2020 systematic review of single-ingredient herbal treatments screened 19 randomized trials — feverfew mixed, butterbur “positive, if limited”, curcumin and coriander preliminary, high risk of bias in many — and its list of plants ends without a single mushroom.

And the separating sentence that has to be said: if you read “mushrooms for cluster headache” or “mushrooms for migraine” in English — that is psilocybin. A 2021 crossover trial in 10 adults with migraine found a reduction of 1.65 migraine days a week after a single dose of psilocybin versus 0.15 after placebo (p=0.003), with no correlation to the intensity of the psychotropic effect. That is a different mushroom, a controlled substance, a study of ten people — and it has nothing to do with reishi, lion’s mane or cordyceps. Whoever mixes the two is selling you something.

Are mushrooms in food a migraine trigger?

Not measured. The 2016 “Diet and Headache” review lists triggers backed by repeated provocation trials — caffeine withdrawal and MSG dissolved in liquid — and triggers with “modest evidence” in subgroups: gluten, histamine, alcohol, and aspartame with conflicting results. Mushrooms are not on the list, and no study has tested them as a trigger. Neither confirmed nor denied.

“mushroom migraine trigger” is Google’s first English completion for “mushroom migraine”, so it gets an answer here — even when the answer is “no measurement”. The trigger lists online are mostly built around tyramine, and mushrooms sometimes appear on them; but the 2016 review found that the strong evidence belongs to caffeine withdrawal and MSG, and that an IgG-guided elimination diet reduced frequency in two of three trials. A 2023 review adds that elimination diets must be individualized, that ketogenic and DASH diets reach “moderate-quality evidence” for reducing frequency and duration in adults, and that the microbiome in migraine is different — with probiotics as “further research needed”. The honest answer for anyone asking whether mushrooms on the plate set off their migraine: your diary answers that better than any review — and if there is a pattern, it is a data point for the neurologist.

What are the side effects of the mushrooms themselves — and is headache among them?

Measured in humans: in a survey of 1,374 cancer patients taking reishi, 9.1% reported a side effect — vertigo in 3%; headache not on the list. In a Cochrane review, reishi for 4 months carried a 1.67-fold side-effect risk — not significant, not serious. Lion’s mane: dropouts for stomach, nausea, rash, and one anaphylaxis from the fresh mushroom.

This is the fourth evidence hole on the page — and perhaps the most practical, because anyone living with migraine knows how to tell a new headache from the old one. Reishi. The 2024 survey is the largest that exists, but it is a survey of people who chose to continue, with no control group, and one author from an industry group; vertigo in 3% is the closest figure to headache, and it is not headache. The 2015 Cochrane review of reishi found a risk ratio of 1.67 for any adverse effect, with a confidence interval crossing 1, “and no serious effects”. In 42 Alzheimer’s patients, 6 weeks of spore powder — “all adverse effects were mild, with no significant difference from placebo”. And then the 2023 case report: headache and abdominal pain that turned out to be acute hepatitis after reishi powder with alcohol — rare, reversible, and added to the list on the “who shouldn’t take reishi” page. Lion’s mane. The 2025 systematic review lists headache as possible and “generally not reported”; in the 49-week trial four dropped out for abdominal discomfort, nausea and rash; in 30 adults with mild cognitive impairment “laboratory tests showed no adverse effect”; and one case of anaphylaxis was documented after eating the fresh mushroom — the review that cites it, from an ALS journal, adds that the cognition trial is “very small, temporary improvement, not yet replicated”. What this means for you: supplements are not subject to adverse-event reporting the way drugs are, so the absence of “headache” from the lists is also the absence of a reporting system. A new headache after a new supplement — stop, record it in your migraine diary, and tell your doctor. The overall picture is gathered on the side effects page.

What we actually measure in our bottle

After a whole page of “not measured”, you deserve to know what was measured — and about what exactly. We grow the mushrooms ourselves, on a farm in the Galilee: fresh fruiting body, not mycelium grown on grain — like the one in most of the lion’s mane studies you read above — and not imported powder whose name on the sack cannot be verified. The mushroom goes from harvest straight to extraction, with no drying step in between; as far as we know, we are among the few in the world who work this way. The extraction is triple, and its alcohol stage runs for 7 weeks. Extraction ratios on a fresh-mushroom basis: lion’s mane 1:2 and reishi 1:3. Alcohol in the finished extract: 32% — a figure worth bringing to the pharmacist together with the names of your drugs, especially if you are on a drug that restricts alcohol.

And the numbers are not ours to set. We sent the finished extracts for testing at TÜV Austria, and what came back is the beta-glucan percentage on a dry-matter basis — and alongside it alpha-glucan, meaning starch, which was not detected in any of them. Alpha-glucan not detected is the chemical proof that there is no grain in the bottle. To understand why that matters, it helps to know the market’s three-step ladder: mycelium grown on grain, where beta-glucan is usually below 7% and most of the weight is the grain’s starch; imported dried fruiting body, whose quality depends on who dried it and when; and fresh fruiting body from the farm, which is what we do. And on a page that talks about magnesium, it should also be said: we have no data on the magnesium content of our extracts, and there is no data in the literature on reishi or lion’s mane — so we will not make any magnesium claim. Why beta-glucan and not “total polysaccharides” — we explained separately.

All our tests are public, and anyone who wants to read the report themselves will find our explanation of how to read a COA. Kosher certification — Mateh Yehuda Rabbinate, Rabbi Gad Atias. That is what we know how to measure and prove about what is in the bottle. What it will do for migraine or headaches was not measured — so it is not written.

What this page does not say — and what we do not claim

We do not claim that reishi, lion’s mane, cordyceps or turkey tail prevent migraine, shorten an attack, reduce headache or “calm the nervous system” — at any dose and in any form; none of them has been measured in migraine, in any organism. We do not claim the opposite either — that lion’s mane causes headaches: the evidence is one sentence in a review, not a measurement. We do not claim that reishi raises Imitrex or Zomig levels in the blood — that was not measured in humans; and we do not claim the combination is safe — that was not measured either. We do not claim that magnesium, B2 or CoQ10 are “proven” — the meta-analyses contradict each other, and we do not sell them. We do not claim that mushrooms on the plate are a trigger, or that they are not. And we do not deal here with disability benefits, disability ratings or chronic migraine as a recognized condition — we have no expertise in those and no sources on them. What we do say: migraine is treated by a physician or a neurologist; anyone taking a triptan, a preventive drug or a CGRP injection — talks to the doctor or pharmacist before any supplement, including ours. Under DSHEA, a dietary supplement may not claim to diagnose, treat, cure or prevent any disease. We sell mushroom extracts, and we are telling you explicitly not to buy them for migraine.

The bottom line

Medicinal mushrooms have not been tested in migraine — not in humans, not in animals, not in a dish. The only record linking lion’s mane to headache lists it as a possible side effect. What was measured — magnesium, vitamin B2 and CoQ10 — gave contradictory results in meta-analyses, and we do not sell it. On triptans: Zomig is broken down almost alone by CYP1A2, the enzyme reishi inhibited in a dish, and nobody has measured the combination in a person — a question for the pharmacist. On Topamax and Ajovy: there is no interaction axis, and still no measurement. And if someone sells you a mushroom “for migraine” — send them this page, and go to a neurologist.

Frequently asked questions

Does lion’s mane help with migraine?

Not measured — in any human or any animal. Searching lion’s mane with “migraine” or “headache” returns one record in all of PubMed: a 2025 systematic review that lists headache among the possible side effects. What was measured on lion’s mane in humans is cognition and mood, in small trials, and headache was not an endpoint in any of them.

Does lion’s mane cause headaches?

The evidence is one sentence: a 2025 systematic review writes that possible side effects, “although generally not reported”, include stomach discomfort, headache and allergic reactions. In the 49-week trial four dropped out for stomach, nausea and rash — not headache. “Not measured” is not “does not happen” and not “happens”. A new headache after a new supplement — stop and tell your doctor.

Can I take reishi with Imitrex or Zomig?

Not measured in humans — a question for the pharmacist. What is known: zolmitriptan (Zomig) is broken down in human hepatocytes almost exclusively by CYP1A2, and sumatriptan (Imitrex) partly; reishi inhibited CYP1A2 in rat liver microsomes. The clinical relevance is unknown, and mushroom studies with a triptan — 0. Bring the pharmacist the name of the drug and the name of the supplement.

And with Topamax?

Not tested — but the calmer side. Topiramate is mostly excreted by the kidneys, only about 20% is metabolized, and its pharmacokinetics review writes that it “is not subject to drug interaction through enzyme inhibition”. In other words, the pathway through which a supplement could change the drug’s level barely exists. “Not expected” is not “measured”; tell your doctor.

And with Ajovy or CGRP injections?

There is no known interaction axis: CGRP antibodies are proteins that are broken down into amino acids, with no liver enzymes and no kidney. What was not measured: whether any mushroom affects CGRP itself — 0 studies. And by the way, Ajovy is a migraine drug; Wegovy is a weight-loss drug — do not confuse them.

Which supplement was actually measured in migraine?

Vitamin B2 — 673 subjects in a meta-analysis, 400 mg a day for 3 months, fewer migraine days and attacks; magnesium and CoQ10 — with contradictory meta-analyses: OR 0.20 for frequency in one and “unknown whether effective” in another. We sell none of them, and the choice of dose belongs with a neurologist. Medicinal mushrooms were not measured at all.

Are mushrooms a migraine trigger?

Not measured. The “Diet and Headache” review lists caffeine withdrawal and MSG dissolved in liquid as proven triggers, and — with modest evidence — gluten, histamine and alcohol in subgroups. Mushrooms are not on the list and no study has tested them. Your migraine diary answers this question better than any review.

I read about “mushrooms for migraine” in English — is that reishi?

No. “Mushrooms for migraine” and “mushrooms for cluster headache” in English mean psilocybin — a 2021 crossover trial in 10 adults found a reduction of 1.65 migraine days a week after a single dose, versus 0.15 on placebo. That is a different mushroom, a controlled substance, and it has nothing to do with reishi, lion’s mane or cordyceps.

Scientific sources (peer-reviewed)

• Systematic review of lion’s mane as a supplement (5 randomized trials, 3 pilots, a cohort, a case report — all cognition): “although generally not reported, possible side effects include stomach discomfort, headache and allergic reactions”. The only PubMed record linking lion’s mane to headache — Menon A, et al. Frontiers in Nutrition, 2025. View on PubMed
• Case report: a 47-year-old man presented with headache and abdominal pain after reishi powder with alcohol — acute hepatitis, full resolution within two weeks — Guedikian R, et al. Cureus, 2023. View on PubMed
• Ethnobotanical survey in Nigeria: headache attributed to Pleurotus tuber-regium; reishi attributed to arthritis and tumors — not to headache — Oyetayo OV. African Journal of Traditional, Complementary and Alternative Medicines, 2011. View on PubMed
• 78 interviews with Sherpa people in Tibet, 824 use reports: headache = 7 substances and 63 reports; cordyceps is not attributed to headache — Ding X, et al. Journal of Ethnopharmacology, 2024. View on PubMed
• Retrospective review of 1,816 adverse-event reports: 30 adaptogen × antidepressant cases; “headache and dizziness” — eleuthero with agomelatine (a plant); cordyceps — gastrointestinal bleeding with sertraline — Siwek M, et al. Frontiers in Pharmacology, 2023. View on PubMed
• Only lion’s mane of four mushrooms raised NGF expression and secretion in human astrocytoma cells (JNK pathway); hericenones C, D, E — no; in mice, 5% powder for 7 days — hippocampal NGF — Mori K, et al. Biological & Pharmaceutical Bulletin, 2008. View on PubMed
• Aqueous lion’s mane extract in NG108-15 cells: +60.6% neurite outgrowth with NGF; induced NGF secretion; no protection against oxidative stress — “neurotrophic but not neuroprotective” — Lai PL, et al. International Journal of Medicinal Mushrooms, 2013. View on PubMed
• 30 subjects aged 50–80 with mild cognitive impairment, 250 mg ×4 ×3 a day, 16 weeks: cognitive score above placebo at weeks 8, 12, 16 — and fell 4 weeks after stopping; “laboratory tests showed no adverse effect”. First author from a mushroom producer — Mori K, et al. Phytotherapy Research, 2009. View on PubMed
• 30 women, lion’s mane cookies for 4 weeks: depression and anxiety scores fell from baseline; versus placebo — significance on two questionnaire items; headache not reported as an item — Nagano M, et al. Biomedical Research (Tokyo), 2010. View on PubMed
• Mild Alzheimer’s, erinacine A-enriched mycelium 3×350 mg a day, 49 weeks, double-blind: four subjects dropped out for abdominal discomfort, nausea and rash; “no other adverse events were reported”. Grape King Bio — Li IC, et al. Frontiers in Aging Neuroscience, 2020. View on PubMed
• Erinacine A in microglial cells and astrocytes with LPS prevented NO and TNF-α; in rats with LPS in the substantia nigra — improved movement, lower TNF-α and IL-1β. A Parkinson’s model, not migraine — Lee SL, et al. International Journal of Molecular Sciences, 2022. View on PubMed
• Erinacine C in BV2 cells with LPS: lower NO, IL-6, TNF-α and iNOS through NF-κB and Nrf2/HO-1. Cultured cells only; Grape King Bio — Wang LY, et al. Molecules, 2019. View on PubMed
• Lion’s mane mycelium extracts blocked ATP calcium signaling in cells and delayed tail-flick and hot-plate responses in mice — thermal pain; “further studies are needed to validate the relationship”. Grape King Bio — Liu PS, et al. International Journal of Medicinal Mushrooms, 2017. View on PubMed
• CGRP as the target of the new drug generation: receptor antagonists and antibodies — “the first designed specifically to act on the trigeminal pain system” — Edvinsson L, et al. Nature Reviews Neurology, 2018. View on PubMed
• Interactions of headache drugs, part I: avoid triptans with MAO inhibitors; CYP2D6 and CYP3A4 substrates (ergot, eletriptan); risk higher in chronic headache with medication overuse — Sternieri E, et al. Expert Opinion on Drug Metabolism & Toxicology, 2006. View on PubMed
• Sumatriptan in recombinant human enzymes: CYP1A2, CYP2C19 and CYP2D6 break it down; sumatriptan itself “only a weak substrate” for MAO-A — Pöstges T, Lehr M. Pharmacology Research & Perspectives, 2023. View on PubMed
• Zolmitriptan in human hepatocytes: furafylline (a CYP1A2 inhibitor) almost completely abolished metabolism; CYP1A2 — the only enzyme forming the active metabolite; “interactions with drugs that inhibit CYP1A2 can be expected”. Zeneca — Wild MJ, et al. Xenobiotica, 1999. View on PubMed
• Eletriptan in human microsomes: metabolite formation correlates with CYP3A4 (r²=0.932); erythromycin and miconazole inhibited it; a P-gp substrate. Merck — Evans DC, et al. Drug Metabolism and Disposition, 2003. View on PubMed
• 12 volunteers, crossover: moclobemide 150 mg ×2 for four days, then rizatriptan 10 mg — AUC ×2.2 for rizatriptan and ×5.3 for the active metabolite; “not recommended”. What a measured interaction looks like — Van Haarst AD, et al. British Journal of Clinical Pharmacology, 1999. View on PubMed
• 51 volunteers: rizatriptan 10 mg after 7 days of propranolol — AUC +67%, Cmax +75%; nadolol and metoprolol no effect; recommendation: rizatriptan 5 mg under propranolol. Merck — Goldberg MR, et al. British Journal of Clinical Pharmacology, 2001. View on PubMed
• Topiramate: mostly renal clearance, ~20% metabolism, t½ 19–25 hours; “not subject to drug interaction due to enzyme inhibition”; at 200 mg a day — little or no interaction with amitriptyline, sumatriptan, propranolol — Bialer M, et al. Clinical Pharmacokinetics, 2004. View on PubMed
• Propranolol — review of 83 clinical trials: substrate of CYP2D6, CYP1A2 and CYP2C19 “with potential for pharmacokinetic interactions”; dose-dependent bioavailability — Kalam MN, et al. Current Drug Metabolism, 2020. View on PubMed
• CPIC 2016 guideline for tricyclic antidepressants: amitriptyline is affected by CYP2D6 and CYP2C19 genotype, which determines dose adjustment — Hicks JK, et al. Clinical Pharmacology & Therapeutics, 2017. View on PubMed
• CGRP antibodies: parenteral administration, lymphatic absorption, “most clearance by intracellular catabolism into peptides and amino acids” — not CYP, not kidney. Eli Lilly — Kielbasa W, Helton DL. Cephalalgia, 2019. View on PubMed
• Erenumab — first global approval (2018): a fully human antibody against the CGRP receptor, significant reduction in migraine frequency in phase II/III — Markham A. Drugs, 2018. View on PubMed
• A reishi polysaccharide dose-dependently inhibited CYP2E1, CYP1A2 and CYP3A in rat liver microsomes; “pharmacokinetics may be altered in herb–drug interaction” — Wang X, et al. Biological & Pharmaceutical Bulletin, 2007. View on PubMed
• In human liver microsomes, on CYP3A: reishi — “lesser effect”, IC50 above 10 micrograms per milliliter; Curcuma zedoaria IC50 4.18 — Rodseeda C, et al. Toxicology Reports, 2022. View on PubMed
• The only trial of a mushroom with a psychiatric drug: 59 patients with depression and insomnia, cordyceps alongside duloxetine versus placebo, 6 weeks — adverse effects no different; insomnia: the placebo improved more (p<0.05) — Zhou J, et al. Frontiers in Psychiatry, 2021. View on PubMed
• Magnesium — meta-analysis of 21 trials: intravenous in acute attacks (948) OR 0.23–0.25; oral for prevention (789) — frequency OR 0.20, intensity OR 0.27; some trials without proper randomization — Chiu HY, et al. Pain Physician, 2016. View on PubMed
• Vitamins and minerals for prevention — 18 trials: CoQ10 frequency −0.44 (2 trials, 97) not significant; magnesium severity RoM −0.17 (3 trials, 226) not significant; “it is unknown whether CoQ10 and magnesium are effective” — Okoli GN, et al. Canadian Journal of Neurological Sciences, 2019. View on PubMed
• Riboflavin — review of 11 trials: 5 consistently positive in adults, mixed in children; side effects “generally mild” — Thompson DF, Saluja HS. Journal of Clinical Pharmacy and Therapeutics, 2017. View on PubMed
• Vitamin B2 — meta-analysis of 8 randomized trials and one controlled study, 673 subjects, 400 mg a day for 3 months: fewer migraine days (p=.005), duration (p=.003), frequency (p=.001), pain score (p=.015); high heterogeneity — Chen YS, et al. Nutritional Neuroscience, 2022. View on PubMed
• CoQ10 — 6 trials, 371: frequency −1.52 attacks (p<0.001), duration −0.19; severity — no significant reduction — Sazali S, et al. BMJ Open, 2021. View on PubMed
• CoQ10 — 4 trials, 221: frequency −1.87 attacks a month (p<0.001); severity −2.35 (p=0.105) and duration −6.14 hours (p=0.086) — not significant — Parohan M, et al. Nutritional Neuroscience, 2020. View on PubMed
• 22 trials, dose-response meta-analysis: magnesium −2.51 attacks; CoQ10 −1.73; riboflavin −1.34; vitamin D −1.69; probiotics −1.16; omega-3 — zero on every measure. No mushroom — Talandashti MK, et al. Neurological Sciences, 2025. View on PubMed
• Network meta-analysis, 14 trials, 791: probiotics −2.60 attacks a month (one trial); CoQ10 −1.91; magnesium frequency −0.82 not significant — but severity −3.56 on a 0–10 scale. No mushroom among the nodes — Peng J, et al. Frontiers in Nutrition, 2026. View on PubMed
• Cochrane on feverfew: 6 trials, 561; in the large trial (218) — from 4.8 to 2.9 attacks a month versus 4.8 to 3.5 on placebo, a difference of 0.6; “low-quality evidence” — Wider B, et al. Cochrane Database of Systematic Reviews, 2015. View on PubMed
• Systematic review of 19 randomized herbal trials for migraine — feverfew, butterbur, curcumin, peppermint, coriander, chamomile, lavender: high risk of bias in many; no mushroom — Lopresti AL, et al. Phytotherapy Research, 2020. View on PubMed
• Diet and headache: strong trigger evidence — caffeine withdrawal and MSG in liquid; gluten, histamine, alcohol — “modest evidence” in subgroups; aspartame conflicting. Mushrooms not on the list — Martin VT, Vij B. Headache, 2016. View on PubMed
• Diet and migraine 2023: individualized elimination diets; ketogenic and DASH — “moderate-quality evidence”; a different microbiome, probiotics — “further research needed” — Gazerani P. Current Opinion in Neurology, 2023. View on PubMed
• Psilocybin in migraine — 10 adults, double-blind crossover: −1.65 migraine days a week versus −0.15 on placebo (p=0.003). Not a medicinal mushroom, not our product — Schindler EAD, et al. Neurotherapeutics, 2021. View on PubMed
• Cross-sectional survey of 1,374 cancer patients taking reishi: 9.1% reported adverse effects — dry mouth 5%, constipation 4%, insomnia 3%, itching 3%, vertigo 3%; headache not on the list. No control — Li X, et al. Integrative Medicine Research, 2024. View on PubMed
• Cochrane review: 5 trials, 398; people taking reishi for 4 months at a 1.67-fold risk of an adverse effect (95% CI 0.86–3.24) — not significant, not serious — Klupp NL, et al. Cochrane Database of Systematic Reviews, 2015. View on PubMed
• 42 Alzheimer’s patients, reishi spore powder for 6 weeks: zero efficacy (ADAS-cog P=.31); “all adverse effects were mild, with no significant difference” — Wang GH, et al. Medicine, 2018. View on PubMed
• 41 healthy young adults, 1.8 grams of lion’s mane, single dose + 28 days: faster Stroop after 60 minutes; subjective stress p=0.051 — not significant; side effects not reported in the abstract — Docherty S, et al. Nutrients, 2023. View on PubMed
• ALSUntangled #73: lion’s mane “appears safe and inexpensive” as powder or capsule — “but one case of anaphylaxis after eating the fresh mushroom has been reported”; the cognition trial “very small, temporary improvement, not yet replicated” — Muhanna M, et al. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2024. View on PubMed
• GBD 2021: 1.2 billion people with migraine and 2.0 billion with tension-type headache in 2021; burden higher in women aged 30–44 — GBD 2021 Headache Collaborators. Cell Reports Medicine, 2025. View on PubMed
• GBD 2019: “Migraine remains second among the world’s causes of disability, and first among young women” (title; no abstract — no number taken from it) — Steiner TJ, et al. The Journal of Headache and Pain, 2020. View on PubMed

Read next

• Medicinal mushrooms by goal — the hub
• Fibromyalgia and supplements — Lyrica and Cymbalta
• Lion’s mane and brain fog
• Who shouldn’t take lion’s mane
• Who shouldn’t take reishi
• Who shouldn’t take cordyceps
• Drug interactions
• Do medicinal mushrooms have side effects?
• Reishi for sleep — what was measured and what was not
• Reishi for stress and anxiety
• Medicinal mushrooms and the liver
• Research hub — lion’s mane
• Lab results — beta-glucan
• How to read a certificate of analysis (COA)

This page is educational and does not constitute medical advice, diagnosis or a substitute for professional care. Medicinal mushroom extracts are dietary supplements, not drugs, and are not intended to treat migraine, headache or any other medical condition. Migraine requires medical diagnosis and follow-up; a new, unusual or “worst of your life” headache requires urgent medical attention. Do not stop, replace or change the dose of a triptan, a preventive drug, a CGRP antibody or any other medication without your treating physician’s guidance. It describes what published trials and case reports recorded — and what was not recorded; it is not a prediction of what any individual will experience, and it is not a recommendation to start, stop or combine any supplement with any medication — those decisions belong with your physician, especially if you take regular medication, are pregnant or breastfeeding, have surgery planned, or have liver or kidney disease. *These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.*