Fibromyalgia and Supplements: What Was Measured, and What About Lyrica and Cymbalta

In brief5 points · 1-minute read

• Three human trials exist on medicinal mushrooms in fibromyalgia — all reishi powder, 6 grams daily over 6 weeks — and none used pain as a primary endpoint.
• Reishi improved fitness tests in 64 women against carob flour, but changed nothing in mood against placebo or in glucose, lipids and weight.
• Duloxetine (Cymbalta) depends on the enzyme CYP1A2, which reishi inhibited in rat liver microsomes; no human study has combined the two, so ask a pharmacist.
• Pregabalin (Lyrica) is less than 2% metabolized and skips CYP enzymes, so a pharmacokinetic interaction is not expected — though drowsiness stacking was never tested.
• In 29 men with Gulf War illness, high-dose reishi raised symptom severity versus placebo (p=0.012) — the closest population measured, and the direction was worse.

Questions about this article? Ask the Triterra bot ›

Fibromyalgia is a condition where “which dietary supplements help” is asked constantly — and the medicinal mushrooms offered for it are reishi (Ganoderma lucidum, the lingzhi of Chinese medicine), lion’s mane (Hericium erinaceus) and cordyceps. The honest answer: three human trials, all reishi, one Spanish group — none measured pain as a primary endpoint. Combined with Cymbalta (duloxetine), Lyrica (pregabalin) or amitriptyline: no human measurement in fibromyalgia. What is known, and what to ask the pharmacist — here.

The kinds of evidence that do exist, from closest to a person to furthest away: one randomized trial in 64 women with fibromyalgia that measured physical fitness, and two randomized pilots in the same population that measured mood and metabolic markers; one randomized trial in which a mushroom was given together with duloxetine — in people with depression, not fibromyalgia; pharmacology reviews on how the drugs themselves are broken down in the body; enzyme inhibition in a dish with rat liver tissue; pain studies on lion’s mane — all in mice, rats and cells; and one human study in which reishi made symptoms worse in a population with chronic fatigue and pain. For each of these we will say exactly what it is, and what it is not.

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

Three human trials, all from one Spanish group, all reishi, 6 grams of powder daily, 6 weeks. One: fitness improved against carob flour. Two: mood and quality of life against placebo — no difference. Three: glucose, lipids and weight — no difference. Pain was not a primary endpoint in any. Lion’s mane and cordyceps in fibromyalgia: zero trials.

“Help” is a word that hides three different questions: does the mushroom change the pain, does it change the fatigue and the sleep, and is it safe next to the drug you already take. On the first question there is no measurement. On the second there are measurements — in other populations, and for some of them the answer is the opposite of what the market promises. On the third there is the pharmacology of the drugs, one finding in a dish, and one human trial that was not done in fibromyalgia. This page goes through all three in that order, and does not try to bridge them where the evidence does not bridge. One note before we begin: fibromyalgia is not an autoimmune disease, and so it is not part of our autoimmune disease page; anyone who arrived here from there will find an entirely different axis — drugs, pain and sleep, not the immune system.

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

The table sorts your questions by what was measured, and in which organism. Only three rows contain a human trial in fibromyalgia. The pain row is empty. The drug rows hold pharmacology and test tubes, not a measurement of the combination in a person. One row — symptom worsening — is the human finding no marketing page shows.

What did the trial in 64 women find — and why was the comparison carob flour?

64 women with fibromyalgia received 6 grams of reishi a day or carob flour, for 6 weeks, double-blind. In the reishi group aerobic endurance, lower-body flexibility and speed improved significantly (p<.05); in the carob group no test improved. The endpoints: physical fitness. Not pain, not sleep, not anxiety.

This is the trial quoted online as “reishi proven in fibromyalgia”, so it is worth reading slowly. It is real, randomized and double-blind, and its result is positive — on fitness tests. Two things change what it means. First: the comparison group did not receive an inert placebo but carob flour, a food with contents of its own; “reishi is better than carob” is not the same claim as “reishi is better than nothing”. Second: what was measured is how far you walk in six minutes and how flexible your lower back is — not how much it hurts. An improvement in aerobic endurance in someone living with fibromyalgia is a finding that deserves respect; it simply does not answer the question that brought you to this page.

The full breakdown of the three Spanish trials — dose, duration, measures and what happened in each arm — we have already written on the reishi for stress and anxiety page, and we will not duplicate it here. Here one thing matters: these are the only three trials in the world of a medicinal mushroom in people with fibromyalgia. Everything you read beyond them is about a different population, a different animal, or a dish.

And what happened when they measured mood, glucose and lipids?

Same group, same dose, same 6 weeks, in two randomized double-blind pilots in women with fibromyalgia. Against placebo: happiness, depression, life satisfaction and health-related quality of life — “no statistically significant differences were found between the groups”. Against carob flour: fasting glucose, cholesterol, triglycerides, weight, fat mass, waist-to-hip ratio and blood pressure — no difference on any measure.

The mood pilot, published in 2020, is the only one of the three that compared reishi to an actual placebo — 6 grams a day of ground fruiting body, 6 weeks. The authors report a trend toward better happiness and satisfaction and lower depression within the reishi group compared with its own baseline; but in the comparison a trial is run for — against the group that received placebo — the difference was not significant. The number of participants is not stated in the abstract, and so it is not stated here either. Whoever quotes the trend without the sentence about the placebo has not quoted the study.

The metabolic pilot, published in 2021, tested the side many people look for in supplements “for fibromyalgia” — weight, glucose and lipids — and found zero on every measure. That is consistent with what has been measured on reishi in far larger groups, which we laid out on the blood sugar page. The summary line of the three trials, in plain words: reishi powder improved fitness tests against carob, and changed nothing in mood against placebo or in blood markers against carob. And what matters most to you — the pain — was not measured as a primary outcome in any of them.

Why did no trial measure the pain itself?

Because the trials were designed to measure fitness, mood and blood markers — not pain. Pain defines fibromyalgia, and it was not a primary endpoint in any of the three. That is not evidence that reishi does not help pain, and not evidence that it does. It is a hole exactly where you would expect the evidence to be.

What the market claims. “Reishi is anti-inflammatory and therefore eases pain”, “lion’s mane regenerates nerves and therefore eases neuropathic pain”, “cordyceps gives energy”. Each of these claims starts from a mechanism measured in an animal or in a dish, and skips straight to a conclusion about a person with fibromyalgia.

What exactly was measured. On reishi — fitness, mood, glucose and lipids in women with fibromyalgia; 6 grams of powder, 6 weeks; one trial against carob, one against placebo, one against carob. On lion’s mane — thermal pain, neuropathic pain and diabetic neuropathy, in mice and rats, mostly mycelium extract (the next chapter). On cordyceps — fatigue in cyclists, not pain, and combined with another plant. None of these measurements was made on a pain scale in a person with fibromyalgia.

Why it does not carry over automatically to a person. A mouse with a ligated nerve and a diabetic rat are models of pain from peripheral nerve injury, and a rat with osteoarthritis is a model of inflammatory joint pain — fibromyalgia is diagnosed by neither, and so none of these models is a model of it. Even when reishi improved fitness in 64 women, the authors did not report that pain fell — because they did not measure it as a primary outcome. And the only trial that tested the effect on mood against placebo came out at zero.

What can be known today. Three trials, 6 weeks each, reported no unusual adverse effects from reishi powder in women with fibromyalgia — that is a tolerability finding, not an efficacy finding. And that there is one human population with chronic pain and fatigue in which high-dose reishi actually made symptoms worse (the chapter “Can a mushroom make symptoms worse”). In other words, the direction of the effect on symptoms is not known in advance.

What to ask the doctor. Not “does reishi help pain” — on that they have no data, and neither does anyone. Rather: “I am considering a mushroom supplement; which of my drugs are sensitive to changes in liver metabolism, and how would we know if something changed?” That is a question with an answer, and the drug chapters below give the background to it.

Does lion’s mane help with pain in fibromyalgia?

Not measured — in any human being. A search for “lion’s mane and pain” returns 9 publications: thermal pain, neuropathic pain and diabetic neuropathy in mice and rats, osteoarthritis in rats, cultured microglial cells, and two retrospective human studies on abdominal pain — with a multi-ingredient blend and no control group. Trials on chronic pain or fibromyalgia in humans: 0.

This is the mushroom that comes up in the English search “lions mane fibromyalgia”, so let us go through what exists, up close. In mice: a lion’s mane extract changed the response to thermal pain in a behavioral test in 2017; mycelium extracts reduced neuropathic pain in mice with spinal nerve ligation (L5) in 2020; hericenone C, an isolated compound, reduced the second phase of the pain response to formalin in 2024. In rats: an ethanol extract improved alloxan-induced diabetic neuropathy in 2015; lion’s mane mycelium slowed the progression of osteoarthritis in 2022, and combined with type II collagen in 2026. In cells: a mycelium extract affected the migration of cultured microglial cells in response to morphine in 2019. Note the two words that keep recurring: “mycelium” — not the fruiting body we grow, and “mice”. And in some of these studies, some of the authors are affiliated with Grape King Bio, a manufacturer of mushroom supplements; that does not disqualify a finding, but it is part of what you need to know when you read it.

And in humans? Two publications: a multi-ingredient supplement for people with symptomatic diverticular disease from 2026, and a retrospective two-arm analysis of a lion’s mane-based preparation after colonoscopy from 2025. Both on abdominal pain, both on a blend in which lion’s mane is one ingredient among several, and both without a placebo group. You cannot isolate the mushroom from them, and you cannot carry anything from them to widespread muscle pain. A mouse with a ligated nerve is not a woman with fibromyalgia; mycelium on a substrate is not a fruiting body; and an eight-ingredient supplement is not lion’s mane. Whoever writes “lion’s mane eases pain in fibromyalgia” is describing a future that may one day be measured — not a present that has been.

What can be known: lion’s mane has been tested in humans in other contexts — cognition and mood — and there, there is tolerability data: in a 49-week trial with an enriched mycelium, four subjects dropped out because of abdominal discomfort, nausea and skin rash; the NIH’s LiverTox database gives it a score of E (an unlikely cause of liver injury), and adds that it “has not undergone prospective safety trials”, and that at least one acute hypersensitivity reaction has been documented. Those are the human data; pain is not among them.

And what about “fibro fog” — lion’s mane for brain fog?

Not measured in fibromyalgia. What exists: 30 adults aged 50–80 with mild cognitive impairment, 3 grams daily, 16 weeks — the score rose significantly at weeks 8, 12 and 16, and fell significantly 4 weeks after stopping; a 12-week trial where only one of three tests improved; in healthy young adults — a one-off effect on one test, or zero.

“Fibro fog” — the concentration and memory difficulties that accompany fibromyalgia — is a search people actually run, and lion’s mane is the mushroom offered for it. The human evidence on it is stronger than for any other mushroom on this page — and it too is far from your situation. The 2009 trial is the best known: 30 subjects with mild cognitive impairment, four 250 mg tablets three times a day, 16 weeks. The cognitive score rose significantly at weeks 8, 12 and 16 against placebo — and 4 weeks after stopping it fell significantly. That says something about an effect that exists as long as you take it, not about a change that stays. A 2019 trial measured three cognitive tests, and only one of them — the MMSE — improved significantly. In healthy young adults: a single 1.8 gram dose speeded up a Stroop test after 60 minutes, and after 28 days the drop in subjective stress reached p=0.051 — not significant; and a crossover trial in 18 young adults with 3 grams of fruiting-body extract found no significant effect on general cognition or on mood — only the pegboard test improved.

None of these studies recruited people with fibromyalgia, and none measured the kind of “fog” that comes with chronic pain and broken sleep. What has been measured on lion’s mane and brain fog — and what has not — we laid out on the lion’s mane and brain fog page.

Taking Cymbalta (duloxetine) — what do you need to know?

Three things. Duloxetine is broken down mainly by CYP1A2 and CYP2D6, and inhibiting CYP1A2 raised exposure by 460% — that is the enzyme that makes Cymbalta sensitive to other drugs. Reishi inhibited CYP1A2 — in rat liver microsomes. In humans: nobody has measured reishi with duloxetine. So it is a question for the pharmacist, not a decision to make alone.

What is known about the drug. The 2011 pharmacokinetics review of duloxetine — written by researchers from Eli Lilly, the drug’s manufacturer — describes breakdown mainly by two cytochrome enzymes: CYP1A2 and CYP2D6. The critical point: inhibiting CYP1A2 raises exposure to duloxetine “clinically significantly” — combined with fluvoxamine, a strong inhibitor of the enzyme, the area under the curve rose by 460% and the peak concentration by 141%. Inhibiting CYP2D6, by contrast, has a smaller effect, with no need for dose adjustment. Smoking, which speeds up CYP1A2, lowers exposure by 30%. A 2008 review adds that duloxetine is itself a moderate inhibitor of CYP2D6. In other words: if something changes the activity of CYP1A2 — the amount of duloxetine in the blood changes, and in a direction the doctor did not plan.

What is known about reishi. A 2007 study tested a reishi polysaccharide in rat liver microsomes, and found dose-dependent inhibition of three enzymes: CYP2E1, CYP1A2 and CYP3A. The authors themselves write that the pharmacokinetics of drugs “may be altered in herb–drug interaction”. This is the point where the two lines meet on paper: the enzyme reishi inhibited in the dish is exactly the enzyme whose inhibition multiplies duloxetine. But the meeting is on paper only. Inhibition in rat microsomes, at concentrations that may or may not be reached in the blood after swallowing, does not predict inhibition in a person; the Memorial Sloan Kettering cancer center summarizes the same finding and adds explicitly that the clinical relevance “is unknown”. A search for a study that measured reishi with duloxetine in humans — zero. A search for a human CYP probe study with reishi — zero.

What was measured in humans. The only trial in the world that tested a mushroom together with duloxetine: 59 patients with depression and insomnia, cordyceps as an add-on to duloxetine versus placebo, 6 weeks, double-blind, published in 2021. Adverse effects — no difference between the groups; the authors write “safe, with rare side effects”. And on insomnia — the placebo group improved more (p<0.05); on depression — no difference. That is a finding on cordyceps, not on reishi; on depression, not on fibromyalgia; and without measuring duloxetine levels in the blood. It says that in one group, over 6 weeks, the combination did not produce adverse effects different from placebo. It does not say that reishi, whose enzyme was tested in a dish, will behave the same way.

The wording we can stand behind: this is the enzyme that makes Cymbalta sensitive to other drugs; reishi inhibited it in the test tube; in humans that has not been tested — so it is a question for the pharmacist, not a decision to make alone. Not “reishi raises Cymbalta levels” — that was not measured. Not “dangerous to combine” — that was not measured. And not “safe to combine” — that was not measured either. What to bring to the pharmacist: the fact that you are on duloxetine, the name of the supplement and its dose, and the question of whether any other drug of yours depends on CYP1A2. The wider picture of what has and has not been measured on mushrooms and drugs is gathered on the drug interactions page.

Taking Lyrica (pregabalin) or amitriptyline — is there a concern?

Lyrica is the calmer case: less than 2% of pregabalin is metabolized, it leaves almost unchanged via the kidneys and neither inhibits nor induces CYP enzymes — so a pharmacokinetic interaction with a supplement is “unlikely”. Amitriptyline (Elavil) is broken down via CYP2D6 and CYP2C19 — not the enzymes reishi inhibited. Not tested: any study of mushrooms with either drug.

Pregabalin. The 2004 pharmacology review describes a drug that barely touches the liver’s enzyme system: less than 2% metabolism, renal excretion almost unchanged, no inhibition or induction of cytochrome P450. The meaning: the pathway through which a supplement can change a drug’s concentration in the blood — like duloxetine’s — barely exists for pregabalin. That is the big pharmacological difference between the two most common fibromyalgia drugs, and very few pages online explain it. And now the caveat, at eye level: “pharmacokinetic interaction not expected” is not “no interaction”. Pregabalin causes drowsiness, and reishi is offered for sleep; whether there is an additive effect on drowsiness — nobody has measured. A search for mushrooms with pregabalin on PubMed — zero studies. “Not tested” and “safe” are two different words, and on this page we will use only the first.

Amitriptyline. The 2016 CPIC consortium guideline on tricyclic antidepressants establishes that amitriptyline is affected by CYP2D6 and CYP2C19 genotype — to the point that genetic polymorphism in those enzymes determines dose adjustment. The only data that exist on reishi and liver enzymes — in rat microsomes — concern CYP1A2, CYP3A and CYP2E1; not CYP2D6 and not CYP2C19. In other words, here there is not even a direct theoretical link, and there is no study. That does not make the combination “safe” — it means the specific concern that exists on paper for duloxetine does not exist on paper for amitriptyline. The question for the pharmacist remains the same question, and their answer will probably be: not tested, tell me what you are taking.

Do medicinal mushrooms affect clotting and bleeding?

Two human studies on reishi, opposite answers: 3 grams daily for two weeks inhibited platelet aggregation by 31.49% in 33 patients, no control group; a randomized double-blind trial in 40 volunteers, 1.5 grams daily for 4 weeks, found no change in any coagulation measure. On cordyceps — one case report of gastrointestinal bleeding with sertraline, out of 1,816 adverse-event reports.

The study quoted as a warning. In 1990, 33 patients with atherosclerotic disease took reishi 1 gram three times a day for two weeks; inhibition of ADP-induced platelet aggregation reached 31.49% (P<0.01), and the length of the extracorporeal thrombus fell from 30.05 to 20.4 mm. In parallel, in the test tube, a reishi extract inhibited platelet aggregation in 15 healthy volunteers. That is a real finding — but before/after, without a control group, and a laboratory measure, not clinical bleeding. The molecular mechanism is documented: ganodermic acid S, at 7.5 micromolar in human platelets in a dish, amplified the PGE1-induced rise in cAMP 1.8-fold — that is, the effect adds to other substances.

The study that contradicts the warning. In 2005, a prospective randomized double-blind trial: 20 healthy volunteers received reishi 1.5 grams a day and 20 received placebo, 4 weeks, with measurements before, at 4 and at 8 weeks — routine coagulation, fibrinogen, vWF activity, PFA-100 and thromboelastography. No difference between the groups; all measurements within the normal range. The authors’ conclusion: use of reishi before surgery “is unlikely to increase surgical bleeding” in healthy people. The differences between the two studies: the dose (3 grams versus 1.5), the population (atherosclerotic patients versus healthy people), the measure (platelet aggregation versus a full coagulation panel) and the design (uncontrolled versus randomized). The correct wording is to write both, and in this order: the controlled study found no impairment of hemostasis; the uncontrolled study at double the dose found platelet inhibition. Whoever quotes only the first — or only the second — is selling you half a picture.

Cordyceps and antidepressants. A 2023 retrospective review of 1,816 adverse-event reports at a clinic in Kraków identified 30 cases with a probable causal link between an adaptogen and an antidepressant. One of them: cordyceps together with sertraline, and upper gastrointestinal bleeding. A single case report is not a proven interaction — it is a signal that someone wrote down. And two clarifications that must not be skipped: sertraline is not duloxetine, and what was documented with one has not been measured with the other; and duloxetine appeared in the same review with other plants — not with mushrooms. The Memorial Sloan Kettering center additionally notes a case report of increased bleeding after a tooth extraction in a person taking cordyceps daily. Everything converges on one point: anyone taking an anticoagulant or an antiplatelet, or facing a procedure — tells the doctor about every supplement, including ours. The full list of who should stop before reishi — on the “who shouldn’t take reishi” page.

Reishi for sleep in fibromyalgia — what was measured?

Nothing — not in fibromyalgia and not in any human population. There is not one controlled trial of reishi on sleep in humans. In normal rats reishi did not change sleep architecture; it “worked” only in rats given pentobarbital. The only trial where a mushroom was given alongside duloxetine measured insomnia precisely — and the placebo group improved more.

“Sleep problems” and “insomnia” are among the most common searches next to the word fibromyalgia, and “reishi for sleep” is the most common search next to the word reishi. The two demands meet — and the evidence does not. A systematic PubMed search for reishi and sleep in humans returned, as the only relevant result, the fibromyalgia trial on physical fitness — which did not measure sleep at all. What exists is in rats: an aqueous reishi extract at 80 and 120 mg per kg did not affect sleep architecture in normal rats; only in rats given pentobarbital, an anesthetic, did it shorten sleep latency and lengthen sleep duration — and flumazenil, a benzodiazepine-receptor blocker, abolished the effect. An anesthetized rat that falls asleep faster is not a person with fibromyalgia who wakes at three in the morning.

And there are two human findings that point the other way. The first: in clinical trials of reishi, insomnia appears as an adverse effect — the 2016 Cochrane review lists “nausea and insomnia” among the minimal adverse effects reported, and a 2024 cross-sectional survey of 1,374 cancer patients taking reishi found 9.1% reporting adverse effects, insomnia among them in 3%. The second: the 2021 trial in which cordyceps was given alongside duloxetine to 59 patients with depression and insomnia measured sleep as a primary outcome — and the placebo group improved more (p<0.05). That is cordyceps and not reishi, but it is the only measurement of a mushroom on insomnia alongside the drug many of you take, and it is not in the mushroom’s favor. Sleep was measured on lion’s mane too — in a 2010 trial in 30 women, the PSQI questionnaire was among the measures and was not reported as a significant result. Everything that has and has not been measured on reishi and sleep — and what we did with it on the page that carries that name — we wrote on the reishi for sleep page.

Cordyceps for fatigue — and what was measured on reishi and chronic fatigue?

Cordyceps, “the energy mushroom”: the only human evidence found is a trial in cyclists, cordyceps together with rhodiola — zero difference in muscle oxygen saturation, VO2max, ventilatory threshold and time to exhaustion. Reishi: fatigue relief in 132 neurasthenia patients and 48 breast-cancer patients. In fibromyalgia — fatigue was not measured.

“Chronic fatigue” appears next to fibromyalgia in search, and rightly — it is part of the condition. And what the market offers for it is cordyceps. The human trial we found on this axis, from 2005, gave cyclists a supplement combining cordyceps and rhodiola, and found no difference on any performance measure. That is a trial in athletes, not in people with chronic fatigue, and a blend in which the mushroom cannot be isolated; but it is the only data point, and it is negative.

On reishi there is more, and in other populations. In 2005, 132 patients with neurasthenia — a syndrome of persistent fatigue — received a polysaccharide extract at 1,800 mg three times a day or placebo, 8 weeks, in a multicenter double-blind trial. The sense of fatigue fell by 28.3% in the reishi group — and by 20.1% in the placebo group; the clinical severity score fell by 15.5% versus 4.9%; “more than minimal improvement” was reported in 51.6% versus 24.6% (P=.002). Always write both numbers: the net difference in fatigue is about 8 percentage points, not 28. And in 2012, a clinical pilot in 48 breast-cancer patients on endocrine therapy found improvement on the FACT-F fatigue subscale after 4 weeks of spore powder — a pilot, not a randomized controlled trial according to the record’s classification. Two populations, two products, a small effect. Neither of them is fibromyalgia, and in the fibromyalgia trials themselves fatigue was not measured as an endpoint. And before you carry this finding over to yourself — the next chapter.

Can a mushroom make symptoms worse?

Measured once, in a close but different population: 29 men with Gulf War illness — chronic fatigue, pain and a neuroinflammatory component — in a placebo-controlled crossover trial. Low-dose reishi: no difference from placebo (p=0.603). High dose: symptom severity higher than placebo (p=0.012). Not fibromyalgia — and the closest thing that has been measured.

If there is one finding on this page that no sales page will show you, this is it. The trial, published in 2021, tested three botanicals — reishi, stinging nettle and epimedium — in 29 men with Gulf War illness, in a crossover design: 30 days baseline, 30 days placebo, 30 days low dose, 30 days high dose. With reishi at the low dose, symptom severity did not differ from placebo; at the high dose it was higher, at a significance of p=0.012. The authors’ conclusion, word for word: reishi “may exacerbate symptoms in some sufferers”; and they add that the sample is small and the results preliminary.

Why this matters here specifically, and why it must not be exaggerated. Gulf War illness is not fibromyalgia: a different population, men only, a different exposure history. But the symptoms overlap — chronic fatigue, widespread pain, sleep and cognitive disturbances — and so this is the human population closest to fibromyalgia in which reishi was measured against the question “does this help or harm”. The answer was dose-dependent, and at the high dose — worse. The three fibromyalgia trials reported no worsening — but they also did not measure overall symptom severity. Both things are true at once: there is no evidence that reishi worsens fibromyalgia, and there is evidence that in a condition with similar symptoms it made things worse. Anyone who starts a supplement — any supplement — and feels their symptoms getting worse should not “give it time”; they should stop and tell the doctor. And anyone who cites this study to you as proof that “reishi is dangerous in fibromyalgia” — has not read it either.

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: reishi 1:3 and lion’s mane 1:2. Alcohol in the finished extract: 32% — a figure worth bringing to the pharmacist together with the names of your drugs.

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 one more distinction that has to be said on this page: the trials in women with fibromyalgia gave 6 grams a day of ground fruiting-body powder; what is in our bottle is a liquid extract. Those are two different products, and we do not convert between them — we will not write “how many drops equal 6 grams”, because nobody has measured that. 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 pain, fatigue or sleep in fibromyalgia 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 or cordyceps ease fibromyalgia pain, improve sleep, relieve fatigue or “balance the nervous system” — at any dose and in any form; pain was not measured, sleep was not measured in humans, and fatigue was measured in other populations. We do not claim that reishi raises Cymbalta 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 Lyrica is “safe with mushrooms” — we claim that the pharmacokinetic pathway for an interaction barely exists, and that an additive effect on drowsiness was not tested. We do not claim that one case report of cordyceps with sertraline is a proven interaction, and we do not transfer it to duloxetine. We do not claim that the Gulf War illness trial is a trial in fibromyalgia. And we do not deal here with disability rights, insurance claims or medical cannabis — we have no expertise in those and no sources on them, so we will not write about them. What we do say: fibromyalgia is treated by a physician, and anyone taking duloxetine, pregabalin, amitriptyline, an anticoagulant or any regular medication — 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 fibromyalgia.

The bottom line

On medicinal mushrooms in fibromyalgia there are three human trials, all reishi powder, all 6 weeks — fitness improved against carob, mood against placebo did not, blood markers did not, and pain was not measured. On lion’s mane and pain: mice, rats and cells, and zero humans. On Cymbalta: the enzyme that breaks it down was blocked by reishi in a dish, and in humans nobody has measured — a question for the pharmacist. On Lyrica: the pathway for an interaction barely exists, and the combination was not tested. On bleeding: an uncontrolled study found platelet inhibition, a randomized trial found nothing. On sleep: zero in humans, and in the only trial alongside duloxetine the placebo won. And in the closest population measured, high-dose reishi made symptoms worse. That is the picture. It is not pleasant, but it is accurate — and whoever sells you a mushroom “for fibromyalgia”, send them this page.

Frequently asked questions

Can I take reishi with Cymbalta?

Not tested in humans — so it is a question for the pharmacist. What is known: duloxetine is broken down mainly by CYP1A2 and CYP2D6, and inhibiting CYP1A2 raised exposure to it by 460% in a study with fluvoxamine. Reishi inhibited CYP1A2 in rat liver microsomes. The clinical relevance of the finding in the dish is unknown, and no study has measured reishi with duloxetine in humans. Bring the pharmacist the supplement’s name and your list of drugs.

Can I take medicinal mushrooms with Lyrica?

No study has tested the combination. What is known about the drug itself is more reassuring than with Cymbalta: less than 2% of pregabalin is metabolized, it is excreted almost unchanged by the kidneys and neither inhibits nor induces CYP enzymes — so a pharmacokinetic interaction is not expected. What was not tested: an additive effect on drowsiness. “Not tested” is not “safe”; tell your doctor.

Does lion’s mane help with pain in fibromyalgia?

Not measured in any human being. A search for lion’s mane and pain returns 9 publications: thermal pain, neuropathic pain and diabetic neuropathy in mice and rats, osteoarthritis in rats, cultured cells — mostly mycelium extract — and two retrospective studies on abdominal pain with a multi-ingredient blend and no control group. A trial on chronic pain or fibromyalgia in humans: zero.

How long does it take to see an effect?

There is no figure for “time to effect”, because there is no trial that measured the symptom you are looking for. What exists: the three fibromyalgia trials ran 6 weeks, and at the end they measured physical fitness (improved against carob), mood (no difference against placebo) and blood markers (no difference against carob). Pain was not measured. Six weeks is the length of the trials — not a promise about what happens at the end of them.

Do mushrooms help with “fibro fog”?

Not measured in fibromyalgia. Lion’s mane has been tested on cognition in other populations: in 30 adults with mild cognitive impairment, 3 grams a day for 16 weeks, the score rose significantly and fell 4 weeks after stopping; in another trial only one of three tests improved; in healthy young adults — a one-off effect on a single test, or zero. No trial recruited people with fibromyalgia.

Can I take them with amitriptyline?

Not tested — zero studies of mushrooms with amitriptyline. What is known: the drug is broken down via CYP2D6 and CYP2C19, and those are not the enzymes reishi inhibited in the dish (CYP1A2, CYP3A, CYP2E1). In other words, there is not even a direct theoretical link — but the absence of a link on paper is not a measurement. The question for the pharmacist remains the same question.

Do medicinal mushrooms have side effects?

In reishi trials, a Cochrane review lists nausea and insomnia as minimal adverse effects, and in a survey of 1,374 cancer patients 9.1% reported adverse effects, insomnia among them in 3%. In a Cochrane meta-analysis, people taking reishi for 4 months had a 1.67-fold risk of an adverse effect — not significant, and not serious effects. In 29 men with Gulf War illness, high-dose reishi made symptoms worse. With lion’s mane: abdominal discomfort, nausea and skin rash.

What dose was tested in fibromyalgia?

6 grams a day of ground reishi fruiting-body powder, for 6 weeks, in all three trials. That is a powder — not a liquid extract, and not a mycelium capsule. We do not convert between a powder dose and an extract dose, because nobody has measured such a conversion; “how many drops equal 6 grams” is a question without a measured answer. And even at the dose that was tested — pain was not an endpoint.

Scientific sources (peer-reviewed)

• 64 women with fibromyalgia, 6 grams of reishi a day or carob flour, 6 weeks, double-blind: aerobic endurance, lower-body flexibility and speed improved significantly on reishi (p<.05); carob improved no test. Endpoints: fitness, not pain — Collado Mateo D, et al. Nutricion Hospitalaria, 2015. View on PubMed
• Women with fibromyalgia, 6 grams a day of ground reishi fruiting body or placebo, 6 weeks, randomized double-blind pilot: happiness, depression, satisfaction and quality of life — no significant differences between groups; a trend within the reishi group only — Pazzi F, et al. Healthcare (Basel), 2020. View on PubMed
• Women with fibromyalgia, 6 grams a day of reishi fruiting-body powder versus carob flour, 6 weeks, randomized double-blind pilot: no difference in fasting glucose, cholesterol, triglycerides, weight, fat mass, waist-to-hip ratio or blood pressure — Pazzi F, et al. Nutricion Hospitalaria, 2021. View on PubMed
• Duloxetine pharmacokinetics: metabolism by CYP1A2 and CYP2D6; CYP1A2 inhibition (fluvoxamine) raised AUC by 460% and Cmax by 141%; 2D6 inhibition — smaller effect; smoking lowers exposure by 30%. Authors from Eli Lilly — Knadler MP, et al. Clinical Pharmacokinetics, 2011. View on PubMed
• Review of pharmacokinetic interactions of second-generation antidepressants: duloxetine is a moderate inhibitor of CYP2D6 — Spina E, et al. Clinical Therapeutics, 2008. View on PubMed
• Review of the metabolism of the newest antidepressants: duloxetine — CYP2D6 and CYP1A2 — Caccia S. IDrugs, 2004. View on PubMed
• A reishi polysaccharide dose-dependently inhibited CYP2E1, CYP1A2 and CYP3A in rat liver microsomes; given to rats (50 and 200 mg per kg) it reversed BCG-induced liver injury. The authors: “pharmacokinetics may be altered in herb–drug interaction” — Wang X, et al. Biological & Pharmaceutical Bulletin, 2007. View on PubMed
• The only trial of a mushroom with duloxetine: 59 patients with depression and insomnia, cordyceps as an add-on to duloxetine versus placebo, 6 weeks, double-blind. Insomnia: the placebo improved more (p<0.05); depression — no difference; adverse effects — no difference — Zhou J, et al. Frontiers in Psychiatry, 2021. View on PubMed
• Pregabalin pharmacology: less than 2% metabolism, renal excretion almost unchanged, no hepatic metabolism, no CYP inhibition or induction — pharmacokinetic interaction “unlikely” — Ben-Menachem E. Epilepsia, 2004. 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
• 33 atherosclerotic patients, reishi 1 gram three times a day, two weeks: ADP-induced platelet-aggregation inhibition 31.49% (P<0.01); extracorporeal thrombus length fell from 30.05 to 20.4 mm; in vitro — platelets of 15 volunteers. No control group — Tao J, Feng KY. Journal of Tongji Medical University, 1990. View on PubMed
• Randomized double-blind placebo-controlled trial in 40 healthy volunteers: reishi 1.5 grams a day, 4 weeks — coagulation, fibrinogen, vWF, PFA-100 and thromboelastography no different, all values within the normal range — Kwok Y, et al. Anesthesia and Analgesia, 2005. View on PubMed
• Ganodermic acid S in human platelets in vitro: at 7.5 micromolar it amplified the PGE1-induced cAMP rise 1.8-fold — the effect adds to other substances — Su C, et al. Thrombosis Research, 2000. View on PubMed
• Retrospective review of 1,816 adverse-event reports: 30 cases with a probable causal link between an adaptogen and an antidepressant; one report — cordyceps with sertraline and upper gastrointestinal bleeding. Duloxetine appeared with other plants, not with mushrooms — Siwek M, et al. Frontiers in Pharmacology, 2023. View on PubMed
• Cochrane review: 5 trials, 398 participants; people taking reishi for 4 months at a 1.67-fold risk of an adverse effect (RR 1.67; 95% CI 0.86–3.24) — not significant, no serious effects — Klupp NL, et al. Cochrane Database of Systematic Reviews, 2015. View on PubMed
• Reishi extract at 80 and 120 mg per kg did not affect sleep architecture in normal rats; only with pentobarbital did it shorten latency and lengthen sleep; flumazenil abolished the effect. Rats and mice — Chu QP, et al. Pharmacology, Biochemistry, and Behavior, 2007. View on PubMed
• 2016 Cochrane review of reishi in cancer: minimal adverse effects — nausea and insomnia; no significant hematological or hepatic toxicity — Jin X, et al. Cochrane Database of Systematic Reviews, 2016. 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%, dizziness 3%. No control — Li X, et al. Integrative Medicine Research, 2024. View on PubMed
• 30 women, lion’s mane in cookies, 4 weeks: against placebo, significance on only two questionnaire items; the PSQI sleep questionnaire was measured and not reported as a significant result — Nagano M, et al. Biomedical Research (Tokyo), 2010. View on PubMed
• Cordyceps together with rhodiola in male cyclists: zero difference in muscle oxygen saturation, VO2max, ventilatory threshold and time to exhaustion — Colson SN, et al. Journal of Strength and Conditioning Research, 2005. View on PubMed
• 132 neurasthenia patients, polysaccharide extract 1,800 mg three times a day or placebo, 8 weeks, multicenter double-blind: fatigue fell 28.3% versus 20.1%; CGI fell 15.5% versus 4.9%; “more than minimal improvement” 51.6% versus 24.6% (P=.002) — Tang W, et al. Journal of Medicinal Food, 2005. View on PubMed
• Clinical pilot in 48 breast-cancer patients on endocrine therapy, reishi spore powder, 4 weeks: improvement on the FACT-F fatigue subscale, less anxiety and depression — Zhao H, et al. Evidence-Based Complementary and Alternative Medicine, 2012. View on PubMed
• 29 men with Gulf War illness, placebo-controlled pseudo-randomized crossover trial, 30-day blocks: low-dose reishi no different from placebo (p=0.603); high dose — higher symptom severity (p=0.012). “Reishi may exacerbate symptoms in some sufferers” — Younger J, et al. International Journal of Environmental Research and Public Health, 2021. View on PubMed
• Lion’s mane and purinoceptor-coupled calcium signaling; thermal nociceptive behavior in mice — Liu PS, et al. International Journal of Medicinal Mushrooms, 2017. View on PubMed
• Lion’s mane mycelium extracts and neuropathic pain in mice with L5 spinal nerve ligation — Yang PP, et al. Evidence-Based Complementary and Alternative Medicine, 2020. View on PubMed
• Ethanol extract of lion’s mane and alloxan-induced diabetic neuropathy in rats — Yi Z, et al. Evidence-Based Complementary and Alternative Medicine, 2015. View on PubMed
• Hericenone C, an isolated lion’s mane compound, reduced the second phase of the formalin pain response in mice — Li J, et al. Biochemical and Biophysical Research Communications, 2024. View on PubMed
• Lion’s mane mycelium and osteoarthritis progression in an animal model — Yang SY, et al. Nutrients, 2022. View on PubMed
• Lion’s mane mycelium combined with type II collagen and osteoarthritis progression in a preclinical animal model — Lee KT, et al. International Journal of Medical Sciences, 2026. View on PubMed
• Ethanol extract of lion’s mane mycelium and microglial migration in response to morphine — cultured cells — Yeh CH, et al. Molecular Medicine Reports, 2019. View on PubMed
• Multi-ingredient supplement in symptomatic uncomplicated diverticular disease — a blend, no control group; abdominal pain, not widespread pain — Bertani L, et al. Minerva Gastroenterology, 2026. View on PubMed
• Retrospective two-arm multicenter analysis of a lion’s mane-based preparation after colonoscopy — retrospective, a blend, abdominal pain — Tursi A, et al. Nutrients, 2025. View on PubMed
• 30 subjects aged 50–80 with mild cognitive impairment, lion’s mane 3 grams a day, 16 weeks, double-blind: the score rose significantly at weeks 8, 12 and 16, and fell significantly 4 weeks after stopping; laboratory tests with no adverse effect — Mori K, et al. Phytotherapy Research, 2009. View on PubMed
• Lion’s mane for 12 weeks: of three cognitive tests (MMSE, Benton, S-PA) — only the MMSE improved significantly — Saitsu Y, et al. Biomedical Research (Tokyo), 2019. View on PubMed
• 41 young adults, pilot: a single 1.8 gram dose of lion’s mane — faster Stroop after 60 minutes; after 28 days a drop in subjective stress at p=0.051 — not significant — Docherty S, et al. Nutrients, 2023. View on PubMed
• 18 healthy young adults, crossover trial, 3 grams of 10:1 fruiting-body extract: no significant effect on general cognition or on mood; only the pegboard test improved — Surendran G, et al. Frontiers in Nutrition, 2025. View on PubMed
• Double-blind placebo-controlled trial, 49 weeks, erinacine A-enriched lion’s mane mycelium, 3 capsules of 350 mg a day: four subjects dropped out because of abdominal discomfort, nausea and skin rash — Li IC, et al. Frontiers in Aging Neuroscience, 2020. View on PubMed

Read next

• Chronic Pain and Medicinal Mushrooms: Back, Joints, Neuropathy — and What About NSAIDs
• Migraine, Natural Treatment and Supplements: What Was Measured, and What About Imitrex and Topamax
• IBS and Medicinal Mushrooms: What Was Measured, What Actually Helps, and What About Imodium
• Medicinal mushrooms by goal — the hub
• Reishi for stress and anxiety — the full breakdown of the fibromyalgia trials
• Reishi for sleep — what was measured and what was not
• Lion’s mane and brain fog
• Drug interactions
• Who shouldn’t take reishi
• Reishi benefits — the evidence ledger
• Reishi dosage — what was tested
• Medicinal mushrooms and autoimmune disease
• Medicinal mushrooms and blood sugar
• Medicinal mushrooms and sleep
• Reishi and the inflammatory response
• Joint inflammation — what the science says
• Do medicinal mushrooms have side effects?
• Lab results — beta-glucan

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 fibromyalgia or any other medical condition. Fibromyalgia requires medical diagnosis and follow-up; do not stop, replace or change the dose of duloxetine, pregabalin, amitriptyline 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, anticoagulants or antiplatelets, 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.*