Chronic Pain and Medicinal Mushrooms: Back, Joints, Neuropathy — and What About NSAIDs

In brief5 points · 1-minute read

• No controlled human trial has tested reishi, lion's mane, cordyceps or turkey tail in back pain, osteoarthritis or neuropathy; the evidence is rats, mice and cells.
• The nerve-regeneration claim rests on rats with a crushed nerve, where vitamin B12 worked equally well; a 2026 systematic review found 11 records, none clinical.
• The single human trial, 65 rheumatoid arthritis patients given reishi inside a Chinese formula, missed its primary endpoint: ACR20 15% versus 9.1%.
• Reishi's most potent triterpene left the enzymes that clear etoricoxib, ibuprofen and tramadol uninhibited in a dish; no combination has been measured in people, so ask a pharmacist.
• For chronic back pain, exercise cut pain by 15.2 points across 249 trials; paracetamol and gabapentin scored near zero. We sell none of these.

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Chronic pain — low back, osteoarthritis, neuropathy — gets searched by body part; the mushrooms offered are lion’s mane (Hericium erinaceus), reishi (Ganoderma lucidum, lingzhi in Chinese medicine), cordyceps and turkey tail. The honest answer: not one randomized human trial of any of them in back pain, osteoarthritis or neuropathy. What exists: one rheumatoid arthritis trial that missed its primary endpoint, four patients from 1998, and rats. What is proven (and we do not sell) is below.

The kinds of evidence that do exist, from closest to a person to furthest away: one randomized trial in 65 patients with rheumatoid arthritis, in which reishi was given inside a Chinese formula; a case series of four patients with postherpetic neuralgia, at 36 to 72 grams a day, with no control group; a library of reishi triterpenes tested against seven liver enzymes in a dish; rats with a crushed nerve, mice with a ligated nerve, rats with a cut knee ligament — most of them on mycelium extract, and in some of them the authors work for a supplement manufacturer; human disc cells and cartilage cells in a dish; and, facing all that, on things we do not sell, Cochrane reviews and meta-analyses of tens of thousands of patients — exercise, curcuminoids, paracetamol/acetaminophen, gabapentin, opioids — that say exactly what works and what does not. On “mushroom × chronic pain in humans” there is nothing at all.

Do medicinal mushrooms help with chronic pain — what was actually tested?

In the three kinds of pain people search for — low back, osteoarthritis, neuropathy — no mushroom has a randomized human trial. In humans there is one rheumatoid arthritis trial (65 patients, reishi inside a formula, primary endpoint not met) and four uncontrolled neuralgia patients from 1998. Everything else: about 25 rodent and cell studies.

To understand the scale: a representative internet survey in Israel in 2022 — 8,300 adults invited, 1,647 responded — found 515 respondents (31.3%) with pain lasting more than three months, at an average daily intensity of 5.8 out of 10; the most common sites were the axial skeleton and headache, and more than half had pain in several regions. The response rate was 19.8%, so the figure is “among responders”, not the population. Worldwide, according to a 2021 Lancet seminar, chronic pain affects more than 30% of people in some studies, and the experts classify it as nociceptive, neuropathic and nociplastic — with many seeing it as a continuum. And low back pain, according to the 2018 Lancet series, is “the leading cause of disability worldwide”, with a 54% rise in years lived with disability between 1990 and 2015 — and in almost every case “a specific nociceptive cause cannot be identified”.

For a condition on that scale, nobody has tested a mushroom in a controlled trial. Not because they tested and found zero — they simply did not test. Which is why this page is not built around the mushrooms but around what you are asking: does lion’s mane regenerate nerves, is there anything for the knee and the back, can you combine it with etoricoxib or tramadol, and what actually is proven. On fibromyalgia — the fourth chronic pain, with Lyrica and Cymbalta — we wrote a separate page: fibromyalgia and supplements.

What was measured, in which kind of pain, and in which system?

The table sorts the kinds of pain by mushroom, by the highest evidence that exists and by the form tested — mycelium, fruiting body or an isolated compound. The “humans” row appears only twice, and neither is back, osteoarthritis or neuropathy. Everything else is rats, mice and cells in a dish.

Does lion’s mane regenerate nerves and help with neuropathy?

In humans — never measured: 0 trials and 0 case reports of lion’s mane in neuropathy, nerve pain or nerve regeneration. Rats with a crushed nerve, where function returned earlier — as in the vitamin B12 positive-control group; mice with a ligated nerve, on manufacturer-funded mycelium extract; diabetic rats. A 2026 systematic review: 11 records, all preclinical.

This is the biggest door in English — “lions mane nerve regeneration” with ten completions, “lions mane neuropathy” with ten, “lions mane nerve pain” with nine — and in Hebrew “neuropathy natural treatment” is the sixth completion under “neuropathy”. What the market claims. “Lion’s mane raises NGF and regrows nerves”, “helps diabetic neuropathy”, “for neuropathic pain”. What exactly was measured. The study from which the phrase “regenerates nerves” was born: 2011, University of Malaya, female rats with a crushed peroneal nerve, an aqueous extract of fresh fruiting body given orally every day; hind-limb function “returned earlier” in the extract group — and in the mecobalamin (vitamin B12) group, which was the positive control — compared with the negative control; axon regeneration “developed better”. The dose, the number of animals and the difference in days are not in the abstract. In 2016 the same group showed that in the ganglion neurons of the treated rats, Akt, MAPK, c-Jun and c-Fos were higher. In other words: what was measured is that a fruiting-body extract sped up the repair of a crushed nerve in a rat — like a vitamin sold in every pharmacy.

Neuropathic pain. In 2020, mice with L5 spinal nerve ligation: a crude mycelium extract and “erinacine S” — not the erinacine A the market talks about — abolished calcium signaling in human cells, raised the paw withdrawal threshold and lowered activation markers of astrocytes and microglia; erinacine S relieved better than the extract. Dose and number of mice not in the abstract; mycelium; a co-author from Grape King Bio, a supplement manufacturer. In 2015, diabetic (alloxan) rats given an ethanol extract at 40 mg/kg for 6 weeks: the pain threshold rose — and at the same time serum glucose fell, so that the authors themselves describe “improvement of the diabetic condition” — the effect may be glycemic, not analgesic. In 2017, mycelium extracts delayed the thermal pain response in mice (tail-flick, hot plate) — Grape King again. And in 2026, a systematic review of medicinal mushrooms for peripheral nerve injury found 11 records in total, five on lion’s mane, all preclinical, and concluded that the existing approaches “need to undergo clinical research”.

Why it does not carry over to a person. A crushed nerve in a rat heals on its own; the question in the trial is how fast, and the answer was “like B12”. A mouse with a ligated nerve is a model of sharp mechanical injury, not of diabetic neuropathy or of small fibers. And mycelium grown on a substrate is not the fruiting body we sell — and not what the 2011 rats received. What can be known. That diabetic neuropathy has a supplement that was measured in humans — alpha-lipoic acid at 600 mg, across 11 studies — and that we do not sell it (the “what is proven” chapter). And that on the reverse English question, “can lion’s mane cause nerve pain” — we found no documentation; not tested, not recorded. What to ask the doctor. Not “will lion’s mane regenerate my nerve” — but what is causing the neuropathy, and which of the treatments measured in humans are suitable. On brain fog and focus — the thing lion’s mane was actually tested for in humans — the lion’s mane and brain fog page.

Mushrooms for osteoarthritis — what is there beyond rats?

Nothing. Any mushroom — reishi, lion’s mane, cordyceps, turkey tail, shiitake, maitake, agaricus — in a randomized osteoarthritis trial: 0 results. What exists: manufacturer-funded lion’s mane mycelium in rats with a cut knee ligament, no numbers in the abstract; ganoderic acid A in mice; cordycepin in human cartilage cells; turkey tail polysaccharopeptide injected into the spinal cord.

“Joint pain” is a strong search in Hebrew, and “in menopause” is its first completion — so it is worth saying at once what there is. Lion’s mane: in 2022, rats with knee osteoarthritis from cutting the anterior cruciate ligament received mycelium; “weight-bearing asymmetry improved and pain was minimized”, cartilage erosion “decreased significantly”, IL-1β and TNF-α fell — and in the abstract there is no dose, no number of animals and no effect size; the authors are from the research institute of Grape King Bio, a supplement manufacturer. In 2026, the same mycelium combined with undenatured type II collagen, in the same model — “reduced bone pain”; a combination, without isolating the mushroom’s contribution, and without numbers. Reishi: ganoderic acid A — an isolated compound, not an extract — in mice with surgically induced OA and in cartilage cells: histology scores fell, MMP-13 in the synovial fluid fell, inflammation in the cells fell through NF-κB. The only record PubMed tags “humans” for “reishi × osteoarthritis” is tagged that way because of human cartilage cells in a dish — not because of patients. Cordyceps: cordycepin at 10 to 100 micromolar in cartilage cells taken from OA patients lowered PGE2, NO, MMP-13, IL-6 and COX-2 — a dish; and in synovial fibroblasts from 12 rheumatoid arthritis patients it inhibited MMP-1 and MMP-3. Turkey tail: polysaccharopeptide in rats with inflammatory OA pain in the ankle improved the pain threshold and delayed morphine tolerance — intrathecally, by injection into the spinal cord, at 50–200 micrograms per kilogram. An injection into a rat’s spinal cord is not a capsule, and it must not be presented as “turkey tail against joint pain”. And in Wistar rats, 500 mg/kg of turkey tail mycelium powder reduced formalin-induced licking as much as aspirin at 100 mg/kg — an “aspirin-like effect”, with no effect-size numbers.

The honest summary: for osteoarthritis, mushrooms have rats, mice and dishes, mostly mycelium and isolated compounds, in some of them the manufacturer is the author — and zero human trials. What was measured in humans with knee OA: curcuminoids across 15 trials, glucosamine sulfate, topical diclofenac — in the “what is proven” chapter. What we wrote about mushrooms and arthritis and about medicinal mushrooms for menopause — separately.

And low back pain or a herniated disc?

Zero in humans, zero in animals. Closest: ganoderic acid A in human disc cells in a dish — inflammation and matrix breakdown fell, pain not measured; and cordycepin in rat disc cells. Mushrooms with back pain: 5 results — two in cells, the rest noise. What is proven for chronic back pain: exercise, not paracetamol/acetaminophen and not gabapentin.

“Low back pain” is the top of the demand in Hebrew, and “natural treatment for low back pain” exists as a complete search — which is why it matters to say this without rounding: there is no research. In 2022, human disc nucleus pulposus cells stimulated with IL-1β and treated with ganoderic acid A showed less NO, PGE2, COX-2, TNF-α and IL-6, more collagen II and aggrecan, and less MMP-3 and MMP-13 — the NF-κB pathway. In 2016, cordycepin in rat disc cells and in organ culture suppressed MMP-3, MMP-13 and ADAMTS. Two studies on cells in a plate, zero on a human back. What was measured in chronic low back pain — and at scale: a 2021 Cochrane review of 249 trials of exercise, which found a 15.2-point drop in pain on a 0–100 scale versus no treatment, above the threshold of clinical importance; a 2025 overview of 31 Cochrane reviews and 97,183 adults; and two high-quality-evidence “zero” results — paracetamol/acetaminophen (−0.5 points) and gabapentinoids (−0.0). The detail — in the “what is proven” chapter. Herniated disc, sciatica, radicular pain — each of them is a matter for a physician and a physical therapist, and none of them has been tested with a mushroom in any organism.

Reishi for nerve pain — what happened to the four patients from 1998, and why is it not evidence?

In 1998, a Japanese physician reported that two patients with refractory postherpetic neuralgia and two with severe herpes zoster pain had a “dramatic decrease in pain” after a hot-water reishi extract — at 36 to 72 grams dry weight a day. Four patients, no control group, no pain scale, a dose 10–20 times a usual capsule, never replicated.

This is the only human record in all of PubMed on reishi and neuropathic pain, which is why it gets quoted. The same physician published another series in 2005: five herpes zoster patients aged 17–74 who received a formula of eight plants — including cultivated reishi at 0.75 grams per dose alongside wisteria, trapa, nutmeg, ginseng, pomegranate and more — reported relief “within days”, and none of them developed neuralgia after more than a year. Five patients, no control group, eight ingredients — nothing can be attributed to reishi. The wording we can stand behind: described in four patients in 1998 at an extreme dose, without a control group, and never replicated. Not “reishi for neuralgia”. And incidentally — the strongest evidence on reishi in a population with chronic pain points the other way: in 29 men with Gulf War illness, which includes pain and chronic fatigue, high-dose reishi worsened symptoms (p=0.012) — detailed on the fibromyalgia page.

Reishi in rheumatoid arthritis — the only human trial, and what did it actually find?

A randomized double-blind trial in 65 patients with active rheumatoid arthritis: reishi 4 grams + San Miao San 2.4 grams a day, 24 weeks. Primary outcome — ACR20 response — 15% versus 9.1%, not significant. Pain score “improved significantly only in the herbal group”, versus baseline, a secondary outcome. 8 mild adverse events versus 14 on placebo.

This is the trial quoted as “reishi proven as a painkiller in arthritis”, so it is worth reading slowly. Reishi was not given alone but with a Chinese formula of three plants, so it cannot be isolated. The primary outcome was not met. The accompanying immunology publication, from 2006, measured CD4, CD8, NK, B cells and six plasma chemokines at 8 and 24 weeks — no difference in any of them; only IL-18 production in cells outside the body fell. The authors’ conclusion, word for word: “there may be an analgesic effect… however, no significant antioxidant, anti-inflammatory or immunomodulatory effect could be demonstrated”. 89% completed; 13 patients reported 22 mild adverse events — 14 on placebo, 8 in the herbal group. And this is rheumatoid arthritis — an autoimmune disease — not osteoarthritis and not the back; we detailed it on the autoimmune disease page.

And what is there in rodents? A lot, and all of it impressive in a dish and in a cage: reishi spore powder in mice with collagen-induced arthritis reduced pain hypersensitivity through neutrophils; ganoderic acid A at 20 or 40 mg/kg in 40 mice lowered the arthritis score at the higher dose; reishi with San Miao San in rats suppressed allodynia — by intraperitoneal injection, and not when given orally; “Gano oil”, a fatty extract of reishi, inhibited edema in mice by 42%, 58% and 73% and extended hot-plate latency to 30 seconds versus 1.65 — except that its main component, oleamide, is a sedative, and the authors themselves write “hypnotic”; and in the historic 1997 study, out of 134 extracts from 45 mushroom species, ganoderic acids A, B, G and H were identified as the antinociceptive components in mice. None of these was tested in a human being.

Taking etoricoxib, etodolac, ibuprofen or metamizole — is there an interaction with mushrooms?

Not measured in humans — the dish is reassuring. In 2024, 66 reishi triterpenoids were tested against seven liver enzymes: most inhibited CYP1A2, but the most potent compound did not inhibit CYP3A4 (etoricoxib), CYP2C9 (ibuprofen, celecoxib) or CYP2D6 — though the crude extract inhibited “different subtypes” and altered four drugs’ pharmacokinetics in rats. Mushroom-with-NSAID studies in humans: 0.

What is known about the drugs. Etoricoxib (Arcoxia, not marketed in the US) is broken down in human microsomes about 60% by CYP3A and about 10% each by CYP2C9, 2D6 and 1A2; its half-life is about 20 hours; co-administration with other drugs “has been evaluated only to a limited extent”. Etodolac (Lodine) and ibuprofen (Advil) go through CYP2C9 and 2C8 — and for anyone whose enzyme is genetically slow, the risk of gastrointestinal bleeding from an NSAID nearly doubles: OR 1.90 in a meta-analysis. Celecoxib (Celebrex) — CYP2C9, and in carriers of a slow variant, also CYP2D6 up to 30%; in 52 Korean volunteers, carriers of one variant showed 1.63-fold higher exposure. Metamizole (dipyrone; not approved in the US) is a different story: a moderate-to-strong inducer of CYP3A4, 2B6 and 2C19, and a moderate inhibitor of CYP1A2 — and it abolishes the effect of aspirin when taken together. What is known about the mushrooms. In 2007, a reishi polysaccharide inhibited CYP1A2, CYP3A and CYP2E1 in rat microsomes. In 2024, the extension: a dichloromethane extract of reishi inhibited different subtypes and interfered with the pharmacokinetics of four drugs in rats; out of the library of 66 triterpenoids, CYP1A2 was inhibited by most of the lanostanes, and one compound inhibited “broadly” — except CYP3A4, 2D6, 2C9 and 2C19. In other words, precisely the pathways of etoricoxib, etodolac and ibuprofen were not inhibited by the most potent compound; and CYP1A2, which was inhibited, is not the pathway of any common painkiller — and metamizole actually inhibits it itself, so there is no counter-axis. Two test-tube studies, two directions, and in humans — zero. On turkey tail there is one pharmacokinetic figure: polysaccharopeptide in rats slowed the absorption of tamoxifen (Tmax rose by 228%) without changing total exposure — absorption, not metabolism. On lion’s mane and cordyceps and CYP enzymes — 0 studies.

And one sentence on “reishi protects the stomach from NSAIDs”, which you will find online: the basis is a 2017 study in which macrophages stimulated with a reishi mycelium extract were transferred into mice given indomethacin — small-intestinal injury decreased. A transfer of cells between mice, not feeding; and mice. A 2021 review counts 22 studies of complementary medicine for NSAID-induced intestinal injury, 19 of them in animals. The wording we can stand behind: reishi’s most potent triterpene did not inhibit, in a dish, the enzymes that break down etoricoxib, etodolac and ibuprofen; the crude extract did alter pharmacokinetics in rats; in humans this was not measured — so it is a question for the pharmacist. Not “safe”, not “dangerous”. The wider list — on the drug interactions page.

Tramadol, Ultracet or OxyContin — what about opioid painkillers?

Tramadol (Ultram, Ultracet) needs CYP2D6 for its active metabolite; a 2D6 inhibitor lowers it — in a model, quinidine: −52% — so inhibition would weaken, not poison. Reishi’s most potent triterpene did not inhibit 2D6 in a dish. On oxycodone (OxyContin) we collected no source on the pathway, so nothing is written. Mushroom plus opioid in humans: 0.

“Tramadol or Ultracet”, “Ultracet dangerous”, “Ultracet for back pain” — all live searches in Hebrew. What is known about tramadol. It is broken down “mainly by CYP2D6 to O-desmethyltramadol, the main active metabolite”, so the enzyme’s genetics and concomitant drugs decide how much of the effect you get. In a 2022 pharmacokinetic model, a single dose of quinidine — a strong 2D6 inhibitor — raised tramadol by 51% and lowered the active metabolite by 52%; the conclusion: avoid the combination. And what an interaction measured in humans looks like: in 2026, 12 volunteers received eight days of celecoxib 200 mg, etoricoxib 120 mg or placebo and then tramadol — celecoxib lowered the metabolite ratio by 24%, etoricoxib changed nothing, and the difference in pharmacological effect was “negligible”. That is the bar: a weak inhibitor changes the metabolite by 24% without changing the effect. What is known about the mushrooms. Compound 25 from reishi did not inhibit CYP2D6 in a dish; and if something did inhibit it — the direction is less relief, not more risk. In rodents and cells there is an entire research line on “morphine tolerance”: lion’s mane mycelium extract suppressed morphine-induced microglial migration in cells; turkey tail polysaccharopeptide injected into the spinal cord delayed tolerance in rats; cordycepin inhibited tolerance in rats through SIRT1. Cells and a rat’s spinal cord — not a person with a prescription.

And what matters more than any supplement: according to a 2022 meta-analysis of 16 placebo-controlled trials, strong opioids for chronic back pain “may cause a clinically relevant reduction in pain” for 4–15 weeks, with more side effects and no effect on disability — and beyond 6 months they “are not superior to non-opioids”, with addiction and “possibly increased all-cause mortality”. And in a network meta-analysis of 14 opioids across 82 trials — “no differences were found between the opioids”. OxyContin, Percocet (oxycodone + acetaminophen) and tramadol differ from each other less than the names suggest; and no mushroom has been tested alongside any of them.

Gabapentin, Neurontin or Lyrica — anything to worry about?

No known interaction axis: gabapentin (Neurontin) and pregabalin (Lyrica) “are not metabolized by liver enzymes and do not inhibit them”, excreted by the kidneys. One caveat — absorption: gabapentin bioavailability falls from 60% to 33% between 900 and 3,600 mg a day; a supplement’s effect was not tested. For low back pain, gabapentinoids do not work: high-quality evidence.

The 2010 pharmacokinetics review, written by researchers from Pfizer, describes two drugs that barely touch the liver: renal excretion, a half-life of about 6 hours, no metabolism and no protein binding — pregabalin is absorbed at 90% and above, gabapentin through a saturable transporter, so that the higher the dose, the lower the percentage absorbed. The pathway through which a supplement could change a drug’s blood level — CYP enzymes — simply does not exist here. What was not tested: an effect on gut absorption, and additive drowsiness. And then the figure that matters more than the interaction: in a 2018 meta-analysis in CMAJ, 9 trials and 859 participants — gabapentinoids for chronic back pain: a difference of −0.0 points (confidence interval −0.8 to 0.7), high-quality evidence, and “high-quality evidence of a higher risk of adverse events”; for radicular pain — −0.1. A 2023 review of chronic back pain without radiculopathy adds that pregabalin was slightly less effective than amitriptyline, than tramadol with acetaminophen and than celecoxib, and that pregabalin with celecoxib added nothing over celecoxib alone. For neuropathy, by contrast, this is first line: NNT 7.7 for pregabalin and 7.2 for gabapentin for 50% relief. On Lyrica with mushrooms — including why there is no CYP axis — we went further on the fibromyalgia page.

Do medicinal mushrooms increase bleeding when you take an NSAID?

Not measured — and the two reishi platelet studies contradict each other: 3 grams a day for two weeks inhibited aggregation by 31.49% in 33 uncontrolled patients; a randomized trial in 40 volunteers, 1.5 grams a day for 4 weeks — zero change in every coagulation measure. On NSAIDs and bleeding: celecoxib OR 1.16, ibuprofen 2.28, ketorolac 20.67.

The reason the question matters: when something that affects platelets meets an NSAID, the risk multiplies. The measured example is SSRIs: across 15 studies and 82,605 patients, an SSRI with an NSAID versus an SSRI alone — OR 2.14 for bleeding, and versus an NSAID alone — OR 1.49. Is reishi “something that affects platelets”? In 1990, 33 atherosclerotic patients who took 1 gram three times a day for two weeks showed 31.49% inhibition of aggregation and a shorter ex-vivo thrombus — before/after, no control group. In 2005, a randomized double-blind trial in 40 healthy volunteers, 1.5 grams a day for 4 weeks, with routine coagulation, fibrinogen, vWF, PFA-100 and thromboelastography — no difference, everything within the normal range; “not expected to increase the risk of surgical bleeding in healthy individuals”. Double the dose, a different population, a different design — we write both. And on the NSAIDs themselves: a 2026 meta-analysis of 25 studies ranked gastrointestinal bleeding risk by drug — celecoxib the lowest (OR 1.16), ibuprofen the lowest among the non-selectives (2.28), ketorolac the highest (20.67), and piroxicam (Feldene) “significantly increased”; etoricoxib, etodolac and metamizole were not listed. And a 2025 meta-analysis of 89,522 participants: ibuprofen at doses up to 1,200–1,800 mg a day versus non-users — OR 2.51 for upper GI bleeding; versus paracetamol/acetaminophen — 0.96. A mushroom combined with an NSAID in humans — 0 measurements. Anyone on a regular NSAID, an antiplatelet or an anticoagulant — tells the doctor about every supplement; the full list of who should stop is gathered on who shouldn’t take reishi.

Medical cannabis for pain — what does Cochrane 2026 say, and where are the mushrooms?

The 2026 Cochrane review of cannabis for neuropathic pain — 21 studies, 2,187 participants: THC-dominant — 50% or greater relief at RD 0.14, unclear, with more nervous-system side effects (RD 0.25); balanced THC/CBD — 0.04; CBD-dominant — −0.08. “No clear evidence”. The review is on neuropathic pain, not the back. Mushrooms with cannabis: 0 studies.

“Medical cannabis back pain” is a live search, so it gets a chapter — a short one, because what we have to say is mostly limits. The most recent review measured neuropathic pain only; for low back pain it does not apply. Within neuropathic pain, the strongest finding was a risk of nervous-system side effects with THC preparations, not relief. The question of combining with mushrooms does not exist in the literature — 0 records — and without a source on how THC and CBD are broken down in the body, we will not write a guess. Anyone treated with medical cannabis for pain manages it with the physician at the pain clinic, and tells them about every supplement.

What is actually proven for chronic pain — and we do not sell?

Chronic back pain: exercise — 249 trials, a 15.2-point drop versus no treatment; multidisciplinary care; CBT — small. Knee: curcuminoids across 15 trials and 1,670 patients — non-inferior to NSAIDs; glucosamine sulfate alone — small; topical diclofenac — first line. Diabetic neuropathy: alpha-lipoic acid 600 mg across 11 studies. Not proven: paracetamol/acetaminophen and gabapentin for the back, long-term opioids.

Chronic low back pain. A 2021 Cochrane review of 249 trials: exercise versus no treatment, usual care or placebo — pain −15.2 points on 0–100 (confidence interval −18.3 to −12.2), above the threshold of clinical importance; function −6.8; versus other conservative treatments −9.1; versus manual therapy — no difference; moderate certainty. The 2025 overview of 31 Cochrane reviews and 97,183 adults adds acupuncture versus no treatment (−10.1), multidisciplinary care (SMD −0.55) and psychological therapy (−5.18 on pain, zero on function). CBT for chronic pain, in a 2020 Cochrane review of 75 studies and 9,401 participants — versus active control SMD −0.09 on pain, “small or very small effects”; for neuropathic pain — 2 studies and 105 participants, “insufficient evidence”. And the 2018 Lancet series sums up the guidelines: a biopsychosocial framework, non-drug treatment first, “judicious use of medication, imaging and surgery” — and in practice “high rates of inappropriate use of imaging, rest, opioids, injections and surgery”. What does not work for the back. Paracetamol/acetaminophen (Tylenol) — high-quality evidence in BMJ 2015: −0.5 pain points (interval −2.9 to 1.9), zero on disability, and abnormal liver function 3.8 times as often; in hip and knee OA — significant but not clinically important (−3.7), and a 2019 Cochrane review of 3,541 patients: 3.23 points against an importance threshold of 9, and a “call to reconsider the recommendations”. NSAIDs for chronic back pain — Cochrane 2016, 13 trials: −3.30 points on 100, “the effect size is small and the evidence is low”; “Arcoxia not helping” from the autocomplete matches the literature roughly. Gabapentinoids — −0.0.

Knee osteoarthritis. Curcuminoids alone — 15 trials, 1,670 patients: pain on VAS −1.77, total WOMAC −7.06, “non-inferior to NSAIDs” in pain and function, side effects like placebo (RR 1.03), with “low quality and considerable heterogeneity”; and a 2024 meta-analysis of 11 meta-analyses “strongly supports” it. Glucosamine: alone — VAS −7.41 mm (p=0.04); chondroitin alone −8.35; the glucosamine + chondroitin combination — −0.28, zero — exactly the pairing people type; and at 12 months and beyond, across 47 trials and 22,037 patients in JAMA, glucosamine sulfate was the only one that stayed significant (SMD −0.29) after removing studies at risk of bias — with “large uncertainty in all estimates”. NSAIDs for OA: in a 2017 Lancet network meta-analysis (76 trials, 58,451), diclofenac 150 mg and etoricoxib 60 mg crossed the importance threshold with 100% probability, and there is “no role for single-agent paracetamol”; in the 2021 BMJ update (192 trials, 102,829) topical diclofenac is recommended first line for the knee, and all opioids — 53% probability or lower of crossing the threshold, “the benefits do not outweigh the harms”. Neuropathy. Alpha-lipoic acid at 600 mg a day for diabetic neuropathy — 8 of 11 studies reported a benefit, SMD −1.05 on the symptom score, side effects mostly gastrointestinal; and drugs — NNT for 50% relief: SNRIs 6.4, pregabalin 7.7, gabapentin 7.2, according to the 2015 NeuPSIG meta-analysis of 229 studies, with a 2025 update of 313 trials whose numbers we did not pull. Those are the numbers — and we do not recommend a drug or set a dose; we write them because they are the bar every supplement has to be measured against, and medicinal mushrooms have not been measured against it at all.

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 and turkey tail pain 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, reishi 1:3 and turkey tail with reishi 1:3. Alcohol in the finished extract: 32% — a figure worth bringing to the pharmacist, 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 on this page in particular: most of the lion’s mane pain studies were done on mycelium — the mushroom’s network growing on a grain substrate — and not on the fruiting body; the market’s three-step ladder is mycelium on grain (beta-glucan usually below 7%, most of the weight starch), imported dried fruiting body, and fresh fruiting body from the farm, which is what we do. And what we did not measure — we say that too: we did not measure triterpenes, so we will not write about “ganoderic acid A” in the bottle. 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 your chronic pain — back, joints or nerves — 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 lion’s mane regenerates nerves in humans, relieves neuropathy or sciatica; we do not claim that reishi, cordyceps or turkey tail relieve back pain, osteoarthritis or neuropathic pain — at any dose and in any form; none of them has been tested in a controlled human trial in any of these conditions. We do not claim that the rheumatoid arthritis trial proved anything — its primary endpoint was not met, and reishi was given in it inside a formula. We do not claim that four patients from 1998 are evidence. We do not claim that the mushrooms are “safe with etoricoxib or tramadol” — the dish is reassuring, and in humans it was not measured; and we do not claim they are dangerous. We do not write anything about oxycodone or cannabis for which we found no source. We do not carry findings from other species — Ganoderma cochlear, Hericium ramosum — over to our mushrooms. And we do not deal with disability benefits, disability ratings or entitlements — we have no expertise in those. What we do say: chronic pain is treated by a physician, at a pain clinic and in physical therapy; anyone taking etoricoxib, etodolac, ibuprofen, metamizole, tramadol, Ultracet, gabapentin, Lyrica, 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 chronic pain.

The bottom line

Medicinal mushrooms have not been tested in a controlled human trial for back pain, osteoarthritis or neuropathy. What exists: one rheumatoid arthritis trial that missed its primary endpoint, four patients from 1998 at an extreme dose, and rats — in which vitamin B12 repaired a crushed nerve just as well as lion’s mane. On etoricoxib, etodolac and tramadol: reishi’s most potent triterpene did not inhibit, in a dish, the enzymes that break them down, and in humans the combination was not measured — a question for the pharmacist. What is proven — exercise for the back, curcumin for the knee, alpha-lipoic acid for diabetic neuropathy — we do not sell; and what is not — paracetamol/acetaminophen for the back, gabapentin for the back, long-term opioids — is worth knowing before your next appointment. And if someone sells you a mushroom “for back pain” — send them this page, and go to a pain clinic.

Frequently asked questions

Does lion’s mane help with sciatica or neuropathic (nerve) pain?

Not measured in humans — 0 trials and 0 case reports of lion’s mane in neuropathy, sciatica or nerve pain. What exists: mice with a ligated nerve (mycelium, funded by the manufacturer) and diabetic rats. A 2026 systematic review found 11 records, all preclinical. For neuropathic pain in humans, what was measured is SNRIs, pregabalin and gabapentin (NNT 6–8) and alpha-lipoic acid for diabetic neuropathy.

Does lion’s mane regenerate damaged nerves?

In rats with a crushed nerve — limb function returned earlier with a fruiting-body extract, and also with vitamin B12, which was the positive control. In humans — never measured. “Nerve regeneration” in a person is a question for a neurologist, and the first question is what caused the injury.

Can I take medicinal mushrooms instead of etoricoxib (Arcoxia) or etodolac?

No — there is not one human trial comparing a mushroom with an NSAID in any kind of pain. What was measured: etoricoxib 60 mg for osteoarthritis crosses the threshold of clinical importance with 100% probability across 76 trials; for chronic low back pain, NSAIDs lower pain by 3.3 points out of 100 — small. Do not stop a drug on your own.

Can I combine mushrooms with Ultracet or tramadol?

Not measured in humans. Tramadol is activated by CYP2D6 into its active metabolite; reishi’s most potent triterpene did not inhibit 2D6 in a dish, and if something did inhibit it — the active metabolite would fall (in a model, −52% with quinidine), meaning less relief, not more risk. Still: “not measured” is not “safe” — a question for the pharmacist.

Is there an interaction between mushrooms and Advil (ibuprofen) or metamizole?

Not measured in humans. Ibuprofen is broken down by CYP2C9, which reishi’s most potent triterpene did not inhibit in a dish; metamizole (dipyrone) itself inhibits CYP1A2 — the only enzyme reishi consistently inhibited — so there is no known counter-axis. The crude reishi extract did alter drug pharmacokinetics in rats. All of it theoretical; in humans — 0 measurements.

How long until you see pain improve with mushrooms?

There is no figure, because there is no human trial that measured back, joint or neuropathic pain with a mushroom. The only human trial, in rheumatoid arthritis, ran 24 weeks — and its primary endpoint was not met. Any other answer you get to “how long” is a guess, not a measurement.

What is the difference between osteoarthritis and rheumatoid arthritis, and why does it matter?

Rheumatoid is an autoimmune disease — the immune system attacks the joint; osteoarthritis is mechanical wear. The only human trial of reishi was in rheumatoid arthritis, with a Chinese formula, and missed its primary endpoint (ACR20 15% versus 9.1%). On osteoarthritis — the common form in the knee and in menopause — there is no human trial at all, only rats and cells.

What actually works for back pain according to the research?

According to Cochrane, exercise — 249 trials, a 15.2-point drop in pain versus no treatment, above the importance threshold; multidisciplinary care; CBT with a small effect. What does not: paracetamol/acetaminophen (−0.5, high-quality evidence), gabapentinoids (−0.0, more side effects), and opioids beyond 6 months. We sell none of them, and mushrooms were not tested.

Scientific sources (peer-reviewed)

• 65 patients with active rheumatoid arthritis, reishi 4 g + San Miao San 2.4 g a day versus placebo, 24 weeks: ACR20 15% versus 9.1% (not significant); pain score improved only in the herbal group versus baseline; 22 mild adverse events — 14 placebo, 8 herbal; “no anti-inflammatory or immunomodulatory effect could be demonstrated” — Li EK, et al. Arthritis and Rheumatism, 2007. View on PubMed
• The same trial, the immunology publication: CD4, CD8, NK, B cells and six plasma chemokines — no difference at 8 and 24 weeks; only ex-vivo IL-18 fell — Bao YX, et al. Immunopharmacology and Immunotoxicology, 2006. View on PubMed
• Hot-water extract of reishi, 36–72 g dry weight a day, “dramatically decreased pain” in two patients with postherpetic neuralgia and two with herpes zoster; n=4, no control group, no pain scale — Hijikata Y, et al. The American Journal of Chinese Medicine, 1998. View on PubMed
• Formula of 8 plants including reishi 0.75 g per dose in 5 herpes zoster patients: relief “within days”; n=5, no control group, 8 ingredients — Hijikata Y, et al. The American Journal of Chinese Medicine, 2005. View on PubMed
• Representative survey in Israel: 8,300 invited, 1,647 responded (19.8%); 515 (31.3%) with pain over 3 months; daily intensity 5.8/10; axial skeleton and headache most common — Sharon H, et al. Pain Research & Management, 2022. View on PubMed
• Lancet seminar: chronic pain affects more than 30% of people in some studies; nociceptive/neuropathic/nociplastic classification as a continuum; multidisciplinary approach — Cohen SP, et al. Lancet, 2021. View on PubMed
• Low back pain — “the leading cause of disability worldwide”; years lived with disability rose 54% between 1990 and 2015; almost always without a specific nociceptive cause — Hartvigsen J, et al. Lancet, 2018. View on PubMed
• Lion’s mane mycelium extracts blocked ATP-evoked calcium signaling in cells and delayed tail-flick and hot-plate responses in mice — thermal pain; doses not in the abstract; Grape King Bio — Liu PS, et al. International Journal of Medicinal Mushrooms, 2017. View on PubMed
• Mice with L5 nerve ligation: mycelium extract and erinacine S raised the paw withdrawal threshold, lowered GFAP, Iba1 and IL-6; erinacine S better than the extract; dose not in the abstract; Grape King Bio — Yang PP, et al. Evidence-Based Complementary and Alternative Medicine, 2020. View on PubMed
• Diabetic (alloxan) rats, ethanol extract 40 mg/kg for 6 weeks: pain threshold rose — and glucose fell; “improvement of the diabetic condition” — Yi Z, et al. Evidence-Based Complementary and Alternative Medicine, 2015. View on PubMed
• Hericenone C suppressed the second phase of the formalin pain response in mice through CD11c-positive cells and p65 — Li J, et al. Biochemical and Biophysical Research Communications, 2024. View on PubMed
• Rats with OA from cruciate ligament transection, lion’s mane mycelium: “weight-bearing asymmetry improved and pain was minimized”, IL-1β and TNF-α fell; no number in the abstract; Grape King Bio — Yang SY, et al. Nutrients, 2022. View on PubMed
• Lion’s mane mycelium + undenatured type II collagen in ACLT rats: “reduced bone pain”; a combination, without isolating the mushroom, without numbers — Lee KT, et al. International Journal of Medical Sciences, 2026. View on PubMed
• BV2 microglial cells: morphine 1 micromolar increased migration; 100 ng/mL of lion’s mane mycelium extract inhibited it — test tube only — Yeh CH, et al. Molecular Medicine Reports, 2019. View on PubMed
• Rats with a crushed peroneal nerve, aqueous extract of fresh fruiting body: limb function returned earlier — in the extract group and in the mecobalamin group (positive control) versus negative control; dose/n not in the abstract — Wong KH, et al. Evidence-Based Complementary and Alternative Medicine, 2011. View on PubMed
• The same group: in the DRG neurons of treated rats — Akt, MAPK, c-Jun and c-Fos higher (P<0.05) — Wong KH, et al. Chinese Journal of Integrative Medicine, 2016. View on PubMed
• Systematic review of medicinal mushrooms for peripheral nerve injury: 11 records 2010–2024, 5 on lion’s mane, all preclinical; “need to undergo clinical research” — Taib NAB, et al. Medical Sciences (Basel), 2026. View on PubMed
• Gano oil from reishi in mice: edema −42%, −58%, −73% at 10/25/50 mg/kg; writhing −44.44%; hot-plate latency 30.0 seconds versus 1.65; main component — oleamide, “hypnotic” — Chen X, et al. Journal of Ethnopharmacology, 2020. View on PubMed
• 134 extracts from 45 mushroom species in the mouse writhing test: ganoderic acids A, B, G, H from reishi — the antinociceptive components — Koyama K, et al. Planta Medica, 1997. View on PubMed
• Ganoderic acid A 20 or 40 mg/kg in 40 mice with collagen-induced RA: arthritis score fell at the higher dose (p<0.05); IL-6, TNF-α fell — Guzel Erdogan D, et al. Scientific Reports, 2025. View on PubMed
• Reishi spore powder in CIA mice: pain hypersensitivity, swelling and joint destruction decreased through neutrophils and TNF-α; dose not in the abstract — Huang S, et al. Frontiers in Immunology, 2025. View on PubMed
• Reishi + San Miao San in rats with monoarthritis: intraperitoneal 50 mg/kg suppressed allodynia; oral 500 mg/kg — edema only, not allodynia — Lam FF, et al. Journal of Ethnopharmacology, 2008. View on PubMed
• Ganoderic acid A in cartilage cells and DMM mice: inflammation and matrix breakdown fell through ER stress and NF-κB; “may slow” OA in the mouse; no number in the abstract — Liu Y, et al. Chemical Biology & Drug Design, 2024. View on PubMed
• Ganoderic acid A in DMM mice and human cartilage cells: histology scores fell; MMP-13 in synovial fluid fell; RANKL/OPG. The only record tagged “humans” — because of cells — Wu W, et al. Chemical Biology & Drug Design, 2022. View on PubMed
• Ganoderic acid A in human disc nucleus pulposus cells with IL-1β: NO, PGE2, COX-2, TNF-α, IL-6, MMP-3/13 fell; collagen II and aggrecan preserved — test tube, zero pain — Zheng S, et al. Inflammation, 2022. View on PubMed
• Cordycepin 10/50/100 micromolar in cartilage cells from OA patients: PGE2, NO, MMP-13, IL-6, iNOS, COX-2 fell — test tube — Ying X, et al. International Orthopaedics, 2014. View on PubMed
• Synovial fibroblasts from 12 RA patients: cordycepin inhibited IL-1β-induced MMP-1 and MMP-3 — test tube — Noh EM, et al. Rheumatology (Oxford), 2009. View on PubMed
• Cordycerebroside A: ICAM-1 and CD86 elevated in human OA synovium and in ACLT rats; the compound inhibited M1 macrophage adhesion — Lee KT, et al. Journal of Food Biochemistry, 2022. View on PubMed
• Cordycepin in rat disc cells and organ culture: MMP-3, MMP-13, ADAMTS-4/5, NO, PGE2 fell — zero pain — Li Y, et al. PeerJ, 2016. View on PubMed
• Cordycepin inhibited the development of morphine tolerance in rats through SIRT1 and ferroptosis in the spinal cord — Li Z, et al. International Journal of Medical Sciences, 2025. View on PubMed
• Wistar rats: turkey tail mycelium powder 500 mg/kg reduced formalin-induced licking as much as aspirin 100 mg/kg; COX-2 and PGE2 fell — “aspirin-like” — Hung PH, et al. Biomedicine & Pharmacotherapy, 2020. View on PubMed
• Turkey tail polysaccharopeptide intrathecally 50–200 micrograms/kg in rats with inflammatory OA pain: pain threshold improved, morphine tolerance delayed, CB2 — injection into the spinal cord — Wang K, et al. International Journal of Biological Macromolecules, 2019. View on PubMed
• 66 reishi triterpenoids against 7 CYP enzymes: most lanostanes inhibited CYP1A2; the most potent compound inhibited “broadly” except CYP3A4, 2D6, 2C9 and 2C19; the crude extract altered the pharmacokinetics of 4 drugs in rats — Li D, et al. Frontiers in Pharmacology, 2024. View on PubMed
• Reishi polysaccharide inhibited CYP2E1, CYP1A2 and CYP3A dose-dependently in rat liver microsomes — Wang X, et al. Biological & Pharmaceutical Bulletin, 2007. View on PubMed
• Turkey tail polysaccharopeptide 340 mg/kg for 7 days in rats with tamoxifen: Tmax rose 228%; AUC and Cmax unchanged — absorption, not metabolism — Razmovski-Naumovski V, et al. Frontiers in Pharmacology, 2022. View on PubMed
• Tramadol “is metabolized mainly by CYP2D6 to O-desmethyltramadol, the main active metabolite” — Barbosa J, et al. Drug Metabolism Reviews, 2016. View on PubMed
• PBPK model: quinidine (2D6 inhibitor) — tramadol +51%, O-desmethyltramadol −52%; “the combination should be avoided” — Long T, et al. Journal of Clinical Pharmacology, 2022. View on PubMed
• 12 volunteers, crossover: celecoxib 200 mg for 8 days lowered the tramadol metabolite ratio by 24%; etoricoxib — no effect; effect differences “negligible” — Saarikoski T, et al. Basic & Clinical Pharmacology & Toxicology, 2026. View on PubMed
• Ibuprofen and diclofenac: metabolism by CYP2C8 and CYP2C9; slow variants linked to hepatotoxicity and GI bleeding — Krasniqi V, et al. Arhiv za Higijenu Rada i Toksikologiju, 2016. View on PubMed
• CYP2C9 poor metabolizers: OR 1.86 for NSAID GI events and OR 1.90 for GI bleeding; CYP2C9*3 a strong predictor — Macías Y, et al. Expert Opinion on Drug Metabolism & Toxicology, 2020. View on PubMed
• Celecoxib 200 mg in 52 healthy Koreans: AUC 1.63-fold in CYP2C9 variant carriers versus normal (P<0.001) — Kim SH, et al. Archives of Pharmacal Research, 2017. View on PubMed
• Celecoxib is also a CYP2D6 substrate: ~0% contribution in normals and up to ~30% in CYP2C9*3 carriers — human microsomes — Siu YA, et al. Drug Metabolism and Pharmacokinetics, 2018. View on PubMed
• Etoricoxib in human microsomes: ~60% CYP3A, ~10% each CYP2C9/2D6/1A2 — Kassahun K, et al. Drug Metabolism and Disposition, 2001. View on PubMed
• Etoricoxib: t½ about 20 hours; “metabolized mainly by CYP3A4”; co-administration with drugs “evaluated only to a limited extent” — Takemoto JK, et al. Clinical Pharmacokinetics, 2008. View on PubMed
• Metamizole (dipyrone): moderate-to-strong inducer of CYP3A4, 2B6, 2C19; moderate inhibitor of CYP1A2; abolishes the aspirin effect when taken together — Brinkman DJ, et al. British Journal of Clinical Pharmacology, 2025. View on PubMed
• Gabapentin and pregabalin: “not metabolized by liver enzymes and do not inhibit them”, no protein binding, renal excretion; gabapentin bioavailability falls from 60% to 33% between 900 and 3,600 mg a day — Bockbrader HN, et al. Clinical Pharmacokinetics, 2010. View on PubMed
• Pregabalin: less than 2% metabolism, renal excretion, no CYP inhibition or induction — Ben-Menachem E. Epilepsia, 2004. View on PubMed
• 33 atherosclerotic patients, reishi 1 g three times a day for two weeks: 31.49% inhibition of platelet aggregation (P<0.01); no control group — Tao J, Feng KY. Journal of Tongji Medical University, 1990. View on PubMed
• Randomized double-blind trial in 40 healthy volunteers, reishi 1.5 g a day for 4 weeks: all coagulation measures without difference, within the normal range — Kwok Y, et al. Anesthesia and Analgesia, 2005. View on PubMed
• NSAIDs and GI bleeding, 25 studies: celecoxib OR 1.16; ibuprofen 2.28; ketorolac 20.67; piroxicam and meloxicam increased; “not a homogeneous group” — Tawfik AG, et al. Clinical Pharmacology and Therapeutics, 2026. View on PubMed
• Ibuprofen and upper GI bleeding, 89,522 participants: versus non-users OR 2.51; versus paracetamol OR 0.96; very low certainty — Gkiouras K, et al. Inflammopharmacology, 2025. View on PubMed
• SSRI + NSAID and GI bleeding, 15 studies, 82,605 patients: versus SSRI alone OR 2.14; versus NSAID alone OR 1.49 — Haghbin H, et al. Digestive Diseases and Sciences, 2023. View on PubMed
• Macrophages stimulated with reishi mycelium extract and transferred into mice with indomethacin: small-intestinal injury decreased through GM-CSF — cell transfer, not feeding — Nagai K, et al. Cellular Immunology, 2017. View on PubMed
• Complementary medicine for NSAID-induced small-intestinal injury — review: 22 studies, 3 clinical and 19 in animals — Cho M, et al. Medicine (Baltimore), 2021. View on PubMed
• Cochrane, 249 trials: exercise for chronic low back pain — pain −15.2 (−18.3 to −12.2) on 0–100 versus no treatment; function −6.8; moderate certainty — Hayden JA, et al. Cochrane Database of Systematic Reviews, 2021. View on PubMed
• Overview of 31 Cochrane reviews, 644 trials, 97,183 adults: acupuncture −10.1; exercise −15.2; multidisciplinary SMD −0.55; psychological −5.18 on pain — Rizzo RR, et al. Cochrane Database of Systematic Reviews, 2025. View on PubMed
• CBT for chronic pain, 75 studies, 9,401 participants: versus active control — pain SMD −0.09; “small or very small effects” — Williams ACC, et al. Cochrane Database of Systematic Reviews, 2020. View on PubMed
• Psychological therapies for neuropathic pain: 2 studies, 105 participants; “insufficient evidence” — Eccleston C, et al. Cochrane Database of Systematic Reviews, 2015. View on PubMed
• Curcuminoids alone for knee OA, 15 trials, 1,670 patients: VAS −1.77; WOMAC −7.06; non-inferior to NSAIDs; adverse events RR 1.03; low quality — Feng J, et al. BMC Complementary Medicine and Therapies, 2022. View on PubMed
• Meta-analysis of 11 meta-analyses: curcumin lowered VAS and WOMAC in OA; “strongly supports” — Bideshki MV, et al. Phytotherapy Research, 2024. View on PubMed
• Knee OA versus placebo: glucosamine VAS −7.41 mm (p=0.04); chondroitin −8.35; the combination −0.28 (p=0.95) — zero — Simental-Mendía M, et al. Rheumatology International, 2018. View on PubMed
• JAMA, 47 trials, 22,037 patients, 12 months and beyond: glucosamine sulfate SMD −0.29 — the only one that stayed significant; “large uncertainty” — Gregori D, et al. JAMA, 2018. View on PubMed
• Alpha-lipoic acid 600 mg for diabetic neuropathy, 11 studies: SMD −1.05 on the symptom score (p=0.04); adverse events mostly GI — Prado MB Jr, et al. Canadian Journal of Diabetes, 2024. View on PubMed
• NeuPSIG, 229 studies: NNT for 50% relief — SNRIs 6.4, pregabalin 7.7, gabapentin 7.2; first line TCA/SNRI/gabapentinoids — Finnerup NB, et al. Lancet Neurology, 2015. View on PubMed
• NeuPSIG 2025 update: 313 trials, 48,789 participants (the updated numbers were not pulled) — Soliman N, et al. Lancet Neurology, 2025. View on PubMed
• Paracetamol for low back pain — high-quality evidence: ineffective (−0.5); in OA — significant but not clinically important (−3.7); abnormal liver function 3.8-fold — Machado GC, et al. BMJ, 2015. View on PubMed
• Cochrane: paracetamol for knee and hip OA, 10 trials, 3,541: pain 3.23 points against a threshold of 9; abnormal liver function RR 3.79 — Leopoldino AO, et al. Cochrane Database of Systematic Reviews, 2019. View on PubMed
• Cochrane: NSAIDs for chronic low back pain, 13 trials: pain −3.30 on 100; “the effect size is small and the evidence is low” — Enthoven WT, et al. Cochrane Database of Systematic Reviews, 2016. View on PubMed
• Lancet, 76 trials, 58,451: diclofenac 150 mg and etoricoxib 60 mg for OA — 100% probability of crossing the importance threshold; “no role for single-agent paracetamol” — da Costa BR, et al. Lancet, 2017. View on PubMed
• BMJ, 192 trials, 102,829: topical diclofenac — first line for the knee; all opioids ≤53% probability of crossing the threshold; “the benefits do not outweigh the harms” — da Costa BR, et al. BMJ, 2021. View on PubMed
• Strong opioids for chronic back pain: 4–15 weeks — pain reduction with more adverse events; beyond 6 months — “not superior to non-opioids”, addiction, “possibly increased mortality” — Nury E, et al. Pain, 2022. View on PubMed
• 14 opioids, 82 trials, 22,619: “no differences were found between the opioids”; all raised GI adverse events — Noori A, et al. British Journal of Anaesthesia, 2022. View on PubMed
• CMAJ, 9 trials, 859: gabapentinoids for chronic back pain −0.0 (−0.8 to 0.7), high-quality evidence; more adverse events — Enke O, et al. CMAJ, 2018. View on PubMed
• Gabapentinoids for chronic back pain without radiculopathy, 5 studies, 242: pregabalin slightly less effective than amitriptyline, tramadol/paracetamol and celecoxib — Tatit RT, et al. Arquivos de Neuro-Psiquiatria, 2023. View on PubMed
• Cochrane 2026: cannabis for neuropathic pain, 21 studies, 2,187: THC-dominant RD 0.14 (unclear), nervous-system adverse events RD 0.25; balanced 0.04; CBD −0.08; “no clear evidence” — Ateş G, et al. Cochrane Database of Systematic Reviews, 2026. View on PubMed
• Lancet 2018: guidelines for low back pain — biopsychosocial framework, non-drug treatment first; in practice “high rates of inappropriate use of imaging, rest, opioids, injections and surgery” — Foster NE, et al. Lancet, 2018. View on PubMed

Read next

• Medicinal mushrooms by goal — the hub
• Fibromyalgia and supplements — Lyrica and Cymbalta
• Medicinal mushrooms and arthritis
• Medicinal mushrooms and gout
• Medicinal mushrooms and autoimmune disease
• Medicinal mushrooms for menopause
• Medicinal mushrooms and blood sugar
• 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?
• 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 chronic pain, back pain, arthritis, neuropathy or any other medical condition. Chronic pain requires medical diagnosis and follow-up; back pain with leg weakness, loss of bladder or bowel control, fever, weight loss or night pain requires urgent medical attention. Do not stop, replace or change the dose of a painkiller, an anti-inflammatory drug, an opioid, a gabapentinoid 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 antiplatelet drugs, 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.*