Phytomedicine & Herbal Therapeutics

By the Clinical Research Explained Editorial Team

Sources checked: October 3, 2026

This article is general educational information, not medical advice. Read the site's Medical Disclaimer before acting on any of it.

Short Answer: Which Medications Raise Concern With Lion's Mane?

The sources reviewed for this article did not identify any prescription drug that a human interaction study has shown to be unsafe with lion's mane (Hericium erinaceus). The concern comes from laboratory and animal research and from a clinical reference monograph. It falls into four medication groups: antiplatelet medicines, anticoagulants, diabetes medicines, and immunosuppressants. Each is rated below as theoretical, case report, or studied. None reached “studied.”

If you take a medicine from any of these groups, or you take several prescriptions, ask a pharmacist or doctor before starting lion's mane. Bring the product label. A printable question list appears near the end of this page.

How the Evidence Ratings Work

• Theoretical: The concern rests on laboratory (cell or test-tube) or animal findings, or on a plausible mechanism. The sources reviewed contained no report of the problem in people taking both products.
• Case report: A published account of a single patient. It can raise a flag, but it cannot show how common a problem is or whether the supplement caused it.
• Studied: A human study that tested the combination or measured the effect. No medication group below reaches this level in the sources reviewed.

Medication-Class Interaction Checklist

1. Antiplatelet Medicines (Examples: Aspirin, Clopidogrel)

Evidence strength: Theoretical (laboratory).

A 2010 laboratory study by Mori and colleagues, summarized in a 2026 scoping review of lion's mane compounds, found that hericenone B, a compound isolated from the mushroom's fruiting bodies, reduced the clumping of human platelets when collagen triggered it. The effect was selective for collagen-triggered clumping. Platelet clumping is an early step in forming a blood clot, and antiplatelet drugs also act on platelets.

The RxList supplement monograph rates lion's mane combined with medicines that slow clotting as “Moderate” and lists aspirin, clopidogrel (Plavix), prasugrel (Effient), dipyridamole (Persantine), and ticlopidine (Ticlid) as examples. The same monograph notes that there are no reports of increased bleeding or bruising in humans.

What is not known: The sources reviewed do not establish whether the amount of hericenone B in a typical supplement is enough to affect platelets in a person.

2. Anticoagulants (“Blood Thinners”)

Evidence strength: Theoretical (indirect).

Anticoagulants work differently from antiplatelet drugs, so the platelet finding above does not map directly onto them. The shared worry is added bruising or bleeding, which is why the RxList monograph groups both under medicines that slow clotting. The sources reviewed contained no study of lion's mane taken with an anticoagulant. If your treatment depends on carefully managed clotting, ask your prescriber whether any extra monitoring would be appropriate.

3. Diabetes Medicines (Examples: Insulin, Metformin, Glimepiride)

Evidence strength: Theoretical (animal and laboratory).

The RxList monograph states that lion's mane might lower blood sugar. It rates the combination with diabetes medicines “Moderate,” warns that blood sugar could go too low, and says the dose of a diabetes medicine might need to change. Examples it lists include glimepiride, glyburide, insulin, metformin, pioglitazone, rosiglitazone, chlorpropamide, glipizide, and tolbutamide. Animal studies, including a 2013 study in diabetic rats, have reported blood-sugar-lowering effects from lion's mane extracts.

The same monograph says there is insufficient evidence to rate lion's mane as a diabetes treatment, so a possible lowering effect is not something to rely on. Any change to a diabetes medicine is a decision for the prescriber.

4. Immunosuppressants

Evidence strength: Theoretical (laboratory).

Published reviews describe lion's mane as having immune-related properties. A 2025 systematic review says the mushroom is valued mainly for neuroprotective and immune-boosting properties, and a 2026 scoping review lists immunomodulatory activity among its reported effects. Immunosuppressant medicines are used to hold immune activity down, for example after an organ transplant or in some autoimmune conditions. The sources reviewed contained no study testing lion's mane alongside these drugs. Because the concern is an unmeasured effect on the same system the medicine is meant to control, ask the prescribing doctor before combining them.

5. Allergic and Immune Reactions (Not a Drug Interaction)

Evidence strength: Case report.

A 2025 systematic review reported that side effects in the included studies were uncommon and mostly mild: stomach discomfort, diarrhea, headache, and allergic reactions. The review also identified one case report describing acute respiratory distress syndrome, a severe lung condition, in a man who had taken lion's mane supplements daily for several months. The case report's authors proposed an allergic reaction. The systematic review's authors cautioned that the cause cannot be entirely attributed to lion's mane without further investigation. One case cannot show how often this happens. Anyone with a past reaction to mushrooms or supplements should mention it to a pharmacist or doctor first.

6. Planned Surgery or Procedures

Evidence strength: Theoretical (extends the clotting concern).

The RxList monograph states that lion's mane might cause extra bleeding during and after surgery and advises stopping it at least two weeks before scheduled surgery. Tell your surgeon, dentist, and anesthesia team about every supplement you take. They decide the timing for your situation.

What This Evidence Cannot Tell You

• It cannot rule out other interactions. A medicine missing from this checklist is not confirmed safe with lion's mane. The sources reviewed simply did not address it.
• Most of the interaction concern rests on early-stage research. The 2025 systematic review covered 26 studies: five randomized controlled trials, three pilot clinical trials, one cohort study, one case report, 15 laboratory studies, and one computer analysis. It does not address drug interactions.
• Products differ. Studies have used powders, tablets, capsules, cookies, and muffins made from different parts of the fungus. Hericenones are mainly isolated from the fruiting body and erinacines mainly from the mycelium, so the type of product may matter, but no interaction study has tested this. Check the label for what a product contains.
• No dose has been established. The RxList monograph says there is not enough scientific information to determine an appropriate dose range.

Who Should Speak With a Pharmacist or Doctor First

• People who take an antiplatelet medicine, an anticoagulant, a diabetes medicine, or an immunosuppressant
• People who take several prescriptions or other supplements
• People with surgery or a dental procedure scheduled
• People who are pregnant or breastfeeding (the RxList monograph says not enough is known about medicinal amounts and advises avoiding them)
• People with a past allergic reaction to mushrooms or supplements

Do not stop or change a prescribed medicine on your own because of this article. Seek urgent medical care for trouble breathing, swelling of the face or throat, or a severe rash after taking a supplement. Contact your care team promptly about unusual bruising or bleeding.

Printable Pharmacist Question List

Print this page or copy the list below. Bring the supplement bottle and a list of every medicine and supplement you take.

1. Here is the product label. Which part of lion's mane does it contain, and are any of the other ingredients a concern with my medicines?
2. Do any of my medicines slow blood clotting or raise bleeding risk, and does that change whether lion's mane makes sense for me?
3. I take a diabetes medicine. Could lion's mane push my blood sugar lower than expected, and how often should I check it?
4. Does any medicine I take work by suppressing my immune system? Is there a reason to avoid immune-active supplements?
5. I have a procedure coming up. Who should I tell about this supplement, and when should I stop it?
6. Which symptoms should lead me to call you, my prescriber, or emergency services?
7. If I decide to start it, when should we review whether to continue?

Where This Fits With the Rest of the Lion's Mane Research

This page covers interaction questions only. For a broader summary of what researchers have examined about lion's mane and nerve health, see Neuroprotective Benefits of Lion’s Mane: What Medical Research Tells Us. That article covers potential benefits and notes that more research is needed. It is not a medication-safety guide. The site's Editorial Standards explain how Clinical Research Explained handles sources and corrections.

Sources

1. RxList. Hericium Erinaceus monograph (interactions, precautions, dosing). RxList supplement monograph
2. Othman A, Amen Y, Shimizu K. Hericenones From Hericium erinaceus (Bull.) Pers.: A Scoping Review of Structural Diversity and Health Benefits. Chemistry & Biodiversity. 2026;23(1):e02560. Full text on PubMed Central
3. Mori K, Kikuchi H, Obara Y, et al. Inhibitory effect of hericenone B from Hericium erinaceus on collagen-induced platelet aggregation. Phytomedicine. 2010;17(14):1082-1085. Original study, as summarized in source 2. Publisher record (DOI)
4. Liang B, Guo Z, Xie F, Zhao A. Antihyperglycemic and antihyperlipidemic activities of aqueous extract of Hericium erinaceus in experimental diabetic rats. BMC Complement Altern Med. 2013;13:253. Full text on PubMed Central
5. Menon A, Jalal A, Arshad Z, Nawaz FA, Kashyap R. Benefits, side effects, and uses of Hericium erinaceus as a supplement: a systematic review. Frontiers in Nutrition. 2025;12:1641246. Full text at Frontiers in Nutrition

By the Clinical Research Explained Editorial Team. Educational information only. Sources last checked October 3, 2026.

Short answer: yes, in laboratory studies. The U.S. Food and Drug Administration (FDA) states that mitragynine and 7-hydroxymitragynine (7-OH), two alkaloids in kratom, bind to the same brain receptors (mu opioid receptors) as opioid drugs such as codeine. The National Institute on Drug Abuse (NIDA) describes both as partially activating those receptors. They are not copies of morphine, though. 7-OH binds far more tightly than mitragynine, and some researchers think mitragynine's own receptor activity is weak and that much of its opioid-like effect comes after the body converts it to 7-OH.

What “binding” does and does not tell you

A compound that binds to a receptor sticks to it. Whether it then switches the receptor on, partly switches it on, or blocks it is a separate question called efficacy. How a compound behaves in a living person is a third question, and it depends on dose, metabolism, other drugs, and product purity. Most of the data below come from cells and animals, so they describe mechanisms, not what any individual will experience.

Receptor-activity comparison

The findings below are summarized from the studies named in each line. Numbers differ between laboratories because the assays differ, so treat them as ranges, not fixed values. A lower Ki means tighter binding. Efficacy percentages are measured against reference compounds chosen by each laboratory, so they are not strictly comparable across studies.

Mitragynine

• Binding (in vitro): A 2016 study in cells with human receptors reported a mu opioid receptor Ki of about 0.233 µM (233 nM). A 2021 study in different cells reported about 7,709 nM, a gap of more than 30-fold between the two laboratories.
• Activity (in vitro): The 2016 study found partial G-protein activation (maximum effect 34%) and no measurable beta-arrestin recruitment. The 2021 study found no significant agonism up to 100 µM.
• Animal findings: In the 2021 rat study, mitragynine did not produce pain-blunting effects in a hot-plate test, though rats partly treated it like morphine in a drug-discrimination test. The 2016 authors also noted that mitragynine acted as an antagonist, not an agonist, at the mouse mu receptor, which complicates reading rodent data.
• Human data: None of the sources reviewed here report human receptor-occupancy measurements for mitragynine.
• Main limits: Conflicting in vitro results, species differences, and no direct human receptor data.

7-hydroxymitragynine (7-OH)

• Binding (in vitro): Reported mu opioid receptor Ki of about 0.047 µM (47 nM) in 2016 and about 77.9 nM in 2021. The two laboratories roughly agree that 7-OH binds much more tightly than mitragynine.
• Activity (in vitro): Partial agonist in both studies (maximum effect 47% in 2016 and 41.3% in 2021), with no measurable beta-arrestin recruitment in the 2016 study.
• Animal findings: Produced pain-blunting effects in rats given by injection, with ED50 values of 11 and 16 mg/kg in two groups of trained rats. A 2019 mouse study concluded that 7-OH formed from mitragynine reaches brain levels high enough to account for mitragynine's pain-blunting effect in mice.
• Human data: A small 2022 study of six healthy adults with prior kratom exposure, who drank a single 2 g kratom tea, measured 7-OH in blood at roughly 24 to 27 percent of mitragynine levels. It measured blood levels, not receptor binding.
• Main limits: Injection doses in rats do not equal swallowed kratom products, the human study was tiny and single-dose, and FDA notes that 7-OH is a minor constituent (under 2 percent of total alkaloids) of natural kratom leaves.

Morphine (reference opioid)

• Binding (in vitro): Ki of about 4.19 nM at the human mu opioid receptor in the 2021 study, much tighter than either kratom alkaloid in that same experiment.
• Activity (in vitro): Full agonist (maximum effect 92.6%) in the same 2021 assay.
• Main limits: Included only as a benchmark in one laboratory's experiment. These studies do not show that kratom is equivalent to, safer than, or weaker than morphine for a person.

Why 7-OH matters even when a product is mostly mitragynine

NIDA reports that the body converts mitragynine into 7-OH. A 2019 study found that this conversion happens in both mouse and human liver preparations, through liver enzymes of the CYP3A family, and its authors concluded that mitragynine itself does not directly engage opioid receptors at relevant doses in mice. That is one reason the cell-based binding numbers for mitragynine should not be read as a prediction of its effect in a person. How much this conversion matters in humans has not been settled by the sources reviewed here.

What this means for dependence and withdrawal

Because these compounds act on the mu opioid receptor, researchers take dependence seriously. NIDA states that people may experience mild to moderate withdrawal symptoms when they stop regular kratom use, that research is limited, and that the diagnostic manual DSM-5 has no specific kratom use disorder criteria. FDA lists physical dependence, withdrawal symptoms, and substance use disorder among its safety concerns. Human abuse-potential research remains limited, and FDA reports that it awarded a grant for a human abuse potential study in September 2024.

For context on recovery-related questions, see our related page, Kratom, Opioids, and Addiction Recovery: What Medical Research Says.

Safety points to know

• FDA states that kratom is not lawfully marketed in the U.S. as a drug, dietary supplement, or food additive, and that it is concerned about liver toxicity, seizures, neonatal abstinence syndrome, and contamination such as Salmonella and heavy metals.
• FDA says deaths associated with kratom have been rare and typically involved other substances, which makes kratom's role unclear. NIDA says nearly all reported cases involved other drugs or contaminants.
• Product content varies, so a laboratory finding about a purified compound cannot be applied directly to a store-bought product.

Who should talk to a professional

• Anyone using kratom regularly who wants to cut back or stop, especially if they notice withdrawal symptoms.
• Anyone taking prescription medicines, opioid or otherwise, who should ask a pharmacist or clinician about possible interactions.
• People who are pregnant or planning pregnancy, and anyone with liver, seizure, or mental health conditions.

For free, confidential treatment referral, the SAMHSA National Helpline is 1-800-662-4357. In a poisoning emergency, contact Poison Control at 1-800-222-1222 or call 911.

What you can do next

1. Bring a list of everything you take, including kratom, to a pharmacist or clinician.
2. Do not stop a prescribed medicine on your own because of anything you read here.
3. Read the primary sources below, and treat any page, including this one, as a starting point and not as personal medical advice.

Glossary of pharmacology terms

• Agonist: A compound that activates a receptor. A full agonist produces the largest response a system can give; a partial agonist produces a smaller maximum.
• Antagonist: A compound that sits on a receptor and blocks other compounds from activating it.
• Binding affinity (Ki): How tightly a compound attaches to a receptor. A smaller Ki means tighter binding.
• Efficacy (Emax): How strongly a compound activates a receptor once bound, compared with a reference compound.
• Beta-arrestin: A cell protein that some receptors recruit after activation. Researchers measure it as one of several signaling pathways.
• CYP3A: A family of liver enzymes that can convert mitragynine to 7-OH.
• In vitro: Done in cells or tissue samples, not in a living body.
• ED50: The dose that produces a given effect in half of tested animals.
• Mu opioid receptor: The main receptor through which morphine and many other opioids act.

Sources

• U.S. Food and Drug Administration. FDA and Kratom (page current as of December 2, 2025).
• National Institute on Drug Abuse. Kratom (page shows last update March 11, 2026).
• Kruegel AC et al. Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators. Journal of the American Chemical Society, 2016 (cell-based binding and signaling data).
• Obeng S et al. Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for mu-Opioid Receptor and Opioid-Like Behavioral Effects in Rats. Journal of Pharmacology and Experimental Therapeutics, 2021.
• Kruegel AC et al. 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. ACS Central Science, 2019 (publication listing and summary; full text not reviewed).
• Paine MF et al. Clinical Pharmacokinetic Assessment of Kratom (Mitragyna speciosa), a Botanical Product with Opioid-like Effects, in Healthy Adult Participants. Pharmaceutics, 2022.
• Substance Abuse and Mental Health Services Administration. National Helpline. Poison Control: poison.org.

This article is independent educational content from Clinical Research Explained and is not medical advice. It contains no product recommendations. See our Editorial Standards and Medical Disclaimer.