Disulfiramlike Mushroom Toxicity

Updated: Apr 08, 2019
Author: Stephen L Thornton, MD; Chief Editor: Sage W Wiener, MD 


Practice Essentials

Edible wild mushrooms often are gathered by foragers and prized for their taste. Occasionally, toxic mushrooms are mistaken for edible species, and human poisoning occurs. In addition, some food aficionados around the globe will intentionally eat certain mushrooms, despite their content of known toxins. For example, Coprinus atramentarius contains the heat-stable toxin coprine, which only causes toxicity when ethanol is consumed after the mushroom. Because victims of mushroom poisoning will most commonly seek initial medical care in emergency departments, it is important that emergency physicians be familiar with the diverse signs and symptoms of mushroom toxicity.

Coprinus atramentarius

C atramentarius, a member of Coprinaceae or inky cap family, is known familiarly as alcohol inky or inky cap. This mushroom is found particularly during autumn months in urban regions and along roadsides throughout the United States. Its cap is gray-brown, egg-shaped, smooth, and 2-3 inches in width. These mushrooms deliquesce, with gill tissue autodigesting to dark inky liquid after picking and with maturation.[1]

Other coprine-containing mushrooms

Other Coprinus mushrooms that contain coprine include C insignis, C quadrifidus, and C variegatus. Some Coprinus mushrooms generally are not toxic, such as C comatus (ie, shaggy mane, lawyer's wig), which is sought for its asparagus-like qualities.

Clitocybe clavipes

Clitocybe clavipes, of the family Tricholomataceae, is also associated with disulfiramlike reactions. However, coprine has not been identified in this species. C clavipes tends to grow in coniferous or mixed woods; it fruits in late autumn or winter. Its cap is gray-brown, mostly flat, and 1-3 inches in width. Its gill extends down a stem that is club shaped and thickened near the base. C clavipes is commonly called fat-footed clitocybe or clubfoot funnel cap.

Lepiota aspera

Lepiota aspera, commonly known as freckled dapperling, has also been associated with disulfiramlike reactions.[2]  It has an orangish brown to pinkish brown cap and white gills.  The cause of the disulfiramlike reaction is unknown.


Coprinus atramentarius contains coprine (N5-1-hydroxycyclopropyl-L-glutamine), a protoxin without intrinsic toxicity. Coprine is metabolized to 1-aminocyclopropanol, which inhibits the enzyme aldehyde dehydrogenase (ALDH). ALDH catalyzes conversion of acetaldehyde to acetic acid.

Inhibition of ALDH produces a clinical syndrome similar to disulfiram (Antabuse) alcohol reaction. Disulfiram has been widely used in the manufacture of rubber since the 1800s. In 1937, an American chemical plant physician noted that employees exposed to disulfiram in the workplace developed a constellation of symptoms after drinking ethanol. These included flushing, headache, nausea, palpitations, and dyspnea, and the symptoms were severe enough to promote abstinence from ethanol. In later years, the basis for this effect, the disulfiram-mediated inhibition of ALDH, was discovered. Ethanol is primarily metabolized by alcohol dehydrogenase to acetaldehyde, which is then metabolized by ALDH to acetate and carbon dioxide. Accumulation of acetaldehyde leads to the clinical manifestations of the disulfiram-ethanol interaction.

Disulfiram has been widely used in the treatment of alcohol dependence,[3]  although its benefits are the subject of controversy.[4]  It has also been used more recently in the management of cocaine dependence.[5, 6]

After ingestion of coprine-containing mushrooms, ALDH is irreversibly inhibited and consumption of ethanol results in acetaldehyde accumulation. This inhibition of ALDH takes at least 30 minutes, which is the time required to metabolize inactive coprine to active 1-aminocyclopropanol. Therefore, small volumes of ethanol ingested concomitantly with mushrooms may not cause toxicity. Enzyme inhibition generally persists for approximately 72 hours but animal studies suggest it may continue for up to 6 days.[7] Ingestion of ethanol up to 3 days after mushroom ingestion may produce acetaldehyde toxicity.

Unlike disulfiram, coprine does not appear to inhibit dopamine beta-hydroxylase, the enzyme that hydroxylates dopamine to form norepinephrine within storage vesicles of presynaptic neurons. In experimental models, rats exposed to coprine are capable of eliciting a tachycardic response to ethanol challenge; those exposed to disulfiram are not capable of eliciting this response (presumably due to inhibition of dopamine beta-hydroxylase[8] ). Whether a similar response occurs in humans is unknown.


According to the American Association of Poison Control Centers' National Poison Data System (NPDS), coprine-containing mushrooms account for a minority of reported mushroom exposures. Of 5781 mushroom exposures reported in 2017, coprine-containing mushrooms accounted for only 10 case mentions, with 9 single exposures. Five of those patients were treated in a health care facility but no major outcomes or deaths were reported.[9]

No adequate database exists to determine frequency of coprine exposure or toxicity internationally, although some sources suggest a 1-3% frequency of all reported mushroom poisonings.

Since ethanol ingestion is necessary for toxicity, children generally are not affected.


The prognosis is excellent. With appropriate supportive care, morbidity associated with coprine-induced acetaldehyde toxicity is minimal and recovery is generally complete.

Mortality and morbidity rates due to secondary effects, such as dehydration or cardiovascular collapse, are unknown. Esophageal rupture attributed to vomiting following co-ingestion of ethanol and coprine-containing mushrooms has been reported, but such cases appear to be infrequent[10] .

Complications from prolonged emesis include the following:

  • Mallory-Weiss esophageal tears (upper GI bleeding)

  • Esophageal rupture (mediastinitis)

  • Volume depletion

Patient Education

Educate patients about the risks of eating unidentified wild mushrooms. If toxic mushrooms were intentionally eaten, educate patients about coprine toxicity with ethanol ingestion.

Patients should be advised to avoid alcohol for approximately 1 week.

For patient education information, see the First Aid and Injuries Center, as well as Food Poisoning and Activated Charcoal.




Obtaining a history of mushroom ingestion is critical in evaluating a patient with a disulfiramlike exposure. Raw and cooked mushrooms as well as the cooking water are capable of producing toxicity through aldehyde dehydrogenase (ALDH) inhibition. As long as the ethanol is ingested after the mushroom, symptoms can begin within minutes or be delayed for several hours after ethanol ingestion. Note that ethanol use may be unintentional (eg, cough syrup).

Patients may relate symptoms to ethanol, not mushrooms. Ascertaining if other species of wild mushrooms were ingested concomitantly and the approximate elapsed time since ingestion is important.

Signs and symptoms of disulfiramlike exposure include[11] :

  • Flushing or blotching red rash (face, neck, thorax)
  • Sense of face and hand swelling
  • Diaphoresis
  • Palpitations/chest pain
  • Dyspnea/hyperventilation
  • Nausea/vomiting
  • Metallic taste
  • Headache
  • Vertigo/dizziness
  • Tingling paresthesias (perhaps due to hyperventilation)
  • Apprehension/sense of impending doom
  • Weakness

The duration of symptoms is generally brief, around 30 min, but occasionally can last up to 24 h.

Physical Examination

Findings on physical examination may include the following:

  • Hypertension
  • Hypotension
  • Tachycardia
  • Flushing, particularly of upper half of body (occasionally blotchy red rash of thorax and neck with facial erythema)
  • Diaphoresis
  • Confusion

Hypotension is less common than with disulfiram and coma is uncommon to rare.[11]



Diagnostic Considerations

Other problems to be considered in the differential diagnosis include the following:

  • Allergic reaction

  • True disulfiram reaction

  • Other disulfiramlike reactions from medications (eg, metronidazole, oral hypoglycemic agents, tacrolimus, cephalosporins)

  • Other disulfiramlike reactions from occupational exposures (eg, carbon disulfide, carbon tetrachloride, thiram fungicides)

  • Carriage of an inactive form of alcohol dehydrogenase (present in many people of East Asian descent—eg, China, Japan, Indonesia, Vietnam29)

Differential Diagnoses



Laboratory Studies

The extent of diagnostic testing is guided by the patient's clinical presentation. Appropriate laboratory studies may include the following:

  • Electrolytes, blood urea nitrogen (BUN), creatinine levels (assess for dehydration and electrolyte abnormalities)

  • Serum ethanol levels (may be of value to determine if more acetaldehyde formation and progression of toxicity can be expected)

  • No clinical role for determination of acetaldehyde concentrations

Other Tests

Obtaining an electrocardiogram (ECG) in patients with chest pain would be prudent. One case report described a 22-year-old chronic alcoholic male on disulfiram who consumed alcohol and then developed anginal symptoms.[12] ECG changes were consistent with an inferior wall myocardial infarction (MI). He underwent coronary angiography, which revealed clean vessels, and his MI was attributed to vasospasm.

A mycologist may positively identify the mushroom species involved. However, unlike identification of Amanita phalloides, positive identification of coprine-containing mushrooms rarely contributes to diagnosis or alters management.



Prehospital Care

Supportive care and parenteral rehydration are essential.

Emergency Department Care

Symptomatic treatment (eg, antiemetics) and supportive maneuvers are mainstays of medical management. Provide intravenous fluids if gastrointestinal effects have not abated.

Hypotension generally responds to volume expansion with normal saline. Patients with severe hypotension may require vasopressor agents once volume restoration is ensured. Direct-acting vasopressors (eg, norepinephrine) are preferred over indirect-acting agents (eg, dopamine). This recommendation derives from the known pharmacology of disulfiram, which inhibits dopamine beta-hydroxylase, thereby depleting presynaptic catecholamines.

Activated charcoal is unlikely to be of benefit if patient already has symptoms.

Fomepizole (4-methylpyrazole) could theoretically be of benefit by blocking alcohol dehydrogenase and formation of acetaldehyde. Its use in the treatment of methanol and ethylene glycol poisoning is well established.[13, 14] Fomepizole is currently very expensive, and its use is not established in this clinical setting.

Histamine-2 blockers (cimetidine is best studied) reduce the severity of flush and hypotension in Asian patients who experience these effects following ethanol ingestion. The Asian flush is due in part to a relative deficiency of aldehyde dehydrogenase.

Antiemetics with alpha-adrenergic blocking properties (eg, aliphatic and piperidine phenothiazines) should be avoided.


Consultation with a regional Poison Control Center, toxicologist, or mycologist is recommended.



Medication Summary

The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to neutralize effects of the toxin.

GI decontaminant

Class Summary

These agents are empirically used to minimize systemic adsorption of the toxin.

Activated charcoal (Actidose-Aqua, Insta-Char, Liqui-Char)

Most useful if administered within 1 h of ingestion. Repeat doses may be used, especially with ingestion of sustained release agents. Limited outcome studies exist, especially when administration is more than 1 h after ingestion.

Administration of charcoal by itself (in aqueous solution), as opposed to coadministration with a cathartic, is becoming the current practice standard because no studies have shown benefit from cathartics and, while most drugs and toxins are adsorbed within 30-90 min, laxatives take hours to work. Dangerous fluid and electrolyte shifts have occurred when cathartics are used in small children.

When ingested dose is known, charcoal may be given at 10 times ingested dose of agent over 1 or 2 doses.


Class Summary

These agents are used to control nausea and vomiting.

Metoclopramide (Reglan)

Prokinetic agent that increases GI motility and accelerates gastric emptying. Works as antiemetic by blocking dopamine receptors in chemoreceptor trigger zone of CNS.

Prochlorperazine (Compazine)

May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system.

In addition to antiemetic effects, it has the advantage of augmenting hypoxic ventilatory response, acting as a respiratory stimulant at high altitude.

H2-receptor antagonists

Class Summary

H2-receptor antagonists are reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells where they inhibit acid secretion. The H2-receptor antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.

Ranitidine (Zantac)

H2-receptor antagonist that may be a useful adjunct in reducing emesis volume.

Antiemetic, Serotonin Antagonist

Class Summary

These agents are used to treat vomiting and symptomatic nausea resulting from radiation therapy and/or chemotherapy, for postoperative nausea and vomiting, and for general symptomatic relief.

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. Indicated for nausea and vomiting due to radiation and/or chemotherapy, for postoperative nausea and vomiting, and for general symptomatic relief. While historically an expensive medication, recent availability of a generic form has removed cost as a consideration.