01Approach to the Critical Patient/attcp50

Immediate stabilization priorities

›Airway and mental status threats

›Severely obtunded patient with loss of airway protective reflexes

›Proceed to definitive airway management

›Rapid sequence intubation preparation

›Aspiration precautions during intubation

›Agitated patient at risk of self-harm or elopement

›1:1 continuous observation

›Low-stimulation resuscitation bay

›Physical restraints only if verbal de-escalation fails and patient is a danger

Alarm features requiring escalation

›Escalation triggers distinguishing psilocybin from dangerous ingestions

›Symptom onset >6 hours post-ingestion

›Raises amatoxin (Amanita phalloides) until proven otherwise

›Obtain serial LFTs at 12 and 24 hours

›Toxicology consult immediately

›Profuse watery diarrhea with severe abdominal pain

›Amatoxin cholera-like syndrome pattern

›Coagulation studies and IV access priority

›Hyperthermia >40 C with rigidity and clonus

›Serotonin syndrome until excluded

›Aggressive cooling measures

›Cyproheptadine protocol initiation

›Seizures

›Rare with isolated psilocybin; consider polydrug ingestion or MAOI interaction

›Benzodiazepines first-line

›Hypertensive emergency (SBP >180 mmHg with end-organ signs)

›MAOI co-ingestion with phenylethylamine interaction

02History/hx55

Ingestion details

›Substance identification

›Wild-foraged versus purchased product

›Chocolate bars, capsules, or dried mushrooms

›Species identification attempted if remnants available

›Dose estimate

›Potency varies by species and within same batch

›Users frequently underestimate dose

›Time of ingestion

›Symptom onset relative to ingestion is most critical historical feature

›Psilocybin onset typically 20 to 60 minutes

›Onset >6 hours is a red flag for alternate mushroom species

Co-ingestants and medications

›Co-ingestant screen

›Cannabis, alcohol, MDMA, amphetamines

›Most common co-ingestants; worsen adverse event severity

›Mushroom-containing chocolate products may contain adulterants

›MAOI medications (tranylcypromine, phenelzine, selegiline)

›Phenylethylamine in mushrooms interacts with MAOIs

›Risk of hypertensive emergency

›SSRIs or SNRIs

›May attenuate psilocybin effects

›Rare reports of serotonin toxicity; risk is low without MAOI involvement

›Lithium

›Anecdotal reports of seizures when combined with psychedelics

›Acetaminophen and salicylates

›Standard co-ingestion screen in undifferentiated poisoning

03Physical Exam/exam55

Vital signs

›Vital sign pattern in psilocybin toxicity

›Tachycardia

›Present in 18 to 76% of cases

›Sinus tachycardia most common

›Hypertension

›Common; typically mild to moderate

›SBP >180 mmHg warrants antihypertensive intervention

›Hyperthermia

›Rare in isolated psilocybin ingestion

›Temperature >40 C triggers serotonin syndrome workup

›Respiratory rate and SpO2

›Typically normal in isolated psilocybin

›Abnormality suggests co-ingestion or aspiration

Neurological and psychiatric exam

›CNS examination

›Pupillary size and reactivity

›Mydriasis is hallmark finding of psilocybin toxicity

›Compare to miosis (opioid), mixed picture (multiple toxins)

›Level of consciousness and orientation

›Mild confusion vs. frank obtundation

›GCS documentation for trending

›Ataxia, nystagmus, hyperreflexia

›Clonus and rigidity assessment

›Clonus (especially ankle) — Hunter Serotonin Toxicity Criteria

›Lead-pipe rigidity — severe serotonin syndrome

›Seizure activity observation

›Psychiatric assessment

04Differential Diagnosis/ddx43

Life-threatening mushroom species

›Amatoxin poisoning (Amanita phalloides — Death Cap)

›ICD-10: T62.0X1A (toxic effect of ingested mushrooms)

›Accounts for >90% of mushroom fatality worldwide

›Phase 1: delayed GI symptoms 6 to 12 hours post-ingestion

›Phase 2: apparent recovery 24 to 48 hours

›Phase 3: acute hepatorenal failure day 3 to 5

›Key differentiator from psilocybin: symptom onset timing >6 hours

›Orellanine poisoning (Cortinarius spp.)

›Onset 2 to 3 weeks post-ingestion

›Causes progressive nephrotoxicity

›Gyromitrin poisoning (Gyromitra esculenta)

›Delayed onset 6 to 12 hours

›Hepatotoxicity, seizures, methemoglobinemia

›Pyridoxine as antidote consideration

Toxic syndromes mimicking psilocybin

›Muscarine poisoning (Inocybe and Clitocybe spp.)

›Cholinergic toxidrome (SLUDGE syndrome)

›Salivation, lacrimation, urination, defecation, GI distress, emesis

›Miosis contrasts with psilocybin mydriasis

›Bradycardia contrasts with psilocybin tachycardia

›Atropine is antidote

›Ibotenic acid and muscimol (Amanita muscaria)

›CNS depression, ataxia, delirium, seizures

›Anticholinergic-like features (dry skin, urinary retention)

›Onset 30 minutes to 2 hours post-ingestion

›Serotonin syndrome

›ICD-10: T43.8X1A

05Laboratory Tests/lt45

Core metabolic and toxicology panel

›Point-of-care glucose

›Immediate in all altered mental status presentations

›Hypoglycemia as reversible cause

›Target glucose 4.0 to 8.0 mmol/l

›Basic or comprehensive metabolic panel

›Electrolytes and renal function

›Hyponatremia possible with MDMA co-ingestion (SIADH)

›Renal function baseline for amatoxin concern

›Hepatic function panel (AST, ALT, bilirubin)

›Critical to rule out amatoxin hepatotoxicity

›Normal at presentation does not exclude early amatoxin (elevates at 24 to 72 hours)

›Repeat at 12 and 24 hours if wild mushroom ingestion suspected

›Urine drug screen

›Will NOT detect psilocybin or psilocin — no routine clinical assay exists

›Useful to identify co-ingestants (amphetamines, PCP, cocaine, cannabis)

›Benzodiazepines screen if administered pre-arrival

›Serum acetaminophen and salicylate levels

›Standard in undifferentiated poisoning or suicidal ingestion

›Acetaminophen therapeutic level <66 mmol/l

›Salicylate toxic level >2.9 mmol/l

Cardiovascular and muscle injury markers

›Troponin

›Indication: chest pain, severe hypertension, tachycardia, ECG changes

›Dynamic myocardial injury documented in Psilocybe keralensis case series

›Elevated in some psilocybin-MAOI-stimulant co-ingestion cases

›Creatine kinase

›Indication: prolonged agitation, rigidity, hyperthermia

06Diagnostic Tests/dt86

Scoring Systems

›Hunter Serotonin Toxicity Criteria (Boyer criteria)

›Designed to diagnose serotonin syndrome in overdose settings

›Spontaneous clonus — most specific finding

›Inducible clonus plus agitation or diaphoresis

›Ocular clonus plus agitation or diaphoresis

›Tremor plus hyperreflexia

›Hypertonia plus temperature >38 C plus ocular or inducible clonus

›Sensitivity 84%, specificity 97% versus Sternbach criteria

›Poison Severity Score (PSS)

›Grading system used by poison centers to standardize outcome reporting

›Grade 0: no symptoms

›Grade 1: mild transient symptoms

›Grade 2: pronounced or prolonged symptoms

›Grade 3: severe or life-threatening symptoms

›Grade 4: death

›Approximately 15% of psilocybin exposures reach PSS grade 2 or higher

›Clinical Opiate Withdrawal Scale (COWS) — not applicable; included for exclusion

›Distinguish opioid withdrawal from psychedelic toxicity when mixed picture

›COWS score <5 argues against opioid withdrawal

›GCS (Glasgow Coma Scale)

›Serial GCS as objective mental status marker during observation

›GCS <14 at any point — immediate re-evaluation and imaging consideration

›GCS trending to 15 — supports psilocybin natural history

Scoring Systems (Mushroom-Specific Risk Stratification)

›Severity stratification by clinical presentation

›Mild exposure

›Euphoria, mild perceptual changes, nausea only

›Vital signs normal or mildly elevated

›Observation and reassurance; anticipated discharge within 4 to 6 hours

›Moderate exposure

›Significant agitation, paranoia, anxiety, tachycardia, hypertension

›Requires benzodiazepines and IV fluids

›Extended ED observation

›Severe exposure (rare, <5% of isolated psilocybin cases)

›Hyperthermia, seizures, coma, hypertensive emergency, myocardial injury, psychosis

›ICU-level care required

MRI

›MRI brain

›Not routinely indicated for isolated psilocybin ingestion

›No MRI signature specific to psilocybin toxicity

›Reserve for persistent neurological deficits unresolved at 12 to 24 hours

›Indications for MRI consideration

›Focal neurological deficit not explained by intoxication

›Persistent altered mental status beyond 24 hours despite normal CT

›Suspected vascular event in patient with cardiovascular risk factors

›Limitations

›MRI not superior to CT for acute hemorrhage in first 6 hours

›Requires patient cooperation not achievable during acute intoxication

CT

›CT head without contrast

›Indications in psilocybin poisoning context

›Suspected head trauma (fall during intoxication)

›Focal neurological deficits

›Seizures with unclear etiology

›Altered mental status not improving as expected at 4 to 6 hours

›GCS <13 without clear explanation

›Not indicated routinely for isolated psilocybin with typical course

›Expected findings: normal in uncomplicated psilocybin toxicity

›CT chest and abdomen

›Indications

›Aspiration concern (high aspiration risk with obtundation)

›Concern for amatoxin with hepatic failure — CT liver for hepatic edema

›Bowel perforation excluded if severe abdominal pain

Ultrasound

›Point-of-care ultrasound (POCUS)

›Cardiac POCUS

›Indication: hypotension, myocardial injury concern, troponin elevation

›Wall motion abnormality assessment

›Pericardial effusion exclusion

›Hepatic POCUS

›Indication: RUQ pain or tenderness when amatoxin concerns raised

›Hepatomegaly or periportal edema may appear in early hepatic injury

›FAST exam

›Indication: trauma from fall during intoxication — free fluid detection

›IVC assessment

›Volume status guidance if hemodynamic instability present

›Collapsibility >50% suggests hypovolemia — IV fluid initiation

ECG

›12-lead electrocardiogram

›Indications

›Chest pain or palpitations

›Severe hypertension

›MAOI or stimulant co-ingestion

›Troponin elevation

›Expected findings

›Sinus tachycardia most common

›Dysrhythmias in 19% of mushroom-chocolate exposures (Gartner 2024 case series)

›Dangerous patterns

›ST-segment changes — reported with psilocybin-MAOI-amphetamine combination

›QTc prolongation — risk if QT-prolonging co-ingestants present

›QTc threshold for concern >480 ms

07Disposition/dispo40

Discharge criteria

›Criteria for safe ED discharge

›Mental status returned to baseline

›Confirmed by collateral informant or reliable self-report

›GCS 15 and oriented x3

›Vital signs normalized

›Heart rate <100 beats/min

›Blood pressure within acceptable range

›Afebrile

›No active suicidal ideation

›Reliable follow-up arranged and patient not alone

›Adequate observation period completed (minimum 4 to 6 hours from ingestion)

›Poison center data: approximately 66% treated and released from ED

Admission indications

›Criteria requiring inpatient admission

›Persistent altered mental status beyond 6 to 8 hours

›Mandates broadened differential and serial LFTs

›Hemodynamic instability

›Hypertensive emergency

›Sustained tachycardia >130 beats/min

›Hyperthermia (serotonin syndrome)

›Seizures

›Myocardial injury (troponin elevation with ECG changes)

›Suicidal ideation or active psychiatric crisis

›Psychiatric evaluation required prior to discharge

›Wild mushroom ingestion with any diagnostic uncertainty

›Serial LFTs at 12 to 24 hours required to exclude amatoxin

›Amatoxin suspected on history or laboratory grounds

08Treatment/t93

Immediate non-pharmacologic measures

›Environmental and supportive interventions

›Calm, low-stimulation environment

›Dim lighting, quiet room, familiar person if available

›Reduces anxiety and psychological distress

›Verbal de-escalation (talk-down technique) — first-line intervention

›Reassurance that effects are temporary and self-limited

›Guided slow breathing for panic and anxiety

›Typically 4 to 6 hour duration of expected effects

›1:1 nursing observation

›Fall and self-harm prevention

›IV access establishment

›IV fluids: normal saline at maintenance to replacement rate

›Most common intervention in poison center data (approximately 50% of cases)

Pharmacologic management of agitation and anxiety

›Benzodiazepines — first-line pharmacotherapy

›Lorazepam IV or IM

›1 to 2 mg IV or IM

›Repeat every 5 to 10 minutes as needed

›Maximum typical acute dose 4 to 8 mg (titrate to effect)

›Diazepam PO or IV

›5 to 10 mg PO or IV

›Onset 2 to 5 minutes IV; 15 to 45 minutes PO

›IV preferred if rapid sedation required

›Midazolam IM (when IV access not yet established)

›5 mg IM in adults

›Fastest onset of IM benzodiazepines

›Rationale

›Preferred over antipsychotics for isolated psilocybin

›ACEP Level B recommendation for benzodiazepines in toxin-induced agitation

›Antipsychotics — second-line for refractory psychosis only

›Olanzapine 5 to 10 mg IM

›Reserved for psychosis not responding to benzodiazepines

›Caution: lowers seizure threshold; avoid in MAOI combination

›Risperidone 1 to 2 mg PO

›Option for cooperative patient requiring antipsychotic

›Haloperidol

›Less preferred: extrapyramidal effects; may worsen dysphoria

›QTc prolongation risk — obtain ECG before use

Nausea and vomiting management

›Antiemetic therapy

›Ondansetron 4 mg IV

›First-line antiemetic; low sedation

›Note: ondansetron has serotonin antagonist properties — generally safe

›QTc monitoring if serotonin syndrome co-concern

›IV fluid replacement

›Normal saline 500 mL to 1000 mL bolus if vomiting-related dehydration

›Reassess electrolytes post-rehydration

Hypertension management

›Antihypertensive therapy indications

›Initiate treatment for SBP >160 mmHg or signs of end-organ involvement

›Oral nifedipine 10 to 20 mg

›First-line for isolated non-emergency hypertension

›Onset 20 to 30 minutes

›IV labetalol

›20 mg IV bolus over 2 minutes

›Repeat 40 to 80 mg every 10 minutes

›Maximum cumulative dose 300 mg

›Preferred for MAOI-associated hypertensive emergency

›Phentolamine (alpha-blocker) — MAOI hypertensive crisis

›5 mg IV bolus; repeat at 5 minute intervals

›Used when phenylethylamine-MAOI interaction suspected

Serotonin syndrome treatment

›Serotonin syndrome management protocol

›Discontinue all serotonergic agents immediately

›Aggressive cooling for hyperthermia

›Ice packs to axilla, groin, neck

›Evaporative cooling with misting and fan

›Target temperature <38.5 C

›Benzodiazepines for agitation and muscle rigidity

›Lorazepam 2 to 4 mg IV titrated to effect

›Cyproheptadine — serotonin antagonist antidote

›Loading dose 12 mg PO (crushed via NGT if unable to swallow)

›Maintenance 2 mg PO every 2 hours

›Maximum 32 mg per 24 hours

›Evidence level: Class IIb (observational data)

›Intubation and paralysis for severe hyperthermia or rigidity

›Succinylcholine or rocuronium for neuromuscular blockade

›Avoid if hyperkalemia risk (rhabdomyolysis)

Seizure management

›Seizure management protocol

›Benzodiazepines — first-line

›Lorazepam 2 to 4 mg IV; may repeat once

›Diazepam 5 to 10 mg IV as alternative

›If benzodiazepine-refractory seizures

›Phenobarbital 15 to 20 mg/kg IV at maximum 50 mg/min

›Levetiracetam 1000 to 3000 mg IV over 15 minutes as alternative

›Anesthesia and EEG monitoring for refractory status epilepticus

›Pyridoxine 5 g IV if gyromitrin (Gyromitra) poisoning suspected

›Replenishes pyridoxal phosphate depleted by monomethylhydrazine

Decontamination

›Activated charcoal considerations

›Generally not indicated for isolated psilocybin

›Rapid absorption of psilocybin within 30 to 60 minutes

›Benign expected course does not justify aspiration risk

›Consider activated charcoal if

›Co-ingestion of dangerous substance (amatoxin not excluded)

›Within 1 to 2 hours of ingestion and airway is protected

›Dose: 1 g/kg PO (maximum 50 g) as single dose

›No specific antidote for psilocybin toxicity

09Special Populations/sp51

Pregnancy

›Pregnancy-specific considerations

›Fetal effects of psilocybin

›No adequate human safety data; classified teratogenic risk category unclear

›Case reports only; avoid extrapolation

›OB consultation for any symptomatic pregnant patient

›Hemodynamic management in pregnancy

›Left lateral decubitus positioning for aortocaval compression relief

›Avoid supine position in third trimester

›Medication safety in pregnancy

›Lorazepam: FDA category D (neonatal withdrawal risk; use only if benefit outweighs risk)

›Diazepam: FDA category D; neonatal respiratory depression risk

›Ondansetron: Category B; first-line antiemetic in pregnancy

›Cyproheptadine: limited human data; use with caution in third trimester

›Fetal monitoring

›Continuous fetal heart rate monitoring in second and third trimester

›Obstetrics consultation for hyperthermia or hemodynamic instability

Geriatric

›Geriatric-specific considerations

›Atypical presentation patterns

›Delirium may be the predominant manifestation rather than hallucinations

›Lower threshold for workup of alternative etiology (UTI, subdural, metabolic)

›Pharmacokinetic changes

›Reduced hepatic metabolism — prolonged drug effects

›Reduced renal clearance — accumulation risk

›Benzodiazepines: start low, go slow (lorazepam 0.5 to 1 mg IV)

›Higher risk of paradoxical agitation with benzodiazepines

›Polypharmacy and drug interaction risk

10Background/b55

Epidemiology

›Incidence and prevalence

›Psilocybin mushroom exposures are the most reported hallucinogenic mushroom ingestion in North America

›AAPCC data: psilocybin mushroom calls more than doubled from 2012 to 2022 (Simon 2024, Annals of Emergency Medicine)

›Approximately 66% treated and released; 15% admitted; fatalities rare with isolated psilocybin

›Demographic distribution

›83.9% of cases aged 13 to 29 years (Leonard 2018, J Psychopharmacology)

›Male predominance (~78% of exposures)

›Exposure routes and products

›Increasing reports of psilocybin-containing chocolate products (2024 case series, Am J Emerg Med)

›Wild foraging remains a major risk for species misidentification

›Dysphoria and bad trips are the most common adverse outcomes reported to poison centers

›Mortality

›Fatalities from psilocybin alone are exceedingly rare

›Deaths attributed to behavioral toxicity (trauma, aspiration) rather than direct cardiac toxicity

›Amatoxin misidentification is the major source of mortality in the foraging context

Pathophysiology

›Mechanism of action

›Psilocybin prodrug rapidly dephosphorylated to active psilocin by alkaline phosphatase

›Psilocin half-life approximately 2 to 3 hours

›Hepatic glucuronidation is primary elimination pathway

›Renal excretion of conjugates

›5-HT2A receptor partial agonism — primary psychedelic mechanism

›Prefrontal cortex 5-HT2A activation produces visual hallucinations and altered cognition

›Locus coeruleus noradrenergic activation contributes to sympathomimetic effects

›Thalamic gating disruption causes sensory flooding and perceptual distortion

›Additional receptor interactions

›5-HT1A agonism — anxiolytic component

11Patient Discharge Instructions/pdi33

copy discharge instructions

›What happened to you

›You were treated in the emergency department for the effects of psilocybin (magic mushrooms)

›These mushrooms contain a chemical called psilocybin that affects how your brain works

›Symptoms typically last 4 to 6 hours and then fully go away

›What to expect at home

›You may feel tired or have a mild headache for 1 to 2 days

›This is normal and will resolve on its own

›Your mood, thoughts, and sleep may feel slightly off for 24 to 48 hours

›You should NOT drive, operate machinery, or make important decisions for at least 24 hours

›Return to the emergency department immediately if you experience

›Confusion, hallucinations, or feeling high again after you left the hospital

›This could mean a delayed reaction or a more dangerous mushroom was ingested

›Severe stomach pain, vomiting, or diarrhea

›This could be a sign of a dangerous mushroom poisoning called amatoxin

›Amatoxin symptoms can start up to 12 hours after eating

›Yellow color to your eyes or skin (jaundice)

›Dark urine or not urinating

›Chest pain or irregular heartbeat

›Thoughts of hurting yourself

›Fever, stiff muscles, or uncontrolled muscle movements

›Important safety information

›Never pick and eat wild mushrooms unless identified by an expert mycologist

›Dangerous look-alikes can cause liver failure and death

›Products labelled as psilocybin mushrooms are unregulated and may contain other substances

›Do not mix mushrooms with alcohol, cannabis, other drugs, or antidepressants

›Follow-up instructions

›See your family doctor or a psychiatrist within 1 to 2 weeks

12References/r36

Guidelines and key sources

›White J, Weinstein SA, De Haro L, et al. Mushroom Poisoning: A Proposed New Clinical Classification. Toxicon. 2019

›PMID 30439442

›Comprehensive classification of mushroom poisoning syndromes including Group 2A (neurotoxic/psilocybin)

›Leonard JB, Anderson B, Klein-Schwartz W. Does Getting High Hurt? Characterization of LSD and Psilocybin-Containing Mushroom Exposures to National Poison Centers 2000-2016. J Psychopharmacology. 2018

›PMID 30182795

›Demographic data: 83.9% aged 13-29; 78% male; disposition outcomes from AAPCC data

›Gartner HT, Wan HZ, Simmons RE, Sollee DR, Sheikh S. Psychedelic Mushroom-Containing Chocolate Exposures: Case Series. Am J Emerg Med. 2024

›PMID 39288500

›19% dysrhythmia rate; IV fluids most common intervention; adulterant concern

›He Z, Tang R, Feng M, et al. Dynamic Myocardial Injury and Variable Hallucination Latency in Psilocybe Keralensis Poisoning. Clin Toxicology. 2025

›PMID 40948398

›Molecularly confirmed case series documenting troponin elevation and variable onset timing

›Malcolm B, Thomas K. Serotonin Toxicity of Serotonergic Psychedelics. Psychopharmacology. 2022

›PMID 34251464

›Serotonin syndrome risk stratification with SSRI and MAOI co-administration

›Barnett BS, Koons CJ, Van den Eynde V, Gillman PK, Bodkin JA. Hypertensive Emergency Secondary to Combining Psilocybin Mushrooms, Extended Release Dextroamphetamine-Amphetamine, and Tranylcypromine. J Psychoactive Drugs. 2025

›PMID 38903003

›MAOI-psilocybin-amphetamine hypertensive emergency mechanism and management

›Simon MW, Olsen HA, Hoyte CO, et al. Clinical Effects of Psychedelic Substances Reported to United States Poison Centers 2012-2022. Ann Emerg Med. 2024

›PMID 39093248

›Trend data showing doubling of psilocybin mushroom exposures over 10 years

Supplementary references

›Hosein MM, Reid MJ, Walser S, et al. Considerations and Cautions for Integration of Psilocybin Into Routine Clinical Care. EClinicalMedicine. 2025

›PMID 41048658

›US National Network of Depression Centers consensus statement

›Yerubandi A, Thomas JE, Bhuiya NMMA, et al. Acute Adverse Effects of Therapeutic Doses of Psilocybin: Systematic Review and Meta-Analysis. JAMA Network Open. 2024

›Therapeutic dose adverse event profile

Evidence & Review

Evidence & Review