Must distinguish from primary psychiatric illness for treatment planning
Metabolic and CNS emergencies
Hypoglycemia
Always exclude with point-of-care glucose
Mimics any altered mental status presentation
CNS infection
Meningitis or encephalitis
Fever plus altered mental status without substance exposure history
Intracranial hemorrhage
Hypertensive emergency from hallucinogens can precipitate
Focal deficits or sudden severe headache prompt CT head
Nonconvulsive status epilepticus
Subtle behavioral changes without overt motor activity
EEG required to exclude
Laboratory Tests
Point-of-care and urgent labs
Glucose
Bedside POC glucose in all altered mental status
Hypoglycemia mimics and co-exists with intoxication
Target normoglycemia
Creatine kinase
CK elevation for rhabdomyolysis screening
Elevated CK in 100% of confirmed 25I-NBOMe cases in one series
Serial CK monitoring every 6 to 12 hours if elevated
CK > 5000 units/L indicates severe rhabdomyolysis
Aggressive IV fluid resuscitation indicated
Monitor for AKI
Comprehensive metabolic panel
Electrolytes
Hyponatremia from MDMA-induced SIADH
Avoid free water overload; use isotonic fluids
Renal function
AKI from rhabdomyolysis or direct toxicity
Creatinine and BUN trending
Hepatic function
MDMA hepatotoxicity possible
Drug metabolism assessment
Toxicology screening
Urine drug screen
Limited utility for classic hallucinogens
LSD, psilocybin, and NBOMes not detected on standard immunoassay
MDMA cross-reacts with amphetamine immunoassay panel
PCP detected on most standard urine screens
Ketamine may not be detected on standard panels
Negative screen does not exclude hallucinogen ingestion
Serum co-ingestion screen
Ethanol level
Co-ingestion common
Modifies clinical presentation
Acetaminophen and salicylate levels
Standard co-ingestion screen
Actionable if elevated
Serum quantitative MDMA level
Available at reference laboratories only
Not available in real-time for ED decisions
Complication-directed labs
Lactate
Metabolic acidosis assessment
Elevated with tissue hypoperfusion from hyperthermia or shock
> 2 mmol/l indicates organ hypoperfusion
Coagulation studies
DIC screening in severe toxicity
PT, aPTT, fibrinogen, D-dimer
NBOMe and MDMA associated DIC reported
Urinalysis
Myoglobinuria
Cola-colored urine
Dipstick positive for blood without red cells on microscopy
Arterial blood gas
Metabolic acidosis severity
pH and base deficit
Anion gap calculation
Oxygenation assessment
PaO2 in mmHg for respiratory compromise
PaCO2 for ventilation adequacy
Troponin
Cardiac injury with chest pain or dysrhythmia
MDMA direct cardiotoxicity reported
NBOMe cardiac effects in vitro and in vivo confirmed
Diagnostic Tests
Scoring Systems
Hunter Serotonin Toxicity Criteria
Diagnostic tool for serotonin syndrome
Requires serotonergic agent exposure
Plus one of: spontaneous clonus, inducible clonus with agitation or diaphoresis, ocular clonus with agitation or diaphoresis, tremor with hyperreflexia, or hypertonia with temperature > 38 degrees C and ocular or inducible clonus
Sensitivity 84% and specificity 97% versus Sternbach criteria
More specific than the original Sternbach criteria
Clonus is the most important clinical feature
Stimulant Observation Scale and Agitation Scoring
Clinical assessment of agitation severity
Guides chemical sedation dosing
Aids monitoring of treatment response
Richmond Agitation Sedation Scale (RASS) for ICU
Target RASS 0 to -1 for sedated patients
Avoid over-sedation with respiratory compromise
MDMA-specific risk stratification
No validated ED risk score
Temperature, CK, sodium, and hemodynamic status guide severity
Clinical trajectory more important than single values
MRI
MRI brain indications in hallucinogen toxicity
Limited acute utility as first-line imaging
CT head preferred for acute hemorrhage exclusion
Availability and patient cooperation constraints
Problem-solving indications
Persistent altered mental status beyond expected drug duration
Suspected encephalitis or posterior reversible encephalopathy syndrome
PRES risk with severe hypertension
T2-FLAIR hyperintensity in posterior regions
Associated with hypertensive emergency from sympathomimetic agents
MRI diffusion weighted imaging
Ischemic stroke exclusion
Cerebral vasospasm or cardioembolism from cardiac dysrhythmia
When focal neurologic deficit present
CT
CT head indications
Non-contrast CT head
Focal neurologic deficits
Prolonged altered mental status beyond expected drug duration
Head trauma during intoxication
Concern for intracranial hemorrhage from hypertensive emergency
Diagnostic performance
Sensitivity 98 to 100% for acute hemorrhage
Not diagnostic for drug effect itself
CT chest indications
Respiratory distress or hypoxemia
Aspiration pneumonia assessment
Pneumothorax reported with hallucinogen use
Evidence and guidance
CT for complication evaluation; imaging not required for uncomplicated intoxication
ACEP Level C recommendation for selective imaging
Ultrasound
Cardiac POCUS
Hemodynamic assessment
LV function estimation
Pericardial effusion exclusion
Fluid responsiveness assessment
IVC collapsibility index in spontaneously breathing patient
Integration with clinical exam required
Vascular access ultrasound
Difficult IV access in agitated patients
Real-time ultrasound guided peripheral IV
Femoral or internal jugular central access if peripheral fails
FAST exam for trauma
Free fluid assessment if fall or trauma during intoxication
Hemoperitoneum exclusion
Pericardial effusion screen
Disposition
Admission criteria
Inpatient admission indications
Persistent hyperthermia
Temperature > 39 degrees C on repeat measurement
Ongoing cooling requirement
Seizures
Any seizure activity warrants observation period
Risk of recurrence especially with NBOMe compounds
Rhabdomyolysis
Elevated CK requiring IV fluid management
Serial renal function monitoring required
Hemodynamic instability
Dysrhythmias requiring monitoring or treatment
Hypertensive emergency
Persistent altered mental status or psychosis
Beyond expected drug duration
LSD patients more likely to require admission than psilocybin
ICU admission indications
Core temperature > 40 degrees C with rigidity or clonus
Multi-organ failure risk
May require intubation for cooling
DIC or multi-organ failure
Coagulopathy, AKI, hepatic injury
High mortality without aggressive support
Cardiac arrest or life-threatening dysrhythmia
Post-resuscitation care
Continuous hemodynamic monitoring
Discharge criteria
Safe discharge criteria
Symptom resolution
Return to baseline mental status
Vital signs normalized
Ambulatory and tolerating oral fluids
No residual ataxia or confusion
Safe to ambulate without fall risk
No suicidal ideation or self-harm plan
Psychiatric clearance required if active ideation
Responsible adult available for observation
Observation periods met
Psilocybin: 4 to 6 hours observation
LSD: 8 to 12 or more hours due to longer half-life
Required consultations before discharge
Psychiatry if substance-induced psychosis or suicidal ideation
Residual psychiatric symptoms requiring follow-up
Substance use disorder evaluation
Toxicology if NBOMe or novel psychoactive substance
Discharge guidance for atypical presentations
Specialist consultations
Nephrology
AKI from rhabdomyolysis
Creatinine rising despite IV fluids
Renal replacement therapy consideration
Psychiatry
Substance-induced psychosis persisting
Cannot distinguish from primary psychiatric illness
Safe medication initiation guidance
Cardiology
Persistent dysrhythmia
QTc prolongation with risk of torsade
Structural cardiac injury suspected
Treatment
Chemical sedation for agitation
Benzodiazepines as cornerstone therapy
Lorazepam IV or IM
2 to 4 mg IV or IM initially
Repeat every 5 to 10 minutes as needed
Preferred when IV access available
Midazolam IM
5 mg IM as initial dose
Fastest onset for agitated patient without IV access
May repeat 5 mg in 10 minutes if inadequate effect
Diazepam IV
5 to 10 mg IV for seizures or severe agitation
Longer duration of action reduces repeat dosing need
Avoid antipsychotics in hallucinogen toxicity
Risk of lowering seizure threshold
Particularly with NBOMe and MDMA
Increased seizure frequency reported
Risk of worsening hyperthermia
Impair heat dissipation
NMS risk in susceptible patients
Risk of hypotension and QTc prolongation
Haloperidol increases QTc
Droperidol and ziprasidone additional QTc risk
Hyperthermia management
Aggressive cooling protocol
First-line evaporative cooling
Mist sprayed on skin with fan
Effective and widely available
Ice water immersion
Preferred for fastest cooling rate
Target temperature < 39 degrees C
Avoid cooling blankets alone
Inferior cooling rate
Acceptable as adjunct only
Pharmacologic adjuncts
Dantrolene
1 to 2.5 mg/kg IV for MDMA-induced hyperthermia
Conflicting evidence; consider if temperature > 39 degrees C refractory to cooling
Maximum 10 mg/kg per day
Benzodiazepines reduce thermogenesis
Decrease agitation-driven muscle heat generation
First-line before dantrolene
Paralysis and ventilation if refractory
Non-depolarizing neuromuscular blockade
Rocuronium 1.2 mg/kg IV
Eliminates muscle rigidity as heat source
Requires intubation and mechanical ventilation
Continuous EEG monitoring to detect occult seizures
Temperature monitoring every 15 minutes
Serotonin syndrome management
Discontinue all serotonergic agents
SSRIs, MAOIs, triptans, tramadol, linezolid
Half-life determines duration of effect
MAOIs may have prolonged effect requiring extended monitoring
Cyproheptadine for moderate to severe serotonin syndrome
12 mg PO loading dose
Then 2 mg every 2 hours until improvement
Only available as oral formulation
Mechanism: serotonin 5-HT2A receptor antagonist
Adjunct to benzodiazepines not replacement
Maximum 32 mg in 24 hours
Benzodiazepines for agitation and rigidity
Lorazepam 2 to 4 mg IV repeated as needed
Reduce muscle heat generation
Titrate to clinical improvement
Rhabdomyolysis management
Aggressive IV fluid resuscitation
Normal saline 1 to 1.5 L per hour initially
Target urine output 1 to 2 mL/kg/hr
Adjust rate based on urine output and cardiac status
Serial CK monitoring
Every 6 to 12 hours until trending down
Creatinine and electrolytes concurrent
Urine alkalinization
Sodium bicarbonate if CK very elevated
Target urine pH > 6.5
Reduces myoglobin precipitation in tubules
Contraindication: avoid urine acidification
Acidification promotes myoglobin precipitation
Contraindicated when CK elevated
Hypertension management
Benzodiazepines as first-line
Reduce sympathomimetic drive
Effective for most cases of drug-induced hypertension
Lorazepam 2 to 4 mg IV titrated to effect
Nitrates for refractory hypertension with chest pain
Nitroglycerin IV infusion
5 to 200 mcg/min titrated to SBP < 160 mmHg
Monitor for reflex tachycardia
Phentolamine IV for alpha-adrenergic excess
5 to 10 mg IV bolus
Alpha blocker preferred when catecholamine excess dominant
Avoid beta-blockers
Risk of unopposed alpha-adrenergic stimulation
Paradoxical severe hypertension possible
Particularly dangerous with phenethylamine class hallucinogens
MDMA-induced hyponatremia
Mechanism: SIADH plus excessive water intake
Free water restriction
Isotonic saline preferred over hypotonic fluids
Avoid free water overload
Sodium monitoring every 2 to 4 hours
Severe hyponatremia < 120 mmol/l requires hypertonic saline
Correction rate < 10 to 12 mmol/l per 24 hours to avoid osmotic demyelination
Special Populations
Pregnancy
Pregnancy-specific considerations
Hallucinogen use in pregnancy
Limited safety data for most agents
Reported spontaneous abortion and preterm labor association with MDMA
Teratogenicity risk
Psilocybin and LSD animal data show embryotoxicity at high doses
Human data insufficient to quantify risk
Management modifications in pregnancy
Imaging
CT head with lead shielding when clinically indicated
MRI preferred over CT if both are acceptable options
Fetal radiation dose from single CT head is < 1 mGy
Medication safety
Benzodiazepines category D but acceptable for life-threatening agitation or seizures
Lorazepam preferred over diazepam for shorter fetal exposure
Maternal hyperthermia treatment
Temperature > 38.5 degrees C associated with neural tube defect risk in first trimester
Aggressive cooling priority same as non-pregnant patients
Fetal monitoring
Continuous fetal heart rate monitoring when viable gestation
Maternal tachycardia and hyperthermia can cause fetal distress
Obstetrics consultation for viable gestations
MDMA-induced vasoconstriction
Reduced uteroplacental blood flow
Fetal acidosis risk
Geriatric
Older adult presentation differences
Atypical presentations more common
Delirium may be the primary symptom
Baseline dementia complicates assessment
Physiologic reserve reduced
Higher risk of severe hyperthermia complications
Rhabdomyolysis with lower CK elevations causing AKI
Pharmacokinetic differences
Reduced hepatic and renal clearance
Prolonged drug effect duration
Accumulation risk with repeated benzodiazepine dosing
Benzodiazepine sensitivity increased
Lower initial doses recommended
Lorazepam 1 to 2 mg IV initial dose
Risk of paradoxical agitation
Co-medication risks
Polypharmacy with serotonergic agents common
SSRIs for depression and anxiety prevalent in older adults
MAOIs used for atypical depression
QTc prolongation risk higher
Baseline QTc review before any QTc-prolonging treatment
Cardiac monitoring mandatory
Disposition tendency toward admission
Limited physiologic reserve
Frailty increases complication risk
Social supports may be limited
Pediatrics
Pediatric epidemiology
Adolescents 13 to 17 years at highest risk
Emerging use of psilocybin and MDMA
NBOMe sold as LSD particular danger
HPPD in adolescents
Case reports in 16-year-olds after single use
Developing brain may have prolonged vulnerability
Pediatric management differences
Weight-based benzodiazepine dosing
Lorazepam 0.05 to 0.1 mg/kg IV or IM, maximum 4 mg per dose
Midazolam 0.1 to 0.15 mg/kg IM, maximum 10 mg per dose
Temperature thresholds
Hyperthermia > 38.5 degrees C warrants treatment in children
Lower threshold than adults due to metabolic rate differences
Rhabdomyolysis fluid targets
Normal saline 20 mL/kg IV bolus for rhabdomyolysis
Target urine output 2 to 3 mL/kg/hr in young children
Mandatory reporting considerations
Child protection assessment if chronic substance use in minors
Neglect or abuse assessment when appropriate
Social work consultation for substance use in young adolescents
Adolescent confidentiality laws vary by jurisdiction
Consult institutional policy
Safety considerations override confidentiality when life-threatening
Background
Epidemiology
Incidence and population data
Age and sex distribution
Age 13 to 29 years predominate in case series
74 to 78% male in poison center data
Poison center exposure trends
Psychedelic exposures to US poison centers increasing 2012 to 2022
LSD and psilocybin most common classic agents reported
Polysubstance co-exposure
41% of psychedelic exposures involve concomitant substances
Alcohol most common co-ingestant
Agent-specific mortality and morbidity
Classic psychedelics low mortality
LSD and psilocybin rarely fatal in isolation
Most treated and released from ED
NBOMe compounds significantly higher morbidity and mortality
Death rate approximately 2.3% in poison center data
Seizures in 8.8% of NBOMe exposures
MDMA mortality associated with hyperthermia
Dance festival deaths predominantly from hyperthermia
Hyponatremia secondary cause of MDMA-associated death
Novel psychoactive substance concern
NBOMes sold as LSD on blotter paper
Users often unaware of actual agent ingested
Dramatically higher toxicity profile than classic LSD
2C series phenethylamines
Potent sympathomimetic and serotonergic activity
Emerging case reports of severe toxicity
Pathophysiology
Classic serotonergic psychedelics mechanism
Primary 5-HT2A receptor agonism
Cortical serotonin receptor activation
Glutamate release in prefrontal cortex mediates perceptual effects
LSD pharmacokinetics
Oral bioavailability high
Half-life approximately 3 to 5 hours with prolonged receptor binding
Duration of effect 8 to 12 hours despite short plasma half-life
Supportive care with benzodiazepines appropriate for all classes
Poison Control consultation essential
Emerging toxicology data for novel agents
Expert guidance for unusual presentations
Patient Discharge Instructions
copy discharge instructions
Hallucinogen toxicity home care
Rest at home with a responsible adult present for 24 hours
Classic psychedelic effects resolve within 6 to 12 hours for LSD
Psilocybin effects resolve within 4 to 6 hours
Mood changes, anxiety, or sleep disturbance may persist days to weeks
This is called the subacute afterglow period
Does not mean lasting brain damage in most cases
Avoid alcohol and other substances
Do not take any new medications without consulting a doctor
Avoid serotonergic medications unless your doctor approves
Stay well hydrated with water or sports drinks
Do not drink excessive amounts of plain water
Isotonic fluids preferred
Warning signs to return to the emergency department immediately
Hallucinations returning hours or days after the drug wore off
This may indicate HPPD (hallucinogen persisting perception disorder)
Can develop after even a single use
Fever, shaking chills, or feeling very hot
Temperature above 38.5 degrees C at home
Do not wait to seek help
Dark or cola-colored urine
Decreased urine output
Signs of muscle breakdown in kidneys
Chest pain, racing heart, or fainting
Cardiac complications from stimulant-type hallucinogens
Call 911 or go to ER immediately
Persistent anxiety, paranoia, or inability to distinguish reality
Lasting more than 24 hours after drug wore off
May indicate substance-induced psychosis
Thoughts of suicide or self-harm
Call 988 (Suicide and Crisis Lifeline) or go to nearest ER
Tell a trusted person if you are having these thoughts
Follow-up instructions
Primary care within 48 to 72 hours
Recheck kidney function and muscle enzyme levels if rhabdomyolysis was present
Review any medications started in ER
Psychiatry or substance use counseling referral at discharge
Substance use disorder is a medical condition with effective treatments
Support resources available through your primary care provider
Important safety information
Illicit LSD may actually be NBOMe which is far more dangerous
There is no safe way to use unregulated street hallucinogens
NBOMe deaths have occurred at doses sold as single doses
Do not drive or operate machinery for at least 24 hours
Judgment and coordination may remain impaired
Perceptual distortions can persist subtly
References
Guidelines and key sources
Primary clinical guidelines
2023 American Heart Association Focused Update on Management of Patients with Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning (Lavonas et al., Circulation 2023)
Management of toxin-associated cardiac arrest
Class recommendations for antidotal and resuscitative therapies
2025 AHA CPR and Emergency Cardiovascular Care Guidelines Part 10 (Cao et al., Circulation 2025)
Adult and pediatric special circumstances of resuscitation
Toxicology resuscitation updates
ACEP Clinical Policy: Critical Issues in Diagnosis and Management of Adult Psychiatric Patient in ED (Nazarian et al., Annals of Emergency Medicine 2017)
ACEP Level recommendations for psychiatric emergencies
Key epidemiologic and pharmacology studies
Leonard JB, Anderson B, Klein-Schwartz W. Journal of Psychopharmacology 2018
LSD and psilocybin-containing mushroom exposures to national poison centers 2000 to 2016
41% polysubstance co-exposure rate; demographic and outcome data
Simon MW, Olsen HA, Hoyte CO et al. Annals of Emergency Medicine 2024
Clinical effects of psychedelic substances reported to US poison centers 2012 to 2022
Adverse events in studies of classic psychedelics: systematic review and meta-analysis
Mori-Kreiner A, Aggarwal A, Bordoloi M. Psychopharmacology Bulletin 2025
HPPD in 16-year-old adolescent case report
Coding references
ICD-10 coding
F16.10 hallucinogen abuse uncomplicated
F16.120 hallucinogen abuse with intoxication uncomplicated
T40.8 poisoning by lysergide (LSD)
T65.891 toxic effects of other specified substances
G21.0 neuroleptic malignant syndrome
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.