LSD is a potent serotonergic hallucinogen that acts primarily as a partial agonist at the 5-HT₂A receptor, with additional binding at 5-HT₁A, 5-HT₂C, 5-HT₂B, and dopamine D₂ receptors. [1] Toxicity is predominantly psychological in nature, with serious medical complications being infrequent but possible. Most patients are managed with supportive care and benzodiazepines and can be discharged from the ED. [2-3]
1. History
- Substance used, route (oral blotter/tab, liquid, rarely insufflated powder), estimated dose, and timing of ingestion [4]
- Intentional recreational use vs. accidental/unknown exposure — ask about substances sold as something else (e.g., NBOMe sold as LSD, which carries significantly higher toxicity and fatality risk) [5]
- Prior psychedelic use and tolerance; frequency of use (higher frequency associated with increased risk of adverse events) [6]
- Onset of symptoms: typically 1–2 hours after oral ingestion, peak effects at 2–3 hours, total duration 6–12 hours depending on dose [7-8]
- Co-ingestions: alcohol, cannabis, MDMA, stimulants — co-ingestion occurs in ~34–41% of cases and worsens outcomes [3][9]
- Psychiatric history: pre-existing anxiety, depression, psychotic disorders, or suicidal ideation [5-6]
- "Set and setting": mindset and environment at time of use — poor set/setting is the most commonly cited contributor to adverse reactions [6]
2. Alarm Features
- Hyperthermia (core temp >40°C): life-threatening, associated with rhabdomyolysis and multi-organ failure [10-11]
- Seizures: rare but reported, especially at high doses or in patients with epilepsy history [2][12]
- Severe agitation/excited delirium: risk of rhabdomyolysis, metabolic acidosis, and death if not rapidly controlled [10]
- Coma or respiratory depression: suggests massive overdose or co-ingestion [2]
- Cardiac arrest: very rare but documented in poison center data [2]
- Suicidal ideation or self-harm: impaired judgment and perceptual disturbances can lead to unintentional self-injury (falls, cuts) or intentional harm [12-13]
- Serotonin syndrome features: clonus, hyperreflexia, diaphoresis, and rigidity — particularly if co-ingested with serotonergic medications [14-15]
- Psychosis refractory to benzodiazepines: may indicate NBOMe or other substituted phenethylamine rather than true LSD [5]
3. Medications
- Benzodiazepines are the cornerstone of treatment:
- Lorazepam 1–2 mg IV/IM or midazolam 2–5 mg IM for agitation, anxiety, and panic [10][16]
- Also first-line for toxin-associated seizures [17]
- Antipsychotics (second-line for refractory agitation):
- Olanzapine 5–10 mg IM or haloperidol 5 mg IM [12][16]
- Avoid in suspected serotonin syndrome (may worsen hyperthermia with some agents)
- Cyproheptadine (5-HT₂A antagonist): if serotonin syndrome is suspected — initial dose 12 mg PO, then 2 mg q2h PRN; maintenance 8 mg q6h; available only in oral form [14]
- Ketanserin (5-HT₂A antagonist): effectively blocks LSD effects in controlled studies but not widely available clinically [7]
- Avoid: physical restraints without chemical sedation (associated with death from rhabdomyolysis and hyperthermia); antipyretics are ineffective (hyperthermia is from muscular activity, not hypothalamic set-point alteration); avoid succinylcholine if paralysis needed (hyperkalemia risk from rhabdomyolysis) [10-11][14]
- Contraindicated medications to consider: MAOIs and SSRIs in combination with LSD increase serotonin syndrome risk [14]
4. Diet
- Not a primary clinical concern in acute toxicity
- Hydration is critical — aggressive IV fluid resuscitation for rhabdomyolysis prevention and treatment
- NPO if altered mental status or risk of aspiration
5. Review of Systems
- Psychiatric: hallucinations (visual > auditory), paranoia, panic, depersonalization, derealization, euphoria or dysphoria, ego dissolution [18-19]
- Neurologic: tremor, hyperreflexia, incoordination, nystagmus, paresthesias, seizures [2][13]
- Cardiovascular: palpitations, chest pain [2-3]
- GI: nausea, vomiting (reported in ~22% of single-substance exposures) [9]
- Musculoskeletal: muscle tension, jaw clenching
- Constitutional: diaphoresis, chills
6. Collateral History and Family History
- Collateral from friends/bystanders is essential — patients may be unable to provide reliable history
- Confirm substance identity if possible; ask about source, appearance (blotter paper, liquid, powder), and whether others are affected (cluster presentations) [4]
- Family history of schizophrenia or psychotic disorders increases risk of LSD-induced psychosis [1]
- Family history of seizure disorders [12]
7. Risk Factors
- Younger age (13–29 years: ~89% of LSD exposures) [2]
- Male sex (~74% of cases) [2]
- Comorbid mental health conditions (anxiety, depression, psychotic spectrum disorders) [6]
- Higher frequency of use [6]
- Co-ingestion with other substances [3][9]
- Poor set and setting (unfamiliar environment, negative mindset) [6]
- Unknown dose or adulterated product (NBOMe, DOx compounds) [5]
- Pre-existing epilepsy [12]
8. Differential Diagnosis
- NBOMe or other substituted phenethylamine toxicity: sold as LSD but far more dangerous; causes severe sympathomimetic toxicity, seizures, and death; bitter/metallic taste on blotter (LSD is tasteless) [5]
- Sympathomimetic toxicity (amphetamines, cocaine, synthetic cathinones): more prominent hypertension, tachycardia, and hyperthermia [13]
- Anticholinergic toxicity: dry skin, urinary retention, absent bowel sounds, true hallucinations (vs. LSD's predominantly visual illusions/distortions with intact sensorium) [13]
- Serotonin syndrome: clonus and hyperreflexia are distinguishing features; consider if on serotonergic medications [14-15]
- PCP/ketamine intoxication: nystagmus (horizontal/vertical/rotatory), dissociation, violence [13]
- Acute psychosis/schizophrenia: new-onset psychotic break; no temporal relationship to substance use; may falsely attribute symptoms to hallucinogen use [13]
- CNS infection, metabolic derangement (hypoglycemia, hyponatremia), seizure disorder, or CNS tumor [13]
- Cannabis-induced psychosis or synthetic cannabinoid toxicity
9. Past Medical History
- Prior psychedelic use and adverse reactions
- Psychiatric history: schizophrenia, bipolar disorder, anxiety disorders, PTSD, prior psychotic episodes [12]
- Seizure disorder [12]
- Current medications — especially SSRIs, SNRIs, MAOIs, lithium, tramadol (serotonin syndrome risk) [14]
- Prior episodes of HPPD or flashbacks [13]
- Substance use history (polysubstance use common)
10. Physical Exam
- Vital signs: mild-moderate tachycardia (38.6% of cases), mild hypertension, mild hyperthermia (temp >38°C in up to 34% at 200 µg doses); peak HR rarely >130 bpm; SBP typically does not exceed 180 mmHg in pure LSD [2][20]
- Eyes: mydriasis (hallmark finding), conjunctival injection [4][13]
- Neurologic: hyperreflexia, tremor, nystagmus, motor incoordination, clonus (if serotonin syndrome) [13]
- Skin: diaphoresis, piloerection, flushing (vs. dry skin in anticholinergic toxicity)
- Mental status: altered perception with generally preserved orientation in mild-moderate cases; agitation, confusion, or combativeness in severe cases [4][21]
- Musculoskeletal: muscle rigidity or fasciculations in severe cases
11. Lab Studies
- Point-of-care glucose: rule out hypoglycemia in altered mental status [17]
- BMP/CMP: electrolytes, renal function (creatinine elevation seen in severe cases) [2]
- CK (creatine kinase): if agitation, hyperthermia, or prolonged restraint — screen for rhabdomyolysis [2]
- Lactate: if concern for metabolic acidosis from prolonged agitation
- Urine drug screen: standard immunoassays do NOT detect LSD — LSD requires specialized GC-MS or LC-MS/MS testing; UDS useful to identify co-ingestants [21]
- CBC, hepatic panel: if severe toxicity or prolonged course
- Coagulation studies: if concern for DIC in severe hyperthermia
- Urinalysis: myoglobinuria if rhabdomyolysis suspected
- LSD is extensively metabolized; only ~1% excreted unchanged in urine; main metabolite is 2-oxo-3-hydroxy-LSD [22]
12. Imaging
- Not routinely indicated for uncomplicated LSD intoxication
- Head CT: if concern for traumatic injury (falls, self-harm), new focal neurologic deficits, or first-time seizure [13]
- Chest X-ray: if aspiration risk, respiratory distress, or concern for pneumothorax (rare complication) [13]
13. Special Tests
- Hunter Serotonin Toxicity Criteria: if serotonin syndrome is suspected — requires spontaneous clonus, inducible clonus with agitation/diaphoresis, ocular clonus with agitation/diaphoresis, tremor with hyperreflexia, or hypertonia with temperature >38°C and ocular/inducible clonus [23]
- Drug checking/reagent testing: Ehrlich reagent turns purple with indole-containing compounds (LSD, psilocybin) but does not react with NBOMe — useful for harm reduction
- Quantitative LSD levels: not clinically useful for acute management; available only at reference labs; therapeutic/recreational levels typically 1–5 ng/mL; severe poisoning cases reported at 40–60 ng/mL [4]
14. ECG
- Obtain ECG if:
- Significant tachycardia or chest pain
- Co-ingestion suspected (especially stimulants)
- Prior to antipsychotic administration (QTc prolongation risk)
- Expected findings: sinus tachycardia
- Dangerous patterns to recognize: QTc prolongation (from co-ingestants or antipsychotic treatment), wide-complex tachycardia (suggests non-LSD substance), ST changes (coronary vasospasm from sympathomimetic effects)
15. Assessment
LSD toxicity is a clinical diagnosis based on history of exposure and characteristic sympathomimetic/serotonergic toxidrome with prominent perceptual disturbances. Key features distinguishing LSD from other hallucinogens and sympathomimetics:
- Predominantly psychological symptoms (hallucinations, anxiety, panic, paranoia) with relatively mild autonomic effects [2][6]
- Most adverse reactions are self-limiting, resolving within 24 hours [6]
- Per-event risk of seeking emergency medical treatment is approximately 0.2% [6]
- Moderate effects are the most common outcome (~62% of poison center cases) [2]
- Serious complications (hyperthermia, seizures, rhabdomyolysis, cardiac arrest) are infrequent but can occur, particularly with massive doses, co-ingestions, or adulterated products [2-3]
16. Treatment Plan
Initial stabilization
- ABCs; protect airway if severely obtunded
- Place in a calm, quiet, low-stimulation environment — this alone may be sufficient for mild cases ("talk-down" approach) [21]
- Continuous monitoring: cardiac, pulse oximetry, temperature
Pharmacologic management
- Mild anxiety/panic ("bad trip"): reassurance, quiet environment ± low-dose benzodiazepine (lorazepam 1–2 mg PO/IV or midazolam 2–5 mg IM) [16][21]
- Moderate-severe agitation: benzodiazepines first-line; may require repeated dosing. Midazolam 5 mg IM has fastest onset for IM route [24]
- Refractory agitation: add olanzapine 5–10 mg IM or haloperidol 5 mg IM; ketamine 2–5 mg/kg IM as last resort (higher intubation risk) [16][24]
- Hyperthermia (>40°C): aggressive external cooling (ice water immersion preferred), IV fluids, immediate sedation/paralysis with nondepolarizing agents if refractory [10-11][14]
- Seizures: benzodiazepines first-line [17]
- Serotonin syndrome: discontinue all serotonergic agents, benzodiazepines, cyproheptadine 12 mg initial dose then 2 mg q2h; severe cases require intubation and neuromuscular paralysis [14]
- Rhabdomyolysis: aggressive IV crystalloid, target UOP 1–2 mL/kg/hr
No specific antidote exists for LSD. Decontamination (activated charcoal, gastric lavage) is generally not indicated given the extremely small doses involved (micrograms) and rapid absorption. [21]
17. Disposition
- Discharge criteria: resolution of agitation and perceptual disturbances, stable vital signs, normal mental status, safe social situation, no suicidal ideation. Most patients can be treated and released from the ED [2]
- Observation: patients requiring repeated sedation, persistent agitation, or mild vital sign abnormalities — observe until effects resolve (typically within 12–24 hours) [6]
- Admission criteria: refractory agitation, hyperthermia, seizures, rhabdomyolysis, persistent psychosis, suicidal ideation, or hemodynamic instability [2]
- ICU admission: intubated patients, severe hyperthermia, serotonin syndrome, multi-organ dysfunction [4]
- Specialist consultation: Poison Control (800-222-1222) for all cases; psychiatry if persistent psychosis, suicidal ideation, or concern for underlying psychiatric disorder; toxicology for severe or atypical presentations [17]
18. Follow Up / Return Precautions
- Expected recovery: most patients feel back to normal within 24 hours; however, ~11% of those seeking emergency treatment in one survey reported persistent issues beyond 4 weeks [6]
- Hallucinogen Persisting Perception Disorder (HPPD): visual disturbances (visual snow, halos, trailing images, intensified colors, afterimages) persisting weeks to years after use; occurs primarily after LSD; does not correlate strongly with number of uses; most cases spontaneously resolve within one year. Benzodiazepines (e.g., clonazepam) may provide symptomatic relief [13][25-26]
- Flashbacks: brief, typically mild reoccurrences of drug-like perceptual experiences reported in up to ~9% of healthy subjects in controlled studies; usually not clinically significant [27]
Return precautions — instruct patients to return for
- Recurrence of severe anxiety, panic, or psychotic symptoms
- Visual disturbances that persist or worsen after drug effects should have resolved
- Suicidal thoughts or self-harm urges
- Fever, dark urine, or muscle pain (rhabdomyolysis)
- Chest pain or palpitations
Counseling points
- Substance use counseling and harm reduction
- Avoid re-use, especially if adverse reaction occurred
- Warn about adulterated products (NBOMe) and unpredictable dosing from illicit sources [5]
- Psychiatric follow-up if underlying mood or anxiety disorder identified [6]
References
1. Psychedelics and Psychedelic-Assisted Psychotherapy. — Reiff CM, Richman EE, Nemeroff CB, et al. The American Journal of Psychiatry. 2020.
2. Does Getting High Hurt? Characterization of Cases of LSD and Psilocybin-Containing Mushroom Exposures to National Poison Centers Between 2000 and 2016. — Leonard JB, Anderson B, Klein-Schwartz W. Journal of Psychopharmacology. 2018.
3. Clinical Effects of Psychedelic Substances Reported to United States Poison Centers: 2012 to 2022. — Simon MW, Olsen HA, Hoyte CO, et al. Annals of Emergency Medicine. 2024.
4. A Cluster of Lysergic Acid Diethylamide (LSD) Poisonings Following Insufflation of a White Powder Sold as Cocaine. — Roberts DM, Premachandra KH, Chan BS, et al. Clinical Toxicology. 2021.
5. Use of Lysergic Acid Diethylamide by Major Depression Status. — Walsh CA, Gorfinkel L, Shmulewitz D, Stohl M, Hasin DS. JAMA Psychiatry. 2024.
6. Adverse Experiences Resulting in Emergency Medical Treatment Seeking Following the Use of Lysergic Acid Diethylamide (LSD). — Kopra EI, Ferris JA, Rucker JJ, et al. Journal of Psychopharmacology. 2022.
7. Acute Dose-Dependent Effects of Lysergic Acid Diethylamide in a Double-Blind Placebo-Controlled Study in Healthy Subjects. — Holze F, Vizeli P, Ley L, et al. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2021.
8. Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects. — Dolder PC, Schmid Y, Steuer AE, et al. Clinical Pharmacokinetics. 2017.
9. The Psychedelic Call: Analysis of Australian Poisons Information Centre Calls Associated With Classic Psychedelics. — Wilkes R, Roberts DM, Liknaitzky P, Brett J. Clinical Toxicology. 2024.
10. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. — Lavonas EJ, Akpunonu PD, Arens AM, et al. Circulation. 2023.
11. Part 10: Adult and Pediatric Special Circumstances of Resuscitation: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. — Cao D, Arens AM, Chow SL, et al. Circulation. 2025.
12. Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis. — Hinkle JT, Graziosi M, Nayak SM, Yaden DB. JAMA Psychiatry. 2024.
13. Diagnostic and Statistical Manual of Mental Disorders. — Dilip V. Jeste, Jeffrey A. Lieberman, David Fassler, et al American Psychiatric Association (2022). 2022.
14. The Serotonin Syndrome. — Boyer EW, Shannon M. The New England Journal of Medicine. 2005.
15. High Risk and Low Prevalence Diseases: Serotonin Syndrome. — Spadaro A, Scott KR, Koyfman A, Long B. The American Journal of Emergency Medicine. 2022.
16. Clinical Policy: Critical Issues in the Diagnosis And Management of the Adult Psychiatric Patient In the Emergency Department. — Nazarian DJ, Broder JS, Thiessen MEW, et al. Annals of Emergency Medicine. 2017.
17. Acute Medication Poisoning. — Vega IL, Griswold MK, Laskey D. American Family Physician. 2024.
18. Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. — Schmid Y, Enzler F, Gasser P, et al. Biological Psychiatry. 2015.
19. Modern Clinical Research on LSD. — Liechti ME. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2017.
20. Safety Pharmacology of Acute LSD Administration in Healthy Subjects. — Holze F, Caluori TV, Vizeli P, Liechti ME. Psychopharmacology. 2022.
21. Clinical Pharmacology of Lysergic Acid Diethylamide: Case Reports and Review of the Treatment of Intoxication. — Blaho K, Merigian K, Winbery S, Geraci SA, Smartt C. American Journal of Therapeutics. 1997.
22. Pharmacokinetics, Pharmacodynamics and Urinary Recovery of Oral Lysergic Acid Diethylamide Administration in Healthy Participants. — Holze F, Erne L, Duthaler U, Liechti ME. British Journal of Clinical Pharmacology. 2024.
23. Prevention, Recognition, and Management of Serotonin Syndrome. — Ables AZ, Nagubilli R. American Family Physician. 2010.
24. Safety and Efficacy of Pharmacologic Agents Used for Rapid Tranquilization of Emergency Department Patients With Acute Agitation or Excited Delirium. — Kim HK, Leonard JB, Corwell BN, Connors NJ. Expert Opinion on Drug Safety. 2021.
25. Flashbacks, Hallucinogen Persisting Perception Disorder (HPPD), and Reactivations Following the Use of Classic Psychedelics: Classification and Therapeutic Management. — Žuljević MF, Majić T. Current Topics in Behavioral Neurosciences. 2026.
26. To Treat or Not to Treat? High-Potency Benzodiazepine Use in a Case of Comorbid Hallucinogen Persisting Perception Disorder and Alcohol Use Disorder. — Christensen JA, Fipps DC, Bostwick JM. Experimental and Clinical Psychopharmacology. 2023.
27. Flashback Phenomena After Administration of LSD and Psilocybin in Controlled Studies With Healthy Participants. — Müller F, Kraus E, Holze F, et al. Psychopharmacology. 2022.