Hallucinations are false perceptions that have no basis in the external environment. Overdoses can cause anxiety, dysphoria, tachycardia, fever, hypertension, seizure, and rhabdomyolysis. Common hallucinogenic drugs include lysergic acid diethylamide (LSD), psilocybin (hallucinogenic mushrooms, “magic mushrooms”), mescaline, peyote, methylenedioxymethamphetamine (ecstasy), phencyclidine (PCP, angel dust), cathinone derivatives (“bath salts”), salvia, Datura genus (Jimson weed, angel trumpet), dextromethorphan, phenethylamines (“smiles”, “N-bomb”), ketamine (“special K,” “vitamin K”), and Δ⁸-THC ( “light weed,” “diet weed”).

Overdose, “OD”

Psychedelics

Entheogen (substance that generates the god/spirit within)

Entactogens (awareness of “the touch within”)

• Clinical presentation varies by amount and type of drug used.
• Overall presentation includes distortions in body image and sensory perception, as well as rapid, intense alterations in mood, emotions, and suggestibility.
• Overdose symptoms may range from acute anxiety, agitation, tachycardia, hypertension, hyponatremia, hyperthermia, severe agitation, rhabdomyolysis, seizure, cardiac dysrhythmia, respiratory failure, and death.
• Classic pure hallucinogens: LSD, psilocybin (hallucinogenic mushrooms, “magic mushrooms”). Individuals rarely present for medical treatment. The patient usually is conscious, alert, and can provide history of drug ingestion. Serious medical problems have been reported to include seizures, hyperthermia, rhabdomyolysis, and acute renal failure. New trends in self-administered “microdosing” of psilocybin or LSD for treatment of depression or other psychological disorders may present as inadvertent overdose.^1-3
• Mescaline: Found in many cacti. Similar structure to LSD; however, there have not been reports of medically significant adverse effects directly from the drug.
• Peyote: Legal for use by the Native American Church. Adverse effects occur first, before hallucinations, and within 1 h of ingestion include severe nausea, vomiting, abdominal pain, dizziness, ataxia, nystagmus, and headache. Mild adrenergic effects of increased temperature, pulse, and blood pressure occurs after the initial symptoms. Hallucinations begin several hours later.²
• Methylenedioxymethamphetamine (ecstasy): Not a true hallucinogenic but with similar effects of increased stimulation. Mild increase in temperature, pulse, hypertension, nausea, bruxism, jaw-clenching, dry mouth, muscle aches, ataxia. Severe effects include significant increases in blood pressure leading to intracranial hemorrhage, brain or heart ischemia, arrhythmia, sudden cardiac death, hyponatremia, malignant hyperthermia, disseminated intravascular coagulation, seizures, and rhabdomyolysis. Symptoms are similar to those of serotonin syndrome.²
• Phencyclidine (PCP, angel dust): Similar to ketamine with multiple effects that include features of hallucinations. Patients may have central nervous system (CNS) stimulation or depression. The most common signs are mild hypertension and vertical nystagmus in 60% of patients. Other important warning signs for the safety of staff and physicians include severe agitation, physical violence, unpredictable behavior, and decreased response to pain. Symptoms may also include disassociation, seizures (up to 3%), rhabdomyolysis with resulting acute renal failure, dystonic reactions, hyperthermia causing hepatic necrosis, and multiorgan failure.²
• Cathinone derivatives (bath salts): Similar to PCP, with sympathomimetic effects of elevated temperature, blood pressure, pulse, sweating. Patients also may be severely agitated, aggressive, and violent toward staff. Severe medical effects include severe hyperthermia, hyponatremia, seizures, and rhabdomyolysis.²
• Salvia: Adverse effects are mild and may include slurred speech, dysphoria, headache, nausea, vomiting, dizziness.²
• Datura genus (Jimson weed, angel trumpet): Anticholinergic alkaloids with symptoms consistent with anticholinergic poisoning: Hyperthermia, delirium, hallucinations, mydriasis, blurry vision, dry mouth, tachycardia, urinary retention.²
• Phenethylamines (25X-NBOME, N-Bombs, smiles): Novel synthetic hallucinogen that appeared in early 2010s. Clinical symptoms include tachycardia, elevated temperature, audio and visual hallucinations, aggression, confusion, and fear. The more concerning presentations involve seizure, metabolic acidosis, cardiac toxicity, acute kidney injury, multiorgan failure, and death.²
• Dextromethorphan: Commonly used by adolescents because of availability in over-the-counter cold and flu products; likely to be associated with salicylate, antihistamine, and acetaminophen overdose due to combination of cold and flu product ingredients.²
• Δ⁸-THC: Naturally occurring THC found in very low levels in Cannabis sativa, sold in the more concentrated form after synthesis from hemp-derived cannabidiol resulting in a drug that is 50% to 75% more psychoactive than main cannabis component, Δ⁹-THC. This concentrated form, sold online, in vape shops, and in gas stations as Δ⁸-THC, needs synthetic conversion to produce enough THC to elicit the desired effects and the byproducts can be toxic. Δ⁸ synthesis, use, and sale are legal and not regulated by the FDA. Typically sold in bright packaging and in gummy form, there are many accidental ingestions in pediatric cases, with two reported deaths. It can cause seizures, coma, alterations in visual and auditory perceptions, euphoria, and drowsiness.⁴

Usually caused by stimulation of various receptors in the brain, including serotonin type 2, dopamine, norepinephrine, acetylcholine, beta-2 adrenergic, NMDA, opioids, and voltage-gated electrolyte channels.

• Alcohol use or withdrawal
• Benzodiazepine withdrawal
• Anticholinergic poisoning
• Serotonin syndrome
• Neuroleptic malignant syndrome
• Thyrotoxicosis
• Central nervous system infections
• Anti-NMDA encephalitis
• Structural brain lesions
• Acute psychosis
• Hypoglycemia
• Hypoxia
• Sepsis
• Acute ischemic or hemorrhagic stroke
• Polysubstance use
• Incidental trauma

• Must rule out nontoxic causes of altered mental status. Vital signs should be examined immediately. History of drug use, dementia, delirium, and risk factors for CNS infection should be considered. Patients should also be examined for occult and incidental trauma that occurred while under the influence of the drugs.

• Consider:
  1. CBC
  2. Glucose level
  3. Comprehensive metabolic panel
  4. Thyroid-stimulating hormone
  5. Creatine phosphokinase
  6. Arterial blood gas
  7. Toxicologic screening for other illegal drugs (urine and serum), acetaminophen, salicylate
  8. Urine Osms
  9. Lumbar puncture

• Consider:
  1. ECG
  2. CT of head
  3. MRI of brain

• Place patient in a calm and quiet area with limited auditory and visual stimulation.
• Patients may benefit from a sitter to reorient him or her and provide a calming presence.
• Physical restraints should be used only if necessary because of increased risk of agitation, hyperthermia, and rhabdomyolysis. Severely violent patients may require chemical restraint in addition to physical restraint.
• Severe hyperthermia may require active cooling measures.
• Supplemental oxygen should be considered.
• Bowel irrigation not usually recommended after 60 min of ingestion; unlikely to be beneficial for most compounds.

• Benzodiazepines are the mainstay of medical treatment
• Aggressive intravenous hydration with isotonic crystalloids
• Naloxone
• Dextrose
• Dantrolene if refractive hyperthermia
• Hypertonic saline if hyponatremic
• Cyproheptadine for serotonin syndrome
• IV nitroprusside or nicardipine for blood pressure control
• Propofol, barbiturate for refractive seizure
• Paralytics for hyperthermia secondary to dystonic reactions
• Physostigmine for severe anticholinergic poisoning

• Patients should be monitored for several hours for improvement of symptoms. If symptoms improve, patients who are mentally lucid and steady on their feet may be discharged under the close supervision of family or friends.
• Patients not improving may require further workup.
• If no organic cause is found, patients may require psychiatric evaluation.
• Patients may need to be admitted until resolution of organ injury.

• Psychiatric referral may be required
• Substance abuse or rehab

• Actual substance used may be unclear.
• Most treatment is supportive care.
• Treat symptoms of hyperthermia, severe hypertension, and possible rhabdomyolysis.
• Chemical restraint with benzodiazepines is safe and effective.