Hallucinogen Toxicity Treatment & Management

Updated: Jan 29, 2021
  • Author: Joseph L D'Orazio, MD, FAAEM, FACMT; Chief Editor: Sage W Wiener, MD  more...
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Prehospital Care

Prehospital care should focus on preventing harm and transporting patients to an appropriate facility for further evaluation. It is important to note that patients under the influence of hallucinogens may exhibit a wide range of behaviors with the potential to rapidly fluctuate from a relaxed, euphoric state to one of extreme agitation and aggression. Calm, reassuring, and nonthreatening behavior can be useful in "talking down" patients to allow care and interventions to proceed. Often times, transporting a severely agitated patient requires numerous responders.

In the setting of significant agitation, the primary goal for transport is to ensure both patient and provider safety through sedation and physical restraint. Whenever possible, adequate sedation should be the primary objective in behavioral control. Cases of arrest-related deaths (ARD) are not infrequent in the setting of physical restraint.

Various mechanisms have been proposed for sudden cardiac death related to restraint use including the combination of marked lactic acidosis due to struggling against restraint combined with impaired chest wall motion. Patients pinned down by law enforcement may also have marked compression of the inferior vena cava. If physical restraint must be used, it should be performed with the patient in the supine position when possible; the “hogtied” approach should be avoided at all costs due to an increased association with sudden death. [34, 35] Physical restraints should be used as a bridge to allow for appropriate sedation.

The choice of agent for pharmacologic restraint may be dictated by local prehospital protocols. Whenever possible, however, benzodiazepines should be the first-line agent, as they are effective both intravenously (IV) and intramuscularly (IM), have rapid onset of activity, and do not have the potential for cardiac conduction delays or decreased seizure threshold associated with antipsychotics such as haloperidol or droperidol. IM diazepam (Valium) or midazolam (Versed) have rapid onset of action and should be used in preference to lorazepam (Ativan) if safe IV access is not obtainable. Diazepam is also a good choice if IV access is available, but absorption can be unpredictable by the IM route.

IM ketamine (4-5 mg/kg IM) may be a promising approach for the pre-hospital management of agitated delirium. [36, 37] When used intramuscularly, ketamine has a rapid onset of action, resulting in complete dissociative sedation within 2-5 min, and duration of action of 30-40 minutes, all while preserving respiratory drive. Ketamine is not contraindicated in the setting of head trauma and may, in some instances, be neuroprotective. [38, 39, 40, 41]

Comparison of prehospital ketamine vs haloperidol in agitated delirium has demonstrated more rapid onset of action and less need for re-dosing with ketamine. Adverse effects were more common with ketamine, mostly related to development of emergence reactions. The need for intubation in the ED setting with ketamine use is rarely reported and appears to be related to underlying medical pathology (intracranial hemorrhage, severe acidosis), higher doses (6 mg/kg IM) or repeated doses. [36] To date, no cases of death have been reported with prehospital or ED use of ketamine for sedation. Still, midazolam remains a safer option and is a better choice for initial management of agitated delirium in the prehospital or ED settings.


Emergency Department Care

The general approach to hallucinogen-induced behavioral changes in the emergency department (ED) mirrors the recommendations for the prehospital setting as described above. As the ED is a potentially more controlled setting, fostering a calm and relaxed environment may obviate physical restraint and sedation. When possible, non-agitated patients should be placed in a quiet room with a one-to-one observer if available. Security personnel, physical restraints, and sedating agents should be prepared and readily available if agitation suddenly develops.

All patients should be evaluated for the presence of emergent medical conditions, including traumatic injuries, at the time of arrival. All patients should be placed on cardiac monitoring and have IV access established. Special attention should be paid to the patient’s temperature, as many hallucinogenic agents can induce hyperthermia, which may be life-threatening if not recognized early. An electrocardiogram should be considered as well, especially in the setting of abnormal vital signs, with attention to the QT interval.

Agitated behavior should be met with liberal doses of benzodiazepines. Haloperidol or droperidol may be useful adjuncts to benzodiazepines, but may associated with QT prolongation and torsade de pointes, decreased seizure threshold, or temperature dysregulation. The use of atypical antipsychotics should be avoided, as these agents could potentiate a serotonin syndrome. The use of ketamine in the ED has been shown to be extremely effective for behavioral control, especially to facilitate appropriate medical screening and trauma evaluations in agitated patients, though benzodiazepines are generally a safer option. [42]

Hyperthermia in patients with agitated delirium from a hallucinogen or other xenobiotic is an ominous and life-threatening emergency and should be managed aggressively. Phencyclidine, dextromethorphan, and the novel hallucinogenic agents have various degrees of stimulant qualities, which may produce marked hyperthermia due to temperature dysregulation and diffuse muscle fasciculation. Rapid initiation of cooling measures is mandatory and may require complete paralysis. Patients with extreme agitation should be given adequate hydration and watched closely for the development of rhabdomyolysis.

The above approach may be applied to any type of excited delirium and is not exclusive to hallucinogen-induced behavioral changes. Patients with only minor agitation and adverse sympathomimetic effects can be safely treated in the ED with observation until symptoms have resolved. Patients with minimal or resolving symptoms can be discharged from the hospital safely. Advise these patients to avoid similar exposures and refer them to a behavioral health specialist for substance abuse evaluation. Discharge with medications is not indicated.

Patients with hyperthermia, uncontrolled hypertension, seizures, or any evidence of cardiovascular instability should be admitted to a monitored patient care area. Consider consultation with a toxicologist or regional poison control center.

Obtain a psychiatric evaluation for patients with signs of persistent or severe psychotic behavior. Transfer patients for inpatient psychiatric care if psychiatric symptoms persist.



Management of simple hallucinogen intoxication that resolves without intervention does not require specialty consultation. Patients may benefit from education information regarding drug addiction and local support groups at the time of discharge.

Patients who present with marked agitation, vital sign abnormalities or instability should be managed through a multidisciplinary approach between critical care specialists, medical toxicologists, and the regional poison control center (1-800-222-1222). While the exact agent causing the symptoms may not be known, clinical features and identification of specific toxidromes may help guide specific management.

Transfer patients with significant psychotic manifestations that are unresponsive to therapy, if appropriate behavioral health specialists are not available for evaluation. Exercise caution when transferring patients who demonstrate signs of continued intoxication.