The diagnosis of serotonin toxicity is based on the history and physical examination of the patient. Diagnostic criteria that have been suggested include the following: (1) a recent addition or increase in a known serotonergic agent; (2) absence of other possible etiologies; (3) no recent increase or addition of a neuroleptic agent (suggesting neuroleptic malignant syndrome); and/or (4) at least 3 of the following symptoms—mental status changes, myoclonus, agitation, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination, fever5 (Figure 2).
The above criteria, though still used by many clinicians, have been criticized by others as not being specific enough for serotonin toxicity, particularly with the heavy emphasis on altered mental status. A later study developed a clinical decision rule that showed ocular clonus, spontaneous clonus, inducible clonus, agitation, diaphoresis, tremor, and hyperreflexia were more accurate in predicting serotonin toxicity.6 In summary, it is important for clinicians to be aware that patients with serotonin toxicity may present with a wide range of clinical findings, but the history may be the most important factor.How should this patient be managed?
The management of serotonin toxicity is primarily supportive with aggressive control of hyperthermia and autonomic instability. The precipitating xenobiotic agent should be immediately discontinued. In general, treatment with intravenous fluids, cooling measures, benzodiazepines, and a nonspecific 5-HT antagonist such as cyproheptadine should greatly improve the patient’s clinical status. Patients with severe toxicity may require induced paralysis and intubation.4 It is not clear in this case if the serotonin hyperactivation was due to the DMT (5-HT2A is associated with serotonin toxicity) or another serotonergic agent (eg, dextromethorphan from a cough and cold preparation) in combination with the MAO-inhibiting harmine alkaloids.
What is the availability of ayahuasca in the United States? How is it used in its nonherbal form?
...[Ayahuasca] is currently available in the United States and is legal for use by members of the UDV and Santo Daime churches. Many clinicians are becoming increasingly familiar with this herbal preparation since the recreational use of ayahuasca is gaining popularity in the United States. Internet fora with information on how to safely use ayahuasca, such as avoiding aged cheeses, are becoming more prevalent.7 A recent article in the New York Times described an ayahuasca gathering in Brooklyn, New York, where participants use the herb in a communal fashion.8 This herbal product is also associated with the Hollywood social scene and has received celebrity endorsements.8
The National Survey on Drug Use and Health found that the number of people in the United States who have used DMT has gone up almost every year since 2006, from an estimated 688,000 in 2006 to 1,475,000 in 2012.9 When used alone (not as ayahuasca), DMT is almost exclusively insufflated as a nasal snuff, bypassing hepatic elimination. It has an onset of around 45 seconds and a duration of 5 to 10 minutes. Insufflating DMT was historically referred to as a “businessman’s trip” because users were able to have a brief hallucinogenic experience on a lunch break and recover rapidly to perform their normal work.10
International law declares that DMT is an illegal substance and its importation is banned. However, its use for religious purposes, as is allowed for mescaline found in peyote, remains controversial.7 The UDV brought suit in United States federal court to prevent interference with the church’s use of ayahuasca during religious ceremonies based on the Religious Freedom Restoration Act. This act states that the government should not cause substantial imposition on religious practices in the absence of a compelling government interest. The court sided with the UDV, finding that the government had not sufficiently proved the alleged health risks posed by ayahuasca and could not show a substantial risk that the drug would be abused recreationally.11 Thus it is currently available in the United States and is legal for use by members of the UDV and Santo Daime churches.
Ayahuasca is not regulated by the US Food and Drug Administration. Many different types of preparations with different ingredients as well as different concentrations may exist, and clinical variability should be expected. Understanding that ayahuasca is capable of inhibiting MAO is important in order to avoid foods and medications, such as dextromethorphan, that may trigger adverse effects.
Case Conclusion
The patient’s hospital course was complicated by an additional seizure 12 hours after her initial presentation. By 36 hours she was back to her baseline mental status with a normal neurological examination.
Dr Fil is a senior fellow in medical toxicology at North Shore University Hospital, Manhasset, New York. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.