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HALLUCINOGENIC TRYPTAMINES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Hallucinogenic derivatives of tryptamine have structures and properties in common with ergotamine, LSD (lysergic acid diethylamide), and serotonin (5-hydroxytryptamine). Tryptamine and DMT and its derivatives are naturally occurring compounds; all other agents are synthetic.
    B) This management includes natural occurring hallucinogenic tryptamines; it excludes psilocin (SEE: MUSHROOMS-HALLUCINOGENIC MANAGEMENT) and LSD (SEE the LSD MANAGEMENT). Plant-based tryptamines may contain DMT, N,N-DMT or 5-MeO-DMT and bufotenine. Synthetic tryptamines used to create designer drugs can include: 5-methoxy-N,N-diisopropyltryptamine [5-MeO-DIPT; slang terms: "foxy methoxy" or "foxy"] or alpha methyltryptamine (AMT). Synthetic tryptamines are used primarily as recreational drugs in Europe and the US. In some cultures, the plant-based agents are used in religious ceremonies.

Specific Substances

    1) 3-(2-dimethylaminoethyl) indol-5-ol (synonym)
    2) 4-acetoxy-N,N-dimethyltryptamine (synonym)
    3) 4-acetoxy-DET (synonym)
    4) 4-acetoxy DiPT (synonym)
    5) 4-acetoxy-DMT (synonym)
    6) 4-AcO-DMT (synonym)
    7) 4-hydroxy-aMT (synonym)
    8) 4-hydroxy-DET (synonym)
    9) 4-HO-MET (synonym)
    10) 4-HO MiPT (synonym)
    11) 4-OHaMT (synonym)
    12) 5-MeO-AMT (synonym)
    13) 5-MeO-DALT (synonym)
    14) 5-MeO-DIPT (synonym)
    15) 5-MeO-DiPT (synonym)
    16) 5-MeO-DMT (synonym)
    17) 5-MeO-MIPT (synonym)
    18) 5-MeO-MiPT (synonym)
    19) 5-methoxy-diisopropyltryptamine (synonym)
    20) 5-methoxy-alpha-methyltryptamine (synonym)
    21) 5-methoxy dimethyltryptamine (synonym)
    22) 5-methoxy-DIPT (synonym)
    23) 5-methoxy-N,N-methylisopropyltryptamine (synonym)
    24) 5-methoxy-N,N-dimethyltryptamine (synonym)
    25) 5-methoxy-N,N-diisopropyltryptamine (synonym)
    26) 5-methoxy-N-methyl,N-isopropyl tryptamine (synonym)
    27) 5-(2-aminopropyl)Indole (synonym)
    28) 5-IT
    29) AMT (synonym)
    30) AET (synonym)
    31) DMT (synonym)
    32) DPT (synonym)
    33) aO-DMS (synonym)
    34) alpha ethyltryptamine (synonym)
    35) alpha methyl tryptamine (synonym)
    36) alpha,O dimethylserotonin (synonym)
    37) dimethyltryptamine (synonym)
    38) diethyltryptamine (synonym)
    39) di-isopropyltryptamine (synonym)
    40) dipropyltryptamine (synonym)
    41) Bufotenine (synonym)
    42) Etryptamine (synonym)
    43) DALT (synonym)
    44) DET (synonym)
    45) DiPT (synonym)
    46) DIPT (synonym)
    47) Diisopropyltryptamine (synonym)
    48) Foxy (synonym)
    49) Foxy (5-MeO-DiPT) (synonym)
    50) Foxy Methoxy (synonym)
    51) Foxy Methoxy (5-MeO-DiPT) (synonym)
    52) N,N-diallytryptamine (synonym)
    53) N,N-dipropyltryptamine (synonym)
    54) N,N-dimethyl-tryptamine (synonym)
    55) N,N-diethyltryptamine (synonym)
    56) N,N-diallyltryptamine (synonym)
    57) O-Acetylpsilocin (synonym)
    58) Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) (synonym)
    59) Psilocin (4-hydroxy-N,N-dimetyltryptamine) (synonym)
    60) Tryptamine (synonym)
    61) Ayahuasca Brew (synonym)

Available Forms Sources

    A) FORMS
    1) NATURAL SOURCES
    a) Tryptamine and DMT and its derivatives are naturally occurring compounds. All other agents are synthetic. All compounds are available in pure powder forms. In pure form, these substances are white to grey crystalline powders.
    b) BUFOTENINE
    1) Bufotenine, an indole alkaloid, has been obtained from the seeds and leaves of Piptadenia peregrina, from which hallucinogenic snuff cohoba is made, and P. macrocarpa (Mimosaceae). It is also present in the skin glands and venoms of frogs and toads of the genera Hyla, Letodactylus, Rana, and Bufo and may cause toxicity if these creatures are licked, chewed, or swallowed (Hitt & Ettinger, 1986), and has also been isolated from species of Amanita (Agaricaceae) (S Sweetman , 2001). It has serotonergic activity; no therapeutic use has been reported (S Sweetman , 2001). Classic symptoms of hallucination are generally lacking and are likely related to its poor ability to cross the blood brain barrier (McBride, 2000). A young adult died after injecting bufotenine thought to be Ecstasy (Kostakis & Byard, 2009).
    c) ETRYPTAMINE
    1) Etryptamine, a monoamine oxidase inhibitor, was withdrawn from the US market in March 1962 due to reports of agranulocytosis. Clandestine laboratories are believed to be responsible for the current production of etryptamine (Lora-Tamayo et al, 1989; Morano et al, 1993).
    d) HALLUCINOGENIC MUSHROOMS
    1) Psilocin (4-hydroxy-N,N-dimethyltryptamine) and Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) are active components of Psilocybe hallucinogenic mushrooms. Psilocybin is converted in vivo by dephosphorylation to psilocin, a DMT analogue, with a hydroxyl group substitution on the fourth position of the ring. Clinically, these mushrooms can produce some sympathetic stimulation (ie, tachycardia, hypertension, mydriasis), however, visual hallucinations dominate (SEE: MUSHROOMS-HALLUCINOGENIC for further information) (Hill & Thomas, 2011).
    2) Psilocin and psilocybin are present in a variety of "magic mushrooms" (eg, genera may include: Psilocybe, Gymnopilus, Paneolus, Conocybe, and Strophorius species).
    e) PLANTS
    1) VARIOUS PLANTS
    1) Genus: Acacia (formerly associated to the genera Mimosa); Family: Leguminosae (Subfamily: mimosoidae)
    2) Genus: Anadenanthera; Family: Leguminosae (Legume Family); Mimosoideae Section: Eumimoseae; Species: Colubrina; Peregrina
    3) Genus: Desmanthus; Family: Leguminosae: Mimosaceae-Fabaceae (Mimosa-like); Subfamily: Mimosoideae; Species: Illinoensis; leptolobus; tenuiflora
    4) Genus: Diplopterys (Former: Banisteriopsis); Family: Malpighiaceae; Species: Cabrerana (Former: rusbyana)
    5) Genus: Justicia; Family: Acanthaceae (Acanthus Family); Species: Pectoralis (thought to contain N,N-DMT in the leaves, but not confirmed)
    6) Genus: Mucuna; Family: Fabaceae (Leguminosae); Species: Pruriens
    7) Genus: Phalaris; Family: Gramineae: Poaceae (Grass family); Species: Arundinacea; Aquatica; Tuberosa
    8) Geunus: Phragmites; Family: Gramineae: Poaceae (Grass family); Species: Australis; Synonyms: Arundo phragmites, Arundo vulgaris
    9) Genus: Psychotria; Family: Rubiaceae (Coffee Family); Species: Viridis; (Other species include: Carthaginensis; Poeppigiana)
    10) Genus: Virola; Family: Myristicaceae (Nutmeg Family); Species: Calophylla; Theiodora; (many other virola species may contain DMT)
    a) The following plants can contain, DMT, N,N-DMT, 5-MeO-DMT, or bufotenine in the seeds, leaves, root or the entire plant (Halpern, 2004; Ratsch, 1998; Long et al, 2003). They may be smoked, insufflated, or used as snuff. Some of these plants have been combined with other plants which act as MAO inhibitors to activate and prolong the effects of DMT (ie, the drink is often referred to as "Ayahuasca brews" or "Ayahuasca analogs" and traditionally was part of religious ceremonies (SEE below)) (Ratsch, 1998).
    b) AYAHUASCA BREW
    1) SUMMARY: These plants do NOT contain tryptamines, but may be combined with a tryptamine (eg, N,N-DMT, 5-MeO-DMT). These plants have been found to act as potent MAO inhibitors and can allow both endogenous and external tryptamines to pass across the blood brain barrier rather than being broken down (Ratsch, 1998):
    1) Genus: Banisteriopsis; Family: Malpighiaceae; Species: Caapi, inebriens
    2) Genus: Peganum; Family: Zygophyllaceae; Species: Harmala
    2) BANISTERIOPSIS: This plant is known to contain alkaloids of the beta-carboline type (primary alkaloids include: harmine, harmaline and tetrahydroharmine). The vine is a potent MAO inhibitor. If used alone, the vine can produce mood enhancing and sedative qualities. It has been used in South America for Ayahuasca brews to treat various conditions and diseases. These drinks are sometimes referred to as "yage" or "yaje". Ayahausca is created by using psychotria viridis (the psychoactive compound found in this plant is DMT) and B. caapi that allows DMT to become orally active (Ratsch, 1998).
    3) PEGANUM: The seeds reportedly have an antidepressant effect and may stimulate the imagination. The alkaloids and the extract of the seeds act as MAO inhibitors, that make it possible for certain substances (eg, N,N-DMT, 5-MeO-DMT, beta-phenethylamines) to be orally efficacious by preventing their breakdown by intestinal MAO (Ratsch, 1998).
    2) SNUFF
    a) Anadenanthera snuff is known as "Cohaba" and "Yopo" in the West Indies and northern South American.
    b) Virola snuff is known as "Yakee" and "Yato" in Columbia and "Parica", "Epena", and "Nyakwana" in Brazil.
    2) SYNTHETIC TRYPTAMINES
    a) SIMPLE UNSUBSTITUTED SYNTHETIC TRYPTAMINES
    1) DMT (dimethyltryptamine)
    2) AET (alpha ethyltryptamine)
    3) AMT (alpha methylated tryptamine or alpha methyltryptamine)
    4) DALT (N,N-diallyltryptamine)
    5) DET (diethyltryptamine)
    6) DiPT (di-isopropyltryptamine)
    7) DPT (dipropyltryptamine)
    1) There is minimal information on synthetic tryptamines. Simple tryptamines produce stimulant effects at lower doses and visual hallucinations at higher doses (Hill & Thomas, 2011).
    2) AMT and alpha ethyltryptamine (AET) have both stimulant and hallucinogenic effects. AMT is active after oral ingestion because the alpha methyl group protects form monamine oxidase (MAO) degradation (Hill & Thomas, 2011). It was investigated in the 1960's as an antidepressant, stimulant, and monamine oxidase inhibitor (Boland et al, 2005).
    3) DMT: Most of the information related to these agents has been associated with the natural source of DMT, a ring-unsubstituted tryptamine which has 2 methyl groups added to the amino group. It is not active after oral ingestion due to extensive first pass metabolism likely due to rapid action of MAO. Therefore, it is commonly used by other routes (ie, insufflation, inhalation, intramuscular or intravenous routes) or drinking an Ayahuascan brew which contains DMT and an MAO inhibitor (eg, Banisteriopsis caapi or Peganum harmala) (Hill & Thomas, 2011).
    4) OTHER: DALT, DET, DiPT and DPT are all active after ingestion with the primary effect being serotonin-mediated visual hallucinations (Hill & Thomas, 2011).
    5) 5-(2-aminopropyl) Indole (5-IT) is a an indole derivative and a positional isomer of alpha-methyltryptamine (AMT). For this chemical, the indole ring is substituted at the 5' positional, instead of the 3' position for the tryptamine. It is not a true tryptamine, and acts as a stimulant rather than a psychedelic agent. The estimated dose reported is between 20 and 100 mg by ingestion or snorting. In Sweden, several deaths have been associated with 5-IT with 2 deaths attributable to 5-IT alone (Kronstrand et al, 1997).
    6) The following are a list of simple unsubstituted synthetic tryptamines (Hill & Thomas, 2011):
    b) 4-SUBSTITUTED TRYPTAMINES
    1) 4-HO-DET (4-hydroxy-N,N-diethyltryptamine)
    2) 4-HO-DiPT (4-hydroxy-N,N-diisopropyltryptamine)
    3) 4-HO-MiPT (4-hydroxy-N-isopropyl,N-methyltryptamine)
    4) 4-acetoxy-DiPT (4-acetoxy-N,N-disopropyltryptamine) [acetic acid derivative]
    5) 4-acetoxy-DET (4-acetoxy-N,N-diethyltryptamine) [acetic acid derivative]
    1) The following are designer synthetic 4-substituted tryptamines, which have similar actions to psilocin (natural source found in hallucinogenic mushrooms) as reported by users. However, there is limited clinical information on these drugs (Hill & Thomas, 2011):
    c) 5-SUBSTITUTED TRYPTAMINES
    1) 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine)
    2) 5-MeO-AMT (5-methoxy-alpha-methyltryptamine)
    3) 5-MeO-DiPT (5-methoxy-N,N-diisopropyltryptamine)
    4) 5-MeO-MIPT (5-methoxy-N,N-methylisopropyltryptamine)
    5) 5-MeO-DALT (5-methoxy-N,N-diallytryptamine)
    1) The addition of a methoxy (or hydroxyl) group at position 5 of the tryptamine ring can produce similar clinical effects, but these substances appear to be more potent than the unsubstituted molecule. These agents can inhibit monoamine reuptake by having limited effects on monoamine release (Hill & Thomas, 2011). Some of these agents are chemically related to Ecstasy (Wilson et al, 2005; Shimizu et al, 2007).
    2) FOXY: 5-MeO-DIPT, a club drug, can be taken orally (available in capsules and tablets) because it is not affected by monamine oxygenase degradation (Meatherall & Sharma, 2003; Wilson et al, 2005).
    3) MOXY or MOXIE: 5-MeO-MIPT is available as a powder and has been purchased over the internet. Purportedly, it has a similar structure and pharmacokinetics as 5-MeO-DIPT (Shimizu et al, 2007).
    4) CONTROLLED SUBSTANCE: 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) and its isomers have been added as a Schedule I agent of the Controlled Substance Act as of January 2011. This chemical is related to other Schedule 1 hallucinogens (ie, N,N-dimethyltryptamine (DMT), 2,5-dimethoxy-4-methylamphetamine (DOM), lysergic acid diethylamide (LSD) and mescaline) based on its pharmacologic and hallucinogenic effects. It is reportedly 4- to 5-fold more potent than DMT when taken by the oral, sublingual, or inhalation routes (Drug Enforcement Administration, 2011).
    d) REPRESENTATIVE HALLUCINOGENIC INDOLEALKYLAMINE
    1) 4-OHaMT (4-hydoxy-aMT)
    2) 4-OH-DMT (4-hydroxy-DMT) (psilocin)
    3) 4-PO-DMT (4-phosphoryloxy-DMT) (psilocybin)
    4) 4-OH-DET (4-hydroxy-DET)
    5) 4-OH-DIPT (4-hydroxy-DIPT)
    6) 5-OMe-aMT (5-methoxy-aMT)
    7) 5 F-aMT (5-fluoro-aMT)
    8) 5-OH-DMT (5-hydroxy-DMT) (bufotenine)
    9) 5-OMe-DMT (5-methoxy-DMT)
    10) 5-OMe-DIPT (5-methoxy-DIPT)
    11) AMT (alpha-methyltryptamine)
    12) aO-DMS (alpha,O dimethylserotonin or 5-methoxy-alpha-methyltryptamine)
    13) Bufotenine (3-(2-dimethylaminoethyl) indol-5-ol
    14) DAT (N,N-diallyltryptamine)
    15) DET (N,N-diethyltryptamine)
    16) DIPT (Diisopropyltryptamine)
    17) DMT (N,N-dimethyltryptamine)
    18) DPT (N,N-dipropyltryptamine)
    19) ET (etryptamine)
    20) IPMT (N-isopropyl, N-methyltryptamine)
    21) T (tryptamine)
    B) USES
    1) SUMMARY
    a) Natural tryptamines are produced from tryptophan, an amino acid, by different biosynthetic (ie, serotonin, melatonin) pathways. These agents have been used for their hallucinogenic effects (ie, psilocybin [mushrooms] and dimethyltryptamine (DMT) in Ayahuasca brews). Tryptamines have an indole ring structure. It contains a bicyclical combination of a benzene ring and pyrrole ring, that is joined to an amino group by a 2 carbon side chain. Designer drugs are produced by substitutions at the amino group, side chain and aromatic ring. For designer tryptamines, substitutions usually occur at positions 4 or 5 to create the optimal amount of hallucinogenic activity (Hill & Thomas, 2011).
    1) For recreational purposes, DMT is smoked, snorted or injected and results in a rapid onset with a duration of action of 30 to 120 minutes. Because of its very quick onset and offset of hallucinogenic effects, it is called "businessman's trip". Both DMT and 5-MeO-DMT are rapidly metabolized by intestinal monoamine oxidase, so not well suited for oral ingestion (Halpern, 2004).
    2) Hallucinogenic effects are related to structural similarities between tryptamines and serotonin (5-hydroxytryptamine, 5-HT) and between phenethylamines and dopamine (Vorce & Sklerov, 2004). Tryptamine-induced hallucinations are due to 5HT2a agonism and partly mediated by agonism at 5HT1a receptors. Enactogenic or stimulant properties are not usually associated with these agents. However, the alpha methylated tryptamines (ie, AMT and 5-MeO-AMT) have stimulant activity due to the presence of an alpha carbon methyl group (similar to amphetamine) (Hill & Thomas, 2011).
    a) Hallucinogenic tryptamine derivatives are primarily used as drugs of abuse in the US and Europe. Many of the newer designer drugs may be incorrectly marketed as Ecstasy (Vorce & Sklerov, 2004). In some cultures, plant-based tryptamines have been used in religious ceremonies (Ratsch, 1998). Toxicity can be severe; fatalities have been reported in some cases (Boland et al, 2005). Exposure may occur via ingestion, mucosal application (mouth, nose, rectum, vagina), parenteral injection or inhalation, depending on the substance.
    3) In most cases, hallucinogenic tryptamines do not cause life-threatening (ie, cardiac, renal or hepatic) adverse events, but have been associated with life-threatening and sometimes fatal behavioral disturbances (ie, severe agitation leading to self-inflicted injuries). Some agents such as AMT (or 5-MeO-AMT) and 5-MeO-DIPT have been associated with deaths (Hill & Thomas, 2011; Tanaka et al, 2006). (Long et al, 2003).
    2) AYAHUASCA BREW
    a) SUMMARY: Ayahausca was traditionally drank at religious ceremonies and used for its hallucinogenic properties. The "brew" combines a plant that contains DMT (eg, psychotria viridis) with Banisteriopsis caapi or Peganum harmala (Syrian Rue), which are potent MAO inhibitors, which allows DMT to become orally active (because it is not metabolized by intestinal MAO). This combination also prolongs the duration of action (Ratsch, 1998; Brush et al, 2004).
    b) The combination of Banisteriopsis and Psychotria (leaves) have also been referred to as Yaje, Caapi, Lage, hoasca or daime in shaman rituals (Brush et al, 2004).
    c) Mimosa hostilis roots are used to make a hallucinogenic drink known as Ajuca and Vinho de Jurema in eastern Brazil.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Hallucinogens are a diverse group of substances that alter perception, thought and mood. In the west, they are used primarily as drugs of abuse. In some cultures they are used in religious ceremonies and traditional healing.
    B) EPIDEMIOLOGY: Poisoning is not common, but may be severe. Exposure may occur via ingestion, mucosal application (mouth, nose, rectum, vagina), parenteral injection, or inhalation, depending on the substance.
    C) TOXICOLOGY: Hallucinogens can be broken down into groups according to their chemical structure. One of the major classes of hallucinogens is the tryptamines, otherwise known as indoalkylamines. All substances in this class are composed of a substituted monoamine group. They may occur endogenously (eg, serotonin, melatonin), in the natural environment (eg, psilocybin {in "magic mushrooms"}, bufotenin {secretion from bufo toads}, 5 methoxydimethyl tryptamine {5-MeO-DMT, secretion from bufo toads}, dimethyltryptamine {DMT, from the bark of the Yakee plant}), or be synthetic (N,N-diisopropyl-5-methoxytryptamine {5-MeO-DiPT, also known as foxy methoxy}, alpha-methyltryptamine {AMT}). These compounds appear to act primarily by stimulating serotonin type 2 (5HT2) receptors. Some compounds are partial 5HT receptor agonists, or mixed agonists-antagonists. Stimulation of dopaminergic and tryptaminergic receptors and inhibition of monoamine oxidase appear to have a minor role in their pharmacologic activity. The pyrrole portion of the indole ring appears to be essential for hallucinogenic activity. Toad secretions may also contain cardioselective steroids, or bufadienolides. Some toad species may also secrete tetrodotoxin. The ingestion of either of these may lead to death. Street drugs may be adulterated by PCP, strychnine or other agents.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE POISONING: All of tryptamines have the potential to cause either pleasant or frightening hallucinations and unpredictable behavior. Nausea, vomiting, anorexia, dizziness, paresthesias, anxiety, mood alterations, time distortion, confusion, hyperreflexia, ataxia, weakness, dysesthesias, drowsiness, enhanced color awareness, and unpleasant retinal activity may occur. 5-MeO-DiPT can cause mydriasis, euphoria, nausea, diarrhea and jaw clenching.
    2) SEVERE POISONING: May manifest as severe anxiety and possibly agitation, leading to hypertension, sinus tachycardia, rhabdomyolysis, and hyperthermia. Death may also be secondary to behavioral effects.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Diaphoresis, pallor, and piloerection can develop.

Laboratory Monitoring

    A) Monitor vital signs, including core temperature, and mental status. Severe hyperthermia is a marker of severe toxicity and requires aggressive treatment.
    B) Monitor serum electrolytes, liver enzymes, renal function and urinalysis. Monitor creatine kinase in patients with prolonged agitation. Assess for myoglobinuria and/or hemoglobinuria following a significant exposure.
    C) Obtain an ECG and institute continuous cardiac monitoring.
    D) Plasma concentrations are not clinically useful or readily available.
    E) A standard urine toxicology screen will generally not detect hallucinogenic tryptamines.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Patients may present with a panic reaction from a "bad trip". These patients require reassurance. Benzodiazepines may be helpful in calming these patients. Mildly intoxicated patients may benefit from quiet, dark rooms with minimal stimulation. Reassure the patient that the effects are drug related and will eventually wear off.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) The goal of treatment is to manage agitation and prevent end-organ damage. Orotracheal intubation for airway protection should be performed early. Consider activated charcoal in large, recent overdoses of an orally ingested drug if the patients is cooperative (GI decontamination should be performed only in patients who can protect their airway or who are intubated). Delirium may develop and require large doses of benzodiazepines for sedation. Antipsychotics may be used as an adjunct treatment for agitation. Monitor core temperature and treat hyperthermia with aggressive benzodiazepine sedation to control agitation, and external cooling. Hypertension and sinus tachycardia usually respond well to sedation. If a patient exhibits evidence of cardiac toxicity due to bufadienolide poisoning from Bufo toad secretions, treat symptomatically and supportively, treat with digoxin-specific Fab fragments and/or cardiac pacing if needed (See: Toad Toxins management as indicated).
    C) DECONTAMINATION
    1) PREHOSPITAL: GI decontamination is usually not recommended since rapid deterioration may occur, and potential for coma, seizures, and aspiration exists.
    2) HOSPITAL: Administer activated charcoal if recent, substantial oral ingestion, and the patient is cooperative and able to protect airway.
    D) AIRWAY MANAGEMENT
    1) Perform early in patients with severe intoxication (eg, seizures, dysrhythmias, severe delirium or hyperthermia).
    E) ANTIDOTE
    1) There is no specific antidote for hallucinogenic amphetamines. Care is symptomatic and supportive. If a patient has evidence of cardioactive steroid toxicity after Bufo toad secretion ingestion or inhalation, treat with digoxin-specific Fab.
    F) HYPERTHERMIA
    1) Severe hyperthermia can be life threatening and must be treated aggressively. Control agitation with benzodiazepines, large doses may be needed. Initiate aggressive external cooling measures; undress the patient, keep skin moist and direct fans at the skin. Ice water immersion may be used in severe cases. If needed, intubate, sedate and paralyze.
    G) DELIRIUM
    1) Minimize external stimuli; place in quiet, dark room. Sedate patient with benzodiazepines as necessary, large doses may be required. Consider antipsychotics in patients not responsive to high doses of benzodiazepines.
    H) RHABDOMYOLYSIS
    1) Administer sufficient 0.9% saline to maintain urine output of 2 to 3 mL/kg/hr. Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output. Urinary alkalinization is NOT routinely recommended.
    I) VOMITING
    1) Treat symptomatically and supportively with IV fluids and antiemetics.
    J) ENHANCED ELIMINATION
    1) Hemodialysis and hemoperfusion are not of value.
    K) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic adults may be monitored at home, but may need referral for substance abuse counseling.
    2) OBSERVATION CRITERIA: Patients with deliberate self-harm ingestions or children with any ingestion, and symptomatic patients should be sent to a health care facility for observation for 6 to 8 hours.
    3) ADMISSION CRITERIA: Patients with significant persistent central nervous system toxicity (eg, hallucinations, delirium, coma), cardiovascular toxicity (tachycardia, hypertension), or with dysrhythmias after ingesting Bufo toad secretions should be admitted.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (eg, dysrhythmias, severe delirium), or in whom the diagnosis is not clear. Refer for substance abuse counseling
    L) PITFALLS
    1) Failure to rapidly control agitation and manage hyperthermia and seizures can result in death and irreversible end-organ damage. Patients with altered mentation should be ruled out for intracranial hemorrhage, infection, metabolic disturbances and hyponatremia.
    M) TOXICOKINETICS
    1) For recreational purposes, DMT is smoked, snorted or injected and results in a rapid onset with a duration of action of 30 to 120 minutes. Because of its very quick onset and offset of hallucinogenic effects, it is called "businessman's trip". Both DMT and 5-MeO-DMT are rapidly metabolized by intestinal monoamine oxidase, so not well suited for oral ingestion. 5-MeO-DMT is rapidly absorbed with an onset of 20 minutes, peak effect of 1 to 6 hours, and a duration of 18 to 24 hours. 5-MeO-DiPT may be orally ingested, smoked or snorted. Low doses produce relaxation, while higher doses produce hallucinogenic effects similar to those of LSD. Onset of effect is 20 to 30 minutes with a peak effect of 60 to 90 minutes, and a duration of 3 to 6 hours. AMT is either ingested, smoked or insufflated. Duration of action is 12 to 16 hours.
    N) DIFFERENTIAL DIAGNOSIS
    1) Hypoglycemia, central nervous system infection, other hallucinogen poisoning (ie, LSD or MDMA), sympathomimetic poisoning (cocaine, methamphetamine), mental illness presenting with mania, anxiety or hallucinations.

Range Of Toxicity

    A) TOXICITY: Toxic doses are difficult to determine, in part due to the difficulty of accurately assessing a dose from a synthetic, illicitly produced drug, or substances derived from natural resources. Patients who develop severe hyperthermia usually develop multiorgan toxicity and often die without aggressive treatment. Alpha-methyltryptamine (AMT) 5 mg to 10 mg may have a mood lifting effect. Euphoria occurs following doses greater than 20 mg. AMT doses greater than 30 mg can cause hallucinations, anxiety, muscle tightness, vomiting, and hyperthermia.
    B) FATALITIES: Fatalities have been reported following exposure to select synthetic "designer" tryptamines including AMT, bufotenine, 5-MeO-DIPT ("foxy"), and etryptamine.
    C) SURVIVAL: A 17-year-old boy developed tachycardia, diaphoresis, agitation, and hallucinations after the ingestion of 100 mg of alpha-methyltryptamine. A man developed status epilepticus after ingesting approximately 200 mg of 5-MeO-DMT.

Clinical Effects

Summary Of Exposure

    A) USES: Hallucinogens are a diverse group of substances that alter perception, thought and mood. In the west, they are used primarily as drugs of abuse. In some cultures they are used in religious ceremonies and traditional healing.
    B) EPIDEMIOLOGY: Poisoning is not common, but may be severe. Exposure may occur via ingestion, mucosal application (mouth, nose, rectum, vagina), parenteral injection, or inhalation, depending on the substance.
    C) TOXICOLOGY: Hallucinogens can be broken down into groups according to their chemical structure. One of the major classes of hallucinogens is the tryptamines, otherwise known as indoalkylamines. All substances in this class are composed of a substituted monoamine group. They may occur endogenously (eg, serotonin, melatonin), in the natural environment (eg, psilocybin {in "magic mushrooms"}, bufotenin {secretion from bufo toads}, 5 methoxydimethyl tryptamine {5-MeO-DMT, secretion from bufo toads}, dimethyltryptamine {DMT, from the bark of the Yakee plant}), or be synthetic (N,N-diisopropyl-5-methoxytryptamine {5-MeO-DiPT, also known as foxy methoxy}, alpha-methyltryptamine {AMT}). These compounds appear to act primarily by stimulating serotonin type 2 (5HT2) receptors. Some compounds are partial 5HT receptor agonists, or mixed agonists-antagonists. Stimulation of dopaminergic and tryptaminergic receptors and inhibition of monoamine oxidase appear to have a minor role in their pharmacologic activity. The pyrrole portion of the indole ring appears to be essential for hallucinogenic activity. Toad secretions may also contain cardioselective steroids, or bufadienolides. Some toad species may also secrete tetrodotoxin. The ingestion of either of these may lead to death. Street drugs may be adulterated by PCP, strychnine or other agents.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE POISONING: All of tryptamines have the potential to cause either pleasant or frightening hallucinations and unpredictable behavior. Nausea, vomiting, anorexia, dizziness, paresthesias, anxiety, mood alterations, time distortion, confusion, hyperreflexia, ataxia, weakness, dysesthesias, drowsiness, enhanced color awareness, and unpleasant retinal activity may occur. 5-MeO-DiPT can cause mydriasis, euphoria, nausea, diarrhea and jaw clenching.
    2) SEVERE POISONING: May manifest as severe anxiety and possibly agitation, leading to hypertension, sinus tachycardia, rhabdomyolysis, and hyperthermia. Death may also be secondary to behavioral effects.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Mild increases in body temperature have been reported (Nyman et al, 2002). Severe hyperthermia (greater than 105 F) has been reported in a patient with severe psychomotor agitation following a significant exposure (Brush et al, 2004).
    2) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Fever/abnormal sweating developed in 11 of 55 patients after use of AMT compared with 33 of 488 patients after use of mephedrone (Kamour et al, 2014).
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) Mild hypertension is common. A 19-year-old man experienced hypertension (BP 191/102 mm Hg), as well as tachycardia, catalepsy and hallucinations after ingesting a "larger than normal" amount of Foxy Methoxy (5-MeO-DIPT) (Smolinske et al, 2005).
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) Mild tachycardia is common. A 19-year-old man experienced tachycardia (138 beats/min), as well as hypertension, catalepsy and hallucinations after ingesting a "larger than normal" amount of Foxy Methoxy (5-MeO-DIPT) (Smolinske et al, 2005). There have also been cases of severe tachycardia 160 beats/min or more) following 5-MeO-DMT and AMT use in 2 young adults (Brush et al, 2004; Long et al, 2003).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) MYDRIASIS is characteristic. Patients may also complain of blurred vision (Smolinske et al, 2005).
    2) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Mydriasis developed in 15 of 55 patients after use of AMT compared with 26 of 488 patients after use of mephedrone (Kamour et al, 2014).
    3) BUFOTENINE: Visual disturbances were reported after intravenous administration of bufotenine; symptoms ceased with drug cessation (McBride, 2000).
    3.4.4) EARS
    A) WITH POISONING/EXPOSURE
    1) HYPERACUSIS has been reported.
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) SALIVATION may be observed.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypertension is frequent but mild and rarely requires treatment.
    b) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Hypertension developed in 2 of 55 patients after use of AMT compared with 17 of 488 patients after use of mephedrone (Kamour et al, 2014).
    c) CASE REPORT: A 19-year-old man was brought into the ED by his girlfriend after ingesting a "larger than normal" amount of Foxy Methoxy (5-MeO-DIPT). He presented with catalepsy, hallucinations, hypertension (BP 191/102 mm Hg) and tachycardia (138 beats/min). A toxicology screen was positive for cocaine and phencyclidine; however, the patient denied the use of cocaine. Following supportive care, he made a full recovery within a few hours (Smolinske et al, 2005).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Hypotension developed in 4 of 55 patients after use of AMT compared with 3 of 488 patients after use of mephedrone (Kamour et al, 2014).
    C) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia (sinus) is frequent, but mild and rarely requires treatment.
    b) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Tachycardia developed in 24 of 55 patients after use of AMT compared with 98 of 488 patients after use of mephedrone (Kamour et al, 2014).
    c) CASE REPORT: A 17-year-old boy developed tachycardia (160 beats/min), diaphoresis, agitation and hallucinations after ingesting 100 mg of alpha-methyltryptamine (AMT) (Long et al, 2003).
    d) CASE REPORT: A 19-year-old man was brought into the ED by his girlfriend after ingesting a "larger than normal" amount of Foxy Methoxy (5-MeO-DIPT). He presented with catalepsy, hallucinations, hypertension (BP 191/102 mm Hg) and tachycardia (138 beats/min). A toxicology screen was positive for cocaine and phencyclidine; however, the patient denied the use of cocaine. Following supportive care, he made a full recovery within a few hours (Smolinske et al, 2005).
    D) CARDIAC ARREST
    1) WITH POISONING/EXPOSURE
    a) ETRYPTAMINE: CASE REPORT: One case of cardiopulmonary arrest occurred in a 19-year-old woman following the ingestion of 2 'dime' sized doses of white powder containing etryptamine and trace amounts of methamphetamine and amphetamine (Morano et al, 1993).
    b) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Cardiac arrest developed in 1 of 55 patients after use of AMT compared with 4 of 488 patients after use of mephedrone (Kamour et al, 2014).
    E) CARDIOVASCULAR FINDING
    1) WITH POISONING/EXPOSURE
    a) BUFOTENINE: In human experimentation with bufotenine, physiologic effects reported with intravenous administration included cardiovascular effects which included a complaint of "heaviness in the chest" and purpling of the head and neck. The effects quickly resolved with drug cessation (McBride, 2000).
    F) PALPITATIONS
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Palpitations developed in 1 of 55 patients after use of AMT compared with 49 of 488 patients after use of mephedrone (Kamour et al, 2014).
    G) CHEST PAIN
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Chest pain developed in 3 of 55 patients after use of AMT compared with 61 of 488 patients after use of mephedrone (Kamour et al, 2014).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) HYPERVENTILATION
    1) WITH POISONING/EXPOSURE
    a) Mild tachypnea is frequently noted.
    B) TACHYPNEA
    1) WITH POISONING/EXPOSURE
    a) BUFOTENINE: In human experimentation with bufotenine, tachypnea was reported with intravenous administration, which stopped quickly with drug cessation (McBride, 2000).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) Confusion, drowsiness, and weakness develop frequently, but the symptoms are mild. However, confusion may be significant in some patients (Shimizu et al, 2007).
    b) Anorexia, agitation, dizziness, ataxia, hyperreflexia, paresthesias, dysesthesias, tremors, muscle twitching, and decreased REM sleep have also been reported.
    c) CASE REPORT: One adult developed severe psychomotor agitation and confusion after ingesting a combination product containing methylone (2-methylamino-1-[3,4-methylenedioxyphenyl]propan-1-one) hallucinogenic amphetamine) and 5-MeO-MIPT ("Moxy") (Shimizu et al, 2007).
    d) CASE REPORT: A 19-year-old man was brought into the emergency department by his girlfriend after ingesting a "larger than normal" amount of Foxy Methoxy (5-MeO-DIPT). He presented with catalepsy, hallucinations, hypertension (BP 191/102 mm Hg) and tachycardia (138 beats/min). A toxicology screen was positive for cocaine and phencyclidine; however, the patient denied the use of cocaine. Following supportive care, he made a full recovery within a few hours (Smolinske et al, 2005).
    e) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Acute mental health disturbance developed in 36 of 55 patients after use of AMT compared with 157 of 488 patients after use of mephedrone (Kamour et al, 2014).
    B) LOSS OF CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Reduced level of consciousness developed in 8 of 55 patients after use of AMT compared with 32 of 488 patients after use of mephedrone (Kamour et al, 2014).
    C) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: An 18-year-old man developed status epilepticus after ingesting approximately 200 mg of 5-MeO-DMT (Nyman et al, 2002).
    b) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Seizures developed in 9 of 55 patients after use of AMT compared with 10 of 488 patients after use of mephedrone (Kamour et al, 2014).
    D) DECREASED MUSCLE TONE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: An 18-year-old man developed muscular hypotonia and weakness (ie, found lying on the ground and unable to get up) after ingesting approximately 200 mg 5-MeO-DMT (Nyman et al, 2002).
    E) PSYCHOMOTOR AGITATION
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of the recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using the reports obtained from the United Kingdom National Poisons Information Service. Agitation/aggression developed in 21 of the 55 patients after using AMT compared with 90 of the 488 patients after using mephedrone (Kamour et al, 2014).
    b) CASE REPORT: A 27-year-old man ingested 200 mg of a powder purchased on the internet and found to contain methylone (120 mg; hallucinogenic amphetamine) and 5-MeO-MIPT ["Moxy"] (76 mg). He developed severe psychomotor agitation, episodes of shouting and confusion about 30 minutes after ingestion, which improved after a single oral dose of risperidone (4 mg). The patient became coherent and was monitored overnight. A toxicology screen was negative. Upon follow-up at 2 weeks, the patient was asymptomatic, but had no recall of the episode (Shimizu et al, 2007).
    F) TREMOR
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Tremor developed in 2 of 55 patients after use of AMT compared with 14 of 488 patients after use of mephedrone (Kamour et al, 2014).
    G) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Confusion developed in 6 of 55 patients after use of AMT compared with 12 of 488 patients after use of mephedrone (Kamour et al, 2014).
    H) MOVEMENT DISORDER
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Movements disorders (eg, dystonia, athetosis) developed in 1 of 55 patients after use of AMT compared with 7 of 488 patients after use of mephedrone. Abnormal muscle contractions developed in 3 of 55 patients after using AMT compared with 12 of 488 patients after use of mephedrone (Kamour et al, 2014).
    I) INSOMNIA
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Insomnia developed in 1 of 55 patients after use of AMT compared with 17 of 488 patients after use of mephedrone (Kamour et al, 2014).
    J) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Headache developed in 1 of 55 patients after use of AMT compared with 16 of 488 patients after use of mephedrone (Kamour et al, 2014).
    K) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Dizziness developed in 2 of 55 patients after use of AMT compared with 27 of 488 patients after use of mephedrone (Kamour et al, 2014).
    L) MALAISE
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Malaise developed in 1 of 55 patients after use of AMT compared with 22 of 488 patients after use of mephedrone (Kamour et al, 2014).
    M) DISTURBANCE IN SPEECH
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Speech disorders developed in 1 of 55 patients after use of AMT compared with 5 of 488 patients after use of mephedrone (Kamour et al, 2014).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea is common. Vomiting may also be seen.
    b) BUFOTENINE: In human experimentation with bufotenine, adverse effects included nausea, vomiting and retching following intravenous administration. The effects quickly stopped with drug cessation (McBride, 2000).
    c) ALPHA-METHYLTRYPTAMINE: In a retrospective study of 15 alpha-methyltryptamine (AMT) users, one patient developed vomiting 45 minutes after using AMT (dose: 30 to 52 mg) and 30 minutes before developing hallucinations (Wilcox, 2012).
    B) GASTROINTESTINAL IRRITATION
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Gastrointestinal upset developed in 11 of 55 patients after use of AMT compared with 68 of 488 patients after use of mephedrone (Kamour et al, 2014).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Acute renal failure secondary to rhabdomyolysis has been reported in several adults with a history of chronic hallucinogenic tryptamine (5-MeO-DIPT or 5-MeO-DMT) use and improved with IV hydration (Kuwahara et al, 2008; Alatrash et al, 2006; Brush et al, 2004). However, one patient required hemodialysis with continuous hemodiafiltration (Kuwahara et al, 2008).
    b) CASE REPORT: A 23-year-old man developed rhabdomyolysis, transient nonoliguric acute renal failure, and elevated anion gap metabolic acidosis after ingesting 25 mg of 5-MeO-DIPT ("Foxy"). Signs and symptoms included agitation, hallucinations, dark red urine, and an elevated anion gap metabolic acidosis (anion gap, 44 mmol/L [10 to 20 mmol/L]). At the time of admission, serum creatinine concentration was 1.7 mg/dL (0.9 to 1.4 mg/dL) and an urinalysis was positive for heme pigment. Peak CK was 38,855 unitls/L and peak myoglobin was 13,415 mg/L. A toxicology screen was negative for other agents. Clinically, the patient improved with aggressive hydration and alkaline diuresis (Alatrash et al, 2006).
    c) CASE REPORT: A 28-year-old HIV infected man with a 2-year history of 5-MeO-DIPT use developed unconsciousness on the day of admission after an episode of use. Initially, the patient had acidosis, acute renal failure, rhabdomyolysis, elevated myoglobin, and increased liver enzymes. The patient was started on hemodialysis with continuous hemodiafiltration. By day 3 , the patient was diagnosed with neuroleptic malignant syndrome and dantrolene was administered. The patient continued to improve and was discharged, but impairments in memory, speech and fine motor movement were still present 3 years later (Kuwahara et al, 2008).
    B) MYOGLOBINURIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 23-year-old man developed rhabdomyolysis, transient nonoliguric acute renal failure, and elevated anion gap metabolic acidosis after ingesting 25 mg of 5-MeO-DIPT ("Foxy"). Signs and symptoms included agitation, hallucinations, dark red urine, and an elevated anion gap metabolic acidosis (anion gap, 44 mmol/L [10 to 20 mmol/L]). Creatine kinase concentration peaked at 38,855 Units/L (30 to 220 Units/L) and myoglobin concentration peaked at 13,415 mg/L (0 to 110 mg/L). Urinalysis was positive for heme pigment. A toxicology screen was negative for other agents. Clinically, the patient improved with aggressive hydration and alkaline diuresis; at the time of discharge serum creatinine and creatine kinase concentrations were 0.9 mg/dL and 233 Units/L, respectively (Alatrash et al, 2006).
    C) RENAL IMPAIRMENT
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Renal impairment developed in 2 of 55 patients after use of AMT compared with 5 of 488 patients after use of mephedrone (Kamour et al, 2014).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) METABOLIC ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Metabolic acidosis developed in 4 of 55 patients after use of AMT compared with 12 of 488 patients after use of mephedrone (Kamour et al, 2014).
    b) CASE REPORT: A 23-year-old man developed rhabdomyolysis, transient nonoliguric acute renal failure, and elevated anion gap metabolic acidosis after ingesting 25 mg of 5-MeO-DIPT ("Foxy"). Signs and symptoms included agitation, hallucinations, dark red urine, and an elevated anion gap metabolic acidosis (anion gap, 44 mmol/L [10 to 20 mmol/L]) and a serum bicarbonate level of 9 mmol/L (22 to 30 mmol/L). A toxicology screen was negative for other agents. Clinically, the patient improved with aggressive hydration and alkaline diuresis (Alatrash et al, 2006).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Diaphoresis, pallor, and piloerection can develop.
    3.14.2) CLINICAL EFFECTS
    A) PILOERECTION
    1) WITH POISONING/EXPOSURE
    a) Piloerection is common.
    B) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Diaphoresis and pallor can develop (Nyman et al, 2002).
    b) CASE REPORT: A 17-year-old boy developed tachycardia (160 beats/min), diaphoresis, agitation and hallucinations after ingesting 100 mg of alpha-methyltryptamine (AMT) (Long et al, 2003).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) SPASMODIC MOVEMENT
    1) WITH POISONING/EXPOSURE
    a) Mild tremors, muscle twitching, and increased physical activity are common.
    B) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) SUMMARY
    1) Rhabdomyolysis secondary to psychomotor agitation has been observed in several adults with a history of acute on chronic hallucinogenic tryptamine (5-MeO-DIPT or 5-MeO-DMT) use (Kuwahara et al, 2008; Alatrash et al, 2006; Brush et al, 2004).
    b) CASE REPORT: A 23-year-old man with a history of hallucinogenic tryptamine use (typical dose: 6 to 20 mg orally of 5-MeO-DIPT) developed rhabdomyolysis, transient nonoliguric acute renal failure, and elevated anion gap metabolic acidosis after ingesting 25 mg of 5-MeO-DIPT ("Foxy Methoxy"). Signs and symptoms included agitation, hallucinations, dark red urine, and an elevated anion gap metabolic acidosis (anion gap, 44 mmol/L [10 to 20 mmol/L]). Creatine kinase concentration peaked at 38,855 Units/L (30 to 220 Units/L) and myoglobin concentration peaked at 13,415 mg/L (0 to 110 mg/L). A toxicology screen was negative for other agents. Clinically, the patient improved with aggressive hydration and alkaline diuresis; at the time of discharge serum creatinine and creatine kinase concentrations were 0.9 mg/dL and 233 Units/L, respectively (Alatrash et al, 2006).
    c) CASE REPORT: A 17-year-old man with a history of daily hallucinogen use began combining 5-MeO-DMT with monoamine oxidase inhibitors (MAOIs) to extend the hallucinogenic effects of 5-MeO-DMT. He created an extract of MAOI harmaline from Syrian rue seeds purchased on the internet. On the day of presentation, he ingested the extract of 3 Syrian rue seeds, smoked 10 mg of 5-MeO-DMT and snorted an additional 15 to 20 mg of 5-MeO-DMT. He became extremely combative, hallucinating and requiring 4 point restraints for severe agitation once he was admitted to the emergency department. Signs and symptoms included hyperthermia (105.2 degrees F axillary), tachycardia (heart rate 186 beats/min), tachypnea (RR 24) and an elevated WBC, BUN, creatinine and mild elevation of transaminases. He was treated with lorazepam and transferred to a higher level of care. Rhabdomyolysis was also observed; peak creatine kinase 26,219 Units/L. Therapy included IV hydration. Mental status and vital signs stabilized and returned to normal within 24 hours; no permanent sequelae occurred (Brush et al, 2004).
    C) INCREASED CREATINE KINASE LEVEL
    1) WITH POISONING/EXPOSURE
    a) ALPHA-METHYLTRYPTAMINE: In one study, the toxic effects of recreational use (ingestion and insufflation) of alpha-methyltryptamine (AMT) and mephedrone were compared using reports obtained from the United Kingdom National Poisons Information Service. Increased creatine kinase activity developed in 4 of 55 patients after use of AMT compared with 27 of 488 patients after use of mephedrone (Kamour et al, 2014).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs, including core temperature, and mental status. Severe hyperthermia is a marker of severe toxicity and requires aggressive treatment.
    B) Monitor serum electrolytes, liver enzymes, renal function and urinalysis. Monitor creatine kinase in patients with prolonged agitation. Assess for myoglobinuria and/or hemoglobinuria following a significant exposure.
    C) Obtain an ECG and institute continuous cardiac monitoring.
    D) Plasma concentrations are not clinically useful or readily available.
    E) A standard urine toxicology screen will generally not detect hallucinogenic tryptamines.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Serum concentrations of tryptamines following hallucinogenic doses are in the range of 5 to 100 ng/mL. Quantitative levels have not been reported to correlate with clinical toxicity and are not helpful in guiding treatment.
    B) Monitor serum electrolytes, liver enzymes, and renal function. Monitor creatine kinase in patients with prolonged agitation.
    4.1.3) URINE
    A) Standard urine toxicology screening will generally not detect hallucinogenic tryptamines.
    B) Monitor for myoglobinuria and/or hemoglobinuria in patients with significant agitation.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Obtain an ECG and institute continuous cardiac monitoring in patients with severe toxicity (eg, agitation, delirium).

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) The following hallucinogenic tryptamines can be detected using LC-MS/MS (liquid chromatography tandem mass spectrometry)(Wohlfarth et al, 2010; Tanaka et al, 2006):
    1) 5MeO-DMT: (2-(1H-indol-5methoxy-3yl)-n,N-dimethylethanamine)
    2) 5-MeO-DIPT: 5-methoxy-N,N-diisopropyltryptamine
    3) AMT: (1-(1H-indol-3-yl)propan-2-amine)
    4) DPT: (2-1Hindol-3-yl)-N,N-dipropylethanamine)
    5) MiPT: (2-1H-indol-3-yl)N-isopropyl, N-methylethanamine)
    2) LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY: LC/MS was able to detect 5-MeO-DIPT and its 2 metabolites (5-OH-DIPT and 5-MeO-NIPT) in blood and urine in a fatal case of 5-MeO-DIPT ("Foxy") poisoning. The 3 compounds were detected in the blood postmortem. The limit of quantification of 5-MeO-DIPT and its metabolites was 0.01 mcg/mL (Tanaka et al, 2006). In another study, LC-MS was also used to confirm and quantify 5-MeO-DiPT in the urine of one subject (Vorce & Sklerov, 2004).
    3) GAS CHROMATOGRAPHY/MASS SPECTROMETRY: General screening and identification of designer hallucinogenic tryptamines (ie, N,N-dimethyltryptamine (DMT), alpha-methyltryptamine (AMT), N,N-diproplyltryptamine (DPT), and 5-MeO-DiPT) was developed using a simple GC-MS method in blood and urine. Limits of detection (in blood and urine) were between 5 and 10 ng/mL (Vorce & Sklerov, 2004).
    4) Indolealkylamines may be detected in serum or plasma by fluorimetry, gas chromatography-mass spectrometry, or gas chromatography. Metabolites may be detected in the urine. Detection of the parent agent in urine is unlikely since only small amounts are excreted in unchanged form.
    5) In one case report, high performance liquid chromatography (HPLC) was used to confirm the presence of AMT in urine (Long et al, 2003).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with significant persistent central nervous system toxicity (eg, hallucinations, delirium, coma), cardiovascular toxicity (tachycardia, hypertension), or with dysrhythmias after ingesting Bufo toad secretions should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic adults may be monitored at home, but may require referral for substance abuse counseling.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (eg, dysrhythmias, severe delirium), or in whom the diagnosis is not clear. Refer for substance abuse counseling.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with deliberate self-harm ingestions or children with any ingestion, and symptomatic patients should be sent to a health care facility for observation for 6 to 8 hours.

Monitoring

    A) Monitor vital signs, including core temperature, and mental status. Severe hyperthermia is a marker of severe toxicity and requires aggressive treatment.
    B) Monitor serum electrolytes, liver enzymes, renal function and urinalysis. Monitor creatine kinase in patients with prolonged agitation. Assess for myoglobinuria and/or hemoglobinuria following a significant exposure.
    C) Obtain an ECG and institute continuous cardiac monitoring.
    D) Plasma concentrations are not clinically useful or readily available.
    E) A standard urine toxicology screen will generally not detect hallucinogenic tryptamines.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital GI decontamination is usually not recommended since rapid deterioration may occur, and potential for coma, seizures, and aspiration exists.
    6.5.2) PREVENTION OF ABSORPTION
    A) Activated charcoal should only be considered in large, recent ingestions in patients who are cooperative, alert, and can protect the airway.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) BODY PACKERS/BODY STUFFERS
    1) Please refer to the appropriate management if body packing or body stuffing is known/suspected.
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs including core temperature, and mental status.
    2) Plasma concentrations are not clinically useful or readily available.
    3) Monitor serum electrolytes, urinalysis, and renal function. Obtain an ECG and institute continuous cardiac monitoring. Monitor creatinine phosphokinase in patients with prolonged agitation.
    4) Standard urine toxicology screen will generally not detect hallucinogenic tryptamines.
    B) PSYCHOMOTOR AGITATION
    1) SUMMARY
    a) BENZODIAZEPINES: are the drugs of choice.
    b) INDICATION
    1) If patient is severely agitated, sedate with IV benzodiazepines.
    c) DIAZEPAM DOSE
    1) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    2) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    d) LORAZEPAM DOSE
    1) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
    2) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    e) Extremely large doses of benzodiazepines may be required in patients with severe intoxication in order to obtain adequate sedation. Titrate dose to clinical response and monitor for hypotension, CNS and respiratory depression, and the need for endotracheal intubation.
    2) Phenothiazines are not recommended because of undesirable side effects (hypotension and lowering of seizure threshold).
    3) Psychological assistance: Reassurance and quiet, dimly-lit room may be helpful in calming an anxious patient, especially those having a "bad trip".
    4) Pharmacological therapy is preferable to physical restraints in patients with acute anxiety or psychosis since restraints may worsen these symptoms.
    C) RHABDOMYOLYSIS
    1) Rhabdomyolysis has been reported in a few cases of tryptamine use associated with psychomotor agitation (Kuwahara et al, 2008; Alatrash et al, 2006; Brush et al, 2004; Alatrash et al, 2006).
    2) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
    3) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
    4) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
    5) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
    6) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
    D) HYPERTENSIVE EPISODE
    1) Usually mild and does not require treatment. May respond to nonspecific sedation with diazepam. If severe, intravenous nitroprusside is the drug of choice.
    E) MALIGNANT HYPERTENSION
    1) SODIUM NITROPRUSSIDE/INDICATIONS
    a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.
    2) SODIUM NITROPRUSSIDE/DOSE
    a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).
    3) SODIUM NITROPRUSSIDE/SOLUTION PREPARATION
    a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    4) SODIUM NITROPRUSSIDE/MAJOR ADVERSE REACTIONS
    a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    5) SODIUM NITROPRUSSIDE/MONITORING PARAMETERS
    a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    F) HYPERTHERMIA TREATMENT
    1) Severe hyperthermia can be life threatening and must be treated aggressively. Control agitation with benzodiazepines, large doses may be needed. Initiate aggressive external cooling measures; undress the patient, keep skin moist and direct fans at the skin. Ice water immersion may be used in severe cases. If needed, intubate, sedate and paralyze.
    G) TACHYARRHYTHMIA
    1) At present, sinus tachycardia is the only dysrhythmia that has been reported. It is usually mild and may respond to nonspecific sedation.

Enhanced Elimination

    A) SUMMARY
    1) Hemodialysis and hemoperfusion are not of value.

Abstracts

Case Reports

    A) ADULT
    1) FATALITIES
    a) ALPHA METHYLTRYPTAMINE
    1) A 22-year-old man ingested a large amount (a 1 g vial of AMT was found at the scene) of AMT and initially became agitated and diaphoretic and threatening to commit suicide. He was restrained by his friend for his own protection and was found dead 12 hours later. AMT was quantified in postmortem analysis (Boland et al, 2005).
    b) BUFOTENINE
    1) A 24-year-old man with a history of intravenous amphetamine use, collapsed and died shortly after injecting himself with 20 to 40 mL of bufotenine (thought to be Ecstasy). Toxicological analysis was positive for bufotenine and bufadienolides (resibufogenin, cinobufagin, and bufalin) found in toad venom. Another companion injected approximately 20 mL of the same drug and vomited, but survived (Kostakis & Byard, 2009).
    c) ETRYPTAMINE
    1) A 19-year-old woman became disorientated, vomited, developed full cardiac arrest, and died following ingestion of two 'dime' sized doses of white powder mixed in a glass of beer. Laboratory analysis of a heart blood sample revealed no ethanol, minor concentrations of methamphetamine (120 mcg/L), and amphetamine (50 mcg/L). Etryptamine was found at a concentration of 5.6 mg/L. Tissue concentrations of etryptamine were 18.3 mg/kg (liver), 16.23 mg/kg (brain), 24 mg/kg (kidney), and 52.9 mg/kg (gastric). Bile concentration was 22 mg/L; vitreous concentration was 2.4 mg/kg (Morano et al, 1993).
    d) 5-MeO-DIPT
    1) CASE REPORT: A 19-year-old male was brought into the ED by his girlfriend after ingesting a "larger than normal" amount of Foxy Methoxy (5-MeO-DIPT). He presented with catalepsy, hallucinations, hypertension (BP 191/102 mmHg) and tachycardia (138 beats/min). A toxicology screen was positive for cocaine and phencyclidine; however, the patient denied the use of cocaine. Following supportive care, he made a full recovery within a few hours (Smolinske et al, 2005).

Range Of Toxicity

Summary

    A) TOXICITY: Toxic doses are difficult to determine, in part due to the difficulty of accurately assessing a dose from a synthetic, illicitly produced drug, or substances derived from natural resources. Patients who develop severe hyperthermia usually develop multiorgan toxicity and often die without aggressive treatment. Alpha-methyltryptamine (AMT) 5 mg to 10 mg may have a mood lifting effect. Euphoria occurs following doses greater than 20 mg. AMT doses greater than 30 mg can cause hallucinations, anxiety, muscle tightness, vomiting, and hyperthermia.
    B) FATALITIES: Fatalities have been reported following exposure to select synthetic "designer" tryptamines including AMT, bufotenine, 5-MeO-DIPT ("foxy"), and etryptamine.
    C) SURVIVAL: A 17-year-old boy developed tachycardia, diaphoresis, agitation, and hallucinations after the ingestion of 100 mg of alpha-methyltryptamine. A man developed status epilepticus after ingesting approximately 200 mg of 5-MeO-DMT.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) Representative hallucinogenic indolealkylamines and their usual adult doses are listed below.
    ABBREVIATIONCHEMICAL NAMEHALLUCINOGENIC DOSE (mg)
    Ttryptamine100
    aMTalpha-methyltryptamine30
    a,O-DMSalpha-0-dimethylserotonin3
    4-OHaMT4-hydroxy-aMT20
    5-OMe-aMT5-methoxy-aMT3
    5 F-aMT5-fluoro-aMT25
    DMTn,n-dimethyltryptamine75-100
    4-OH-DMT4-hydroxy-DMT (psilocin)12
    4-PO-DMT4-phosphoryloxy-DMT (psilocybin)12
    5-OH-DMT5-hydroxy-DMT (bufotenine)4-16
    5-OMe-DMT5-methoxy-DMT6
    DETn,n-diethyltryptamine50-75
    DATn,n-diallyltryptamine60
    4-OH-DET4-hydroxy-DET10-30
    DPTn,n-dipropyltryptamine30-70
    DIPTDi-isopropyltryptamine20-50
    4-OH-DIPT4-hydroxy-DIPT12
    5-OMe-DIPT5-methoxy-DIPT6-10
    IPMT n-isopropyl,n-methyltryptamine6
    MP-809 60
    Psilocin 12
    C2-74 15
    Serotonin 100
    IT-290 30

    2) OTHER -
    a) Other tryptamine derivatives have been shown to be active in animals but have not been studied in humans.
    b) Doses listed for tryptamine, DMT, 5-OMe-DMT, DAT, and DPT are those following intravenous administration. Much higher doses may also produce hallucinations following ingestion. Doses listed for other agents refer to oral administration.
    c) These agents are also active by the nasal (snorting) or pulmonary (smoking) routes of administration.

Minimum Lethal Exposure

    A) ALPHA METHYLTRYPTAMINE
    1) A 22-year-old man ingested a large amount (a 1 g vial of AMT was found at the scene) of AMT and initially became agitated and diaphoretic and threatening to commit suicide. He was restrained by his friend for his own protection and was found dead 12 hours later. AMT was quantified in postmortem analysis (Boland et al, 2005).
    B) BUFOTENINE
    1) A 24-year-old man with a history of intravenous amphetamine use, collapsed and died shortly after injecting himself with 20 to 40 mL of bufotenine (thought to be Ecstasy ("MDMA")). Toxicological analysis was positive for bufotenine and bufadienolides (resibufogenin, cinobufagin, and bufalin) found in toad venom. Another companion injected approximately 20 mL of the same drug and vomited, but survived (Kostakis & Byard, 2009).
    C) ETRYPTAMINE
    1) A 19-year-old woman became disorientated, vomited, developed full cardiac arrest, and died following ingestion of two 'dime' sized doses of white powder mixed in a glass of beer. Laboratory analysis of a heart blood sample revealed no ethanol, minor concentrations of methamphetamine (120 mcg/L), and amphetamine (50 mcg/L). Etryptamine was found at a concentration of 5.6 mg/L (Morano et al, 1993).
    D) FOXY
    1) A man developed severe agitation after receiving an injection of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT; "foxy") and died a short time after admission to the emergency department (Tanaka et al, 2006).

Maximum Tolerated Exposure

    A) ACUTE
    1) CASE REPORT: A 17-year-old boy developed tachycardia (160 beats/min), diaphoresis, agitation, and hallucinations after ingesting 100 mg of alpha-methyltryptamine (AMT) (Long et al, 2003).
    2) CASE REPORT: An 18-year-old man developed status epilepticus after ingesting approximately 200 mg of 5-MeO-DMT (Nyman et al, 2002).
    3) CASE REPORT: A 19-year-old male was brought into the ED after ingesting a "larger than normal" amount of Foxy Methoxy (5-MeO-DIPT). He presented with catalepsy, hallucinations, hypertension, and tachycardia. A toxicology screen was positive for cocaine and phencyclidine; however, the patient denied the use of cocaine. Following supportive care, he made a full recovery within a few hours (Smolinske et al, 2005).
    4) ALPHA-METHYLTRYPTAMINE (AMT): AMT 5 mg to 10 mg may have a mood lifting effect. Euphoria occurs following doses greater than 20 mg. AMT doses greater than 30 mg can cause hallucinations, anxiety, muscle tightness, vomiting, and hyperthermia (Wilcox, 2012).
    a) In a retrospective study of 15 alpha-methyltryptamine (AMT) users, hallucinations (90%), euphoria (87%), anxiety (35%), depressive mood (15%), and vomiting (1 patient) developed after patients used 30 mg to 52 mg (mean: 42 mg) of AMT (Wilcox, 2012).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) Postmortem blood and tissue alpha-methyltryptamine (AMT) concentrations from a 22-year-old man, who ingested an unknown amount of AMT, are as follows (Boland et al, 2005):
    Specimen AMT concentrations
    Iliac vein blood 2.0 mg/L
    Gastric 9.6 mg total (48 g collected at autopsy)
    Liver 24.7 mg/kg
    Brain 7.8 mg/kg

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) BUFOTENINE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 290 mg/kg (RTECS , 2001)
    B) ETRYPTAMINE ACETATE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 75 mg/kg (RTECS , 2001)

Pharmacology Toxicology

Toxicologic Mechanism

    A) The hallucinogenic indolealkylamines have properties in common with LSD (lysergic acid diethylamide), serotonin, ergotamine, and beta-carbolines (eg, harmine). The pyrrole portion of the indole ring appears to be essential for hallucinogenic activity. These compounds appear to act primarily by stimulating serotonin type 2 (5HT2) receptors. Some compounds are partial 5HT receptor agonists, mixed agonist-antagonists. Stimulation of dopaminergic and tryptaminergic receptors and inhibition of monoamine oxidase appear to have a minor role in their pharmacologic activity.

Physicochemical

Molecular Weight

    1) Bufotenine: 204.3
    2) Etryptamine acetate: 250.38

References

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