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Common hallucinogens are listed in Table 188–1.
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LYSERGIC ACID DIETHYLAMIDE
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Lysergic acid diethylamide is a potent psychoactive drug. As little as 25 micrograms produces psychedelic effects. The hallucinogenic effects are believed to be mediated through agonism at the serotonin type 2 (5-HT2) receptor.11,12
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Lysergic acid diethylamide is a colorless, tasteless, odorless, water-soluble substance that is sold in various forms, but most commonly as small squares of dried blotter paper printed with colorful graphics and cartoons that have been perforated and soaked in liquid lysergic acid diethylamide solution. Each square typically delivers a dose of 20 to 80 micrograms. Other forms include "microdots" (tiny tablets), "windowpane" (gelatin sheets), impregnated sugar cubes or candy, and small bottles of "breath drops" (the drug in solution).
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The psychedelic effects begin within 30 minutes of ingestion, peak within 4 hours, and last between 8 to 12 hours.13,14 Sympathomimetic stimulation with mydriasis and elevations of pulse, blood pressure, and temperature usually precede the psychedelic effects.13,14 Marked facial flushing, mild gastric distress, piloerection, increased muscle tension, and hyperreflexia may occur. In massive overdoses, coagulopathy, hyperthermia, seizure, coma, and respiratory arrest have been reported.15
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The psychedelic effects of lysergic acid diethylamide depend on the user's prevailing mood, expectations, and surrounding environment. Effects may be perceived as pleasurable or horrifying. Profound distortions in perception of sensory stimuli, time, emotions, and memories occur and may cause users to experience paranoia, depression, extreme panic, or an acute psychotic reaction known as a dysphoric reaction or "bad trip." Dangerous and impulsive behavior is possible, resulting in serious physical trauma or suicide. Prolonged and sometimes permanent psychosis, known as "flashbacks" or "hallucinogen persisting perception disorder," can result.16
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The typical user is usually conscious, alert, and able to provide history of the drug ingestion.13 Diagnosis is based on history of use, the presence of sympathomimetic signs, and reported psychedelic effects. Lysergic acid diethylamide can be detected in the urine for several days after ingestion using specific radioimmunoassay and enzyme immunoassay techniques. Reassurance and observation in a quiet, safe environment are generally the only interventions required to manage a dysphoric reaction. Oral or parenteral benzodiazepines are indicated for patients with extreme agitation or signs of excessive sympathomimetic stimulation. Patients with paranoid or psychotic symptoms lasting longer than 8 to 12 hours may require hospital admission. Medical complications due to massive overdose are rare, and recovery is usually rapid and requires only supportive care.13,14,15
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Psilocybin is a naturally occurring hallucinogenic compound found in at least six genera of mushrooms, but most notably the Psilocybe genus. Psilocybin is an indolalkylamine that is metabolized to the pharmacologically active compound psilocin. Both psilocybin and psilocin are believed to act as serotonin type 2 receptor agonists similar to lysergic acid diethylamide.
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Psilocybin-containing mushrooms grow naturally in the southern United States and Europe but can also be grown from kits sold over the Internet.17 Most species of psilocybin-containing mushrooms turn bluish when bruised, but this is not a definitive method of identification or determination of potency. Psilocybin-containing mushrooms may be dried or cooked without losing potency. Hallucinogenic mushrooms sold on the street are often nonpsychoactive mushrooms that have been adulterated with lysergic acid diethylamide or phencyclidine.6 Because of the variation in mushroom size and concentration of psychoactive compounds, there is little correlation between the number of mushrooms ingested and the hallucinogenic effects. A user may ingest as few as five or as many as 100 mushrooms for a single "dose."
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Hallucinogenic effects begin within 30 minutes of ingestion and last 4 to 6 hours.18,19 The hallucinogenic effects are similar to, although less powerful than, those produced by lysergic acid diethylamide. Other common effects include mydriasis, tachycardia, nausea, and vomiting. Serious medical complications are extremely rare but include seizures, hyperthermia, rhabdomyolysis, and renal failure.20 Mistaken identity and ingestion of highly toxic mushrooms is possible and can lead to serious outcomes.21
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Management is supportive. There is no routinely available screening test for psilocybin or psilocin in the urine. If the patient's symptoms are not consistent with psilocybin ingestion, consider the possibility that a toxic mushroom (see Chapter 219, Mushroom Poisoning) or other psychoactive substances were ingested.21
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Mescaline is found in many cacti, most notably the Mexican Peyote cactus (Lophophora williamsii) and the Peruvian San Pedro cactus (Trichocereus pachanoi). Peyote is used in Native American religious ceremonies, and its legal use is restricted to the Native American Church. Mescaline is a phenylethylamine, structurally related to amphetamines, making it chemically distinct from lysergic acid diethylamide.22 Mescaline is believed to act as a serotonin type 2 receptor agonist, but is much less potent than lysergic acid diethylamide.
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Peyote is most commonly sold as raw cactus or "buttons," 2- to 3-cm discs sliced off of the top of the cactus. Each button contains approximately 45 milligrams of mescaline. A typical hallucinogenic dose is 200 to 500 milligrams. Pills or capsules sold on the street as "mescaline" are unlikely to be genuine and may instead contain lysergic acid diethylamide or phencyclidine.6
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Peyote is bitter tasting and causes uncomfortable physical side effects within an hour of ingestion—including nausea, vomiting, abdominal discomfort, diaphoresis, dizziness, nystagmus, ataxia, and headache—that generally resolve after about 2 hours. Adrenergic stimulation causes mydriasis and mild elevations in pulse, blood pressure, and temperature. Hallucinogenic effects begin several hours after ingestion and persist for 6 to 12 hours. Significant morbidity or mortality caused by the physiologic effects of mescaline has not been observed, but death can result from aberrant behavior while under the influence of the drug.23 Mescaline-intoxicated patients are managed supportively. Routine urine drug screens do not detect mescaline.
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HALLUCINOGENIC AMPHETAMINES
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More than 50 "designer" amphetamines have been created for their hallucinogenic properties. Best known is methylenedioxymethamphetamine, a synthetic phenylethylamine derivative structurally related to both amphetamines and mescaline and commonly known by the street name "Ecstasy." Other designer amphetamines include methylenedioxyamphetamine and methylenedioxyethamphetamine ("Eve"). Methylenedioxymethamphetamine is known for both its psychedelic properties and unique effects on mood and intimacy, which has led to its reputation as a "love drug" popular in dance clubs.24 Methylenedioxymethamphetamine has complex effects, interacting with dopamine, norepinephrine, acetylcholine, and β2-adrenergic and serotonin type 2A receptors, and affecting the release of several hormones, including prolactin, oxytocin, adrenocorticotrophic hormone, dehydroepiandrosterone, and antidiuretic hormone.25
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Methylenedioxymethamphetamine is usually ingested as tablets in doses of 50 to 200 milligrams. The drug is colorless and tasteless—-properties lending to its use as a date-rape drug.26 Symptoms occur within 30 minutes of ingestion and last about 4 to 6 hours. These include feelings of euphoria, inner peace, enhanced sociability, verbosity, and heightened sexual interest. The drug rarely causes actual hallucinations but can produce sensory effects such as alterations in the intensity of colors or sensation of textures. Other common effects include mydriasis, tachycardia, and elevated blood pressure, as well as nausea, jaw tension, bruxism, dry mouth, muscle aches, and ataxia. Current urinary amphetamine immunoassays incorporate a specific monoclonal antibody for methylenedioxymethamphetamine and should routinely detect this drug.
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Methylenedioxymethamphetamine and related amphetamines can produce serious complications and death.27,28,29,30 As with other amphetamines, large-quantity overdoses can cause severe hypertension, intracranial hemorrhage, and ischemia in the heart or brain.27 Fatal arrhythmias and sudden cardiac death have been reported, both with and without underlying cardiac disease.27,28 The most frequently cited causes of death are hyperthermia and hyponatremia.31,32,33,34 A syndrome of methylenedioxymethamphetamine toxicity manifested by hyperthermia, seizures, disseminated intravascular coagulation, rhabdomyolysis, and hepatotoxicity has been described.35 This pattern shares many features of the serotonin syndrome, and combining methylenedioxymethamphetamine with selective serotonin reuptake inhibitors (see Chapter 178, Atypical and Serotonergic Antidepressants) or monoamine oxidase inhibitors (see Chapter 179, Monoamine Oxidase Inhibitors) can precipitate serotonin syndrome.36
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Hyponatremia is predominantly due to excessive water consumption and inappropriate antidiuretic hormone secretion.31,32 Excessive water drinking from thirst can occur if the drug is taken at hot and crowded club venues, with vigorous dancing and profuse sweating.31,33 Persistent neurotoxic effects are possible from chronic methylenedioxymethamphetamine use. Neuropsychiatric studies of habitual users demonstrate long-lasting cognitive impairment and mood dysfunction, including memory impairment, diminished learning ability, and depression.37
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Gastrointestinal decontamination with activated charcoal may be useful if the drug was ingested within 60 minutes of ED arrival.38 Hypertension and tachycardia often respond to benzodiazepines. Severe hypertension is treated with IV phentolamine or nitroprusside. Rapid IV titration with high doses of benzodiazepines or propofol may be required to control symptoms in patients with refractory agitation or seizures. Arrhythmias are managed with standard therapy.
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Check serum electrolyte concentrations and anticipate and treat abnormalities, especially hyponatremia (see Chapter 17, Fluids and Electrolytes). Hyperthermia is managed with cooling measures and fluid resuscitation.32,33 Patients with temperatures exceeding 40°C (104°F) have increased morbidity and mortality, so rapid cooling is important.39 Although there is no evidence from controlled studies, expert opinion and case reports support the use of dantrolene when methylenedioxymethamphetamine-induced hyperthermia is refractory to sedation and active cooling.38,40,41,42 Specific serotonin antagonists, such as methysergide or cyproheptadine, have been suggested for patients with features of the serotonin syndrome following methylenedioxymethamphetamine use.43
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SYNTHETIC CATHINONE DERIVATIVES
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In the fall of 2010, U.S. Poison Control Centers began receiving calls regarding synthetic cathinone derivatives, and use has increased dramatically since then.44,45 Cathinone is a naturally occurring alkaloid extracted from the leaves of the Catha edulis plant (khat) native to areas of Africa and the Middle East. Cathinone and synthetic derivatives, including mephedrone, methylenedioxypyrovalerone, and methylone, are chemically similar to amphetamines. These drugs likely stimulate the release and inhibit the uptake of biogenic amines such as norepinephrine, dopamine, and serotonin.
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Synthetic cathinone derivatives are abused by individuals seeking a "legal" high with stimulatory effects similar to those of cocaine or methylenedioxymethamphetamine. These drugs are often labeled as "bath salts" or "plant food," with fanciful names such as "Vanilla Sky" or "Ivory Wave." They are often labeled as "not for human consumption" in an attempt to avoid federal regulations.
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Synthetic cathinones can be nasally insufflated ("snorted"), ingested, or injected. Duration of effects depends on method of use—1 to 2 hours with nasal insufflation and up to 4 hours if ingested.46 Approximately 20% of users report adverse effects including sweating, palpitations, nausea, headache, and dizziness.46 Agitation is common, and paranoia, panic attacks, and aggression—including violent behavior—have been reported. Sympathomimetic toxicity, with dilated pupils, tachycardia, and hypertension, is common. Hyperthermia, seizures, hyponatremia, rhabdomyolysis, and deaths have been reported.46,47,48,49,50 Synthetic cathinones are not detected on routine urine toxicology screens.
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Treatment is primarily supportive, including cardiovascular monitoring; benzodiazepines as needed for agitation, sympathomimetic effects, or seizures; and cooling for hyperthermia. Admission to a monitored or intensive care unit setting is appropriate for patients with persistent symptoms.
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In September 2011 the U.S. Drug Enforcement Administration issued an emergency order to place three synthetic cathinones (mephedrone, methylenedioxypyrovalerone, and methylone) temporarily into Schedule 1 under the Controlled Substances Act, making the manufacture, sale, or possession of these agents illegal.51
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Phencyclidine is a synthetic piperidine derivative, structurally related to ketamine. Phencyclidine does not fit easily into a single classification, combining features of hallucinogens, depressants, and stimulants.52 Unlike classic hallucinogens, phencyclidine causes a clouding of the sensorium rather than heightened sensory awareness. The primary pharmacologic action is blockade of N-methyl-D-aspartate receptor channels. At high concentrations, phencyclidine also interacts with other receptors and channels, including the opioid, acetylcholine receptor and voltage-gated electrolyte channels, and exhibits sympathomimetic effects by blocking reuptake of norepinephrine and dopamine.
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Phencyclidine is easily and inexpensively synthesized. Powdered ("angel dust") or liquid ("dippers") drug is often combined with tobacco, marijuana, or other leafy materials and smoked. Phencyclidine can also be ingested orally, snorted, or intravenously injected.53 Phencyclidine may be unknowingly ingested, because it is often sold as another drug or used to adulterate another illicit drug product.17 The onset of action depends on the mode of administration. With smoking the onset is about 5 minutes and effects generally last 4 to 6 hours. With large doses, effects can persist for days due to its lipid solubility and accumulation in fat stores.54,55
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Patients may experience CNS stimulation or depression, with clinical presentations ranging from physically violent to catatonic or comatose states.53,56 A combination of cholinergic, anticholinergic, and sympathomimetic effects causes a confusing clinical toxidrome. Phencyclidine is often coadministered with other drugs such as crack cocaine ("beam me up"), marijuana ("crystal supergrass"), or ethanol, which also complicates the clinical picture.54 The most common findings in phencyclidine-intoxicated patients are nystagmus and hypertension (generally mild), each occurring in almost 60% of cases.54 Feelings of detachment (dissociation) from the environment and self may give the user feelings of strength, power, and invulnerability. Violent actions, agitation, bizarre and unpredictable behavior, and hallucinations or delusions are frequent. Diaphoresis, tachycardia, muscle rigidity, dystonic reactions, ataxia, and a decreased response to painful stimuli can occur. About 10% of patients are described as comatose.55 Pupil size is variable, but widely dilated pupils are uncommon.54
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Medical complications from phencyclidine toxicity are frequent.52,56,57 Seizures occur in about 3% of patients, and rhabdomyolysis, occasionally producing acute renal failure, is reported in up to 70%.55 Hypoglycemia, hypertension causing intracerebral hemorrhage, hyperthermia causing hepatic necrosis, and multiorgan failure can occur.54,55,57,58 Violent behavior can result in self-injury.
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Evaluate patients with suspected phencyclidine toxicity for occult injury, hypoglycemia, and rhabdomyolysis.52,53,56 Phencyclidine can be detected by commercially available urine drug screens up to 8 days after single use and up to several weeks after long-term use.59 Cough and cold medications (dextromethorphan, diphenhydramine, and doxylamine), analgesics (ibuprofen, meperidine, and tramadol), and psychotropics (imipramine, mesoridazine, thioridazine, and venlafaxine) cross-react with the drug screen and produce false-positive results.
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Sedation and physical restraints are frequently required to control violent and aggressive behavior. Parenteral benzodiazepines are preferable to physical restraints because fighting against restraints may contribute to rhabdomyolysis.
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Treatment is generally supportive. Treat seizures with benzodiazepines. Status epilepticus or seizures refractory to benzodiazepines may require intubation and treatment with propofol or barbiturates. Treat hyperthermia with active cooling measures. Hypertension usually responds to sedation, but severe hypertension can be treated with nitroprusside. Rhabdomyolysis is treated with aggressive hydration and close monitoring of urine output.
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Patients exhibiting only minor clinical features of phencyclidine intoxication and no medical complications can be discharged when behavior normalizes.52,53,55,56
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MARIJUANA OR CANNABIS
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Marijuana or cannabis consists of the dried leaves and flowers of the hemp plant Cannabis sativa. Hashish is prepared from the dried resin from the flower tops of this plant. The psychoactive ingredient in marijuana is tetrahydrocannabinol.60
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Marijuana is most often smoked61 but can also be ingested. Symptoms persist for 2 to 4 hours after smoking, or longer if ingested. Clinical effects include drowsiness, euphoria, heightened sensory awareness, paranoia, and distortions of time and space. Hallucinations do not usually occur at usual doses. Common physiologic effects of marijuana are mild tachycardia, injected conjunctiva, bronchodilation, orthostatic hypotension, and impaired motor coordination.62 Medical complications, such as panic reactions, brief toxic psychoses, pneumomediastinum, and pneumothorax, are rare. Acute cardiac events associated with marijuana use have been reported,63,64 possibly the result of aging in the population of marijuana users and the increasing availability of medical marijuana.
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Marijuana is used for treatment of medical conditions such as glaucoma and chemotherapy-related nausea and to promote weight gain in patients with HIV infection and AIDS.
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Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects.65 Cyclic vomiting syndrome can be due to marijuana use.66,67,68 Symptoms are often misdiagnosed as gastroparesis or opiate withdrawal, and cannabis cessation results in symptomatic recovery.
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Acute psychiatric symptoms due to marijuana use can generally be managed with reassurance alone, but benzodiazepines can be used for severe symptoms. Standard urine drug screens are unreliable indicators of acute marijuana intoxication. High lipid solubility results in extensive deposition within body fat and slow excretion in the urine. After a single use, tetrahydrocannabinol is detected by commercially available urine screens for up to 3 days. With long-term use, cannabinoids can be detected up to 30 days or longer after abstinence.69 Ibuprofen, naproxen, pantoprazole, and efavirenz, a non-nucleoside reverse transcriptase inhibitor used to treat HIV infection, can produce false-positive results on the urine cannabinoid screen.
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SYNTHETIC CANNABINOIDS
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Synthetically produced cannabinoid-receptor agonists have been created for hallucinogenic use and are generally combined with herbal blends and labeled as "Spice" or "K2."47 These products contain a variety of compounds that are active at the cannabinoid receptors but are not structurally related to tetrahydrocannabinol. One of the first synthetic cannabinoids (1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone, goes by the term JWH-018 for the initials of J.W. Huffman, who developed this compound to investigate drug-receptor interactions.70
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Products containing synthetic cannabinoids are sold in shops and on the Internet labeled as "incense" and "not for human consumption." The appeal of such products is driven by the desire for a legal "high" that is not detecable by current urine drug assays.
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The product is usually rolled in paper and smoked in a manner similar to marijuana. Effects begin within minutes and may last for several hours, generally disappearing within 4 hours.47 Most users will not seek or require medical attention, but some have experienced adverse reactions, with anxiety and tachycardia being the most common.72 Other reported adverse effects include hypertension, diaphoresis, tremulousness, and agitation.72,73 Synthetic cannabinoids can precipitate psychosis in patients with prior mental illness.74 Symptoms are usually self-limited and short-lived, and treatment is supportive.
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In March 2011 the U.S. Drug Enforcement Administration placed five synthetic cannabinoid compounds (JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol) into Schedule 1, criminalizing their sale or use.75 These will likely be replaced in the illegal hallucinogen marketplace by other related molecules in this class.
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Bromo-benzodifuranyl-isopropylamine, or Bromo-DragonFLY, is a phenethylamine hallucinogen.76 Bromo-DragonFLY stimulates serotonin receptors in the brain, similar to lysergic acid diethylamide. Bromo-DragonFLY was developed as a research chemical to study the relationship between molecular structure and psychedelic activity. The name comes from its chemical structure, two furanyl rings with double bonds and a side amphetamine arm, which gives it the appearance of a dragonfly. In 2005, Bromo-DragonFLY became available in human experimental markets and was soon diverted to hallucinogenic use.
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Bromo-DragonFLY is sold as white to pink powder that can be snorted, smoked, or injected. Bromo-DragonFLY may also be sold on blotter paper, similar to lysergic acid diethylamide, which has led to confusion in users mistakenly consuming Bromo-Dragon-FLY instead. The hallucinogenic dose of Bromo-DragonFLY ranges from 200 to 800 micrograms, with the onset of action within 20 to 90 minutes and a duration of hallucinogenic effects up to 10 to 14 hours. Toxicity includes agitation, hallucinations, and tonic-clonic seizures that may be delayed in onset.77 Bromo-DragonFLY acts as a long-acting vasoconstrictor that can cause necrosis and gangrene several weeks after use. Bromo-DragonFLY has been associated with fatalities in several countries.78 Two similar compounds, 2C-B-FLY and 3C-B-FLY, are also abused as hallucinogens.
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Benzylpiperazine and trifluoromethylphenylpiperazine are synthetic phenylpiperazine analogues used as substitutes for amphetamine-derived designer drugs.47,79 These two compounds are usually combined and sold as "Legal X" in attempt to mimic the effects of methylenedioxymethamphetamine. These drugs are legally available in many countries. Clinical effects include sympathomimetic effects such as palpitations, agitation, anxiety, confusion, dizziness, headache, tremor, mydriasis, insomnia, urinary retention, vomiting, and seizures.47,80 Deaths have been associated, but in most cases, recovery occurs with supportive care and benzodiazepines.81