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Case Studies in Toxicology: You Can’t See Dragonfly or Hear NBOMe, but They Can Still Hurt You
Case
A 24-year-old man was brought to the ED by emergency medical services (EMS) for altered mental status. The EMS crew reported they had picked up the patient at a nearby arts festival and concert series. A bystander at the event reported that the patient had taken something called “dragonfly.”
Initial assessment revealed the patient to be disoriented, with nonlinear thought patterns and an inability to follow commands. His vital signs were: blood pressure, 160/100 mm Hg; heart rate, 120 beats/minute; respiratory rate, 24 breaths/minute; and temperature, 102.2˚F. Oxygen saturation was 99% on room air. He was diaphoretic and agitated, and the nursing staff was concerned he would become aggressive and potentially violent. A quick Web search revealed that the agent the bystander mentioned was most likely Bromo-DragonFLY (BDF).
What is Bromo-DragonFLY?
In the 1960s, an American chemist named Alexander Shulgin ushered in a new era of psychedelic drug use by establishing a simple synthesis of 3,4-methylenedioxy-methamphetamine (MDMA). Following this discovery, he suggested a therapist friend use the drug therapeutically.1 Shulgin then began a process of homologation (ie, creating novel compounds by slightly altering existing ones in an organized fashion) and developed systems for rating the drug experiences and naming the drugs in shorthand, both of which are still in use. The chemical structure common to nearly all of the drugs he studied is phenylethylamine. The Figure shows the structures of several phenylethylamine derivatives that were created by adding functional groups to the phenylethylamine backbone. Although the popularity of psychedelic drugs surged during this time period, 2,5-dimethoxy-N-(2-methoxybenzyl)phenylethylamine) (NBOMe), one of a number of newly popular psychedelics, only became available in 2003.
What is known about the pharmacology of Bromo-DragonFLY and NBOMe?
The major target of psychedelic drugs is the serotonin (5-HT2) receptor, specifically the central 5-HT2A subtype. Bromo-DragonFLY is a classic example of designer pharmacology in that the it was intended to potently exert its effect at this specific receptor site.
As its name suggests, BDF adds the “wings of the fly” to the phenylethylamine backbone furanyl rings at positions 2 and 5, and a halogen (bromine) at position 4. The furanyl ring impairs enzymatic clearance of the drug,2 resulting in a duration of action of up to 3 days.3 The addition of halogens increases drug potency, but the mechanism is not clear. The psychedelic agent NBOMe results from chemical additions of methoxy groups at position 2 and 5, and the halogen moiety (iodine in this case) at position 4 of the phenyl ring of the phenylethylamine structure.4
Through the work of Shulgin, some of his colleagues, and many disparate street chemists, a vast family of substituted phenylethylamines have been synthesized and used. Shulgin’s semiautobiographical book PiHKAL: A Chemical Love Story includes his laboratory notes for the synthesis and initial test-dose experience of 179 compounds1; this does not include research done by others or any work since its publication in 1995.
Notable popular drugs chemically similar to NBOMe and BDF are mescaline (found in peyote), cathinones (“bath salts”), and MDMA (found in ecstasy) (Figure). Naturally occurring (and more complex) compounds with similar effects include ayahuasca, a plant-derived beverage consisting of Banisteriopsis caapi and either Psychotria viridis or Diplopterys cabrerana from the Brazilian rainforest (see Emerg Med. 2014;46[12]:553-556); psilocybin (“magic mushrooms”); and lysergic acid diethylamide.
How are these drugs used and what are their clinical effects?
Most phenylethylamine compounds are well absorbed across the buccal mucosa, which is why BDF and NBOMe are commonly used in liquid form or on blotter paper. Dosing guides also exist for insufflation and claim equipotent dosing for this route.5 Regardless of delivery route, given the high potency, inadvertent exposures to these drugs should be expected.
Users simply seeking to hallucinate may not be aware of the significant risks associated with these potent serotonergic agents, which include both life- and limb-threatening effects.6 The high 5-HT2A potency results both in vasoconstriction and promotion of clot formation due to the presence of 5HT2A receptors on small blood vessels and platelets, respectively. Ergotism, historically called Saint Anthony’s fire, is an example of serotonergic vasoconstriction and hallucination.7 Chronic users of substituted amphetamines can develop necrotic ulcers in distal vascular beds such as the hands and feet; these ulcers may progress to amputation despite treatment attempts with vasodilators.
In addition to the vasoconstrictive properties, there are multiple reports of serotonin toxicity (serotonin syndrome) associated with use of these designer serotonergic amphetamines. This syndrome includes severe psychomotor agitation that can lead to personal injury, along with muscle rigidity, tremor, hyperthermia, rhabdomyolysis, and seizures.8
How are patients with phenylethylamine exposures managed?
Management of a patient with a substituted phenylethylamine exposure is similar to management of those with cocaine overdose. Attention to the life-threatening clinical effects of psychomotor agitation, hyperthermia, and seizures is paramount. Appropriate supportive care includes intravenous (IV) benzodiazepines to control agitation and muscle rigidity, replacement of lost volume with crystalloids, and active cooling measures. Failure of benzodiazepines (preferably in conjunction with continuous electroencephalogram monitoring) to control rigidity may lead to the need for propofol and/or result in paralysis. Similar to patients with cocaine intoxication, some may experience ischemic chest pain, and the usual protocol of sedation, nitroglycerin, morphine, and an antiplatelet drug is appropriate.
Identification of phenylethylamines typically requires specialized laboratory testing since most will not trigger a positive result on a standard urine immunoassay. Many specialized laboratories have test catalogs on their Web sites listing under the “stimulants panel” which drugs can be identified. However, none of these assays is likely truly comprehensive, and minor alterations or substitutions to the compounds result in new analogs that may not be in the reference laboratory’s identification library.
The patient was initially restrained and given 5 mg IV diazepam, which was followed by escalating doses every 5 minutes to a total of 35 mg for effect. He had a rectal temperature of 102.5˚F and was externally cooled after sedation. After 20 minutes, he had a generalized convulsion; an additional 10 mg of IV diazepam terminated the seizure, but he remained hyperthermic at 104˚F. The patient was intubated, placed on a propofol infusion, and admitted to the intensive care unit where his temperature was carefully monitored. The following day his temperature had normalized and he was weaned from the ventilator and discharged to the floor for monitoring. On hospital day 3, he was discharged in stable condition.
Mr Waldrop is a fourth-year medical student at the State University of New York, Upstate Medical University, Syracuse. Dr Nacca is a fellow in medical toxicology, department of emergency medicine, State University of New York, Upstate Medical University, Syracuse. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine, and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.
- Shulgin A, Shulgin A. PiHKAL: A Chemical Love Story. Berkeley, CA: Transform Press; 1995.
- Andreasen MF, Telving R, Birkler RI, Schumacher B, Johannsen M. A fatal poisoning involving bromo-dragonfly. Forensic Sci Int. 2009;183(1-3):91-96.
- Hill SL, Thomas SH. Clinical toxicology of newer recreational drugs. Clin Toxicol (Phila). 2011;49(8):705-719.
- Gentry CL, Egleton RD, Gillespie T, et al. The effect of halogenation on blood-brain barrier permeability of a novel peptide drug. Peptides. 1999;20(10):1229-1238.
- Erowid. Bromo-Dragonfly Dosage. http://www.erowid.org/chemicals/bromo_dragonfly/bromo_dragonfly_dose.shtml. Accessed January 14, 2015.
- Baumann MH, Ayestas MA Jr, Partilla JS, et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology. 2012;37(5):1192-1203.
- Walterscheid JP, Phillips GT, Lopez AE, Gonsoulin ML, Chen HH, Sanchez LA. Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. Am J Forensic Med Pathol. 2014;35(1):20-25.
- Wood DM, Looker JJ, Shaikh L, et al. Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY. J Med Toxicol. 2009;5(4):226-229.
Case
A 24-year-old man was brought to the ED by emergency medical services (EMS) for altered mental status. The EMS crew reported they had picked up the patient at a nearby arts festival and concert series. A bystander at the event reported that the patient had taken something called “dragonfly.”
Initial assessment revealed the patient to be disoriented, with nonlinear thought patterns and an inability to follow commands. His vital signs were: blood pressure, 160/100 mm Hg; heart rate, 120 beats/minute; respiratory rate, 24 breaths/minute; and temperature, 102.2˚F. Oxygen saturation was 99% on room air. He was diaphoretic and agitated, and the nursing staff was concerned he would become aggressive and potentially violent. A quick Web search revealed that the agent the bystander mentioned was most likely Bromo-DragonFLY (BDF).
What is Bromo-DragonFLY?
In the 1960s, an American chemist named Alexander Shulgin ushered in a new era of psychedelic drug use by establishing a simple synthesis of 3,4-methylenedioxy-methamphetamine (MDMA). Following this discovery, he suggested a therapist friend use the drug therapeutically.1 Shulgin then began a process of homologation (ie, creating novel compounds by slightly altering existing ones in an organized fashion) and developed systems for rating the drug experiences and naming the drugs in shorthand, both of which are still in use. The chemical structure common to nearly all of the drugs he studied is phenylethylamine. The Figure shows the structures of several phenylethylamine derivatives that were created by adding functional groups to the phenylethylamine backbone. Although the popularity of psychedelic drugs surged during this time period, 2,5-dimethoxy-N-(2-methoxybenzyl)phenylethylamine) (NBOMe), one of a number of newly popular psychedelics, only became available in 2003.
What is known about the pharmacology of Bromo-DragonFLY and NBOMe?
The major target of psychedelic drugs is the serotonin (5-HT2) receptor, specifically the central 5-HT2A subtype. Bromo-DragonFLY is a classic example of designer pharmacology in that the it was intended to potently exert its effect at this specific receptor site.
As its name suggests, BDF adds the “wings of the fly” to the phenylethylamine backbone furanyl rings at positions 2 and 5, and a halogen (bromine) at position 4. The furanyl ring impairs enzymatic clearance of the drug,2 resulting in a duration of action of up to 3 days.3 The addition of halogens increases drug potency, but the mechanism is not clear. The psychedelic agent NBOMe results from chemical additions of methoxy groups at position 2 and 5, and the halogen moiety (iodine in this case) at position 4 of the phenyl ring of the phenylethylamine structure.4
Through the work of Shulgin, some of his colleagues, and many disparate street chemists, a vast family of substituted phenylethylamines have been synthesized and used. Shulgin’s semiautobiographical book PiHKAL: A Chemical Love Story includes his laboratory notes for the synthesis and initial test-dose experience of 179 compounds1; this does not include research done by others or any work since its publication in 1995.
Notable popular drugs chemically similar to NBOMe and BDF are mescaline (found in peyote), cathinones (“bath salts”), and MDMA (found in ecstasy) (Figure). Naturally occurring (and more complex) compounds with similar effects include ayahuasca, a plant-derived beverage consisting of Banisteriopsis caapi and either Psychotria viridis or Diplopterys cabrerana from the Brazilian rainforest (see Emerg Med. 2014;46[12]:553-556); psilocybin (“magic mushrooms”); and lysergic acid diethylamide.
How are these drugs used and what are their clinical effects?
Most phenylethylamine compounds are well absorbed across the buccal mucosa, which is why BDF and NBOMe are commonly used in liquid form or on blotter paper. Dosing guides also exist for insufflation and claim equipotent dosing for this route.5 Regardless of delivery route, given the high potency, inadvertent exposures to these drugs should be expected.
Users simply seeking to hallucinate may not be aware of the significant risks associated with these potent serotonergic agents, which include both life- and limb-threatening effects.6 The high 5-HT2A potency results both in vasoconstriction and promotion of clot formation due to the presence of 5HT2A receptors on small blood vessels and platelets, respectively. Ergotism, historically called Saint Anthony’s fire, is an example of serotonergic vasoconstriction and hallucination.7 Chronic users of substituted amphetamines can develop necrotic ulcers in distal vascular beds such as the hands and feet; these ulcers may progress to amputation despite treatment attempts with vasodilators.
In addition to the vasoconstrictive properties, there are multiple reports of serotonin toxicity (serotonin syndrome) associated with use of these designer serotonergic amphetamines. This syndrome includes severe psychomotor agitation that can lead to personal injury, along with muscle rigidity, tremor, hyperthermia, rhabdomyolysis, and seizures.8
How are patients with phenylethylamine exposures managed?
Management of a patient with a substituted phenylethylamine exposure is similar to management of those with cocaine overdose. Attention to the life-threatening clinical effects of psychomotor agitation, hyperthermia, and seizures is paramount. Appropriate supportive care includes intravenous (IV) benzodiazepines to control agitation and muscle rigidity, replacement of lost volume with crystalloids, and active cooling measures. Failure of benzodiazepines (preferably in conjunction with continuous electroencephalogram monitoring) to control rigidity may lead to the need for propofol and/or result in paralysis. Similar to patients with cocaine intoxication, some may experience ischemic chest pain, and the usual protocol of sedation, nitroglycerin, morphine, and an antiplatelet drug is appropriate.
Identification of phenylethylamines typically requires specialized laboratory testing since most will not trigger a positive result on a standard urine immunoassay. Many specialized laboratories have test catalogs on their Web sites listing under the “stimulants panel” which drugs can be identified. However, none of these assays is likely truly comprehensive, and minor alterations or substitutions to the compounds result in new analogs that may not be in the reference laboratory’s identification library.
The patient was initially restrained and given 5 mg IV diazepam, which was followed by escalating doses every 5 minutes to a total of 35 mg for effect. He had a rectal temperature of 102.5˚F and was externally cooled after sedation. After 20 minutes, he had a generalized convulsion; an additional 10 mg of IV diazepam terminated the seizure, but he remained hyperthermic at 104˚F. The patient was intubated, placed on a propofol infusion, and admitted to the intensive care unit where his temperature was carefully monitored. The following day his temperature had normalized and he was weaned from the ventilator and discharged to the floor for monitoring. On hospital day 3, he was discharged in stable condition.
Mr Waldrop is a fourth-year medical student at the State University of New York, Upstate Medical University, Syracuse. Dr Nacca is a fellow in medical toxicology, department of emergency medicine, State University of New York, Upstate Medical University, Syracuse. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine, and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.
Case
A 24-year-old man was brought to the ED by emergency medical services (EMS) for altered mental status. The EMS crew reported they had picked up the patient at a nearby arts festival and concert series. A bystander at the event reported that the patient had taken something called “dragonfly.”
Initial assessment revealed the patient to be disoriented, with nonlinear thought patterns and an inability to follow commands. His vital signs were: blood pressure, 160/100 mm Hg; heart rate, 120 beats/minute; respiratory rate, 24 breaths/minute; and temperature, 102.2˚F. Oxygen saturation was 99% on room air. He was diaphoretic and agitated, and the nursing staff was concerned he would become aggressive and potentially violent. A quick Web search revealed that the agent the bystander mentioned was most likely Bromo-DragonFLY (BDF).
What is Bromo-DragonFLY?
In the 1960s, an American chemist named Alexander Shulgin ushered in a new era of psychedelic drug use by establishing a simple synthesis of 3,4-methylenedioxy-methamphetamine (MDMA). Following this discovery, he suggested a therapist friend use the drug therapeutically.1 Shulgin then began a process of homologation (ie, creating novel compounds by slightly altering existing ones in an organized fashion) and developed systems for rating the drug experiences and naming the drugs in shorthand, both of which are still in use. The chemical structure common to nearly all of the drugs he studied is phenylethylamine. The Figure shows the structures of several phenylethylamine derivatives that were created by adding functional groups to the phenylethylamine backbone. Although the popularity of psychedelic drugs surged during this time period, 2,5-dimethoxy-N-(2-methoxybenzyl)phenylethylamine) (NBOMe), one of a number of newly popular psychedelics, only became available in 2003.
What is known about the pharmacology of Bromo-DragonFLY and NBOMe?
The major target of psychedelic drugs is the serotonin (5-HT2) receptor, specifically the central 5-HT2A subtype. Bromo-DragonFLY is a classic example of designer pharmacology in that the it was intended to potently exert its effect at this specific receptor site.
As its name suggests, BDF adds the “wings of the fly” to the phenylethylamine backbone furanyl rings at positions 2 and 5, and a halogen (bromine) at position 4. The furanyl ring impairs enzymatic clearance of the drug,2 resulting in a duration of action of up to 3 days.3 The addition of halogens increases drug potency, but the mechanism is not clear. The psychedelic agent NBOMe results from chemical additions of methoxy groups at position 2 and 5, and the halogen moiety (iodine in this case) at position 4 of the phenyl ring of the phenylethylamine structure.4
Through the work of Shulgin, some of his colleagues, and many disparate street chemists, a vast family of substituted phenylethylamines have been synthesized and used. Shulgin’s semiautobiographical book PiHKAL: A Chemical Love Story includes his laboratory notes for the synthesis and initial test-dose experience of 179 compounds1; this does not include research done by others or any work since its publication in 1995.
Notable popular drugs chemically similar to NBOMe and BDF are mescaline (found in peyote), cathinones (“bath salts”), and MDMA (found in ecstasy) (Figure). Naturally occurring (and more complex) compounds with similar effects include ayahuasca, a plant-derived beverage consisting of Banisteriopsis caapi and either Psychotria viridis or Diplopterys cabrerana from the Brazilian rainforest (see Emerg Med. 2014;46[12]:553-556); psilocybin (“magic mushrooms”); and lysergic acid diethylamide.
How are these drugs used and what are their clinical effects?
Most phenylethylamine compounds are well absorbed across the buccal mucosa, which is why BDF and NBOMe are commonly used in liquid form or on blotter paper. Dosing guides also exist for insufflation and claim equipotent dosing for this route.5 Regardless of delivery route, given the high potency, inadvertent exposures to these drugs should be expected.
Users simply seeking to hallucinate may not be aware of the significant risks associated with these potent serotonergic agents, which include both life- and limb-threatening effects.6 The high 5-HT2A potency results both in vasoconstriction and promotion of clot formation due to the presence of 5HT2A receptors on small blood vessels and platelets, respectively. Ergotism, historically called Saint Anthony’s fire, is an example of serotonergic vasoconstriction and hallucination.7 Chronic users of substituted amphetamines can develop necrotic ulcers in distal vascular beds such as the hands and feet; these ulcers may progress to amputation despite treatment attempts with vasodilators.
In addition to the vasoconstrictive properties, there are multiple reports of serotonin toxicity (serotonin syndrome) associated with use of these designer serotonergic amphetamines. This syndrome includes severe psychomotor agitation that can lead to personal injury, along with muscle rigidity, tremor, hyperthermia, rhabdomyolysis, and seizures.8
How are patients with phenylethylamine exposures managed?
Management of a patient with a substituted phenylethylamine exposure is similar to management of those with cocaine overdose. Attention to the life-threatening clinical effects of psychomotor agitation, hyperthermia, and seizures is paramount. Appropriate supportive care includes intravenous (IV) benzodiazepines to control agitation and muscle rigidity, replacement of lost volume with crystalloids, and active cooling measures. Failure of benzodiazepines (preferably in conjunction with continuous electroencephalogram monitoring) to control rigidity may lead to the need for propofol and/or result in paralysis. Similar to patients with cocaine intoxication, some may experience ischemic chest pain, and the usual protocol of sedation, nitroglycerin, morphine, and an antiplatelet drug is appropriate.
Identification of phenylethylamines typically requires specialized laboratory testing since most will not trigger a positive result on a standard urine immunoassay. Many specialized laboratories have test catalogs on their Web sites listing under the “stimulants panel” which drugs can be identified. However, none of these assays is likely truly comprehensive, and minor alterations or substitutions to the compounds result in new analogs that may not be in the reference laboratory’s identification library.
The patient was initially restrained and given 5 mg IV diazepam, which was followed by escalating doses every 5 minutes to a total of 35 mg for effect. He had a rectal temperature of 102.5˚F and was externally cooled after sedation. After 20 minutes, he had a generalized convulsion; an additional 10 mg of IV diazepam terminated the seizure, but he remained hyperthermic at 104˚F. The patient was intubated, placed on a propofol infusion, and admitted to the intensive care unit where his temperature was carefully monitored. The following day his temperature had normalized and he was weaned from the ventilator and discharged to the floor for monitoring. On hospital day 3, he was discharged in stable condition.
Mr Waldrop is a fourth-year medical student at the State University of New York, Upstate Medical University, Syracuse. Dr Nacca is a fellow in medical toxicology, department of emergency medicine, State University of New York, Upstate Medical University, Syracuse. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine, and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.
- Shulgin A, Shulgin A. PiHKAL: A Chemical Love Story. Berkeley, CA: Transform Press; 1995.
- Andreasen MF, Telving R, Birkler RI, Schumacher B, Johannsen M. A fatal poisoning involving bromo-dragonfly. Forensic Sci Int. 2009;183(1-3):91-96.
- Hill SL, Thomas SH. Clinical toxicology of newer recreational drugs. Clin Toxicol (Phila). 2011;49(8):705-719.
- Gentry CL, Egleton RD, Gillespie T, et al. The effect of halogenation on blood-brain barrier permeability of a novel peptide drug. Peptides. 1999;20(10):1229-1238.
- Erowid. Bromo-Dragonfly Dosage. http://www.erowid.org/chemicals/bromo_dragonfly/bromo_dragonfly_dose.shtml. Accessed January 14, 2015.
- Baumann MH, Ayestas MA Jr, Partilla JS, et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology. 2012;37(5):1192-1203.
- Walterscheid JP, Phillips GT, Lopez AE, Gonsoulin ML, Chen HH, Sanchez LA. Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. Am J Forensic Med Pathol. 2014;35(1):20-25.
- Wood DM, Looker JJ, Shaikh L, et al. Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY. J Med Toxicol. 2009;5(4):226-229.
- Shulgin A, Shulgin A. PiHKAL: A Chemical Love Story. Berkeley, CA: Transform Press; 1995.
- Andreasen MF, Telving R, Birkler RI, Schumacher B, Johannsen M. A fatal poisoning involving bromo-dragonfly. Forensic Sci Int. 2009;183(1-3):91-96.
- Hill SL, Thomas SH. Clinical toxicology of newer recreational drugs. Clin Toxicol (Phila). 2011;49(8):705-719.
- Gentry CL, Egleton RD, Gillespie T, et al. The effect of halogenation on blood-brain barrier permeability of a novel peptide drug. Peptides. 1999;20(10):1229-1238.
- Erowid. Bromo-Dragonfly Dosage. http://www.erowid.org/chemicals/bromo_dragonfly/bromo_dragonfly_dose.shtml. Accessed January 14, 2015.
- Baumann MH, Ayestas MA Jr, Partilla JS, et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology. 2012;37(5):1192-1203.
- Walterscheid JP, Phillips GT, Lopez AE, Gonsoulin ML, Chen HH, Sanchez LA. Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. Am J Forensic Med Pathol. 2014;35(1):20-25.
- Wood DM, Looker JJ, Shaikh L, et al. Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY. J Med Toxicol. 2009;5(4):226-229.
