DEA/OD/ODE page 1 of 14 October 16, 2013

2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25I-NBOMe; 

2C-I-NBOMe; 25I; Cimbi-5), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-

methoxybenzyl)ethanamine (25C-NBOMe; 2C-C-NBOMe; 25C; Cimbi-82) and

2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe; 

2C-B-NBOMe; 25B; Cimbi-36)

Background Information and Evaluation of ‘Three Factor Analysis’ (Factors 4, 5 and 6)

for Temporary Scheduling

Drug and Chemical Evaluation Section, Office of Diversion Control, Drug Enforcement 

Administration, 8701 Morrissette Drive, Springfield, VA 22152

October 2013

Introduction

Since 2011, there has been a marked increase in the law enforcement 

encounters of new synthetic substances as substitutes for Schedule I hallucinogens in 

the United States. Both law enforcement and public health reports suggest the 

sustained popularity of these substances in the designer drug market, most commonly 

purported or mistaken for more well-known hallucinogens, like lysergic acid 

diethylamide (LSD) and extracts of psilocybin mushrooms. These synthetic substances 

are readily available over the Internet and are sold through illicit channels.

These substances have no accepted medical use in the United States and have 

been reported to produce adverse effects in humans. Drug induced toxicity and violent, 

erratic behavior due to the abuse of these synthetic substances has led to numerous 

reports of emergency department admissions and deaths (Kelly et al., 2012; Rose et al., 

2012; Rose et al., 2013; Hill et al., 2013; Stellpflug et al., 2013).

2-(4-Iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25I-NBOMe; 

2C-I-NBOMe; 25I; Cimbi-5), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-

methoxybenzyl)ethanamine (25C-NBOMe; 2C-C-NBOMe; 25C; Cimbi-82) and 2-(4-

bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe; 2C-BNBOMe; 25B; Cimbi-36) (Figure 1) are pharmacologically similar to Schedule I 

hallucinogens like LSD, psilocin, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 2,5-

dimethoxy-4-bromoamphetamine (DOB), 2C-I, 2C-B (Braden et al., 2006; Ettrup et al., 

2011; Nichols, 2012). 25I-NBOMe and 25B-NBOMe were first reported in 2003 by Ralf 
DEA/OD/ODE page 2 of 14 October 16, 2013

Heim at the Free University of Berlin (Heim, 2003), and were subsequently investigated 

as research tools by a group at Purdue University beginning in 2006 (Braden et al., 2006; 

Nichols et al., 2008; Juncosa Jr et al., 2012; Nichols, 2012). 25C-NBOMe was first 

reported in the scientific literature in early 2011 (Ettrup et al., 2011). These substances 

began showing up in forensic laboratory reports on drug seizures later in that same 

year. From November 2011 through June 2013 according to the DEA’s System to 

Retrieve Information on Drug Evidence (STRIDE1) data, there are 54 exhibits involving 27

cases for 25I-NBOMe, 27 exhibits involving 12 cases for 25C-NBOMe and 4 exhibits

involving 4 cases for 25B-NBOMe. From June 2011 through June 2013, the National 

Forensic Laboratory Information System (NFLIS2) registered hundreds of reports 

containing these synthetic substances (25I-NBOMe – 795 reports; 25C-NBOMe – 144

reports; 25B-NBOMe – 20 reports) from all reporting local, state and other federal 

forensic laboratories in the U.S. 25I-NBOMe, 25C-NBOMe, and 25B-NBOMe were not 

reported to NFLIS prior to June of 2011, and the number of reports for these substances 

increased in every quarter of 2012, and in the first quarter of 2013.

With no legitimate medical use and limited pharmacological information, these 

substances (25I-NBOMe, 25C-NBOMe and 25B-NBOMe) have emerged on the designer 

drug market and are being abused for their psychoactive properties. To protect the 

public health and safety, the Drug Enforcement Administration (DEA) is temporarily 

placing 25I-NBOMe, 25C-NBOMe and 25B-NBOMe in Schedule I of the Controlled 

Substances Act (CSA). With respect to finding an imminent hazard to the public safety,

DEA has considered the three factors required under the CSA for the temporary 

scheduling of 25I-NBOMe, 25C-NBOMe and 25B-NBOMe. 21 U.S.C. 811(h)(3) and 

811(c)(4)-(6).

Figure 1. Chemical Structures

 

1

STRIDE, a DEA database which compiles information on exhibits analyzed in DEA laboratories.

2 NFLIS, a DEA database which compiles information on exhibits analyzed in state, local, and federal 

laboratories.

25I-NBOMe 25C-NBOMe 25B-NBOMe
DEA/OD/ODE page 3 of 14 October 16, 2013

25I-NBOMe, 25C-NBOMe and 25B-NBOMe are classified as 2C compounds, a 

structural class with a phenethylamine core substituted with methoxy groups on the 2 

and 5 positions of the phenyl ring. The name “2C” indicates the presence of a twocarbon ethylene group (-CH2CH2-) between the phenyl ring and the amino group. 

Historically, a number of substances from this class of compounds have been abused for 

their psychoactive properties. In 1994, 4-bromo-2,5-dimethoxyphenethylamine (2C-B)

was temporarily added to Schedule I of the CSA, an action that was made permanent 

the following year. 2,5-Dimethoxy-4-n-propylthiophenethylamine (2C-T-7) was 

emergency scheduled in 2002, and permanently added to Schedule I in 2004. In 2012,

Congress passed the Synthetic Drug Abuse Prevention Act placing nine additional 2C 

compounds (2-(2,5-dimethoxy-4-ethylphenyl)ethanamine, 2C-E; 2-(2,5-dimethoxy-4-

methylphenyl)ethanamine, 2C-D; 2-(4-chloro-2,5-dimethoxyphenyl)ethanamine, 2C-C;

2-(4-iodo-2,5-dimethoxyphenyl)ethanamine, 2C-I; 2-(4-ethylthio-2,5-

dimethoxyphenyl)ethanamine, 2C-T-2; 2-(4-isopropylthio-2,5-

dimethoxyphenyl)ethanamine, 2C-T-4; 2-(2,5-dimethoxyphenyl)ethanamine, 2C-H; 2-

(2,5-dimethoxy-4-nitrophenyl)ethanamine, 2C-N; and 2-(2,5-dimethoxy-4-npropylphenyl)ethanamine, 2C-P) in Schedule I of the CSA. 25I-NBOMe, 25C-NBOMe and

25B-NBOMe are structurally similar to these 2C compounds, with the addition of the 2-

methoxybenzyl group to the nitrogen atom (NBOMe) of 2C-I, 2C-C, and 2C-B, 

respectively. This addition has been shown to substantially enhance the 

pharmacological potency of these drugs (Braden et al., 2006, Juncosa Jr et al., 2012).

General Information

2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25I-NBOMe; 2C-INBOMe; 25I; Cimbi-5)

25I-NBOMe has been shown to bind to rat and human 5-HT2A (serotonin) receptors

with nanomolar affinity and is described as a “superpotent” 5-HT2A agonist in those

research models (Braden et al., 2006; Ettrup et al., 2011). The 5-HT2A receptor is a critical 

site of action for hallucinogens like LSD, psilocin, and 5-MeO-DMT (Braden et al., 2006).

Researchers have explored using radioactively labeled 25I-NBOMe as a research tool to map 

5-HT2A receptors in the brain (Ettrup et al., 2010; Ettrup et al., 2011). 25I-NBOMe is 

structurally similar to 2C-I, a Schedule I hallucinogen that can be used as a synthetic 

precursor for 25I-NBOMe. The addition of the N-2-methoxybenzyl (NBOMe) group 

significantly increases the 5-HT2A affinity of 2C-I (Braden et al., 2006). 25I-NBOMe has been 

shown to produce hallucinogen-like behavioral effects in mice, and it was 14-fold more 

potent than 2C-I in this model (Halberstadt and Geyer, 2013). 25I-NBOMe was first 

encountered by law enforcement in the United States in the second quarter of 2011
DEA/OD/ODE page 4 of 14 October 16, 2013

(Appendix 1). It has been encountered in bulk powder forms and on blotter paper. The first 

reported fatality attributed to 25I-NBOMe, confirmed by postmortem blood toxicology, 

occurred in March of 2012.

2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25C-NBOMe; 2CC-NBOMe; 25C; Cimbi-82)

25C-NBOMe has been shown to bind to the 5-HT2A receptor with nanomolar affinity 

and acts as a 5-HT2A agonist in a rat model (Ettrup et al., 2011). The 5-HT2A receptor is a 

critical site of action for hallucinogens like LSD, psilocin, and 5-MeO-DMT (Braden et al.,

2006). Researchers have explored using radioactively labeled 25C-NBOMe as a research tool 

to map 5-HT2A receptors in the brain (Ettrup et al., 2011). 25C-NBOMe is structurally similar 

to 2C-C, a Schedule I hallucinogen that can be used as a synthetic precursor for 25CNBOMe. Blotter papers containing 25C-NBOMe first appeared on the designer drug market 

in 2011 and a number of law enforcement encounters were reported in the first half of 

2012 (Zuba et al., 2013; NFLIS). The first reported fatality attributed to 25C-NBOMe, 

confirmed by postmortem blood toxicology, occurred in June of 2012.

2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe; 2CB-NBOMe; 25B; Cimbi-36)

25B-NBOMe has been shown to bind to rat and human 5-HT2A receptors with 

nanomolar affinity and is a 5-HT2A agonist in the rat model (Ettrup et al., 2011; Juncosa Jr et 

al., 2012). The 5-HT2A receptor is a critical site of action for hallucinogens like LSD, psilocin, 

and 5-MeO-DMT (Braden et al., 2006). Researchers have explored using radioactively 

labeled 25B-NBOMe as a research tool to map 5-HT2A receptors in the brain (Ettrup et al., 

2011; Ettrup et al., 2013). 25B-NBOMe is structurally similar to 2C-B, a Schedule I 

hallucinogen that can be used as a synthetic precursor for 25B-NBOMe. There is a roughly 

30-fold increase in affinity at the human 5-HT2A receptor when the N-2-methoxybenzyl 

(NBOMe) group is added to 2C-B (Juncosa Jr et al., 2012). 25B-NBOMe was first 

encountered by law enforcement in the United States in the fourth quarter of 2012 (NFLIS).

It has been encountered in bulk forms and on blotter paper. The first reported fatality 

attributed to 25B-NBOMe, confirmed by postmortem blood toxicology, occurred in 

February of 2013.
DEA/OD/ODE page 5 of 14 October 16, 2013

Table 1. Summary of Available Pharmacology Data for 25I-NBOMe, 25C-NBOMe and 

25B-NBOMe

Binding (Ki) at

Rat 5-HT2A

a

Rat 5-HT2A

Activation (ED50)

b

Intrinsic 

Activityc

Binding (Ki) at 

Human 5-HT2A

Human 5-HT2A

Activation (EC50)

Intrinsic 

Activityh

25I-NBOMe 1.49±0.35 nM 1.02±0.08 nM 91 % 0.044±0.006 nMd0.44±0.07 nMg81 %

25C-NBOMe 2.89±1.05 nM 2.31±0.11 nM 88 % 0.9 nMe– –

25B-NBOMe 1.01±0.17 nM 0.51±0.19 nM 87 % 0.19±0.01 nMf– –

All values are reported in nM (± SEM). Fields marked with – indicate unavailability of data.

a Measured against [3

H]MDL100907 at GF-62 cells (a NIH-3T3 cell line) overexpressing rat 5-HT2A receptors

(Ettrup et al., 2011)

b

Rat 5-HT2A activation (PI hydrolysis) at GF-62 cells (Ettrup et al., 2011)

c Mean maximal activation compared to 10 μM 5-HT (Ettrup et al., 2011)

d Measured against (± )[125I]DOI at human embryonic kidney (HEK) 293 cells expressing wild-type human 

5-HT2A receptors (Braden et al., 2006)

e Measured against [3

H]LSD (Ettrup et al., 2011)

f Measured against [3

H]ketanserin at HEK 293 cells expressing wild-type human 5-HT2A receptors (Juncosa 

Jr et al., 2012)

g

Human 5-HT2A activation (PI hydrolysis) at HEK 293 cells (Braden et al., 2006)

h Mean maximal activation (Braden et al., 2006)

Factor 4. Its history and current pattern of abuse 

The 2-methoxybenzyl series of 2C substances has been developed over the last 10 

years to be used as tools for mapping and investigating the 5-HT2A receptors in the brain

(Ettrup et al., 2010; Ettrup et al., 2011; Ettrup et al., 2013). The first reported seizure of 25INBOMe in the United States was by the Milwaukee Police Department in June of 2011. Law 

enforcement reports since that time have documented encounters with bulk quantities of 

powdered substances or blotter papers identified as containing one or more of 25I-NBOMe, 

25C-NBOMe and 25B-NBOMe. From November 2011 through June 2013 according to 

STRIDE data, there are 54 exhibits involving 27 cases for 25I-NBOMe, 27 exhibits involving 

12 cases for 25C-NBOMe and 4 exhibits involving 4 cases for 25B-NBOMe. From June 2011 

through June 2013, NFLIS registered hundreds of reports containing these synthetic 

substances (25I-NBOMe – 795 reports; 25C-NBOMe – 144 reports; 25B-NBOMe – 20

reports) across all reporting local, state and other federal agencies (Appendix 1).

Information and data from published studies, law enforcement reports, discussions 

on Internet forum websites, and personal communications document numerous routes of 

administration for these substances. 25I-NBOMe, 25C-NBOMe and 25B-NBOMe are 

administered as powders by nasal insufflation, as liquids by intravenous injection or applied 

to the nasal membrane, or the substances are dissolved in solutions and soaked onto

blotter paper and delivered by sublingual or buccal administration (Zuba & Sekuła, 2012; Hill
DEA/OD/ODE page 6 of 14 October 16, 2013

et al., 2013; Stellpflug et al., 2013). In a number of cases, food items were laced with the 

drugs. Severe adverse reactions have been reported for each of these routes of 

administration. Deaths have been reported for most routes of administration, including 

nasal insufflation, liquid solutions applied to nasal membrane, sublingual or buccal 

administration of blotter paper, and consumption of adulterated food items.

Law enforcement reports, discussions on Internet forum websites, and personal 

communications confirm that these substances are commonly purported to be other

Schedule I hallucinogens like LSD, psilocin, and 2C-B. Users and sellers have reported they

believed they were abusing and trafficking LSD, although subsequent laboratory analysis 

revealed the blotter papers, liquids, or powders contain some combination of 25I-NBOMe, 

25C-NBOMe and 25B-NBOMe instead.

Bulk quantities of powdered 25I-NBOMe, 25C-NBOMe and 25B-NBOMe have been 

seized from shipments originating overseas, particularly from Asia (Customs and Border 

Protection Data). Given the relatively small quantity of these substances predicted to 

produce a hallucinogenic effect in humans (Ettrup et al., 2013), some of these international 

shipments of bulk powder are sufficient to produce more than 300,000 dosage units when 

applied to blotter papers. Based on the suggested human dosages from online drug user 

reports, a single bulk seizure of 25I-NBOMe in 2012 contained enough powdered material 

to produce over 3.5 million individual dosage units. Single seizures of nearly 40,000 

individual dosage units of 25B-NBOMe prepared on blotter papers have been reported. 

Abuse of 25I-NBOMe, 25C-NBOMe and 25B-NBOMe has been characterized with 

acute public health and safety issues both domestically and abroad (Advisory Council on 

the Misuse of Drugs, 2013). In response, a number of states, including Arkansas, Florida, 

Louisiana, Nebraska, Ohio, Utah and Virginia have controlled one or more of these 

substances. Abuse of these substances abroad has prompted the United Kingdom, Israel, 

and Russia to control these substances as well.

Youth appear to be the primary abusers of these synthetic substances, as supported 

by the available emergency department reports and reports of death. Case reports detailing 

25I-NBOMe toxicity in emergency departments often describe groups of teens and young 

adults presented simultaneously, or within a short period of time. In 2012, four males, age 

17 to 18 years were presented simultaneously to emergency departments in Michigan after

25I-NBOMe exposure (Kelly et al., 2012). In the first quarter of 2012, ten teens and young 

adults (average age 17 years, range 14 to 20 years) were presented to emergency 

departments in Virginia after 25I-NBOMe exposure (Rose et al., 2012). Two publications in 
DEA/OD/ODE page 7 of 14 October 16, 2013

2013 detail 25I-NBOMe exposure in a male and female (age 18 years) patient who 

presented to emergency departments in Virginia and Minnesota, respectively (Rose et al.,

2013; Stellpflug et al., 2013). A case series of seven males, age 19 to 29 years (average age 

22 years), detailed emergency department treatment of 25I-NBOMe toxicity in Northeast 

England over a one week period in January 2013 (Hill et al., 2013). In 2013, a male, age 19 

years presented to an emergency department in Virginia after exposure to 25B-NBOMe 

(Poklis et al., 2013). The average age of decedents where 25I-NBOMe, 25C-NBOMe or 25BNBOMe was confirmed to be a contributing factor in the death is 20 years (n=17). 

Individuals, including minors, are purchasing synthetic substances through 

traditional illicit channels and from Internet websites. There is at least one law enforcement

encounter with 25I-NBOMe in the United States that described prepared dosage units on 

blotter paper with a printed disclaimer of ‘not for human consumption’. Most seizure 

reports suggest that 25I-NBOMe, 25C-NBOMe and 25B-NBOMe prepared on blotter paper 

are claimed to be LSD and the actual chemical composition or quantity of the adulterant is 

not specified.

Summary

Recently, law enforcement has been encountering 25I-NBOMe, 25C-NBOMe and 

25B-NBOMe with increasing frequency. Synthetic substances are available over the 

Internet and sold through illicit channels, often purported to be Schedule I

hallucinogens, like LSD. 25I-NBOMe, 25C-NBOMe and 25B-NBOMe have been seized as 

powders, solutions, on blotter paper, and laced on food items. Reports of 25I-NBOMe, 

25C-NBOMe and 25B-NBOMe abuse leading to emergency department intervention or 

death describe primarily teens and young adults.

Factor 5. The scope, duration, and significance of abuse

NFLIS, a national database capturing data from forensic laboratories, has a total 

of 959 drug reports (June 2011 through June 2013) in which 25I-NBOMe, 25C-NBOMe or

25B-NBOMe were identified from a number of states including, Alabama, Arkansas, 

Arizona, California, Colorado, Connecticut, Florida, Georgia, Iowa, Indiana, Illinois, 

Kansas, Kentucky, Louisiana, Maryland, Maine, Michigan, Minnesota, Missouri, New 

Hampshire, New Jersey, New Mexico, North Dakota, Nebraska, Nevada, Ohio, 

Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Utah, Virginia, Wisconsin 

and Wyoming as of June 2013. (query date: October 9, 2013). STRIDE has 54, 27, and 4

exhibits for 25I-NBOMe, 25C-NBOMe and 25B-NBOMe, respectively, from November 

2011 through June 2013 (query date: October 9, 2013). 
DEA/OD/ODE page 8 of 14 October 16, 2013

A variety of 2-methoxybenzyl analogues of 2C compounds have been available 

over the Internet since 2010 (Zuba & Sekuła, 2012; Zuba et al., 2013), and the first 

identified domestic law enforcement encounter with 25I-NBOMe occurred in June of 

2011 in Milwaukee, Wisconsin. Since that time, the number of encounters involving 25INBOMe, 25C-NBOMe and 25B-NBOMe has steadily increased, reflecting the increased 

abuse of these substances. Throughout 2012 and 2013, in the United States, there has 

been a significant increase in availability, trafficking and abuse of 25I-NBOMe, 25CNBOMe and 25B-NBOMe, evident from the increasing number of encounters reported 

by forensic laboratories and continued reports toxicity and death reported by 

emergency departments and medical examiners. Evidence of abuse of 25I-NBOMe 

initially appeared in 2011, and evidence of abuse of 25C-NBOMe and 25B-NBOMe 

appeared in 2012. 

In response to this increased abuse and threat to public health, a number of 

states and foreign governments have controlled one or more of these substances. 

Florida, Louisiana, Ohio and Virginia have controlled 25I-NBOMe. 25C-NBOMe is 

controlled in Arkansas. Nebraska and Utah have controlled all three substances 

discussed here. Internationally, several countries have controlled one or more of these 

substances, including the United Kingdom, Israel, and Russia.

Summary

The abuse of this new generation of synthetic substances including 25I-NBOMe, 

25C-NBOMe and 25B-NBOMe is characterized in the public health reports, scientific 

literature and by law enforcement encounters with reports of bizarre behavior, acute 

toxicity, and death. These adverse effect reports, and the number of law enforcement 

encounters with these substances have steadily increased since 2011. In response to 

these increased encounters and adverse health effects, a number of states and foreign

governments have controlled one or more of these synthetic substances.

Factor 6. What, if any, risk there is to the public health

The scientific literature and reports received by DEA suggest that there is a 

significant risk of acute toxicity from the abuse of 25I-NBOMe, 25C-NBOMe and 25BNBOMe. Law enforcement and public health officials have reported exposure incidents that 

demonstrate the dangers associated with abuse of these substances to both the individual 

abusers and those around them. Warnings regarding the dangers associated with abuse of

these synthetic substances have been issued by numerous public health departments, law 
DEA/OD/ODE page 9 of 14 October 16, 2013

enforcement organizations, and the families impacted by the death of someone abusing 

25I-NBOMe, 25C-NBOMe, or 25B-NBOMe. 

At the 2012 North American Congress of Clinical Toxicology Conference, Dr. Adam 

Kelly and coworkers detailed a case series of four males, age 17 to 18 years, simultaneously 

presented to emergency departments in Michigan after 25I-NBOMe exposure (Kelly et al.,

2012). Laboratory analysis confirmed 25I-NBOMe exposure in three of the four cases. The 

clinical features observed for the suspected and confirmed 25I-NBOMe toxicity include 

tachycardia (n=4), psychomotor agitation (4), prolonged seizures (3), rhabdomyolysis (1), 

and renal failure (1). The three patients with prolonged seizures “necessitated aggressive 

pharmacologic therapy” and supportive measures that included intubation and mechanical 

ventilation.

At the same conference, Dr. S. Rutherfoord Rose and coworkers reported a case 

series of ten teens and young adults (average age 17 years, range 14 to 20 years) who 

presented to emergency departments in Virginia after 25I-NBOMe exposure (Rose et al., 

2012). All cases occurred in the first quarter of 2012. Although each patient self-reported 

25I-NBOMe use, confirmatory laboratory test results are not available. The clinical features 

observed for the suspected 25I-NBOMe toxicity include tachycardia (n=9), hypertension (7), 

agitation (6) and hallucinations (5). One patient was found unresponsive, and two were in a 

state of persistent seizure. For one of the seizing patients, Dr. Rose and coworkers observed

multiple, discrete intraparenchymal hemorrhages and acute kidney injury.

Dr. S. Rutherfoord Rose and coworkers later published another case report of 25INBOMe toxicity where they describe a male, age 18 years, who presented to an emergency 

department in Virginia after jumping from a moving vehicle (Rose et al., 2013). Laboratory 

analysis confirmed 25I-NBOMe exposure. Clinical features were consistent with previous 

cases, namely tachycardia, hypertension, hallucinations, and severe agitation, which 

required continuous sedation for approximately three days.

Later in 2013, Dr. Simon Hill and coworkers published a case series of seven males,

age 19 to 29 years, who presented to emergency departments in Northeast England over a 

one week period in January 2013 (Hill et al., 2013). Laboratory testing confirmed 25INBOMe exposure in each case. The clinical features were consistent with previous reports, 

namely tachycardia (n=7), hypertension (4), agitation (6), hallucinations (6), seizures (3), 

hyperpyrexia (3), clonus (2), elevated white cell count (2), elevated creatine kinase (7), 

metabolic acidosis (3), and acute kidney injury (1). One of the most striking cases of 

recorded survival after 25I-NBOMe toxicity described a male, age 29 years, who injected a 
DEA/OD/ODE page 10 of 14 October 16, 2013

solution of 25I-NBOMe and required a total of 43 days in the hospital, 38 of which were in 

the intensive care unit.

Dr. Samuel Stellpflug reported a similar case in 2013, with laboratory confirmation of 

a self-reported sublingual dose of 25I-NBOMe (Stellpflug et al., 2013). The female, age 18 

years, was admitted to an emergency department in Minnesota after a reported grand mal 

seizure. The clinical features reported include tachycardia, hypertension, agitation, and 

confusion.

A clinical case study of 25B-NBOMe exposure confirmed by laboratory analysis of 

biological samples was published by Justin Poklis and coworkers in 2013 (Poklis et al., 2013).

The male, age 19 years, was admitted to an emergency department in Virginia after he was

found unresponsive and with seizure activity. The seizure activity continued for nearly three 

days and required continuous administration of sedatives. In addition to clinical features 

consistent with 25I-NBOMe exposures, the patient had elevated creatine kinase levels that 

indicated rhabdomyolysis.

In addition to the risk of acute toxicity, abusers of these substances put themselves 

and others in danger due to unpredictable, violent behavior. 25I-NBOMe, 25C-NBOMe, and 

25B-NBOMe, similar to other Schedule I hallucinogens (e.g., DOM) bind to and activate 5-

HT2A receptors.

As of October, 2013, DEA has obtained medical examiner and postmortem 

toxicology reports implicating some combination of 25I-NBOMe, 25C-NBOMe and 25BNBOMe in the death of 17 individuals. The average age of these individuals is 20 years 

(range 15 to 29 years). The circumstances surrounding the deaths include acute toxicity 

(14), or unpredictable, violent behavior due to 25I-NBOMe toxicity ultimately leading to 

death (3). Reports describe deaths in a number of states, including Alabama, Arizona, 

California, Florida, Louisiana, North Carolina, North Dakota, Ohio, Tennessee, Texas, and 

West Virginia.

In three of the postmortem toxicology reports, fluoxetine, an FDA approved 

selective serotonin reuptake inhibitor (SSRI), and its metabolite, norfluoxetine, were 

detected. In one of the published emergency department admissions, fluoxetine was also 

reported (Hill et al., 2013). The authors noted greater toxicity in this case, relative to other 

admissions, and questioned whether 25I-NBOMe combined with this SSRI may have led to 

enhanced effects of the substance.
DEA/OD/ODE page 11 of 14 October 16, 2013

Since abusers obtain these substances through unknown sources, the identity, 

purity, and quantity of these substances are uncertain and inconsistent, thus posing 

significant adverse health risk to these users (Hill et al., 2013). As detailed above, there are 

reported instances of emergency department admissions and deaths associated with the 

abuse of these synthetic substances. There is no accepted medical use of these substances 

in the United States.

Summary

The clinical features of severe toxicity following 25I-NBOMe exposure have been 

documented in the scientific literature by a number of independent emergency room 

physicians and toxicologists (Kelly et al., 2012; Rose et al., 2012; Rose et al., 2013; Hill et al., 

2013; Stellpflug et al., 2013). In addition to the risk of acute toxicity, the behavioral effects 

of these substances pose risks to the abuser and the general public. Since they first 

appeared in 2011, 25I-NBOMe, 25C-NBOMe and 25B-NBOMe have been implicated in the 

death of 17 individuals in the United States, primarily teenagers. The possibility of deadly 

drug interactions with FDA approved medications has been noted.

Conclusion of 3-Factor Analysis

After a careful review of the scientific literature, Factors 4, 5, and 6, NFLIS, STRIDE, 

and other law enforcement data and other sources of information, it is evident that 25INBOMe, 25C-NBOMe and 25B-NBOMe are trafficked and abused, and that they pose an 

imminent hazard to public safety. These drugs have become popular among young due to 

their purported pharmacological similarity to Schedule I hallucinogens.

DEA has considered the three criteria for placing a substance into Schedule I of the 

CSA (21 U.S.C. 812). The data available and reviewed for 25I-NBOMe, 25C-NBOMe, and 

25B-NBOMe indicated that these substances, including their optical, positional, and 

geometric isomers, salts, and salts of isomers, pose an imminent hazard to public safety 

and health, have no currently accepted medical use in treatment in the United States, and 

lack accepted safety for use under medical supervision.

References

Advisory Council on the Misuse of Drugs. (2013). 'NBOMe' compounds: A review of the 

evidence of use and harm. London: Advisory Council on the Misuse of Drugs.

Braden, M., Parrish, J., Naylor, J., & Nichols, D. (2006). Molecular interaction of 

serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent 

N-benzyl phenethylamine agonists. Molecular Pharmacology, 70(6), 1956-1964.
DEA/OD/ODE page 12 of 14 October 16, 2013

Ettrup, A., Hansen, M., Santini, M., Paine, J., Gillings, N., Palner, M., Lehel, S., Herth, M.,

Madsen, J., Kristensen, J., Begtrup, M., & Knudsen, G. (2011). Radiosynthesis and 

in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A

agonist PET tracers. European Journal of Nuclear Medicine and Molecular 

Imaging, 38(4), 681-693.

Ettrup, A., Holm, S., Hansen, M., Wasim, M., Santini, M., Palner, M., Madsen, J., Svarer, 

C., Kristensen, J., & Knudsen, G. (2013). Preclinical Safety Assessment of the 5-

HT2A Receptor Agonist PET Radioligand [11C]Cimbi-36. Molecular Imaging and 

Biology, 15(4), 376-383.

Ettrup, A., Palner, M., Gillings, N., Santini, M., Hansen, M., Kornum, B., Rasmussen, L., 

Någren, K., Madsen, J., Begtrup, M., & Knudsen, G. (2010). Radiosynthesis and 

evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET. 

Journal of Nuclear Medicine, 51(11), 1763-1770.

Halberstadt, A. L., & Geyer, M. A. (2013). Effects of the hallucinogen 2,5-dimethoxy-4-

iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head 

twitch response. Neuropharmacology. In Press.

Heim, R. (2003). Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N2-Methoxybenzyl-Partialstruktur. Free Universität Berlin.

Hill, S., Doris, T., Gurung, S., Katebe, S., Lomas, A., Dunn, M., Blain, P., & Thomas, S. 

(2013). Severe clinical toxicity associated with analytically confirmed recreational 

use of 25I-NBOMe: case series. Clinical Toxicology, 51(6), 487-492.

Juncosa Jr, J., Hansen, M., Bonner, L., Cueva, J., Maglathlin, R., McCorvy, J., MaronaLewicka, D., Lill, M., & Nichols, D. (2012). Extensive rigid analogue design maps 

the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin 

receptor agonist ligands. ACS Chemical Neuroscience, 4(1), 96-109.

Kelly, A., Eisenga, B., Riley, B., & Judge, B. (2012). Case series of 25I-NBOMe exposures 

with laboratory confirmation. Clinical Toxicology, 50, 702-702.

Nichols, D. (2012). Structure–activity relationships of serotonin 5-HT2A agonists. WIREs 

Membrane Transport and Signaling, 1(5), 559-579.

Nichols, D., Frescas, S., Chemel, B., Rehder, K., Zhong, D., & Lewin, A. (2008). High 

specific activity tritium-labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-

iodophenethylamine (INBMeO): A high-affinity 5-HT2A receptor-selective agonist 

radioligand. Bioorganic & Medicinal Chemistry, 16(11), 6116-6123.

Poklis, J. L., Nanco, C. R., Troendle, M. M., Wolf, C. E., & Poklis, A. (2013). Determination 

of 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine 

(25B-NBOMe) in serum and urine by high performance liquid chromatography 

with tandem mass spectrometry in a case of severe intoxication. Drug Testing 

and Analysis. In Press.
DEA/OD/ODE page 13 of 14 October 16, 2013

Rose, S. R., Cumpston, K. L., Stromberg, P. E., & Wills, B. K. (2012). Severe poisoning 

following self-reported use of 25-I, a novel substituted amphetamine. Clinical 

Toxicology, 50, 707-708.

Rose, S., Poklis, J., & Poklis, A. (2013). A case of 25I-NBOMe (25-I) intoxication: a new 

potent 5-HT2A agonist designer drug. Clinical Toxicology, 51(3), 174-177.

Stellpflug, S. J., Kealey, S. E., Hegarty, C. B., & Janis, G. C. (2013). 2-(4-Iodo-2,5-

dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe): 

Clinical Case with Unique Confirmatory Testing. Journal of Medical Toxicology.

Zuba, D., Sekuła, K., & Buczek, A. (2013). 25C-NBOMe–New potent hallucinogenic 

substance identified on the drug market. Forensic Science International, 227(1-

3), 7-14.

Zuba, D., & Sekuła, K. (2012). Analytical characterization of three hallucinogenic N-(2-

methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs. Drug 

Testing and Analysis.
DEA/OD/ODE page 14 of 14 October 16, 2013

Appendix 1

NFLIS Reports (as of October 9, 2013)*:

Q2 

2011

Q3

2011

Q4 

2011

Q1 

2012

Q2 

2012

Q3 

2012

Q4 

2012

Q1

2013

Q2

2013‡ TOTAL

25I-NBOMe 3 6 1 24 91 144 148 200 178 795

25C-NBOMe 1 1 13 31 54 44 144

25B-NBOMe 1 13 6 20

* No reports identified in NFLIS regarding 25I-NBOMe, 25C-NBOMe, or 25B-NBOMe prior to June, 2011.

‡

Data collection ongoing for 2013.

STRIDE Records (November, 2011 through June, 2013, retrieved October 9, 2013)*:

Cases Exhibits

25I-NBOMe 27 54

25C-NBOMe 12 27

25B-NBOMe 4 4

* No reports identified in STRIDE regarding 25I-NBOMe, 25C-NBOMe, or 25B-NBOMe prior to November, 

2011