This document provides a rapid review of recommendations to reduce harm from recreational use of novel NBOMe psychedelic compounds. It summarizes the pharmacology, patterns of use, toxicity case studies, and limitations of testing for NBOMe compounds like 25I-NBOMe. The author recommends that hospitals implement LC-MS/MS testing, educate healthcare providers on clinical presentation and testing for 25I-NBOMe intoxication, and focus on educating the public and targeting distributors rather than punishing simple possession criminally.

1. Rapid Review: Recommendations to reduce public harm associated with recreational use
of novel NBOMe psychedelic compounds
Name: Andreea-Diana Moisa
Student #: 100705607
Course: NEUR 3306
Professor: Dr. Zachary Patterson
Date: August 11th 2015

2. Background:
The NBOMe compounds are a novel series of psychedelic drugs that are potent agonists of the 5-
HT2A receptor, have a short history of human consumption and are available to buy online, in
most countries (Lawn et al., 2014). The research compound 25I-NBOMe is a relatively new
serotonergic psychedelic in the 2C family which was created in an academic laboratory as a
potent serotonin receptor agonist. It has an extremely high affinity for the receptor and
ambiguous legal status, leading to recreational drug enthusiasts using this compound as a
powerful alternative to other psychedelics such as LSD (Walterscheid et al., 2014).
The 2C designer drugs have been used recreationally since the 1970s, but new compounds with
slight alterations to the base phenethylamine structure are continuously emerging, which creates
new clinical profiles and problems with testing for the substance (Halberstadt, 2015).
The 2Cs gained popularity recently and are being abused in increasing amounts due to the easy
access and perceived technical legality. The phenethylamine-based structure of the 2C drugs is
shared among amphetamines, catecholamines, cathinones, and many other drugs. The term “2C”
is an acronym created by Alexander Shulgin to describe the two carbons between the amino
group and the benzene ring in the chemical structure. In this review, “2C” is used to refer to
substituted designer hallucinogens with methoxy groups at positions 2 and 5 on the ring (Fig.1),
rather than the larger group of phenethylamine-based compounds that would include
epinephrine, dopamine, bupropion, MDMA, methamphetamine, cathinones, and a multitude of
other commonly known similarly structured agents. Designer substitution to the 2C structure can
result in altered hallucinogenic and stimulant activity. For example, substitution of iodine or
bromine at position 4 results in increased hallucinogenic effects, as does changing the carbon
branch chain attached to the amine group (Dean et al., 2014).

3. In 1991, Alexander and Ann Shulgin published the book “PIHKAL, A Chemical Love Story”.
PIHKAL refers to “Phenethylamines I Have Known And Loved”. This book contains detailed
instructions for the synthesis of over 200 psychedelic compounds which includes bioassays,
dosages, and anecdotal accounts of onset and duration of euphoric effects after oral ingestion of
phenethylamines. Table 1 lists some 2C compounds and their corresponding and dosages and
durations of effect according to Shulgin. However, pharmacokinetics and pharmacodynamics
may vary between users, and some users may be more susceptible to toxicity. Also, it is
important to emphasize that drugs currently sold on the internet frequently do not contain the
substance or dosage for which they are labeled or given when purchased.
Pharmacology:
There is little information available about the pharmacology of 2Cs. Research shows they have
an affinity for 5-HT2 and alpha-adrenergic receptors. However, 2Cs can be either agonists or
antagonists, which depends on the specific receptor subtype. The hallucinogenic effects result
from a primary amine separated by two carbon atoms from the phenyl ring, methoxy groups at
positions 2 and 5 on the phenyl ring, and a hydrophobic substituent at position 4 on the phenyl
ring (Fig. 1). It is possible to create new hallucinogenic 2Cs by placing different substituents on
the aromatic ring at positions 2, 4, or 5.
The 2Cs are available in tablet, capsule, powder, or liquid form, and they are taken orally or
insufflated. Insufflating the compound produces more rapid and intense effects and is a more
dangerous route of administration. For example, oral administration of 2C-T-7 has an onset of 1–
2.5 h and duration of 5–7 h, whereas insufflation of 2C-T-7 has an onset of 5–15 min and
duration of 2–4 h. (Dean et al., 2013)

4. Patients with 2C intoxication present with either a sympathomimetic syndrome, serotonin
toxicity, a hallucinogenic picture, or some combination thereof. Signs and symptoms include
hallucinations, euphoria, empathy, nausea, vomiting, agitation, tachycardia, hypertension,
respiratory depression, and seizures. Users claim increased tactile, visual, auditory, and olfactory
sensations. Effects from use of 2C-E are reportedly more intense compared to 2C-B and 2C-I
(Dean et al., 2013).
At low doses, 2Cs have stimulating effects and increased visual, auditory, and tactile sensations.
At moderate doses, hallucinations may be produced. At higher doses, users may experience
unpleasant hallucinations and sympathomimetic signs such as tachycardia, hypertension, and
hyperthermia (Dean et al., 2013).
Patterns of Use:
A cross-sectional anonymous online survey was conducted in 2012 (n = 22,289), which included
questions about the use of 25B-NBOMe, 25C-NBOMe, 25I-NBOMe and comparison drugs
(Lawn et al., 2014). The results were that 2.6% of respondents (n = 582) had tried one of the
three NBOMe drugs at least once and that at 2.0%, 25I-NBOMe was the most popular (n = 442).
Almost all (93.5%) respondents whose last new drug tried was a NBOMe drug tried it in 2012,
and 81.2% of this group administered the drug orally or sublingually/buccally. Descriptions of
effects were similar to comparison serotonergic hallucinogens, though higher ‘negative effects
while high’ and greater ‘value for money’ were reported. The most common (41.7%) drug source
was via a website. The NBOMe drugs have emerged recently, are frequently bought using the
internet and have similar effects to other hallucinogenic drugs; however, they may pose larger
risks, due to the limited knowledge about them, their relatively low price and availability via the
internet.

5. Toxicology Case Studies
Case 1: Seven young adult males presented to hospitals in England with clinical toxicity after
recreational drug use in January 2013 (Hill et al, 2013). Clinical features included tachycardia (n
= 7), hypertension (4), agitation (6), aggression, visual and auditory 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). LC–MS/MS analysis identified 25I-NBOMe
as the main active substance in the plasma of all seven cases.
Case 2: An 18-year-old male presented to the emergency room with severe agitation and
hallucinations after jumping out of a moving car (Rose et al., 2013). He was tachycardiac (150–
160 bpm) and hypertensive (150–170 mm Hg systolic and 110 mg Hg diastolic), and required
physical restraints and treatment with intravenous lorazepam administration. His symptoms
gradually improved and vital signs returned to normal over 48 h, though he continued to have
episodes of aggressiveness. An assay was developed by our analytical toxicology laboratory for
25-I, and serum was found to contain 0.76 ng/ml of 25-I.
Case 3: An 18-year-old female presented following use of 25I-NBOMe (Stellpflug et al., 2014).
She had an isolated brief seizure, tachycardia, hypertension, agitation, and confusion. She
improved with intravenously administered fluids and benzodiazepines and was discharged 7 h
postingestion. Urine was analyzed using quantitative LC-MS/MS and 25I-NBOMe was found at
a concentration of 7.5 ng/mL.
Testing Limitations:
Testing for the 2C drugs in general is evolving, however, specific testing for newly developed
analogs such as 25I-NBOMe has proved to be a challenge (Stellpflug et al., 2014). These drugs,

6. and specifically 25I-NBOMe, are detected on standard rapid drug screen urine immunoassays,
and even facilities that have advanced confirmatory testing capabilities do not have clearly
described methods for discovering presence of the parent compound or metabolites.
Liquid chromatography and mass spectrometry (HPLC/MS/MS) methods demonstrated
acceptable reliability and reproducibility for the detection and quantification of 2CC-NBOMe
and 25I-NBOMe in serum specimens. The assay uses a simple SPE extraction procedure prior to
chromatographic analysis. The assay is particularly well suited for analysis of serum samples
from emergency room patients. Further, the assay may be easily adapted for the analysis of 2CC-
NBOMe and 25I-NBOMe in research specimens (Polkis et al., 2013).
Recommendations:
Liquid chromatography and mass spectrometry (HPLC/MS/MS) methods should be
implemented in every hospital’s emergency department to allow health care providers to
accurately diagnose patients.
Health providers need to be educated on the background, clinical presentation, and testing
aspects specific to 25I-NBOMe intoxication and trained to maintain current in their knowledge
and skills related to new health care challenges.
It is not recommended that policies be implemented to punish simple possession criminally since
it has been shown that decriminalizing all drugs decreases use in the population drastically
(Gonçalves et al., 2015). Educating the public about the truth and treating users as a medical
issue instead of a criminal issue would lower harm and use based on this newly proven model.
However, criminal code policies should be instilled for the unauthorized manufacturing and
distribution of these substances for profit. Since almost half of people who used them acquired
them on websites, laws should be targeting distributors and focusing on internet retailers.

7. References:
1. Dean, B. V., Stellpflug, S. J., Burnett, A. M., & Engebretsen, K. M. (2013). 2C or not 2C:
phenethylamine designer drug review. Journal of Medical Toxicology,9(2), 172-178.
2. Halberstadt, A. L. (2015). Recent advances in the neuropsychopharmacology of serotonergic
hallucinogens. Behavioural brain research, 277, 99-120.
3. Hill, S. L., Doris, T., Gurung, S., Katebe, S., Lomas, A., Dunn, M. & Thomas, S. H. (2013).
Severe clinical toxicity associated with analytically confirmed recreational use of 25I–
NBOMe: case series. Clinical toxicology,51(6), 487-492.
4. Gonçalves, R., Lourenço, A., & da Silva, S. N. (2015). A social cost perspective in the wake
of the Portuguese strategy for the fight against drugs. International Journal of Drug
Policy, 26(2), 199-209.
5. Lawn, W., Barratt, M., Williams, M., Horne, A., & Winstock, A. (2014). The NBOMe
hallucinogenic drug series: patterns of use, characteristics of users and self-reported
effects in a large international sample. Journal of Psychopharmacology, 28(8), 780-788.
6. Poklis, J. L., Charles, J., Wolf, C. E., & Poklis, A. (2013). High-performance liquid
chromatography tandem mass spectrometry method for the determination of 2CC-
NBOMe and 25I-NBOMe in human serum. Biomedical Chromatography,27(12), 1794-
1800.
7. Rose, S. R., Poklis, J. L., & 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.
8. Stellpflug, S. J., Kealey, S. E., Hegarty, C. B., & Janis, G. C. (2014). 2-(4-Iodo-2, 5-
dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl] ethanamine (25I-NBOMe): clinical
case with unique confirmatory testing. Journal of Medical Toxicology,10(1), 45-50.
9. Walterscheid, J. P., Phillips, G. T., Lopez, A. E., Gonsoulin, M. L., Chen, H. H., & Sanchez,
L. A. (2014). Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. The
American journal of forensic medicine and pathology,35(1), 20-25.

8. Appendix
Fig. 1
General structure of 2C with labeled positions
Table 1: Reported dosages and duration of action for 2Cs per Shulgin (Dean et al.,2013)
2C Chemical name Dosage
Duration
(h)
2C-B 4-Bromo-2,5-dimethoxyphenethylamine 12–24 mg 4–8
2C-C 4-Chloro-2,5-dimethoxyphenethylamine 20–40 mg 4–8
2C-D 4-Methyl-2,5-dimethoxyphenethylamine 20–60 g 4–6
2C-E 4-Ethyl-2,5-dimethoxyphenethylamine 10–25 mg 8–12
2C-G 3,4-Dimethyl-2,5-dimethoxyphenethylamine 20–35 mg 18–30
2C-G-3 3,4-Trimethylene-2,5-dimethoxyphenethylamine 16–25 mg 12–24
2C-G-5 3,4-Norbornyl-2,5-dimethoxyphenethylamine 10–16 mg 32–48

9. 2C Chemical name Dosage
Duration
(h)
2C-I 4-Iodo-2,5-dimethoxyphenethylamine 14–22 mg 6–10
2C-N 4-Nitro-2,5-dimethoxyphenethylamine
100–
150 mg 4–6
2C-P 4-Propyl-2,5-dimethoxyphenethylamine 6–10 mg 10–16
2C-SE 4-Methylseleno-2,5-dimethoxyphenethylamine ∼100 mg 6–8
2C-T 4-Methylthio-2,5-dimethoxyphenethylamine 60–100 mg 3–5
2C-T-2 4-Ethylthio-2,5-dimethoxyphenethylamine 12–25 mg 6–8
2C-T-4 4-Isopropylthio-2,5-dimethoxyphenethylamine 8–20 mg 12–18
2C-T-7 4-Propylthio-2,5-dimethoxyphenethylamine 10–30 mg 8–15
2C-T-8
4-Cyclopropylmethylthio-2,5-
dimethoxyphenethylamine 30–50 mg 10–15
2C-T-9 4-(t)-Butylthio-2,5-dimethoxyphenethylamine 60–100 mg 12–18
2C-T-
13
4-(2-Methoxyethylthio)-2,5-
dimethoxyphenethylamine 25–40 mg 6–8
2C-T-
15 4-Cyclopropylthio-2,5-dimethoxyphenethylamine >30 mg
Several
hours
2C-T-
17 4-(s)-Butylthio-2,5-dimethoxyphenethylamine 60–100 mg 10–15
2C-T-
21 4-(2-Fluoroehtylthio)-2,5-dimethoxyphenethylamine 8–12 mg 7–10