In the last few years, the recreational use of novel psychoactive substances (NPS) has rapidly increased as well as their availability in the drug market. This new phenomenon represents not only an unprecedented challenge in the field of drug addiction, but also a fast growing problem from social, cultural, legal, and political perspectives [
Throughout 2013, a new group of toxic phenethylamine derivatives called NBOMe have gained prominence [
One of the most common substances within NBOMe group is 25C-NBOMe [
Scientific evidence on pharmacology and effects of 25C-NBOMe are poor. Through a systematic analysis of medical-scientific literature and online resources (e.g., websites, drug fora, and chat-rooms), the aim of the present paper was to provide an initial comprehensive review of the pharmacology, metabolism, toxicity, and psychoactive effects of the 25C-NBOMe compound, namely, 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine.
A literature search on 25C-NBOMe was carried out in PsycINFO, Scopus, and PubMed databases. Results were integrated with a multilingual qualitative assessment of a range of websites, drug fora, and other online resources (i.e., e-newsgroups, chat-rooms, mailing lists, e-newsletters, and bulletin boards); between January 2013 and January 2014 exploratory qualitative searches of 153 websites in English and Italian took place using generic and specific keywords, such as “legal highs,” “research chemicals,” “online pharmacy,” “25C-NBOMe,” “NBOMe,” “hallucinogens,” “hallucinogenic substances,” and “online pharmacies” in Google search engine. Of these, 43 were considered to be relevant for the study and as such were monitored on a regular daily, weekly, or monthly basis, depending on their relevance. The remaining 110 websites were considered not to bear any interest for the present study and thus were no longer monitored.
Further specific searches in the database provided by the Global Public Health Intelligence Network (GPHIN) also took place. This is a secure Internet-based early warning system that gathers preliminary reports of public health significance by monitoring global media sources near “real time,” 24 hours a day, 7 days a week basis. GPHIN is operated by the Public Health Agency of Canada and monitors news sources and websites across the globe in 9 languages (e.g., English, French, Farsi, Portuguese, Arabic, Russian, Spanish, and Chinese simplified/traditional) [
Permission for the study was granted by the School of Pharmacy Ethics Committee, University of Hertfordshire, Hatfield, UK (November 2013; PHAEC/10-42).
25C-NBOMe, also known as NBOMe-2CC, Boom, C-Boom, Cimbi-82, Pandora, N-bomb, Holland film, and Dime [
25C-NBOMe is a N-(2-methoxy)benzyl derivative of the psychedelic phenethylamine 2C-C (4-chloro-2,5-dimethoxyphenethylamine) [
Chemical structure of 25C-NBOMe.
The pharmacological properties of NBOMe series were first investigated by Heim and collaborators [
25C-NBOMe is characterized by nanomolar affinity towards the 5-HT2A receptor and has an agonistic binding affinity of
25C-NBOMe has entered the drug market in 2010 in the forms of blotter papers and liquid and less commonly as tabs [
25C-NBOMe can be consumed through several routes of administration. The most common route of administration is the oral or sublingual ingestion (mixed with solvents such as alcohol) by soaking the liquid on a blotter and keeping it on the buccal mucosa for several minutes or swallowing it; Lawn et al. undertook a survey study through the Global Drugs Survey reporting that 81.2% of users administered the drug orally or sublingually [
Several independent reports suggest that doses of swallowed 25C-NBOMe range between 50 and 1200
Example doses reported on the drug fora involving more rare routes of administration include “830
Summary of 25C-NBOMe effects.
Sublingual numbness | Metallic chemical taste |
|
|
Body high | Body tingling sensation |
|
|
Stimulation | Physical energetic stimulation |
|
|
Psychedelic effects | Introspection, euphoria, acceleration of thought, conceptual thinking, time distortion, increased empathy, and sociability |
A user reported the effects of a 500
Onset and duration of the effects largely depend on the doses and the routes of administration (more details are given in Table
Onset and duration of 25C-NBOMe effects in relation to the routes of administration.
Oral/sublingual | Insufflation | |
---|---|---|
Total duration | 4–10 hours | 3–8 hours |
Onset | 0–15 minutes | 0–5 minutes |
Coming up | 30–90 minutes | 15–30 minutes |
Coming down | 1–4 hours | 1–3 hours |
Common negative physical side effects of 25C-NBOMe include vasoconstriction, nausea, vomiting, headache, irregular heartbeat, sweating, and temporary dysuria [
As 25C-NBOMe is a potent serotonergic agonist, these toxic effects may represent the clinical manifestations of serotonin toxidrome, which is known to potentially produce acute toxicity involving metabolic acidosis, rhabdomyolysis, seizures, renal failure, and disseminated intravascular coagulation.
25C-NBOMe is strongly active at extremely small doses (it exerts its effects even at microgramic levels) and users may not have precise weighing scale; therefore, the possibility of accidental overdoses is not irrelevant. In addition, the lack of knowledge of an experimentally recognized median lethal dosage (LD50), the frequent poor or mistaken dilution, and the improper handlings especially by teenagers (including the concomitant use with other drugs like methoxetamine,
Since June 2012, more than 10 fatalities have been reported as a result of the ingestion of substances in the NBOMe class [
From a legislative point of view, NPSs are often identified as temporary class drugs (TCDs); the TCD is a relatively new status for controlled drugs which has been adopted in some jurisdictions, notably New Zealand, USA, and the United Kingdom, to attempt to bring newly synthesized designer drugs under legal control [
In the United States the Controlled Substance Act (CSA) is the federal drug policy under which the manufacture, importation, possession, use, and distribution of certain substances are regulated. CSA created five schedules (classifications), with varying qualifications for a substance to be included in each; two federal agencies, the Drug Enforcement Administration (DEA) and the Food and Drug Administration (FDA), determine which substances are added to or removed from the various schedules. Classification decisions are required to be made on criteria including potential for abuse, currently accepted medical use in treatment in the United States, and international treaties. On November 2013 the DEA added 25I-, 25B-, and 25C-NBOMe to Schedule I making these NBOMe compounds “temporarily” controlled for two years. Sale, possession, manufacture, and distribution of these three compounds are crimes under the US federal law [
For what concerns the United Kingdom, a total of 10 benzofuran and indole analogues and four NBOMe hallucinogens (25C-, 25B-, 25I-, and 25D-NBOMe) have been classified as TCDs from June 2013 to be reviewed in June 2014. This means that sale and import of the named substances are considered criminal offences and are treated as Class B drugs [
In New Zealand, 25C-NBOMe is considered to be substantially similar in chemical structure to the illegal hallucinogen dimethoxybromoamphetamine (DOB), being therefore considered a Class C controlled drug analogue [
In addition, 25C-NBOMe is currently controlled under drug control legislation in Denmark, Hungary, Israel, Lithuania, New Zealand, Portugal, Romania, Russia (the first country that officially banned the compounds of NBOME series in 2011), Slovenia, Sweden, and areas of Australia (Queensland and New South Wales) [
Differently from the prevalence rates of the use of internationally controlled drugs which seem generally to have stabilized in recent years, the market of NPS, also known as “designer drugs,” “herbal highs,” “synthetic drugs,” “research chemicals,” and “legal highs,” has significantly grown over the past decade [
Scientific literature on pharmacology and effects of 25C-NBOMe is limited. Through a systematic analysis of the current literature and other online resources (e.g., websites, drug fora, and chat-rooms), the present paper aimed to provide fresh insights into the properties, effects, and potential toxicity of this emerging psychoactive drug.
The lack of awareness on its potential risks and unclear legal status of phenethylamine-class drug in various countries may favor the diffusion of 25C-NBOMe among drug users. According to anecdotal and media reports and scientific testing [
The patients may require benzodiazepines and other drugs for the control of overdose-related psychiatric symptoms such as agitation, aggression, or hallucinations [
A similar challenge emerged in the last few years with the diffusion of the highly toxic and long lasting (up to 3 days) hallucinogenic drug Bromo-Dragonfly, which caused a number of fatalities among LSD users before it was recognized [
From a psychiatric point of view, there is a lack of data about long-lasting mental effects of 25C-NBOMe; however, residual symptoms have been reported even several months after its consumption [
The 25C-NBOMe incompletely characterized profile and the lack of routine toxicological screening tests in many laboratories make the substance hardly identifiable. Large studies are needed to systematically investigate effects, toxicity, and potential fatal role of 25C-NBOMe. Meanwhile, the attention and clinical suspicion of families and healthcare professionals towards this new substance is warranted.
One could wonder about the limitations of carrying out an assessment of substance use whilst taking into account online and media reports; in fact, it may be inappropriate to trust information obtained from the Internet without independent verification. However, the Internet plays a central role in the NPS business and therefore, given the limited amount of relevant peer-reviewed data, this seems to be the only method to obtain preliminary information about new and emergent phenomena [
The authors declare that there is no conflict of interests regarding the publication of this paper.
This publication arises from collaborative activities and staff exchanges among the collaborating institutions funded by the European Commission (Erasmus Project). The authors would also like to acknowledge the contribution of the Canadian Centre on Substance Abuse (CCSA), the Public Health Agency of Canada, and the World Health Organization (WHO) for granting access to the GPHIN database.