2C-B was manufactured in the 1980s and early 1990s under the names Nexus, Erox, Performax, Toonies, Bromo, Spectrum, and Venus and marketed as MDMA’s replacement after MDMA became scheduled in the USA. In 1974, 4-bromo-2,5-dimethoxyphenethylamine (2C-B), the first of the 2Cs, was synthesized by Alexander Shulgin as he was exploring homologs from 2,5-dimethoxy-4-bromoamphetamine. For example, additions of methoxy groups at the 2 and 5 positions on the base structure ring or the substitution of iodine or bromine at the 4 position results in increased hallucinogenic effects. General structure of 2C with labeled positions ĭesigner substitution to the 2C structure can result in increased hallucinogenic activity. In this article, we will continue to use “2C” to refer to the group of newly substituted designer hallucinogens with methoxy groups at the 2 and 5 positions on the ring, 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. The terminology “2Cs” is in reference to an acronym invented by Alexander Shulgin to describe the two carbons between the amino group and the benzene ring in the chemical structure (Fig.
The phenethylamine-based structure is actually shared among amphetamines, catecholamines, cathinones, and many other drugs. The 2Cs are just one of the designer drug classes currently being promoted and disseminated on the internet and at raves. Structure manipulation to produce new compounds, advertisement of these compounds as “legal” highs, and ease of access of designer drugs from the internet, raves, night clubs, and sale in head shops have rejuvenated and promoted the current designer drug resurgence. Manufacturers of designer drugs purposely change the structure of these drugs to stay ahead of drug laws, making it difficult for clinicians to stay informed.
Designer drugs including the 2C class discussed in this article are not new but have been increasing in popularity. Designer drugs were created in the 1960s to avoid the provisions of existing drug laws by preparing analogs or derivatives of currently available drugs. The general public has long been aware of traditional illicit drugs such as cocaine, marijuana, and methamphetamine. Treatment of 2C intoxication is primarily supportive, but immediate action is required in the context of excited delirium, hyperthermia, and seizure activity. These drugs may be characterized by either serotonergic toxicity or a sympathomimetic toxidrome, but a presentation consistent with excited delirium is consistent amongst the reported 2C-related deaths. 2C drugs are a group of designer intoxicants, many of which are marketed as legal, but may carry risks that consumers are unaware of. Patients may exhibit sympathomimetic symptoms or symptoms consistent with serotonin toxicity, but an excited delirium presentation seems to be consistent amongst deaths attributed to 2C drugs at least five deaths have been reported in the literature in patients intoxicated with 2C drugs. Common features identified in patients intoxicated with 2Cs included hallucinations, agitation, aggression, violence, dysphoria, hypertension, tachycardia, seizures, and hyperthermia. Multiple names under which 2C drugs are sold were identified and tabulated. This review focuses on the pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication based on available published literature. Understanding the pharmacology and toxicology of these agents is essential in order to provide the best medical care for these patients. The 2C series drugs are ring-substituted phenethylamines that belong to a group of designer agents similar in structure to 3,4-methylenedioxy- N-methylamphetamine (MDMA, Ecstasy). These products mimic the euphoric effects of other well-known illicit drugs but are advertised as “legal” highs and are sold over the internet, at raves and night clubs, and in head shops. New groups of synthetic “designer drugs” have increased in popularity over the past several years.