Smiles: 2C-I or not 2C-I?
Oct01

Smiles: 2C-I or not 2C-I?

Designer drugs in the news This is tiring enough for a science writer. I cannot imagine being in law enforcement. The pace at which psychoactive designer drugs are appearing on the street is about as challenging for me as keeping up with dietary supplement companies that adulterate their products with actual prescription drugs (an area I've been covering since 2007 but a practice that goes back decades.) This week's designer drug hullabaloo comes to us courtesy of last week's frightful murder-suicide by Sons of Anarchy actor, the late Johnny Lewis. ABC News is reporting today that Lewis was reportedly taking "Smiles," a street name for 2C-I, the phenethylamine hallucinogen first synthesized by Alexander Shulgin. 2C-I is more properly known as 2,5-dimethoxy-4-iodophenethylamine. This structural analog of mescaline (3,4,5-trimethoxyphenylethylamine) was among a litany of designer drugs that was criminalized in the US back in July with the Synthetic Drug Abuse Prevention Act of 2012 (Cheryl Hogue had a nice discussion of the Act, including some quotes from yours truly, in the 27 August 2012 issue of C&EN.). But the psychedelic drug information website, Erowid, is proposing that the effects reported for "Smiles" are more likely due to the compound 25I-NBOMe (or 2C-I-NBOMe): the more complex and much more potent 5-HT2A agonist, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine. The radiolabelled version of this drug was made, it turns out, by some radiochemistry colleagues down the road at RTI International and characterized by Purdue pharmacologist, David E. Nichols (Bioorg Med Chem 2008;16:6116-6123 DOI:10.1016/j.bmc.2008.04.050. Depending on your institutional access, the DOI may not work so you can view the PDF here through the NIH Public Access Program. Again, here is a case of where a laboratory tool has been co-opted by the recreational drug market, a case that Nichols himself lamented in Nature at the beginning of 2011. Why should the non-chemist or general reader care about this structural gobbledygook? 25I-NBOMe/2C-I-NBOMe is about 20 times more potent than 2C-I in binding those 5-HT2A receptors in the brain, the same ones that mediate the psychedelic effects of old-fashioned hallucinogens such as LSD and mescaline. This means that it takes a very low dose of this chemical -- low, sub-milligram doses -- to experience rather complex sensory and behavioral effects. Here at Erowid is a user experience after a very high dose reported at 3.75 mg - the individual had previously reported a "very enjoyable night" after taking only 0.75 mg. With an unemotional view of the user's experience, I find it stunning that the human brain is capable of such complex sensory activity after being tickled with some synthetic molecules. But in the context of the Lewis murder-suicide, one would not...

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