NBOMics: The Science of “Smiles”

An earlier version of this post appeared originally on 1 October 2012 at Terra Sigillata.

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 Chemical & Engineering News.).

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.

25I-NBOMe or 2C-I-NBOMe as shown in Nichols et al. as cited in the text.

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 care about this structural gobbledygook?

25I-NBOMe/2C-I-NBOMe is about 20 times more potent than 2C-I in binding those receptors in the brain, the same ones that mediate the hallucinogenic 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 consuming only 0.75 mg.

Taking 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 be surprised for an inexperienced user to be led to commit such heinous acts in reality.

Unfortunately, it takes a high-profile case like Lewis’s for mass media to pay attention to what law enforcement officials deal with on the streets daily (and nightly). And after all the work on the Synthetic Drug Abuse Prevention Act of 2012, 25I-NBOMe is not explictly criminalized.

Analog Act, anyone?


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8 Responses to NBOMics: The Science of “Smiles”

  1. Van says:

    That’s a big assumption you are making here David. NBOMics: The Science of “Smiles”…really?! Did you actually read the experiences on Erowid about 2C-I and 25I-NBOME and came to that conclusion? Shows that you don’t know anything about psychedelics and how they effect the mind.
    Not only that, you are distorting the real story, in the report the police said they found no drugs and the condition of Mr. Lewis resembled someone having an amphetamine psychosis. How about blaming meth, crack or even alcohol? For a Hollywood actor I really suspect the guy was doing bath salts or exotic research chemicals, he could afford mainstream drugs, we can all agree on that.
    It would be fair if you removed you’re pointless article from the web and replaced it with something more truthful and logical.
    Also, street names for new rc drugs change constantly and I can personally tell you that “smiles” is not a common nickname for 25I-NBOME.
    I hope your future articles will be less biased towards the media and more on the level of your academic professionalism.

  2. David Kroll says:

    Van, re-read the post, particularly the paragraph above the chemical structure. I note that what’s being called “Smiles” is probably 2C-I. Erowid editors instead posit that Lewis might have taken 25I-NBOMe.

    The intent of the post was to educate readers about the possibilities in the absence of any toxicology report – note that the post was written on 3 October. As of today, 9 November, no toxicology information has been made public.

    In any case, I’m not blaming any particular compound at this point. I was only constructing hypotheses based on the information available at the time.

    Thanks for taking the time to comment.

  3. Yalo says:

    Woah, I’m shocked! This is like a flashback from the 60’s when the government with its media blamed LSD for alleged homicides and other crimes just to get it scheduled as soon as possible. It’s crazy how history repeats itself and they are still using their old games on us!

  4. Jonathan says:

    No doubt it is sad that a man committed homicide and suicide but blaming drug use is far out of question. Every year millions, if not hundreds of millions, of people use drugs. If we are fair and include alcohol, which is a drug heavily affecting peoples mental state, then it’s easily in the billions. Yet each year the media cling to bashing psychedelics when more people are killed each year by alcohol and prescription drugs approved by the government. Furthermore the DEA spends too much of their time shutting down state legalized marijuana facilities and imprisoning young adults for exercising their free will and pursuit of happiness.
    It is important to remember that the united states government gives new drugs little thought or research before claiming that it has no medical benefit. The only logical way to help the people be safe is to heavily promote safe drug education to high-school and college kids before their “drug dealer” does it for them. Rather than imprisoning over half a million non-violent drug offenders at the cost of $30,000 dollars per year per prisoner, we could be ensuring that these drugs are properly researched and the findings made available to potential users. With prohibition repealed people who find themselves on a trip that seems too much would not be afraid of calling for help because they would not need to fear punishment.
    It is obvious that America’s War on Drugs is a failed prospect that has only brought the imprisonment of hundreds of thousands of free men and women, and given the upper hand to the drug cartels and chemists who know that their is billions of dollars to be made in the underground market. By ending prohibition and educating the population properly you can incredibly limit the amount of accidental overdoses and ensure that consumers are only getting what they paid for. It’s time to promote safety over War. The dangers of use belong to the individual not to the government. Give people the facts, let them choose for themselves.

  5. Walker says:

    I agree with Jonathan. Also Van is correct, I dont know where everyone on the internet is getting “smiles” from, but Ive been around this drug for over a year, and Ive never heard that before, although it does sound rather appropriate.

    The fact of the matter is though, Jonathan is right. Its sort of like guns, the best you can do is harm-reduction. There will never be a day when the government says “hey guys we finally won the war on drugs” because thats impossible. Ti even attempt to is ridiculous and foolhardy. New drugs come out more frequently than any one person even has time to try them all. Additionally, with each new drug, the trend leans more and more toward dangerous compounds with the added bonus that theyre “legal” and therefore have a greater appeal to the general public. This bass-ackwards mentality is EXACTLY what leads to stories like the Lewis’s. Resorting to these hardly known and incredibly potent RC’s like 25i nbome (whose safe dosage and lethal dosage can vary by as little as 3-5mg) is the problem. And with each new legislation, the most recent example being this past July with the scheduling of the 2C-x family of drugs, is the sole reason why drug analogues like the nBome family are created. The new nBome family can mimic the effects of the newly scheduled drugs with less physical material AND its legal! Why would we ever go back? Maybe because these chemicals have literally no research done on their toxicity. Maybe because if you DO overdose, the EMT’s will have no clue what to do because they’ve never heard of 25i nBome. Maybe because the extensive knowledge of the illegal drugs is enough to properly educate people and keep them from overdosing as much as possible.
    There will always be problems, they cannot be stopped. Guns, Drugs, Child Abuse, Rape, they’re all sociological issues, however none of them will ever cease completely. Its time that we try to reduce the extensive harm that new and easily created drugs can cause to society. Something that’s active in the sub-milligrams, can be lethal above 5mg, and is technically legal is acutally prffered by the government over its Illegal, safe, well-known alternative. Something is very wrong here. The DEA, while often annoying, is noble in its purpose, and as a drug user I admit that. But the way theyre going about it is WRONG. I think drugs can be used safely and correctly. However, not by everyone and not every drug, and respectively that is the validity i see in the DEA’s actions, but in a case like this, where self harm among curious users is inevitable, wouldnt you prefer that they at least experiment safely and with the best knowledge possible? Jonathan makes a good point that many fatal OD’s happen because people either wait too long to call for help or don’t call at all out of fear of punishment and because of it, someone ends up dead.

    So, when it comes to our governments jump-the-gun policy on scheduling new compounds, I think much more time needs to be taken to determine their safety and possible benefits. Our government is too quick to turn a potential gift and turn it into a scapegoat. Ecstasy is a great example. MDMA had huge potential in the theraputic field, and if you look up its history, prior to being palced under Schedule 1 on an emergency scheduling, it was supposed to be a Schedule 3 and was about to become that, but last minute the DEA stepped in and made it schedule 1 on the claims of an emergency. Obviously this must have been a big 35 year long Emergency because MDMA is still Schedule 1 today.

    Its just an example of how we shot ourselves in the foot turning something that couldve been a great help to us all into an illegal (and therefore more appealing to the Underground Market) way to get high.

  6. Sky says:

    I just want to make abundantly clear that simply researching something online and then spewing words about it is harmful. First of all, the drug advice and reports available online are less than the tip of the iceberg when it comes to information on any of these chemicals. To be clear sites like Erowid are a great resource but they leave much to be desired. Secondly, only uninformed reporters and researchers call 2c-i “smiles”, that is the slang term for 25i-nBOME, and the two drugs also differ heavily from one another in experience. The misuses of this slang term can be traced back to another ill informed news report that stated 2c-i was a killer new drug that is hurting our kids despite no one having died from a confirmed overdose of 2c-i as of yet. Thirdly, did you take any time to meet with or consult anyone who had actual experience with this drug other than a cursory glance or “science project”. In all instances where the drug used could be verified as 2c-i or 25i-nBOME there has never been ANY realistic evidence to support that these drugs could cause violent outbursts, and personally I believe it to be no more than another LSD witch hunt out to stop man from opening his mind to things other than greed and proliferation; Lastly I wish to say that you also failed to mention that the man who discovered this chemical was Ralf Heim, the noted chemist from the Free University of Berlin. Please give credit where it is due, the people who have made drugs into an evil entity are not the ones who made these novel resources, but those who seek to remove them and their insights from society. In no way do i seek to undermine your research, but I ask that perhaps you consider that the rabbit hole goes much deeper and that you have to ask REAL people REAL questions if you want to get REAL answers. Thankyou

  7. David Kroll says:

    You might care to read the post in greater detail.

  8. Padma says:

    Murder suicides? Try looking at SSRIs, much more dangerous than any NBOMes. (Most mass murder suicides are connected to prescription medications.)