Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug
Aug30

Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug

The U.S. Centers for Disease Control and Prevention has released a summary on a cluster of 14 deaths in Rhode Island earlier this year attributed to “acetyl fentanyl,” an analog of the potent, short-lived opioid used in pain management and outpatient anesthesia. The report, “Notes from the Field: Acetyl Fentanyl Overdose Fatalities — Rhode Island, March–May 2013,” appears in the August 30, 2013 issue of Morbidity and Mortality Weekly Report (MMWR). The first 10 deaths were reported in the Providence Journal on May 13, 2013, leading CDC officials to join the team in the investigation. A total of 14 deaths were identified. Samples from the decedents gave positive ELISA results for fentanyl but GC/MS revealed an analog that authorities are calling acetyl fentanyl. A CDC health advisory released in June briefly details the chromatographic pattern and mass spectra. Cayman Chemical Company, who offers the reference material, also calls it acetyl fentanyl, but offers desmethyl fentanyl as an alternative. The IUPAC name is N-​phenyl-​N-​[1-​(2-​phenylethyl)-​4-​piperidinyl]-​acetamide; fentanyl has a propionamide instead of the acetamide. A CBC news story described a late April series of drug busts in Montreal that included seizure of a compound they called desmethyl fentanyl. The current MMWR release also links to an alert from the Pennsylvania Department of Drug and Alcohol Problems that reports 50 acetyl fentanyl deaths in the state this year, through June 27th (PDF). Most curious is that the compound has not been described before as a recreational drug. It’s not available as a prescription drug anywhere in the world and is only a minor side product (0.04%) found in prescription fentanyl (DOI: 10.1016/j.jpba.2010.04.004). In a lengthy discussion on Twitter last night and this morning with Chemjobber, SeeArrOh, and others, I initially asked whether acetic anhydride could have been used to acetylate fentanyl, thinking — without looking at the structure — that it was truly acetylated. I found later that fentanyl is made from 4-anilino-N-phenethylpiperidine (ANPP) using either propionyl chloride or propionic anhydride. Hence, acetyl fentanyl could be made by reacting ANPP with either acetyl chloride or acetic anhydride (That’s the extent of my synthetic expertise, Dear Reader.). The major problem with acetyl fentanyl — or fentanyl for that matter — is its high potency relative to natural opioids like morphine or the more potent synthetic, heroin. As a result, the CDC recommends that emergency rooms and other facilities providing substance misuse care services stock up on the opiate receptor antagonist naloxone in anticipation of an increase in overdoses across North America. But it looks like we’re stuck with acetyl fentanyl as the name. Any...

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Okay, Who’s Huffing Vicks VapoRub?
Nov14

Okay, Who’s Huffing Vicks VapoRub?

One of the fun things about having a blog is the traffic analytics feature on the dashboard of WordPress (although I really miss the features of SiteMeter that don’t run on WordPress because it doesn’t accept JavaScript. But I digress.) Besides the addictive nature of looking at one’s traffic numbers, I always find it interesting to look at the search terms that bring people to our humble little corner of CENtral Science. I became hooked on this way back when I started the original version of Terra Sig on Blogger: in February 2006, I had an unusual spike in traffic originating from the UK via the search term “terra sigillata.” So, I posted this and learned this. Usually, search term hits tell me that something has come up in the news. But, alas, I cannot find anything recent that would account for Vicks VapoRub to elicit much searching. Perhaps telling is that all 27 searches came via a misspelled search for “vicks vapor rub.” (By the way, the search term brought folks here to read this post I wrote on Vicks VapoRub after a 2011 PR snafu with journalists like Ivan Oransky at Reuters Health. I ended up writing a bit more about the North Carolina pharmacy history that brought the world this lovely concoction.) I do know that misguided youth will huff volatile chemicals for the acute high one might get. Vicks is most commonly used to enhance the experience of MDMA (ecstasy) – I’ve seen kids at raves wearing N95 facemasks inside which they have smeared the VapoRub. So, what’s with you people wanting to know about Vicks...

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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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RTI scientists solving forensic, designer drug mysteries
Sep09

RTI scientists solving forensic, designer drug mysteries

Catching up on my reading this Sunday morning, I’m beaming with pride on the collective accomplishments and coverage of some old friends and colleagues. Kerstin Nordstrom, a AAAS Mass Media Fellow with the Raleigh News & Observer, had a nice story on 3 September about the work of Dr. Peter Stout at RTI International. You old-timers will know this non-profit entity as Research Triangle Institute, home to the discoveries of Taxol and camptothecin by Wall and Wani and colleagues. Kerstin, or Dr. Nordstrom I should say as she holds a PhD in physics, interviews RTI’s Dr. Peter Stout on the institute’s forensic analytical chemistry capabilities with regard to the “designer drug” industry. Yes, here we go again with my long-running commentary on the “synthetic marijuana,” “herbal incense,” “plant food,” and “bath salts” products that have recently taken a direct hit from “Operation Log Jam,” a coordinated, federal operation to shut down the industry. In my post on the federal takedown, I referred to a paper by Stout’s RTI colleagues where mass defect filtering was used to identify unknown analogs of known illegal compounds, particularly the JWH group of cannabimimetic naphthoylindoles (Anal. Chem., DOI:10.1021/ac300509h). (Addendum: That paper was also covered nicely in the 15 June C&EN by Erika Gebel.) Coincidentally, both Kerstin and Peter are dear to me – hence the following disclosures before singing the praises of the article: Peter earned his Ph.D. in molecular toxicology from Dr. Jim Ruth’s lab at my former home, the Department of Pharmaceutical Sciences at the University of Colorado Denver’s Skaggs School of Pharmacy. My time at RTI’s Natural Products Laboratory (2002-2008) overlapped with Peter’s hiring. As an aside, I had not known Peter was hired until he saw a cart outside of my laboratory with my name and hunted me down, guessing there weren’t many Krolls in biochemical pharmacology. An equally lighthearted observation is that Peter has almost completely shaved his head as long as I’ve know him; I’m certain that’s a coincidence with his dissertation research project, “Mechanisms of Drug Disposition into Hair.” Disclosure #2: Kerstin is a fellow graduate of the 2011 Santa Fe Science Writing Workshop and serendipitously ended up here in the Triangle for her AAAS Mass Media Fellowship. What I like about the story is how both of them describe analytical techniques in relatively approachable language: Kerstin on HPLC: For liquid chromatography, an unknown chemical is pushed through a pipe. The pipe is filled with tiny silica particles – 1 to 10 micrometers in size – that attract some molecules and repel others. Each chemical has a different attraction, and so some, attracted to the grains, go slower than...

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DEA jams synthetic marijuana and “bath salts” industry
Jul28

DEA jams synthetic marijuana and “bath salts” industry

With all the discord in Washington these days, it’s rare to see several US governmental organizations working together to address a significant public health problem. This week, the US Drug Enforcement Agency (DEA) mobilized Operation Log Jam, an unusual and highly-coordinated action with six other federal agencies aimed to shut down the synthetic designer drug industry in 109 US cities. The products targeted were of two broad classes: 1) synthetic marijuana “incense” products comprised of naphthoylindole cannabimimetic compounds first synthesized by John W. Huffman’s lab at Clemson in the mid-1990s, and 2) “bath salts” or “plant food” products containing the stimulant/empathogen mephedrone (4-methylmethcathinone) or the stimulant MDPV (3,4-methylenedioxypyrovalerone). This compilation of posts on synthetic marijuana and, to a lesser extent, “bath salts” serves as a good primer on the subject. These products were sold widely on the internet, headshops, and convenience stores and were associated with 13,000 poison control calls last year, 60% of which were in individuals under 25. Disturbing acute and chronic side effects have been reported by users that include severe anxiety and paranoia, unnerving hallucinations, and even heart attacks. Several specific compounds were criminalized by an emergency DEA action and numerous state and local laws over the last two years. Still, products continued to be available containing compounds not explicitly criminalized, with marketers claiming legal status. Commenters here and elsewhere have argued that this industry would go away if marijuana would simply be decriminalized in the US. Earlier this week, TIME Healthland writer Maia Szalavitz made a good argument for this (or at least FDA regulation of recreational drugs) in the context of Operation Log Jam. Comprehensive action I find two aspects of this initiative quite unique since I began covering the synthetic formerly-legal highs phenomenon. First, Operation Log Jam aimed to address every level of the synthetic designer drug industry: manufacturers, wholesalers, and retailers. From the DEA press release: As of today [26 July], more than 4.8 million packets of synthetic cannabinoids (ex. K2, Spice) and the products to produce nearly 13.6 million more, as well as 167,000 packets of synthetic cathinones (ex. bath salts), and the products to produce an additional 392,000 were seized. In addition, $36 million was also seized in the raids. Among the federal agencies involved was the US Postal Service since the internet-marketed products are sometimes shipped via regular mail. US Customs and Border Protection acted to target the flow of compounds synthesized non-domestically into the country. And, of course, the IRS was involved to, “trace the path of illicit drug proceeds by identifying the financial linkages among the various co-conspirators,” as indicated by Richard Weber, Chief, IRS Criminal...

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NIDA seeks SBIR/STTR apps on Spice, bath salts

C&EN senior business editor Melody Bomgardner dropped me a note yesterday about a new request for applications from NIH’s National Institute on Drug Abuse (NIDA) for small business grants. Read the text below but here’s what I find interesting as a pharmacologist who plays well with chemists: the call for applications is not for analytical methods for designer drugs. Rather the announcement solicits novel methods for detecting some biochemical or pharmacological endpoint of these agents (a bioassay, in old-speak) that doesn’t require new method development every time a new structural analogue pops onto the market. Other areas of substance abuse are also fair game but Melody thought the Spice and bath salts angle would be of greatest interest to our readers here at Terra Sig. Here’s the text directly from NIDA – I can’t find an exact RFA to link to, however: (see update below) NIDA seeks innovative solutions from small businesses, including developing new tests for designer drugs such as Spice, Bath Salts The National Institute on Drug Abuse (NIDA) is seeking new ways of detecting “designer drug” use (e.g., “K2/Spice” or “Bath Salts”) by promoting the development of biofluid drug screens based on pharmacological activity (how the drug works in the body) rather than chemical structure. Because these “designer drugs” are constantly evolving, they frequently evade currently available structure-based drug screens. NIDA is also seeking solutions to a variety of other drug abuse issues. Specific topics of interest could include, but are not limited to: Human Brain Neurochemical and Molecular Imaging Discovery of New Chemical Probes Nanoscience-based Design of Therapies for Substance Abuse Treatment Drug Discovery – Chemistry and Pharmaceutics Preclinical Drug Development Clinical Drug Development High priority will be given to research that seeks to (1) develop innovative technologies, methods or tools or (2) apply emerging and existing methods to develop medications to treat addiction. Grant application deadlines are April 5, August 5, or December 5, 2012. For more information, see the Omnibus Solicitation, issued by the U.S. Department of Health and Human Services: http://grants.nih.gov/grants/funding/sbirsttr1/2012-2_SBIR-STTR-topics.pdf. For more information on NIDA’s SBIR/STTR Program, including tips to improve a grant application, go to: www.drugabuse.gov/funding/funding-opportunities/science-education-grants-contracts/sbirsttr/about-national-institute-drug-abuse-sbirsttr-progra. Here’s an update I received from NIDA Deputy Press Officer Sheri Grabus: Hi, David. We read your post (http://cenblog.org/terra-sigillata/2012/03/15/nida-seeks-sbirsttr-apps-on-spice-bath-salts/), and we greatly appreciate your getting the word out to your readers. You mentioned in your post that you could not find the RFA. This was part of a large “omnibus” solicitation – one that covered various agencies at HHS. The link to the Omnibus Solicitation can be found at http://grants.nih.gov/grants/funding/sbirsttr1/2012-2_SBIR-STTR-topics.pdf. NIDA’s portion starts on page 53. The part specific to developing assays for “designer” drugs of abuse...

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