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Category → Toxicology

Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug

Acetyl fentanyl HCl, courtesy of Cayman Chemical Company. Click on the image to view the source page.

Acetyl fentanyl HCl, courtesy of Cayman Chemical Company. Click on the image to view the source page.

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 thoughts?

The Cinnamon Challenge: On Being Charged with #Chemophobia

Consider cinnamaldehyde.

Consider cinnamaldehyde.

As many of you are likely to have heard yesterday, a paper from Steven Lipshultz, MD, at the University of Miami appeared in the journal Pediatrics detailing poison control center reports on an adolescent misadventure called The Cinnamon Challenge. The challenge: to swallow a teaspoon of cinnamon powder in 60 seconds without any liquids.

The practice has been rummaging about the internet since 2001 but really took off on YouTube over the last three years. Lipshultz’s report discusses the risks of such tomfoolery, particularly due to the inhalation of cinnamon powder while one is choking.

I planned to write about this practice both here and at my Forbes.com blog since I thought both chemists and the general public would be interested in the topic. I wrote the Forbes post earlier this morning and drew a series of comments from a kindly San Diego-area chemist who took issue with my facetious comparison of cinnamaldehyde (cinnamic aldehyde) to formaldehyde.

While Lipshultz states that much of the acute pulmonary toxicity of cinnamon powder is likely due to the cellulose content, I submit that some damage could be due to protein adducts formed by cinnamaldehyde. Yes, yes, it’s not as dangerous as formaldehyde. But even at roughly 1% (w/w) in the powder, I hypothesize that the cinnamaldehyde could cause epithelial damage. Also note that cinnamaldehyde is not just any aldehyde but rather an unsaturated aldehyde. That makes me think of acrolein.

The experiments have not been done. But one animal study has been published showing that intratracheal administration of cinnamon powder — not pure cinnamaldehyde — can cause acute lung injury in rats and trigger pulmonary fibrosis within a month.

Alas, my concerns about cinnamaldehyde rubbed two commenters the wrong way and one, well, sought to chemsplain me.

I was originally trained in toxicology so I know the whole Paracelsan story that the dose makes the poison (to which I’d also add “route of administration”). But do you chemists, especially those in chemical toxicology, think that I’m overreacting (as it were) to the potentially reactive nature of cinnamaldehyde in inhaled cinnamon powder?

I’m willing to be corrected if I appear to suffer from #chemophobia. But I hypothesize that 1% (w/w) cinnamaldehyde can be cytotoxic.

Criminal Poisoning Arrest at a Hometown Chemical Company

Here’s a brief on a sad story I came across while trolling for news at home via northjersey.com.

 A former employee at a Carlstadt chemical plant allegedly attempted to poison a coworker’s coffee with an antifreeze ingredient and sprayed acid on her coat, Carlstadt Police said.

[. . .]

A supervisor had allegedly observed a video of DeJesus putting methanol, commonly used in antifreeze, into a coworker’s coffee, Carlstadt Det. John Cleary said. The chemist was also accused of spraying [t]richloroacetic acid, which is used to chemically peel skin, on the same employee’s coat, purse and workspace. These substances were part of the company’s inventory, authorities said.

I think I understand why she’s a former employee.

The accused listed her address in my hometown of 11,000, Wallington, just on the other side of the tracks (literally) from her employer, Sonar Products.

The writer, Meghan Grant of the South Bergenite newspaper, seemed to underestimate the risk of drinking methanol. She cited liver and kidney injury without noting that formic acid and formaldehyde metabolites could cause blindness in the victim.

I left a note for Grant to keep us apprised on the status of the victim.

Source:
Grant, Meghan. Carlstadt chemist accused of poisoning coworker. South Bergenite, 15 November 2012.

 

Naming Genes Unlike Named Reactions

Our best wishes to all of you in the Northeast getting ready for Hurricane Sandy. I understand that even DC is closed today. So if you still have power at home, let me share a bit of levity with you.

Meghan Radford, science writer and NC State graduate student in zoology. Credit: Meghan Radford.

Over the weekend I learned that my science writing student, Meghan Radford (@meradfor), had a clever piece published at mental_floss, the magazine and website, “where knowledge junkies get their fix.”

Megan’s article entitled, “18 Gene Names that Cover the Gamut, From Movies to Pop Culture to Cartoons,” illustrates the comical yet discordant and unscientific process behind naming genes.

Her article reminded me of C&EN’s Carmen Drahl when she wrote about named reactions in both the magazine (C&EN, 17 May 2010) and her Newscripts blog here at CENtral Science.

I’m not familiar with any genes that are named after the person who discovered them but, as Radford points out, a great many have been given interesting colloquial names. International gene nomenclature organizations exist but the standardized rules of these committees still make refer to the less formal names.

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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.).
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Poisons and Policy: Arsenic and Aflatoxins

The other problem. Credit: Nakhonsawan Field Crop Research Center, Thailand.

In the past 24 hours, do you recall hearing anything about arsenic in rice? If you’re in the United States, the answer is very likely, “yes!”

A great many pixels were spilled yesterday when Consumer Reports and the US Food and Drug Administration released — almost simultaneously — analytical data on inorganic arsenic concentrations in 200 samples of commercial rice products, particularly those grown in the southern US.

You can’t do any better in understanding this story than reading, “Arsenic and Rice. Yes, again,” on Deborah Blum’s Elemental blog at Wired Science Blogs. Professor Blum has been discussing arsenic in the diet for a few years, an interest she developed while composing her superb book, The Poisoner’s Handbook: Murder and the Birth of Forensic Science in Jazz Age New York.

Deborah’s post puts in perspective the risks of inorganic (and organic) arsenic concentrations in food products such as rice relative to drinking water. Arsenic occurs in nature but exists in higher concentrations in water from areas where arsenical pesticides have been used in cotton farming or poultry deworming (the latter discussed in 2006 at NYTimes). While she closes in being critical of the FDA for lack of clear consumer guidance, let it suffice to say that no character in Blum’s book was killed by poisoning with rice from Louisiana.

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RTI scientists solving forensic, designer drug mysteries

Kerstin Nordstrom, PhD, AAAS Mass Media Fellow, News & Observer. Credit: Losert Laboratory/Univ of Maryland.

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.

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How Do You Like Your Caffeine?

Inhaled or oral?

Natural or synthetic?

Two interesting reports came across the interwebs over the last couple of days.

Earlier this week, the US Food and Drug Administration issued a warning letter (press release) to makers of Aeroshot brand of inhaled caffeine. No, it’s not an asthma medicine (although oral theophylline is). It’s billed as a non-caloric caffeine delivery system, 100 mg per hit. That’s roughly the amount in two 12 fl oz/355 mL cans of Mountain Dew or one gulp more than a 8.4 fl oz/250 mL can of Red Bull energy drink. However, the company claims that only 15-25 mg are delivered – perhaps half the amount in a Coca-Cola.

The FDA has concerns about the dual promotion of the product for swallowing and inhalation, the relative safety of inhaled caffeine, and the potential for children and adolescents to use the product in combination with alcohol. The company’s FAQ specifically notes that the product is not marketed for use in children. Readers will recall that Four Loko caffeinated alcohol drinks were withdrawn from the market in late 2010 and replaced with alcohol-only versions.

From Zhang et al., doi:10.1021/ac203197d

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Was Demi Moore smoking synthetic marijuana?

My substance abuser writer and researcher friend DrugMonkey (@drugmonkeyblog) just tweeted a CNN story suggesting that actress Demi Moore may have suffered adverse reactions after smoking a synthetic cannabimimetic product:

A woman called 911 soliciting help for actress Demi Moore, whom she said was “convulsing” and “burning up” after “smoking something,” according to a recording of the call obtained Friday from the Los Angeles Fire Department.

[. . .]

“She smoked something — it’s not marijuana, but it’s similar to incense. And she seems to be having convulsions of some sort.”

Reports of tremors and seizures have been accumulating in association with synthetic marijuana products. These products are generally composed of an herbal material that is spiked with one or more synthetic compounds that act at cannabinoid CB1 receptors.

The “burning up” described by the 911 caller in the story would be consistent with some reports of serotonin-like syndrome associated with synthetic marijuana use.

The US Drug Enforcement Agency is currently regulating some of the psychoactive compounds as Schedule I substances, illegal for use or sale as they are deemed as having no medical value. Individual states have also issued bans on compounds containing even more related compounds in these products. However, marketers have been skirting laws by using compounds not expressly deemed illegal in state or federal statutes.

Moreover, analytical crime laboratories across the nation have suffered extensive budget cuts making it difficult to keep up with the demands in determinig which products are illicit.

On a personal note, the synthetic marijuana story that DrugMonkey, dr_leigh, and I have been writing about for two years is growing increasingly disturbing. I just received my second reader email in three months from a father whose son shot himself to death while allegedly addicted to synthetic marijuana products. We’ve been in touch with the US DEA to inquire as to whether similar cases are currently under investigation.

Just as DrugMonkey wrote awhile back (I have to find the post), adverse drug effects with celebrities are usually required before aggressive government action is taken against illicit drugs (death of University of Maryland basketball player Len Bias from cocaine and a congenital cardiac abnormality).

FDA Withdraws Avastin Approval for Breast Cancer

Schematic of humanized anti-VEGF antibodies. Credit: Steinbrook R. NEJM 2006; 355:1409-1412. Click on illustration for the source article.


 
As reported around the wires today, US FDA Commissioner Dr. Margaret A. Hamburg formally revoked the accelerated approval of the antiangiogenic drug Avastin (bevacizumab) for breast cancer treatment. Avastin is a humanized mouse antibody that binds and inactivates the vascular endothelial growth factor VEGF-A, a mediator of blood vessel growth. Andrew Pollack at The New York Times does a nice job condensing this episode for us.

The highlights are that Avastin was approved based on the surrogate endpoint of progression-free survival in metastatic breast cancer, meaning that it appeared to increase the time from treatment to return of the growth of cancer metastases. However, the true endpoint is long-term patient survival. There, subsequent studies showed that Avastin had no benefit.

Moreover, Avastin also use appears to increase the risk of hemorrhage and bowel perforation. These are potentially life-threatening side effects and are considered too great of a risk when no statistical benefit of survival or quality of life are apparent.

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