Tox on the Web: deadly French drug trial, fatal food, and more!

January 23, 2016, 6:42 pm



Must-read post about the catastrophic phase 1 French drug trial: In a superb must-read post at the Forbes magazine website,  David Kroll discusses what we know about the disastrous drug safety trial in France that left 1 subject dead and 4 others with varying degrees of neurological damage.The drug in question — named BIA 10-2474 — is an inhibitor of the enzyme fatty acid amide hydrolase (FAAH) that was being developed as a new oral analgesic. As Kroll explains:

What’s so important about FAAH? Our bodies make several fatty acid amides that include anandamide, a natural stimulator of the cannabinoid receptors upon which chemicals in the marijuana plant act. Anandamide is referred to as an endocannabinoid. The rational is that a drug blocking FAAH will allow naturally-occuring anandamide to accumulate and act on cannabinoid receptors in a manner that won’t produce the psychoactive effects of cannabis.

However, since the inhibitory effect of BIA 10-2474 on FAAH is likely irreversible, there are potential problems:

. . . any time a small molecule is designed to irreversibly bind to an enzyme, an opportunity arise [sic] for the immune system to recognize it as foreign. In rare cases, the immune system will mount an inflammatory response against it, but also against regions of the normal enzyme surrounding where the drug binds. This response can result in a hypersensitivity or autoimmune reaction in a subset of individuals whereby the immune system attacks everywhere the enzyme is present.

Much is not yet known about what caused this tragedy, and the story continues to unfold. For now, this is by far the most important post of the week. (HT @DavidJuurlink)



Casu Marzu

Casu Marzu

Deadly delicacies: The “Food & Drink” section of features an article on the 10 dishes that might kill you. The list includes the usual suspects (fugu, cassava) and some more exotic choices such as sannakji (Korean live baby octopus) and casu marzu (a Sardinian sheep milk cheese that contains live maggots.) Bon appetit! H/T @JillianTheobald

Litvinenko poisoned:
Although its conclusion was not a surprise, an official British report issued this week concluded that former K.G.B. agent Alexander V. Litvinenko — who died in 2006 after ingesting tea at a London hotel — had been poisoned with the radioactive isotope polonium 210. The New York Times reported that the murder was “probably” carried out with the approval of Russian President Vladimir V. Putin.

Podcast Pick: The current edition of the Journal of Medical Toxicology podcast reviews the December 2015 edition. Howard Greller and Dan Rusyniak have a nice discussion of take-home lessons from the article purple glove syndrome that TPR reviewed several days ago. They also discuss papers about use of methylene blue for drug-induced vasodilatory shock, adult lead encephalopathy — with a level of 148 μg/dL! — from drinking moonshine, and burn injuries from attempts to home brew butane hash oil,


By the way, Howard and Dan announced that this edition will be their next-to-last at the helm of the podcast. JMT is looking for suitable replacements. Those interested should contact the editor, Mark Mycyk.


  1. Lars Says:

    New things have emerged in the BIA 10-2474 trial since Kroll wrote about it, such as a trial protocol: (for starters, the compound is supposedly a reversible inhibitor)

  2. Leon Says:


    Thank you for the comment. Although I can’t say I’ve read all that has been written about BIA 10-2474, my sense is that at this point it is not clear whether the compound’s inhibition of FAAH is reversible or irreversible.