Translating Knowledge of Synthetic Cannabinoids to Help Treat Poisonings

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By Krista Greenwood posted 03-15-2018 06:38

  

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The Clinical and Translational Toxicology Specialty Section (CTTSS), founded in 2011, is one of the newer SOT Specialty Sections. A focus of the CTTSS is improving the management of human poisoning by using a translational approach that links molecular mechanisms to rational therapy. The “Clinical and Translational Toxicology: From Theory to Therapy” session during the 2018 Annual Meeting and ToxExpo had many good talks about exposure to nerve agents, identification of new biomarkers, and translation from in vitro testing to approved products and treatments.

The one presentation that really exemplified improving the management of human poisoning was given by Dr. Sally Bradberry, National Poisons Information Service (United Kingdom, Birmingham Unit). She described the patients she encounters daily who are suffering from intoxication by synthetic cannabinoids. Synthetic cannabinoids are potent agonists at CB1 and CB2 receptors, ten to 100 times more potent than Δ9‑THC, which is only a partial agonist of the receptors.

Patients present in the Emergency Room with variable and unpredictable symptoms, such as agitation, delirium, and psychosis, and sometimes with respiratory failure. They are also typically tachycardic and hypotensive. Many of these symptoms are also associated with other medical conditions, so it is in the benefit of the doctors, and the patients, to identify early on if synthetic cannabinoids are responsible for their visit to the Emergency Room, otherwise there are many additional resources that are used trying to find the cause of their symptoms. One of the difficulties with synthetic cannabinoids is that there are thousands of potential analogs, so having a drug screen that covers all of them is nearly impossible. Dr. Bradberry was able to work closely with an analytical group at a hospital to devise a UPLC-MS/TOF assay. They collected samples from synthetic cannabinoids that were seized by police and were able to identify one compound, 5F-AKB-48, that was in 82% of the samples. They then collected urine samples from patients thought to be suffering from synthetic cannabinoid intoxication and were not able to identify the parent compound; however, they were able to find one of the metabolites.

There are now ultra‑potent, fourth-generation synthetic cannabinoids that began showing up in samples collected in 2016 and 2017 which were not present in screening that was done in 2014 and 2015. This shows just how quickly the synthetic cannabinoids are changing and it provides an analytical challenge for them to keep up with the identification of new parent or metabolite compounds.

This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email SOT Communications Director Michelle Werts.

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