First large study links synthetic cannabinoid blood levels to consciousness impairment in 71 patients | Research

The takeaway

In 71 patients who used the synthetic cannabinoid 5F-MDMB-PICA, blood concentrations of the drug correlated with CB1 receptor activation in a sigmoidal pattern, and higher activation was linked to decreased consciousness.

Emergency physicians, toxicologists, and public health officials dealing with synthetic cannabinoid poisonings.

71 patients; higher blood levels predicted decreased consciousness

What the researchers found

Serum concentrations of 5F-MDMB-PICA correlated with ex vivo CB1 receptor activation in a sigmoidal relationship. The Glasgow Coma Scale showed a significant decreasing trend with increasing cannabinoid activity, meaning higher drug levels corresponded with greater impairment of consciousness. In vitro testing of five metabolites revealed two theoretically active metabolites, but in vivo their contribution to overall cannabinoid activity was negligible.

Why it matters

Synthetic cannabinoids are far more dangerous than natural cannabis, and this is the first large patient cohort study to link 5F-MDMB-PICA blood levels to clinical outcomes. The dose-response relationship between drug levels and consciousness impairment provides crucial toxicological data.

The numbers in context

71 patients. 5F-MDMB-PICA and five metabolites identified. Sigmoidal relationship between serum concentration and CB1 activation. Significant trend of decreasing GCS with increasing cannabinoid activity. Two metabolites showed in vitro activity but negligible in vivo contribution.

How the study worked

Evaluation of 71 patients presenting with recreational drug toxicity from 5F-MDMB-PICA. LC-HRMS confirmed and quantified the drug in serum. A CB1 bioassay measured ex vivo cannabinoid activity. Clinical features including Glasgow Coma Scale were correlated with drug levels.

What this study cannot tell us

Single synthetic cannabinoid studied. Patients may have used other substances not detected. GCS is a crude measure of impairment. The correlation between blood levels and clinical effects may not hold for other synthetic cannabinoids with different pharmacology.

How to read the evidence

Large clinical cohort with quantitative pharmacological analysis linking drug levels to clinical outcomes.

When this study was published

Published in 2022.

The bigger picture

The ability to predict clinical severity from blood levels and in vitro pharmacological data represents a step toward rapid risk assessment for synthetic cannabinoid poisonings, which are becoming more common.

Questions still open

Can this pharmacological prediction approach be applied to other synthetic cannabinoids? Would point-of-care testing for these compounds improve emergency treatment?

Common questions

How dangerous are synthetic cannabinoids?

In this study of 71 patients who used 5F-MDMB-PICA, higher blood concentrations were significantly associated with decreased consciousness, as measured by the Glasgow Coma Scale.

Can doctors predict how sick someone will get from synthetic cannabinoids?

This study showed that blood levels of 5F-MDMB-PICA correlated with CB1 receptor activation in a predictable sigmoidal pattern, and that activation level predicted the degree of consciousness impairment.

Read the original research

Linking in vitro and ex vivo CB1 activity with serum concentrations and clinical features in 5F-MDMB-PICA users to better understand SCRAs and their metabolites.

Archives of toxicology, 96(11), 2935-2945

View on PubMed ↗Publisher’s paper ↗

Citation

Janssens, Liesl K; Hudson, Simon; Wood, David M; Wolfe, Caitlin; Dargan, Paul I; Stove, Christophe P. (2022). Linking in vitro and ex vivo CB1 activity with serum concentrations and clinical features in 5F-MDMB-PICA users to better understand SCRAs and their metabolites.. Archives of toxicology, 96(11), 2935-2945. https://doi.org/10.1007/s00204-022-03355-6