Systematic review of deaths involving synthetic cannabinoids found no reliable toxic dose ranges | Research

The takeaway

A systematic review of 34 published reports of deaths involving synthetic cannabinoid receptor agonists found that typical toxic dose ranges have not been identified, and cause of death often remained unclear even after thorough investigation.

Forensic pathologists, toxicologists, emergency physicians, and drug policy researchers.

No typical toxic dose ranges established for synthetic cannabinoids

What the researchers found

No reliable toxic or lethal concentration ranges have been established for synthetic cannabinoids. Even after comprehensive post-mortem examination, toxicology, and circumstantial analysis, the cause and manner of death remained unclear in some cases.

Why it matters

Synthetic cannabinoids are the largest group of new psychoactive substances in Europe, yet forensic pathologists and toxicologists still lack basic reference data for determining whether these substances caused a death.

The numbers in context

380 studies identified, 34 included. 8 case series and 26 case reports analyzed. Toxicological results must be interpreted with caution due to the absence of established toxic ranges.

How the study worked

Systematic literature search through January 2019 across multiple databases. Included death cases with toxicological confirmation of synthetic cannabinoids in blood or urine and at least an external examination. 34 manuscripts (8 case series, 26 case reports) were included.

What this study cannot tell us

Limited to published case reports and series, which may not represent all deaths. Post-mortem redistribution can alter drug concentrations. Many cases involved polydrug use, complicating attribution.

How to read the evidence

Moderate: systematic review methodology applied to inherently limited case report data.

When this study was published

Published in 2020 in Frontiers in Psychiatry.

The bigger picture

The inability to establish toxic dose ranges reflects both the rapid emergence of new synthetic cannabinoid compounds and their unpredictable pharmacology, making these substances uniquely challenging for forensic medicine.

Questions still open

Will toxic ranges eventually be established as more data accumulates? How should medical examiners approach cases where synthetic cannabinoid involvement is uncertain?

Common questions

Why can't scientists determine lethal doses?

Synthetic cannabinoids are a rapidly changing class of drugs with hundreds of different compounds. Each has different potency, and post-mortem drug levels can change after death, making it very difficult to establish what concentration is lethal.

How do people die from synthetic cannabinoids?

The mechanisms vary and are often unclear. Reported causes include cardiac events, respiratory failure, and accidents while intoxicated. In many cases, even thorough investigation could not definitively determine whether the synthetic cannabinoid caused the death.

Read the original research

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists.

Frontiers in psychiatry, 11, 464

View on PubMed ↗Publisher’s paper ↗

Citation

Giorgetti, Arianna; Busardò, Francesco Paolo; Tittarelli, Roberta; Auwärter, Volker; Giorgetti, Raffaele. (2020). Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists.. Frontiers in psychiatry, 11, 464. https://doi.org/10.3389/fpsyt.2020.00464