Synthetic cannabinoid CUMYL-4CN-BINACA causes seizures at extremely low doses in mice | Research

The takeaway

CUMYL-4CN-BINACA is one of the most potent synthetic cannabinoids tested to date, triggering seizures in mice at just 0.3 mg/kg.

Toxicologists, harm reduction workers, emergency physicians, and anyone tracking synthetic cannabinoid risks.

0.3 mg/kg

What the researchers found

CUMYL-4CN-BINACA acted as a potent CB1 receptor agonist and produced seizures at a lower dose than any previously tested synthetic cannabinoid. A CB1 antagonist blocked the seizure activity, while a CB2 antagonist had no effect.

Why it matters

Synthetic cannabinoids keep getting more potent. Understanding which compounds cause seizures and at what doses helps explain why emergency room visits linked to these drugs continue to rise.

The numbers in context

CB1 receptor binding affinity Ki = 2.6 nM; functional potency EC50 = 0.58 nM; seizures observed at 0.3 mg/kg (lowest dose reported for any SCRA).

How the study worked

Researchers tested the compound in mice, measuring hypothermic and pro-convulsant effects, and used receptor antagonists to determine which cannabinoid receptors mediated the effects.

What this study cannot tell us

Mouse study only. Human responses to this compound may differ. The study did not examine chronic exposure or dose-response across a wide range.

How to read the evidence

Preliminary: single animal study with a novel compound, no human data.

When this study was published

Published in 2019.

The bigger picture

The synthetic cannabinoid market evolves rapidly, with new compounds appearing constantly. This study highlights that some newer variants are extraordinarily potent, raising the stakes for users who may not know what they are consuming.

Questions still open

Could structural features like the terminal nitrile group predict seizure risk in other novel synthetic cannabinoids? What is the margin between recreational dose and seizure-inducing dose in humans?

Common questions

What makes CUMYL-4CN-BINACA different from other synthetic cannabinoids?

It contains an unusual terminal nitrile group and caused seizures at a lower dose than any previously tested synthetic cannabinoid.

Does this compound affect CB2 receptors?

Blocking CB2 receptors did not prevent seizures, suggesting the pro-convulsant effects are driven primarily through CB1 receptors.

Read the original research

CUMYL-4CN-BINACA Is an Efficacious and Potent Pro-Convulsant Synthetic Cannabinoid Receptor Agonist.

Frontiers in pharmacology, 10, 595

View on PubMed ↗Publisher’s paper ↗

Citation

Kevin, Richard C; Anderson, Lyndsey; McGregor, Iain S; Boyd, Rochelle; Manning, Jamie J; Glass, Michelle; Connor, Mark; Banister, Samuel D. (2019). CUMYL-4CN-BINACA Is an Efficacious and Potent Pro-Convulsant Synthetic Cannabinoid Receptor Agonist.. Frontiers in pharmacology, 10, 595. https://doi.org/10.3389/fphar.2019.00595