Synthetic cannabinoids produced significantly more seizures than THC in mice | Research

The takeaway

In a direct comparison, synthetic cannabinoids JWH-073 and AM-2201 produced significantly more convulsions than THC in mice, while the endogenous cannabinoid analog methanandamide caused zero seizures despite producing greater hypothermia than THC.

Harm reduction advocates, poison control professionals, people using or considering synthetic cannabinoids

Synthetic cannabinoids caused significantly more seizures than THC; endogenous cannabinoid analogs caused none

What the researchers found

JWH-073 and AM-2201 produced significantly more convulsions than THC, HU-210, methanandamide, or CBD. Methanandamide caused no seizures but produced greater hypothermia than THC. Convulsions and hypothermia from several agonists were blocked by a CB1 antagonist but not a CB2 antagonist.

Why it matters

Synthetic cannabinoids found in street products have been linked to seizures and deaths in humans. This study provides controlled evidence that synthetics are genuinely more seizure-prone than THC.

The numbers in context

JWH-073 and AM-2201 produced significantly more convulsions than THC. Methanandamide and CBD produced zero convulsions. Seizure-inducing effects were CB1-mediated (blocked by CB1 but not CB2 antagonist).

How the study worked

Mice received intraperitoneal injections of THC (50 mg/kg), JWH-073 (30 mg/kg), AM-2201 (1 mg/kg), or other cannabinoids at various doses. Convulsions and body temperature changes were quantified. Chronic dosing with tolerance and withdrawal assessment was also performed.

What this study cannot tell us

Mouse model; doses were matched for equivalent analgesic/hypothermic potency rather than recreational potency; limited number of synthetic compounds tested relative to the hundreds on the market.

How to read the evidence

Controlled animal study comparing multiple compounds, but limited to a mouse model with a small subset of available synthetic cannabinoids.

When this study was published

Published in 2020.

The bigger picture

The stark difference between THC and synthetic cannabinoids in seizure potential helps explain the clinical reports of severe adverse events from synthetic products and supports harm reduction messaging that synthetics carry qualitatively different risks.

Questions still open

What structural features of synthetic cannabinoids make them more seizure-prone? Could this information guide risk classification of novel synthetic compounds?

Common questions

Why are synthetic cannabinoids more dangerous than THC?

This study found synthetics like JWH-073 and AM-2201 produced significantly more seizures than THC at equivalent potency doses. The effects were CB1-mediated, but the specific structural features that make synthetics more seizure-prone are still being investigated.

Did CBD cause seizures in this study?

No. CBD produced zero convulsions, consistent with its known anticonvulsant properties and its approval as an anti-seizure medication.

Read the original research

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.

Cannabis and cannabinoid research, 5(1), 32-41

View on PubMed ↗Publisher’s paper ↗

Citation

Breivogel, Chris S; Wells, Jacob R; Jonas, Amreen; Mistry, Artik H; Gravley, Morgan L; Patel, Rajul M; Whithorn, Brianna E; Brenseke, Bonnie M. (2020). Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.. Cannabis and cannabinoid research, 5(1), 32-41. https://doi.org/10.1089/can.2019.0003