Even Low Doses of Synthetic Cannabinoid JWH-018 Caused Lasting Heart Damage and Multi-Organ Injury in Rats | Research

The takeaway

Two weeks of low-dose JWH-018 in rats produced persistent cardiovascular stimulation, cardiac lesions, mitochondrial dysfunction in heart cells, and multi-organ damage that persisted or worsened after the drug was stopped.

Emergency physicians, cardiologists treating synthetic cannabinoid users, and toxicologists.

Cardiac and multi-organ damage persisted and worsened even after stopping JWH-018

What the researchers found

Repeated JWH-018 at 0.25 mg/kg for 14 days caused persistent hypothermia, increased blood pressure and heart rate throughout treatment. One day after stopping, cardiac lesions (vacuolization, waving, edema) were found. Seven days later, lung, kidney, and liver degeneration appeared. Heart mitochondria showed defective lipid oxidation, suggesting a mechanism for JWH-018's cardiac toxicity.

Why it matters

This study demonstrates that even low doses of a common synthetic cannabinoid can cause lasting organ damage, particularly to the heart. The finding that damage worsens after stopping the drug suggests ongoing pathological processes that outlast drug exposure.

The numbers in context

JWH-018 dose: 0.25 mg/kg for 14 days; cardiac lesions at day 1 post-discontinuation; multi-organ damage at day 7; mitochondrial dysfunction in cardiomyocytes; in silico screening of 36 SCRAs

How the study worked

In silico toxicity screening of 36 synthetic cannabinoids, followed by 14-day repeated dosing of JWH-018 (0.25 mg/kg IP) in male rats, with cardiovascular monitoring during treatment and post-mortem tissue analysis at 1 and 7 days after discontinuation.

What this study cannot tell us

Animal study with a single synthetic cannabinoid and dose level. IP injection does not mimic human smoking/vaping routes. Only male rats studied. Short treatment period relative to human use patterns.

How to read the evidence

Comprehensive animal study combining in silico, in vivo, and ex vivo approaches, but limited to one compound and dose.

When this study was published

Published in 2024.

The bigger picture

Reports of sudden cardiac deaths among synthetic cannabinoid users have been increasing. This study provides a biological mechanism (mitochondrial dysfunction) and shows that damage can progress even after stopping use, which has important clinical implications.

Questions still open

Would cardiac damage from JWH-018 be reversible with longer recovery periods?
Do other commonly used synthetic cannabinoids produce similar cardiac toxicity?

Common questions

Can synthetic cannabinoids damage the heart?

Yes. This study found that even low doses of JWH-018 caused cardiac lesions, mitochondrial dysfunction, and damage that worsened after stopping the drug.

Is the damage reversible?

In this study, damage actually progressed after the drug was stopped, with multi-organ effects appearing a week later. Whether longer recovery leads to healing is unknown.

Read the original research

Evidence for enduring cardiac and multiorgan toxicity after repeated exposure to the synthetic cannabinoid JWH-018 in male rats.

Toxicology, 507, 153878

View on PubMed ↗Publisher’s paper ↗

Citation

Pintori, Nicholas; Serra, Maria Pina; Carai, Antonio; Lobina, Carla; Isola, Raffaella; Noli, Roberta; Piras, Gessica; Spano, Enrica; Baumann, Michael H; Quartu, Marina; De Luca, Maria Antonietta. (2024). Evidence for enduring cardiac and multiorgan toxicity after repeated exposure to the synthetic cannabinoid JWH-018 in male rats.. Toxicology, 507, 153878. https://doi.org/10.1016/j.tox.2024.153878