Synthetic cannabinoids cause severe toxicity including heart damage and death, unlike natural cannabis | Research

The takeaway

Synthetic cannabinoid receptor agonists, the most commonly abused new psychoactive substances, act as full receptor agonists and cause severe toxicity including cardiotoxicity, immunotoxicity, and death, unlike natural THC.

Emergency physicians, substance use counselors, public health officials, anyone encountering synthetic cannabinoid products

Full agonist activity makes synthetic cannabinoids fundamentally more dangerous than natural cannabis

What the researchers found

SCRAs are the most commonly abused new psychoactive substances worldwide. Unlike natural THC (a partial agonist), most SCRAs are full CB1 and CB2 agonists, producing much greater effects. Associated toxicities include cardiotoxicity, immunotoxicity, and death.

Why it matters

The fundamental pharmacological difference between natural cannabis (partial agonist) and synthetic cannabinoids (full agonists) explains why synthetics are so much more dangerous and why natural cannabis safety data cannot be applied to them.

The numbers in context

NPS classified into six groups; SCRAs are the largest class; sold as herbal incense, bath salts, legal highs; some classified as Schedule 1 in the US

How the study worked

Review of the general pharmacological characteristics, recent findings, and adverse effects of synthetic cannabinoid receptor agonists, focusing on their mechanism of action and clinical toxicity.

What this study cannot tell us

Rapidly evolving landscape of new compounds makes any review potentially outdated. Clinical data is primarily from case reports and poison control data rather than systematic studies.

How to read the evidence

Review synthesizing pharmacological data and clinical toxicology reports

When this study was published

Published in 2021. New synthetic cannabinoid compounds continue to emerge on the illicit market.

The bigger picture

Understanding the pharmacological basis for synthetic cannabinoid toxicity is essential for emergency physicians and for public messaging that distinguishes these products from natural cannabis.

Questions still open

Can emergency departments reliably detect synthetic cannabinoids? Would wider access to natural cannabis reduce synthetic cannabinoid use? Are there effective treatments for acute synthetic cannabinoid toxicity?

Common questions

Why are synthetic cannabinoids more dangerous than natural cannabis?

Natural THC is a partial agonist at cannabinoid receptors, meaning it only partially activates them. Synthetic cannabinoids are full agonists, maximally activating the receptors and causing much more severe effects including organ toxicity and death.

What are the health risks of synthetic cannabinoids?

Documented toxicities include cardiotoxicity (heart damage), immunotoxicity (immune system damage), and death. These effects are not seen with natural cannabis at typical doses because of the fundamental pharmacological difference.

Read the original research

Pharmacology and adverse effects of new psychoactive substances: synthetic cannabinoid receptor agonists.

Archives of pharmacal research, 44(4), 402-413

View on PubMed ↗Publisher’s paper ↗

Citation

Chung, Eun Yong; Cha, Hye Jin; Min, Hyun Kyu; Yun, Jaesuk. (2021). Pharmacology and adverse effects of new psychoactive substances: synthetic cannabinoid receptor agonists.. Archives of pharmacal research, 44(4), 402-413. https://doi.org/10.1007/s12272-021-01326-6