Synthetic cannabinoid receptor agonists act as MAO-A-specific inhibitors, which could explain severe side effects like cardiac arrest that are inconsistent with cannabinoid receptor activation alone.
Toxicologists, emergency physicians, forensic scientists, and synthetic cannabinoid researchers.
MAO-A specificinhibition by synthetic cannabinoids, with potency varying by SCRA head group structure
What the researchers found
Combining computational and experimental kinetics, researchers demonstrated that synthetic cannabinoids are MAO-A-specific inhibitors, with potency varying significantly based on the SCRA head group structure.
Why it matters
Synthetic cannabinoids cause severe, sometimes fatal side effects that cannot be explained by cannabinoid receptor activity. MAO-A inhibition provides a mechanistic explanation for hypertensive crises and cardiac events.
The numbers in context
Multiple commonly used UK SCRAs tested. MAO-A specific inhibition confirmed. Potency varied significantly between SCRA structures. MAO-B was not inhibited.
How the study worked
Combined in silico molecular modeling and experimental kinetic studies assessing MAO-A and MAO-B inhibition by a range of SCRAs and structural analogues.
Who was studied
Not applicable (in vitro and computational pharmacology study).
What this study cannot tell us
In vitro and in silico data; clinical relevance of MAO-A inhibition at recreational SCRA doses not established. Limited to UK-prevalent SCRAs. Does not address all SCRA side effects.
How to read the evidence
Novel mechanistic discovery combining computational and experimental approaches; clinical validation needed.
When this study was published
Recent pharmacological discovery with implications for SCRA toxicology.
The bigger picture
This discovery that synthetic cannabinoids have off-target MAO-A activity fundamentally changes our understanding of their toxicology and could inform emergency treatment approaches for SCRA overdoses.
Replication
Novel mechanism; clinical validation and broader SCRA testing needed.
Funding
Not specified in abstract
Conflicts of interest
Not specified in abstract
Questions still open
- Should SCRA overdose treatment include MAO-inhibitor toxicity protocols?
- Do other off-target activities contribute to the diverse side effect profile of SCRAs?
Read the original research
Synthetic cannabinoid receptor agonists are monoamine oxidase-A selective inhibitors.
The FEBS journal, 290(12), 3243-3257
Citation
Hindson, Sarah A; Andrews, Rachael C; Danson, Michael J; van der Kamp, Marc W; Manley, Amy E; Sutcliffe, Oliver B; Haines, Tom S F; Freeman, Tom P; Scott, Jennifer; Husbands, Stephen M; Blagbrough, Ian S; Anderson, J L Ross; Carbery, David R; Pudney, Christopher R. (2023). Synthetic cannabinoid receptor agonists are monoamine oxidase-A selective inhibitors.. The FEBS journal, 290(12), 3243-3257. https://doi.org/10.1111/febs.16741