Parrots lost their CB2 cannabinoid receptor gene and are more vulnerable to brain inflammation | Research

The takeaway

Parrots evolutionarily lost the CB2 cannabinoid receptor gene, and experiments show this makes their brains more susceptible to inflammation compared to birds that retained the gene.

Neuroscience enthusiasts and researchers interested in the endocannabinoid system's role in brain protection.

All parrot species lost their CB2 gene through evolution

What the researchers found

All parrots (Psittaciformes) have a nonfunctional CB2 gene due to chromosomal rearrangements. When exposed to an inflammatory stimulus, parrot brains showed significant upregulation of pro-inflammatory cytokines (IL1B and IL6), while birds with intact CB2 genes (passerines) did not show the same neuroinflammatory response.

Why it matters

This is one of the clearest demonstrations of how important the CB2 cannabinoid receptor is for controlling brain inflammation, using a natural evolutionary "knockout" experiment.

The numbers in context

CB2 gene loss confirmed across all Psittaciformes. Six parrot species tested. Pro-inflammatory cytokines IL1B and IL6 were significantly upregulated in parrot brains but not in passerine brains after inflammatory challenge.

How the study worked

Comparative genomic analysis across bird species to identify CB2 gene losses, followed by experimental brain inflammation studies comparing CB2-deficient parrots (budgerigars and 5 other species) with CB2-intact passerines (zebra finches) using lipopolysaccharide stimulation and transcriptomic analysis.

What this study cannot tell us

Bird brains differ significantly from mammalian brains. The absence of compensatory CB1 adaptations in parrots does not mean the same would apply to mammals.

How to read the evidence

Robust genomic analysis combined with experimental validation across multiple species, though cross-species extrapolation to humans is limited.

When this study was published

Published in 2022.

The bigger picture

Understanding what happens when the CB2 receptor is naturally absent helps researchers grasp why the endocannabinoid system matters for brain health, with implications for conditions involving neuroinflammation in humans.

Questions still open

Are parrots more prone to neurodegenerative conditions because of this gene loss? Could CB2-targeting drugs reduce neuroinflammation more effectively than broad-spectrum cannabinoids?

Common questions

Why does losing CB2 matter for brain inflammation?

CB2 receptors help regulate immune responses. Without them, parrots showed significant increases in pro-inflammatory molecules (IL1B and IL6) in their brains when exposed to an inflammatory trigger, while birds with CB2 did not.

Could the CB1 receptor compensate for the loss?

The researchers found no evidence that parrot CB1 receptors evolved special adaptations to compensate for the missing CB2, suggesting the two receptors have distinct and non-interchangeable roles in neuroimmune regulation.

Read the original research

Cannabinoid receptor 2 evolutionary gene loss makes parrots more susceptible to neuroinflammation.

Proceedings. Biological sciences, 289(1988), 20221941

View on PubMed ↗Publisher’s paper ↗

Citation

Divín, Daniel; Goméz Samblas, Mercedes; Kuttiyarthu Veetil, Nithya; Voukali, Eleni; Świderská, Zuzana; Krajzingrová, Tereza; Těšický, Martin; Beneš, Vladimír; Elleder, Daniel; Bartoš, Oldřich; Vinkler, Michal. (2022). Cannabinoid receptor 2 evolutionary gene loss makes parrots more susceptible to neuroinflammation.. Proceedings. Biological sciences, 289(1988), 20221941. https://doi.org/10.1098/rspb.2022.1941