Researchers found important structural differences between baboon and human endocannabinoid system genes, meaning drug safety results from primate studies may not directly translate to humans.
Read this if you are interested in how animal studies of cannabis translate to human health, especially regarding pregnancy safety.
CB2 receptor gene differed between baboons and humans at the only known clinically relevant human polymorphism site.
What the researchers found
Researchers cloned and characterized the genes encoding key components of the endocannabinoid system in baboons and compared them to human versions. They found that while CB1 receptor genes were highly conserved between species, there were meaningful differences in other components.
The CB2 receptor gene showed a difference in the exact region containing the only known clinically relevant human polymorphism, suggesting this receptor may function differently in baboons than humans.
The enzyme DAGL-alpha, which helps produce the endocannabinoid 2-AG, showed differences near critical phosphorylation sites. These differences could affect how the enzyme is regulated.
The findings mean that studies testing cannabis effects in baboons and other non-human primates need to account for these species-specific differences, particularly in developmental toxicology studies relevant to cannabis use during pregnancy.
Why it matters
Non-human primates are used to study the developmental effects of cannabis, particularly for understanding risks during pregnancy. If their endocannabinoid systems differ from humans in functionally important ways, safety conclusions from these studies may not directly apply to human pregnancy.
The numbers in context
CNR1 (CB1 receptor gene) was the best conserved between species. CB2 receptor showed a difference at the only known clinically relevant human polymorphism site. All DAGL-alpha differences were near phosphorylation sites in the hydroxylase domain.
How the study worked
Researchers used PCR to amplify endocannabinoid system genes (CNR1, CNR2, FAAH, MAGL, DAGL-alpha) from baboon tissues. The sequences were cloned, verified, and compared to known human sequences including single nucleotide polymorphisms and haplotypes.
What this study cannot tell us
This was a comparative genomics study focused on gene structure, not function. The actual functional consequences of the sequence differences have not been tested. The sample size of baboon tissues was not specified. The study characterized cDNA sequences but did not measure protein expression or receptor binding differences.
How to read the evidence
Preliminary evidence from a comparative genomics study. The structural differences are documented but their functional significance remains to be tested.
When this study was published
Published in 2016. Species differences in cannabinoid receptors continue to be relevant for translational research.
The bigger picture
As cannabis use during pregnancy increases, developmental toxicology studies in primates are used to assess risks. This study highlights that even closely related primates have evolved differences in their endocannabinoid systems, and these differences may affect how they respond to cannabinoids. Researchers need to factor in these differences when extrapolating from primate studies to human health.
Questions still open
- Do the CB2 receptor differences between baboons and humans affect actual receptor function? How do endocannabinoid system differences across primate species affect the interpretation of cannabis developmental toxicology studies? Should primate cannabis studies account for species-specific receptor variants?
Common questions
Can animal studies of cannabis be trusted for human health?
Why does this matter for cannabis and pregnancy research?
Read the original research
The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology.
Neurotoxicology and teratology, 58, 23-30
Citation
Rodriguez-Sanchez, Iram P; Guindon, Josee; Ruiz, Marco; Tejero, M Elizabeth; Hubbard, Gene; Martinez-de-Villarreal, Laura E; Barrera-Saldaña, Hugo A; Dick, Edward J; Comuzzie, Anthony G; Schlabritz-Loutsevitch, Natalia E. (2016). The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology.. Neurotoxicology and teratology, 58, 23-30. https://doi.org/10.1016/j.ntt.2016.06.006
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