CB1 cannabinoid receptors mediate endochondral skeletal growth attenuation by Δ9-tetrahydrocannabinol

Elad Wasserman, Joseph Tam, Raphael Mechoulam, Andreas Zimmer, Gila Maor, Itai Bab

Research output: Contribution to journalArticlepeer-review


The endocannabinoid (EC) system regulates bone mass. Because cannabis use during pregnancy results in stature shorter than normal, we examined the role of the EC system in skeletal elongation. We show that CB1 and CB2 cannabinoid receptors are expressed specifically in hypertrophic chondrocytes of the epiphyseal growth cartilage (EGC), which drives vertebrate growth. These cells also express diacylglycerol lipases, critical biosynthetic enzymes of the main EC, and 2-arachidonoylglycerol (2-AG), which is present at significant levels in the EGC. Femora of CB1- and/or CB2-deficient mice at the end of the rapid growth phase are longer compared to wild-type (WT) animals. We find that Δ9-tetrahydrocannabinol (THC) slows skeletal elongation of female WT and CB2-, but not CB1-, deficient mice, which is reflected in femoral and lumbar vertebral body length. This in turn results in lower body weight, but unaltered fat content. THC inhibits EGC chondrocyte hypertrophy in ex vivo cultures and reduces the hypertrophic cell zone thickness of CB1-, but not CB2-, deficient mice. These results demonstrate a local growth-restraining EC system in the EGC. The relevance of the present findings to humans remains to be studied.

Original languageAmerican English
Pages (from-to)110-119
Number of pages10
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - 1 Jan 2015


  • Cannabinoid receptors
  • Cannabinoids
  • Diacylglicerol lipases
  • Epiphyseal growth cartilage
  • Hypertrophic chondrocytes
  • Tetrahydrocannabinol

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • General Neuroscience
  • History and Philosophy of Science


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