Juvenile cannabidiol chronic treatments produce robust changes in metabolic markers in adult male Wistar rats

Eur J Pharmacol. 2021 Nov 5:910:174463. doi: 10.1016/j.ejphar.2021.174463. Epub 2021 Sep 1.


The use of cannabidiol (CBD), the non-psychotropic compound derived from Cannabis sativa, for therapeutic purposes is growing exponentially by targeting the management of multiple medical disorders, including metabolic-related diseases. Nevertheless, substantial questions have emerged in concerning the potential metabolic disturbances in adulthood as consequence of the long-term uses of CBD during early years of life. Therefore, we studied whether chronic CBD injections (5, 10 or 30 mg/kg; i.p.) given to juvenile rats (from post-natal day [PND] 30) for 14 days might influence in adulthood the activity of metabolic markers, such as glucose, total cholesterol, triglycerides as well as activity of antioxidants (DPPH) from plasma, white adipose tissue (WAT), brown adipose tissue (BAT), liver, and hypothalamus. Our results showed that adult rats treated during juvenile ages with CBD (5, 10 or 30 mg/kg) for two weeks increased the contents of glucose whereas with no changes on total cholesterol in adulthood were observed. Additionally, a significant decrease in the levels of triglycerides were found in plasma, WAT, BAT, and liver in adult rats treated with chronic injections of CBD during the adolescence. However, unexpectedly, the contents of triglycerides in hypothalamus were found enhanced. Finally, the DPPH assay showed a significant enhancement in triglycerides analyzed from WAT and liver whereas opposite findings were observed in BAT and no significant changes were found in hypothalamus in adult rats that received during the adolescence chronic injections of CBD. In conclusion, repeated CBD administration to juvenile rats induced significant alterations in multiple metabolic markers analyzed in the adulthood. Our findings highlight the relevance of chronic CBD treatment in disturbed metabolic activity and remark the need for studying the underlying mechanisms involved.

Keywords: Adolescence; Brain; Cannabidiol; Metabolism.

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Animals
  • Cannabidiol / administration & dosage
  • Cannabidiol / adverse effects*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Humans
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Metabolic Diseases / chemically induced*
  • Metabolic Diseases / diagnosis
  • Metabolic Diseases / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors


  • Cannabidiol