Cannabinoid 2 receptor- and beta Arrestin 2-dependent upregulation of serotonin 2A receptors

J. M. Franklin, T. Vasiljevik, T. E. Prisinzano, G. A. Carrasco

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Recent evidence suggests that cannabinoid receptor agonists may regulate serotonin 2A (5-HT2A) receptor neurotransmission in the brain, although no molecular mechanism has been identified. Here, we present experimental evidence that sustained treatment with a non-selective cannabinoid agonist (CP55,940) or selective CB2 receptor agonists (JWH133 or GP1a) upregulate 5-HT2A receptors in a neuronal cell line. Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT2A receptors was prevented in cells stably transfected with either CB2 or Β-Arrestin 2 shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis also prevented the cannabinoid receptor-induced upregulation of 5-HT2A receptors. Our results indicate that cannabinoid agonists might upregulate 5-HT2A receptors by a mechanism that requires CB2 receptors and Β-Arrestin 2 in cells that express both CB2 and 5-HT2A receptors. 5-HT2A receptors have been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety and depression, and schizophrenia. Therefore, these results might provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to some cognitive and mood disorders in humans.

Original languageEnglish
Pages (from-to)760-767
Number of pages8
JournalEuropean Neuropsychopharmacology
Issue number7
StatePublished - Jul 2013

Bibliographical note

Funding Information:
Funding for this study was provided by National Institute of Health/National Institute on Drug Abuse DA024329 and University of Kansas Startup Funds; neither NIDA nor University of Kansas had a further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.


  • 5-HT receptor
  • CB2 receptors
  • Cannabinoids
  • Marijuana
  • Receptor internalization
  • Serotonin
  • Β-Arrestins

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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