1. ¹Molecular Neuropsychiatry Branch, NIH, BRC, Baltimore, MD, USA
2. ²Ciphergen Biosystems, Freemont, CA, USA
3. ³Office of the Clinical Director, National Institute on Drug Abuse-Intramural Research Program, NIH, BRC, Baltimore, MD, USA

Correspondence: Dr JL Cadet, Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, Intramural Research Program, NIH Biomedical Research Center, 251 Bayview Boulevard, Baltimore, MD 21224, USA. E-mail: jcadet@intra.nida.nih.gov

Received 14 January 2008; Revised 24 March 2008; Accepted 2 April 2008; Published online 13 May 2008.

Abstract

Marijuana (MJ) is the most commonly used illicit drug in the United States. Its abuse is associated with cognitive dysfunctions and increased resistance to blood flow in the cerebral vasculature. In addition, MJ abuse is associated with increased risks of potentially serious cardiovascular disorders. In the present study, we used the protein chip platform based on surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to test the possibility that MJ abuse might be associated with changes in serum protein levels. Indeed, MJ users showed significant increases in three protein peaks, which were identified as three isoforms of apolipoprotein (apo) C-III. Immunoprecipitation using an apoC-III antibody also validated the identification of the proteins. Marijuana-induced increases in apoC-III levels might occur through chronic stimulation of hepatic cannabinoid receptors (CB1 and/or CB2) by its active ingredient, ⁹tetrahydrocannibol (THC). Thus, chronic MJ abuse might cause increased transcription and/or translation of apoC-III in the liver with corresponding changes reflected in the plasma of these patients. In any case, because apoC-III is a cardiovascular risk factor, the increased levels observed in MJ users might explain, in part, the cardiac and cerebral abnormalities reported in these patients.