Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

: Hirvonen J, Goodwin RS, Li CT, Terry GE, Zoghbi SS, Morse C, Pike VW, Volkow ND, Huestis MA, Innis RB

Publisher: NATURE PUBLISHING GROUP

: 2012

: Molecular Psychiatry

: MOLECULAR PSYCHIATRY

: MOL PSYCHIATR

: 6

: 17

: 6

: 642

: 649

: 8

: 1359-4184

DOI: https://doi.org/10.1038/mp.2011.82

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After similar to 4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB1 receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB1 receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain. Molecular Psychiatry (2012) 17, 642-649; doi:10.1038/mp.2011.82; published online 12 July 2011