Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers
J. Hirvonen, R. Goodwin, Cheng-Ta Li, Garth E Terry, Sami S Zoghbi, Cheryl L. Morse, Victor W Pike, N. Volkow, Marilyn A. Huestis, Robert B Innis
Molecular Psychiatry July 12, 2011 DOI: 10.1038/mp.2011.82 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Human subjects who chronically smoke cannabis and controls |
| Duration | ~4 weeks of monitored abstinence |
| Topics | Cannabis |
| Key findings | Chronic cannabis smokers showed reversible and regionally selective downregulation of cortical CB1 receptors, which correlated with years of smoking and normalized after ~4 weeks of abstinence. The authors argue this neuroadaptation may promote cannabis dependence. |
Abstract
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 ∼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.