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

• Published in: Molecular psychiatry Vol. 17; no. 6; pp. 642 - 649
• Main Authors: Hirvonen, J, Goodwin, R S, Li, C-T, Terry, G E, Zoghbi, S S, Morse, C, Pike, V W, Volkow, N D, Huestis, M A, Innis, R B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2012; Nature Publishing Group
• Subjects: Abstinence; Adult; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Body mass index; Brain research; Cannabinoid CB1 receptors; Cannabinoids; Cannabis; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Chronic exposure; Down-Regulation - drug effects; Drug abuse; Drug withdrawal; Fluorine Radioisotopes; Functional Neuroimaging - methods; Functional Neuroimaging - psychology; Humans; Male; Marijuana; Marijuana Smoking - metabolism; Medical sciences; Medicine; Medicine & Public Health; Mental health; Neuroimaging; Neurosciences; original-article; Pharmacotherapy; Positron emission tomography; Positron-Emission Tomography - methods; Positron-Emission Tomography - psychology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Pyrrolidinones; Receptor density; Receptor, Cannabinoid, CB1 - metabolism; Smoke; Smoking; Substance Withdrawal Syndrome - metabolism; Time Factors; Tobacco; Tomography; Urine; United States > US; Baltimore Maryland; cannabis; receptor; positron emission tomography; receptor imaging; addiction; CB; Radionuclide study; CB1 cannabinoid receptor; Central nervous system; Cannabidaceae; Encephalon; Cannabis; Chronic; Addiction; Smoker; Dicotyledones; Imaging; Cannabinoid receptor; Angiospermae; Spermatophyta; Drug of abuse; Positron emission tomography; Recreational drug; Biological receptor; Emission tomography
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2011.82

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB 1 (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 CB 1 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, CB 1 receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB 1 receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.