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J Nucl Med. 2011; 52 (Supplement 1):10
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Neurosciences: Special Session

Brain Imaging Council Young Investigator Award Symposium

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

Jussi Hirvonen1, Robert Goodwin2, Cheng-Ta Li1, Garth Terry1, Sami Zoghbi1, Cheryl Morse1, Victor Pike1, Nora Volkow2, Marilyn Huestis2 and Robert Innis1

1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD 2 Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, Baltimore, MD

Abstract No. 10

Objectives: Cannabis is the most widely used illicit drug, and chronic cannabis smoking can result in dependence. The effects of cannabis are mediated via cannabinoid CB1 receptors in the brain. In rodent brain, cannabinoid CB1 receptors downregulate after chronic exposure to cannabis but recover during abstinence. To see if such reversible downregulation occurs in humans, we used positron emission tomography (PET) to image brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

Methods: We admitted male chronic daily cannabis smokers (N=30) to a closed and monitored inpatient research unit for about four weeks. We imaged cannabis smokers with PET and [18F]FMPEP-d2 at two time points: on the day following admission and after about four weeks of abstinence. Healthy male subjects (N=28) with less than 10 times lifetime cannabis exposure were scanned once. Arterial blood was sampled during PET scans to estimate receptor binding as distribution volume (VT).

Results: At baseline, VT of [18F]FMPEP-d2 was about 20% lower in cannabis smokers than in healthy control subjects in cortical, but not in subcortical brain regions or cerebellum (Fig.1.). Decrease in VT correlated with years of cannabis smoking. In the 14 cannabis smokers that had the second PET scan after four weeks of monitored abstinence, VT increased only in those regions that had showed decreased VT at baseline. Free fraction of radioligand in plasma was not different between groups at baseline, or between two time points among cannabis smokers.

Conclusions: Chronic daily cannabis smoking is associated with reversible downregulation of cortical cannabinoid CB1 receptors in human brain. Cannabinoid CB1 receptor downregulation could be among neuroadaptations that promote cannabis dependence in human brain.

Research Support: This research was supported by the Intramural Program of NIMH (project # Z01-MH-002852-04)





This Article
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Right arrow Email this article to a friend
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Right arrow Alert me to new issues of the journal
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Right arrow Articles by Hirvonen, J.
Right arrow Articles by Innis, R.
PubMed
Right arrow Articles by Hirvonen, J.
Right arrow Articles by Innis, R.