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Biol Psychiatry. 2016 Nov 1;80(9):691-701. doi: 10.1016/j.biopsych.2016.04.012. Epub 2016 Apr 25.

Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [11C]CURB.

Author information

1
Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada. Electronic address: isabelle.boileau@camh.ca.
2
Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
3
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Departments of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
4
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada.
5
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
6
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Departments of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada.
7
Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland.
8
Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada.
9
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
10
Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Departments of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
11
Human Brain Lab, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Abstract

BACKGROUND:

One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence. However, the status of brain FAAH in cannabis use disorder is unknown.

METHODS:

Brain FAAH binding was measured with positron emission tomography and [11C]CURB in 22 healthy control subjects and ten chronic cannabis users during early abstinence. The FAAH genetic polymorphism (rs324420) and blood, urine, and hair levels of cannabinoids and metabolites were determined.

RESULTS:

In cannabis users, FAAH binding was significantly lower by 14%-20% across the brain regions examined than in matched control subjects (overall Cohen's d = 0.96). Lower binding was negatively correlated with cannabinoid concentrations in blood and urine and was associated with higher trait impulsiveness.

CONCLUSIONS:

Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids. Further studies are needed to examine possible changes in FAAH binding during prolonged cannabis abstinence and whether lower FAAH binding predates drug use.

KEYWORDS:

Cannabis use disorder; Endocannabinoid; FAAH; Fatty acid amide hydrolase; Positron emission tomography; [(11)C]CURB

PMID:
27345297
PMCID:
PMC5050070
DOI:
10.1016/j.biopsych.2016.04.012
[Indexed for MEDLINE]
Free PMC Article

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