Original Article

Molecular Psychiatry (2013) 18, 1034–1040; doi:10.1038/mp.2013.61; published online 14 May 2013

Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study

A Neumeister1,2, M D Normandin3,4, R H Pietrzak5,6, D Piomelli7, M Q Zheng3, A Gujarro-Anton7, M N Potenza6,8, C R Bailey9, S F Lin3, S Najafzadeh3, J Ropchan3, S Henry3, S Corsi-Travali1,2, R E Carson3 and Y Huang3

  1. 1Molecular Imaging Program, Department of Psychiatry and Radiology, New York University School of Medicine, New York, NY, USA
  2. 2Steven and Alexandra Cohen Veterans Center for the Study of Posttraumatic Stress and Traumatic Brain Injury, Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA
  3. 3Positron Emission Tomography Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA
  4. 4Center for Advanced Medical Imaging Sciences, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  5. 5Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, West Haven, CT, USA
  6. 6Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
  7. 7Department of Anatomy and Biology, and Biological Chemistry, University of California, Irvine, CA, USA
  8. 8Department of Neurobiology and Child Study Center, Yale University School of Medicine, New Haven, CT, USA
  9. 9John Hopkins School of Medicine, Baltimore, MD, USA

Correspondence: Dr A Neumeister, Molecular Imaging Program, Department of Psychiatry and Radiology, New York University School of Medicine, One Park Avenue, 8th Floor, Room 225, New York, NY 10016, USA. E-mail: alexander.neumeister@nyumc.org

Received 11 January 2013; Revised 18 February 2013; Accepted 2 April 2013
Advance online publication 14 May 2013

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Abstract

Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma-exposed controls (TC)) and those without such histories (healthy controls (HC)). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures the volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, palmitoylethanolamide and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, P=0.001; 19.5% and 14.5% higher, respectively), which were most pronounced in women (F(1,53)=5.52, P=0.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder.

Keywords:

brain imaging; cannabinoid receptors; OMAR; PET; PTSD