CB1 Receptor PET Imaging Reveals Gender Differences in PTSD

The objective of the proposed translational study is to test a model, based upon basic science studies, exploring multisystem impairments in PTSD including endocannabinoid (eCB) and glucocorticoids in the modulation of fear memories by examining the cannabinoid type 1 (CB1) receptor in a PTSD fear circuit as well as glucocorticoid function. The investigators propose that impaired eCB signaling in PTSD resulting in the maladaptive neurobehavioral response to the stressor is associated with an upregulation of the CB1 receptors and insufficient glucocorticoid signaling.

The eCB - anandamide and 2-arachidonoylglycerol (2-AG) - and their attending cannabinoid (CB) receptors which are found in high densities in a fear circuitry involving the amygdala, hippocampus, the anterior cingulate cortex and prefrontal cortex serve important functions in the regulation of stress-coping behaviors. Besides eCB regulation there is strong evidence from ongoing research of the investigators group and others suggesting an important role for glucocorticoid signaling as an endpoint of the biochemical sequelae initiated by stressful or aversive stimuli. One of the long-term research goals of our lab is to understand such functions and determine their relevance to the pathogenesis of PTSD and to provide a more integrative view on neurobiological mechanisms that are involved in the regulation of the neuroadaptive response to stress. The objective of the proposed translational study is to test a model, based upon basic science studies, exploring multisystem impairments in PTSD including eCB and glucocorticoids in the modulation of fear memories by examining the CB1 receptor in a PTSD fear circuit as well as glucocorticoid function. The investigators propose that impaired eCB signaling in PTSD resulting in the maladaptive neurobehavioral response to the stressor is associated with an upregulation of the CB1 receptors and insufficient glucocorticoid signaling.

Eligibility Criteria:
Inclusion Criteria for Patients with PTSD:

1. age 18-55 years old
2. currently diagnosed with PTSD and symptomatic with a Clinician-Administered PTSD Scale (CAPS) score \> 50.

Inclusion Criteria for healthy subjects:

1. age 18-55 years old
2. no personal or first-degree family history of any Axis I diagnosis.

Exclusion criteria for Patients with PTSD:

1. any primary Axis I disorder other than PTSD (e.g. psychosis);
2. medical or neurological illnesses likely to affect physiology or anatomy, i.e. uncontrolled hypertension, cardiovascular disorders;
3. a history of drug (including benzodiazepines (BZD)) dependence (DSM IV criteria) within 1 year of the study and lasting longer than 2 years, except for alcohol dependence
4. current pregnancy (as documented by pregnancy testing at screening or on the day of PET imaging study)
5. current breast feeding
6. nicotine dependence
7. suicidal ideation or behavior
8. general MRI exclusion criteria, i.e. pacemakers, metals in the body
9. Human immunodeficiency virus (HIV) (due to possible neuropsychiatric effects);
10. use of opioid medications within 2 weeks of the PET study
11. having an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participation in the study
12. seriously claustrophobic
13. blood donation within 8 weeks prior to the study.

Exclusion criteria for healthy subjects:

1. any history or current primary Axis I disorder
2. medical or neurological illnesses likely to affect physiology or anatomy, i.e. uncontrolled hypertension, cardiovascular disorders
3. a history of drug (including benzodiazepines \[BZD\]) dependence (DSM IV criteria) within 1 year of the study and lasting longer than 2 years, except for alcohol dependence
4. current pregnancy (as documented by pregnancy testing at screening or on the day of PET imaging study)
5. current breast feeding
6. nicotine dependence
7. suicidal ideation or behavior
8. general MRI exclusion criteria, i.e. pacemakers, metals in the body
9. HIV (due to possible neuropsychiatric effects)
10. use of opioid medications within 2 weeks of the PET study
11. having an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participation in the study
12. seriously claustrophobic
13. blood donation within 8 weeks prior to the study.