Cannabinoid Control of Fear Extinction Neural Circuits in Post-traumatic Stress Disorder
Cannabinoid Control of Fear Extinction Neural Circuits in Post-traumatic Stress Disorder
The goal of this study is to look at how a type of drug called cannabinoids are related to
 the processing of fear signals, the experience of emotions and fear, and the pattern of
 activity in the brain that is involved in these processes and how this relates to the
 development of post-traumatic stress disorder (PTSD). PTSD is an anxiety disorder that occurs
 after experiencing a traumatic event(s) and is characterized by unwanted memories of the
 trauma(s) through flashbacks or nightmares, avoidance of situations that remind the person of
 the event, difficulty experiencing emotions, loss of interest in activities the person used
 to enjoy, and increased arousal, such as difficulty falling asleep or staying asleep, anger
 and hypervigilance. The information gained from this study could lead to the development of
 new treatments for persons who suffer from anxiety or fear-based disorders.
The total time that for each participant involved in this study is 4 visits, as outlined
 below:

 Visit 1: Questionnaires, Screening, and Orientation: During this visit the potential
 participant will learn about the study procedures, sign the informed consent documents, and
 fill out a packet of forms that ask about his or her race and ethnic background, use of drugs
 and alcohol and physical and mental health.

 Visit 2: Behavioral Tests: During this visit the participant will complete several computer
 tasks, and the study staff will be measuring reaction time and psychophysiological
 measures.The tasks that the participant will perform will show three different images and an
 aversive stimulus (e.g. loud burst of noise or mild wrist shock) may follow one image most of
 the time, while the other images may never be followed by a noise or mild wrist shock. The
 participant will need to try to predict whether the aversive cue will occur or not based on
 which image is shown and will be asked to repeatedly rate on a scale how likely it is that he
 or she thinks a noise/shock will occur after each image. Lastly, during the session the
 participant will also be asked to report his or her level of anxiety on a scale from 0 to
 100.

 Visit 3: Behavioral Tests with Drug or Placebo and MRI scan: For safety reasons participant
 will not be allowed to take any drugs for at least 24 hours before this visit, and should not
 use marijuana for at least 2 weeks before. Participants will be required to pass a urine drug
 test (and pregnancy test for women) and breathalyzer test before being allowed to continue
 with this visit. The participant will also not be allowed to drive himself or herself home
 from this visit, so he or she should arrange a friend or family member to pick him or her up
 or a taxi can be called by our research staff.

 The participant will view the same images he or she did on the previous day (Visit 2), and
 may experience the same aversive stimulus as during Visit 2. The participant will again be
 asked to rate how much he or she expects to experience the aversive stimulus after each image
 and he or she will also be asked to report his or her level of anxiety on a scale from 0 to
 100. However, about 2 hours before the task begins, the participant will be asked to swallow
 a capsule containing either a marijuana-like drug (Dronabinol) or a placebo (sugar pill).
 Dronabinol is a Food & Drug Administration (FDA) approved drug and the dose (7.5mg; one time)
 is unlikely to have any effects that last beyond the duration of the study visit. About every
 30 minutes after taking the pill, the participant will fill out some questionnaires about
 mood and how he or she is feeling at the moment.

 There will be three additional tasks that the participant will perform during this visit as
 well. The first task will involve looking at some unpleasant images and scenes and either
 maintaining his or her emotional response to the image, or using some techniques the study
 staff will practice with the participant to reinterpret the content of the image in a less
 unpleasant way. The second task will involve viewing a series of black and white line drawing
 of single objects and deciding whether or not each would fit into a shoe box. The third task
 will involve viewing a white fixation cross on a black background while the participant
 relaxes.

 Visit 4: Behavioral Tests and MRI scan: This visit will be very similar to Visit 2.
 Participants will participate in the same type of task inside the MRI scanner, while the
 study staff measures reaction time and psychophysiological responding and brain activation.
 Participants will view the same images he or she did previously, and may experience the same
 aversive stimulus as during Visit 2. Participants will again be asked to rate how much they
 expect to experience the aversive stimulus after each image and will also be asked to report
 their level of anxiety on a scale from 0 to 100. Lastly participants will also complete
 another decision making task involving single objects similar to that during the previous day
 (Visit 3).
Inclusion Criteria for All Participants:

 -  Able to give informed consent

 -  Physically and neurologically healthy [confirmed by a comprehensive medical history]

 -  Age between 21-45 years old

 -  Right-handed

 Inclusion Criteria for Participants with PTSD:

 -  Current PTSD diagnosis [related to civilian trauma]

 Inclusion Criteria for Trauma-Exposed Participants without PTSD:

 -  Experience with a civilian trauma without a PTSD diagnosis

 -  Free of a lifetime Axis I or Axis II diagnosis

 Inclusion Criteria for Non-Trauma-Exposed Healthy Participants:

 -  Free of a lifetime Axis I or Axis II diagnosis

 Exclusion Criteria for All Participants:

 -  Clinically significant medical or neurological condition

 -  Less than a high school education

 -  Lack of fluency in English

 -  Night shift work

 -  Currently pregnant; planning pregnancy; or lactating

 -  Unwilling/unable to sign informed consent document

 -  Inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia)

 -  Left-handed

 -  Presence of ferrous-containing metals within the body (e.g., aneurysm clips,
 shrapnel/retained particles)

 -  Under 21 or over 45 years of age

 -  Anticipation of a required drug test in the 4 weeks following study participation

 -  Positive urine drug screen and/or alcohol breathalyzer

 -  Current or past allergic or adverse reaction or known sensitivity to cannabinoid-like
 substances [dronabinol/marijuana/cannabis/thc, cannabinoid oil, sesame oil, gelatin,
 glycerin, and titanium dioxide]

 -  Participation in an experiment involving white noise bursts or shocks in the last 6
 months

 Exclusion Criteria for Participants with PTSD:

 -  Primary comorbid anxiety disorder (defined by which disorder was the more debilitating
 and clinically salient)

 -  Life history of bipolar disorder, schizophrenia, or presence of an organic mental
 syndrome, mental retardation, or pervasive developmental disorder

 -  Current or in the past 6 months alcohol/drug abuse of dependence

 -  Current or in the past 6 months major depressive disorder

 -  Current suicidal ideation

 -  Diagnosis of an Axis II personality disorder

 -  Concomitant treatments with psychotropic/psychoactive medication [including
 beta-adrenergic blockers, selective serotonin reuptake inhibitor (SSRI),
 benzodiazepines, tricyclic or monoamine oxidase inhibitor (MAOI) antidepressants,
 lithium, antiepileptic/anticonvulsants, neuroleptics/antipsychotics, etc.) or in the
 past two weeks [8 weeks for fluoxetine and 4 weeks for MAOIs) before screening (Visit
 1)

 -  currently receiving exposure-based therapy for PTSD

 Exclusion Criteria for Trauma-Exposed Participants without PTSD and Non-Trauma Exposed
 Healthy Participants:

 -  Current or past Axis I psychiatric disorder [including alcohol/substance abuse of
 dependence disorder]