Effects of Delta-9 Tetrahydrocannabinol (THC) on Retention of Memory for Fear Extinction Learning in PTSD: R61 Study
Effects of Delta-9 Tetrahydrocannabinol (THC) on Retention of Memory for Fear Extinction Learning in PTSD: R61 Study
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 5 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 animated snake) may follow one image most of
 the time, while the other images may never be followed by the aversive cue. 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 an aversive cue 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 Magnetic Resonance (MR) 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 doses (5mg or 10mg;
 one time) are 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.

 Visit 4: Behavioral Tests and MR scan: This visit will be very similar to Visit 2.
 Participants will participate in the same type of task inside the MR 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.

 Visit 5: Behavioral Tests and MR scan: This visit will occur approximately 1 week after Visit
 4 and will have the same procedure. Participants will participate in the same type of task
 inside the MR scanner, while the study staff measures reaction time and psychophysiological
 responding and brain activation. 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.
Inclusion Criteria:

 -  Able to give informed consent

 -  Right-handed

 -  Age between 18-50 years old,

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

 -  Current PTSD diagnosis

 Exclusion Criteria:

 -  clinically significant medical or neurologic condition or neurocognitive dysfunction
 that would affect function and/or task performance and/or interfere with the study
 protocol

 -  any current (or within past 2 months) medical condition requiring medication that
 would interact with dronabinol or interfere with the study protocol

 -  risk of harm to self or others that requires immediate intervention

 -  presence of contraindications, 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)

 -  lack of fluency in English

 -  positive drug screen or alcohol breathalyzer

 -  unwilling/unable to sign informed consent document

 -  currently pregnant (positive pregnancy test), planning pregnancy, or lactating (women)

 -  under 18 or over 50 years of age

 -  traumatic brain injury (as defined by The American Congress of Rehabilitation as a
 person who has had a traumatically induced physiological disruption of brain function
 (i.e., the head being struck, the head striking an object, and/or the brain undergoing
 an acceleration/deceleration movement (i.e., whiplash) without direct external trauma
 to the head), as manifested by at least one of the following: any loss of
 consciousness; any loss of memory for events immediately before or after the injury;
 any alteration in mental status at the time of the incident; or focal neurological
 deficits that may or may not be transient)

 -  inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia), as
 determined by self-report and/or a preliminary session in a mock scanner

 -  left-handed;

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

 -  anticipation of a required drug test in the 4 weeks following the study.

 -  current diagnosis of a mood, anxiety, or other disorder that is more clinically
 salient than PTSD

 -  current moderate or severe alcohol/drug use disorder or in the past 8 weeks

 -  current or past diagnosis of bipolar and other related disorders, schizophrenia
 spectrum, or other psychotic disorders

 -  concomitant treatments with medication known to have drug interactions with
 dronabinol, such as, central nervous system depressants (barbiturates,
 benzodiazepines, buspirone, lithium, etc) and anticholinergic agents (atropine,
 scopolamine, antihistamines, etc).