Please select the eligibility criteria that correspond to the clinical trial below.
Title: Cannabinoid Control of Fear Extinction Neural Circuits in Post-traumatic Stress Disorder
Brief Summary: 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.


Options:
A: Inclusion Criteria:

1. Age ≥ 18 years
2. Weight: 99 lb - 242 lbs
3. Experienced a traumatic event less than 6 hours ago

Secondary Inclusion Criteria:

ED staff note marked anxiety emotional distress and or dissociation in relation to index trauma as assessed by meeting a minimum of 2 out of 4 of the peritraumatic characteristics that have been associated with the development of PTSD below:

1. Anxiety Visual Analog Scale minimum score of 4 on a scale of 0 to 10
2. Peritraumatic dissociation (PDEQ) with a cut-point of 15 (lowest possible score is 10)
3. Peritraumatic distress (Peritraumatic Distress Inventory) (PDI) with a cut-point of 15 (lowest possible score is 0)
4. Heart rate at 80 bpm or more

Exclusion Criteria:

1. Severe physical injury as assessed with the Abbreviated Injury Scale (AIS \> 2); Examples include severe burn injury, life-threatening medical or surgical condition, condition requiring surgical intervention under general anesthesia, as indicated by clinical judgment.
2. Inability to provide informed consent or cooperate with the screening or collection of initial measures.
3. Intoxication to a degree that would interfere with the ability to provide informed consent or high level or intoxication reported at the time of trauma.
4. Moderate to severe head injury associated with current trauma exposure as defined by a loss of consciousness \>30 minutes following injury.
5. Medical conditions e.g., Cushing's syndrome, current acute infectious or viral disease, tuberculosis, unstable diabetes or hypertension, myasthenia gravis, heart failure.
6. Currently taking oral steroids
7. Use of benzodiazepine within 24 hours of trauma exposure will not be eligible to participate in the study
8. Individuals prescribed a narcotic medication to alleviate acute pain in the ED will not be eligible to participate in the treatment study.
9. Weight below 45kg or above 110 kg (99 lbs - 242 lbs)
10. Pregnancy (a urine pregnancy test will be performed in the ED)
11. Individuals experiencing on-going trauma (i.e., domestic violence).
12. Reported diagnoses of schizophrenia, bipolar I disorder, or other psychotic illness.
13. Current or past history of dementia, amnesia or other cognitive disorder predating trauma exposure
14. Residence outside local area, which would hinder attendance at follow up visits due to long travel time.
B: Inclusion Criteria:

* Female patients between the ages of 18 years and 50 years
* Victim of sexual assault/rape
* Able to understand consent procedure
* Discharged to home

Exclusion Criteria:

* Admitted to inpatient unit
* Previous diagnosis of PTSD
* Contra-indications to prazosin: orthostatic hypotension, right heart failure, use of anti-hypertensive medication, 5-phosphodiesterase inhibitors (sildenafil) or diuretic, history of syncope or severe unexplained faintness, known hypersensitivity to quinazolines
* Hemodynamically unstable
* Current use of over the counter, prescribed, or use of other drugs for insomnia
* Dependence on alcohol, opiates or other illegal drugs
* History of psychotic disorder
* Suicidal risk defined by a positive response on the 3-item assessment, standard protocol in the ED
* Current use of morphine or methadone
* Pregnant or breastfeeding
* Known hepatic dysfunction
* Cardiac or vascular history including coronary artery disease
* Narcolepsy
* History of sleep apnea
* Returning to chronic domestic abuse situation
C: 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 \[including alcohol/substance abuse of dependence disorder\]
D: Inclusion Criteria:

* Adult patients admitted to an intensive care unit requiring mechanical ventilation and anticipated to require mechanical ventilation \>48h
* Patient has a sedation target (e.g. using the Richmond Agitation Sedation Scale or Sedation Agitation Scale) that is anticipated to be stable \>48h
* Minimum sedative infusion doses (any one of):

  * Propofol \>/=1.5 mg/kg/h \>24h
  * Midazolam \>/=3.0 mg/h \>24h

Exclusion Criteria:

* Sedation for paralysis
* Use of neuromuscular blocking agents (patients may be eligible once these are discontinued)
* Asthma or known reactive airways disease
* 1st, 2nd or 3rd-degree heart block (with no permanent pacemaker) at the time of screening
* Known history of congestive heart failure with ejection fraction \<20%
* HR\<60 bpm at baseline
* Hypotension requiring vasopressor support above the following levels

  * Norepinephrine dose \>0.15mcg/kg/min or equivalent (\>0.15mcg/kg/min epinephrine; \>22.5 mcg/kg/min dopamine; \>0.06 U/min vasopressin)
  * Phenylephrine \>2.0 mcg/kg/min
  * Receiving 3 or more vasopressors, regardless of dose
* Pregnancy or lactation
* Allergy to propranolol
* Patients for whom an enteral route of drug administration is not available
* Patients who are on digoxin, diltiazem, or verapamil
* Patients on chronic betablockers are eligible for enrolment. Patients allocated to the intervention arm will have their betablocker replaced with propranolol. Once propranolol is discontinued, the treating team may resume their usual betablocker. Control patients may continue their usual betablocker (unless it is propranolol) at the treating team's discretion.

Answer: C