Intervention: Yohimbine
Trial phase: Phase 2
ATC code: G04BE04
SMILES: COC(=O)C1C(O)CCC2CN3CCc4c([nH]c5ccccc45)C3CC21
Sex: Male
Age groups: Adult
Healthy volunteers: No
Participants at risk: 26
Group description: Patients will take one 21.6 mg. dose of yohimbine one hour before first imaginal exposure in PE.

Yohimbine: alpha-2 adrenergic receptor antagonist
Eligibility criteria:
Inclusion Criteria:

Subjects must be competent to provide informed consent for research participation.
Subjects must be male veterans and post deployed active duty male personnel of OEF/OIF.
Subjects must be between the ages of 18 and 45.
Subjects must meet DSM-IV diagnostic criteria for PTSD on the CAPS.
For subjects taking SSRI's, subjects must be stabilized on the current prescribed dose for a period of at least 14 days prior to the trial and remain at that dose for the remainder of the study. Subjects who change their SSRI status or dosage during the study will continue to receive services via the study resources but data generated will not be used in analyses. Subjects will be eligible for the study if they are willing to titrate off potentially confounding agents prior to yohimbine administration (for a period of five half-lives), given that such titration is also clinically appropriate and deemed to be in the patient's best interests.

Exclusion Criteria:

Subjects with a recent (< 2 month) history of psychiatric hospitalization or suicide attempt. Recent work with veterans with severe mental illness suggests that a 2-month period of stabilization is sufficient to minimize risk and possible relapse (Frueh, 2005). Subjects with an existing diagnosis of schizophrenia or other Axis I serious mental illnesses (SMI, besides PTSD) will be excluded. SMI will include any severe and persistent mental illness.
Subjects with a current diagnosis of drug dependence, due to potential interactions with study measurements and treatments. Alcohol use disorders will be allowed given that subjects can pass exclusion criterion 12 without withdrawal symptoms.
Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation.
Subjects with evidence of or a history of clinically significant hematological, endocrine, cardiovascular, hepatic, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect physiological/subjective responses.
Subjects with SCID-diagnosed panic disorder, as yohimbine may precipitate panic attacks.
Subjects with an abnormal ECG.
Subjects with a blood pressure of 140/90 or higher, as yohimbine has been shown to elevate blood pressure.
Subjects taking Beta blockers, alpha-adrenergic agents, Beta-agonist inhalers, opiates or opiate antagonists and any psychotropic medications other than SSRI's because these may affect test response.
Subjects who are unwilling or unable to maintain abstinence for three days prior to yohimbine administration from over-the-counter drugs with sympathomimetic properties, e.g., asthma medications, cold medicines with ephedrine, dietary supplements with ephedrine alkaloids, and illegal drugs, e.g., amphetamines, methamphetamine, cocaine, and MNDA as well as alcohol because these may exacerbate the action of yohimbine.
Subjects taking alpha-adrenergic antagonists, e.g. prazosin for hypertension; and beta-adrenergic antagonists, e.g. propranolol. Because they may attenuate effects of yohimbine. Subjects will be eligible for the study if they are willing to titrate off potentially confounding agents prior to yohimbine administration (for a period of five half-lives), given that such titration is also clinically appropriate and deemed to be in the patient's best interests.
Asthmatic subjects and subjects on medications for hypertension, due to criteria 9 and 10.

These inclusion/exclusion criteria will allow the majority of veterans treated in the PCT to be study eligible. Accordingly, the sample will be likely generalizable to the population of interest.