Biomarker Changes and Anxiolytic Effects-Phase 2

Phase 2

Completed

Brief Summary: This study will examine the utility of plasma and urinary based biomarkers for the anxiolytic properties of kava. The investigators will conduct a one week, double blind, randomized placebo controlled trial of kava, dosed at three 75 mg capsules per day, vs placebo, in adults with generalized anxiety disorder.

Detailed Description: This study will examine the utility of plasma and urinary based biomarkers for the anxiolytic properties of kava, a natural dietary supplement. The investigators will conduct a one week, double blind, randomized placebo controlled trial of kava, dosed at three 75 mg capsules per day, vs placebo, in adults with generalized anxiety disorder. Clinical measures of anxiety, blood, and urine will be obtained. Biomarkers of interest include PRKACA, cortisol, urinary TCE, and NA5HT. Participants will be assessed pre- and post-treatment. The participants will also be followed for 12 weeks after the end of treatment to identify any potential rare adverse events, particularly liver toxicity, that appear in a delayed fashion.

Recruitment & Eligibility

Inclusion Criteria

Adults ages 18-50 who meet Diagnostic Statistical Manual (DSM)-5 criteria for GAD as the primary psychiatric diagnosis
No more than one failed therapeutic trial of an FDA approved medication for the treatment of GAD
Score of>14 on the Hamilton Anxiety Rating Scale at both screening and baseline
At least a 4 (moderate) on the Clinical Global Impressions Severity Scale at both screening and baseline
Females of potential childbearing status must use adequate contraceptive precautions.

Exclusion Criteria

Unwilling/unable/unsafe to stop psychotropic medications (if on any) for the duration of the study
Inability to refrain from acetaminophen, alcohol or other potentially hepatotoxic substances
History of liver disease or current liver disease or clinically significant elevation in serum liver chemistries
Unstable medical or neurological condition
Positive urine drug screen for substances of abuse
Active substance abuse/dependence
Lifetime history of a psychotic disorder, bipolar disorder, PTSD or Obsessive Compulsive Disorder
Any significant risk for self-harm or suicidality as determined by the principal investigator or suicide attempt within the last 6 months
Psychotherapy newly instituted during the 6 weeks leading up to enrollment in the study. Subjects established in psychotherapy without change during the course of the study may participate
Montgomery-Asberg Depression Rating Scale (MADRS) > 17 (moderate or severe depressive symptoms)

Arm && Interventions

Group	Intervention	Description
Kava Pharmacokinetics Group	Kava Dietary Supplement	75 mg kava dietary supplement capsules per day for one week.
Placebo	Placebo	Three placebo capsule per day for one week

Primary Outcome Measures

Name	Time	Method
Mean PRKACA Change	From Baseline (pre dose) to 1 week after taking the first dose (post dose)	The change in mean PRKACA value from pre to post-treatment

Secondary Outcome Measures