St. John's Wort is a popular dietary supplement that many people take to elevate mood or
relieve stress. This study will test in normal volunteers whether this preparation may
alter mood and if so, by what means. Animal studies suggest that St. John's Wort may work
similarly to some antidepressants that affect levels of the chemical serotonin in the brain.
Participants in this study must also be enrolled in NIMH protocol #98-M-0094 (SPECT Imaging
of Dopamine and Serotonin Transporters in Neuropsychiatric Patients and Normal Volunteers)
and protocol #91-M-014 (MRI Imaging of Neuropsychiatric Patients and Controls). Separate
consent forms are required for each study. Candidates will undergo medical and psychiatric
evaluations that may include blood and urine tests, electroencephalogram and
Normal volunteers will have a mood assessment at the beginning of the study. They will then
be randomly assigned to take either placebo (a pill with no active ingredient) or St. John's
Wort 3 times a day for 2 weeks, and will be told what they are taking. After an 11-week
hiatus, they will again start treatment on the same schedule, but will not be told which
preparation they are receiving. Each evening during the 2-week treatment periods, subjects
will complete a brief self-rating mood assessment questionnaire. At the end of each
treatment period, they will undergo SPECT brain imaging (a type of CT scan) to determine
dopamine and serotonin distribution and density in the brain.
For this procedure, study subjects take three drops of potassium iodide solution within 24
hours before the scan and two drops nightly for 3 days following the procedure. About 10 ml
(less than two teaspoons) of blood are drawn before a radioactive tracer is injected.
SPECT imaging is done the next day. After about 1 hour of imaging, subjects are given
either a placebo or St. John's Wort, and then imaging continues for another 2 hours. During
the procedure, up to five blood samples of 6 ml each may be drawn. At some point during the
study, a MRI scan of the brain will be done.
Extracts of hypericum perforatum (St. John's wort) have become increasingly popular for the
treatment of mood disorders. Hypericum extracts have been approved in Germany for the
treatment of mild to moderate depression and are now available in standardized preparations.
In the United States, hypericum extracts are frequently purchased as over the counter
preparations. Inhibition of the serotonin transporter, similar to clinically used selective
serotonin reuptake inhibitors (SSRIs), has been suggested as a possible mechanism of action
for the antidepressant properties of hypericum extracts. We propose to study the effects of
hypericum extracts on mood states in normal volunteers who are concurrently volunteering
under NIMH protocol 98-M-0094 for SPECT imaging of serotonin and dopamine transporter
availability with [I-123] Beta-CIT. A placebo-controlled, double-blind, within-subject
design will be employed with two two-week periods of drug/placebo administration, clinical
assessment and SPECT imaging separated by eleven weeks. We plan to test three hypotheses:
1) that hypericum alters mood state, 2) that hypericum reduces serotonin transporter
availability, and 3) that these actions are quantitatively associated with one another.
Free of concomitant medications and must be willing to take hypericum for a period of two
weeks and a placebo for two weeks.
No subjects with a relevant Axis I or Axis II disorder.
No subjects with concomitant medical or neurological disorders which require ongoing
medication, or which may affect the central nervous system; or taking medication with
which St. John's wort may interact.
Must not be pregnant.
Must not be breastfeeding.
No subjects with a prior reaction to iodine, iodine compounds, or shellfish.
No subjects with a history of thyroid disease or dysfunction.
No subjects with a history of recent substance abuse.
No subjects with metal objects in their bodies.
No subjects with a prior adverse reaction to hypericum extracts.
No women who taking birth control pills.