Re: Supplements and personality features

Anders Sandberg (
12 Jan 1998 15:44:23 +0100

Michael Lorrey <> writes:

> > Huh? Is there any evidence at all that Hypericum acts as a SSRI?
> I was reading an article last week that said that Hypericum has SSRI
> properties, but also does one or two other things that allow for a more
> stable treatment, minimizing side effects.

I got interested, and did a medline search. Some abstracts included
below. It does not seem to be an SSRI, although it appears to be a a SRI.

> Most things in nature that work typically aren't promoted by the
> medical establishment because they can't patent them, and therefore
> make multi-millions off of them.

True, although you shouldn't make too much of this. Volz article
(below) says that hypericum extracts are among the most widely
prescribed antidepressants in Germany, and the Nordenfors article was
published in the journal of the swedish medical association. It seems
to me that this is more of an american problem than an international

Even unpatentable drugs can be sold for profit, just look at the
health food stores and nutrient industry - certainly smaller than the
pharmaceutical industry, but earning good money anyway.

Pharmacopsychiatry 1997 Sep;30 Suppl 2:72-76

Controlled clinical trials of hypericum extracts in depressed
patients--an overview.

Volz HP

In Germany, hypericum extracts are among the most widely prescribed
antidepressants. Additionally, many preparations of St. John's wort
are sold on the free market and one extract is even the best selling
antidepressant in the country. In contrast to synthetic
antidepressants, the approval procedures are not so strict, which
implies that the pharmaceutical industry is not forced to conduct
clinical trials suitable for licensing. Nevertheless, numerous studies
on hypericum extracts including depressed patients have been published
in the last 20 years. The purpose of this paper is to review these
investigations in respect of methodological considerations and to draw
conclusions pertaining to the proof of antidepressant efficacy. To
this effect, a computer-assisted literature research was performed and
manufacturers were asked to supply the author with study results. A
total of 12 placebo-controlled trials with hypericum extracts were
performed, mostly with positive results. Also in comparison with
synthetic antidepressants (3 studies published), a similar reduction
of depressive symptomatology was seen, although the comparators were
not adequately dosed. No trials in severely depressed patients have
been published yet. Since most studies on hypericum have
methodological flaws, further studies are warranted.

St John's wort for depression--an overview and meta-analysis of
randomised clinical trials [see comments]
Linde K; Ramirez G; Mulrow CD; Pauls A; Weidenhammer W; Melchart D
Projekt Münchener Modell, Ludwig-Maximilians-Universität, Munich,
BMJ, 1996 Aug 3, 313:7052, 253-8
OBJECTIVE--To investigate if extracts of Hypericum perforatum (St
John's wort) are more effective than placebo in the treatment of
depression, are as effective as standard antidepressive treatment, and
have fewer side effects than standard antidepressant drugs.
DESIGN--Systematic review and meta-analysis of trials revealed by
searches. TRIALS--23 randomised trials including a total of 1757
outpatients with mainly mild or moderately severe depressive disorders:
15 (14 testing single preparations and one a combination with other
plant extracts) were placebo controlled, and eight (six testing single
preparations and two combinations) compared hypericum with another
drug treatment. MAIN OUTCOME MEASURES--A pooled estimate of
the responder rate ratio (responder rate in treatment group/responder
rate in control group), and numbers of patients reporting and dropping
out for side effects. RESULTS--Hypericum extracts were significantly
superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01)
and similarly effective as standard antidepressants (single preparations
1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two
(0.8%) drop outs for side effects with hypericum and seven (3.0%) with
standard antidepressant drugs. Side effects occurred in 50 (19.8%)
patients on hypericum and 84 (52.8%) patients on standard
antidepressants. CONCLUSION--There is evidence that extracts of
hypericum are more effective than placebo for the treatment of mild to
moderately severe depressive disorders. Further studies comparing
extracts with standard antidepressants in well defined groups of patients
and comparing different extracts and doses are needed.

[St John's wort against depression in favour again]
Nordfors M; Hartvig P
Södra Stockholms sjukvÁrdsomrÁde.
Lakartidningen, 1997 Jun 18, 94:25, 2365-7
Extracts of Hypericum perforatum St. John's wort, have been used since
antiquity for the treatment of depressive symptoms. In 25 controlled
clinical trials where hypericum extract was compared with placebo and
established antidepressants, improvement was obtained in 61 percent of
patients on low-dose treatment (< 1.2 mg hypericum extract), and in 75
percent of patients treated with a higher dose (2.7 mg). The side effects
were mild and occurred at lower frequency than did those of other
antidepressants. The constituent of hypericum extract that is responsible
for the antidepressant effect has not been identified. Nor is the
mechanism of action known, but a combination of low-grade monoamine
oxidase inhibition and noradrenaline and serotonin reuptake blockade
seems the most likely alternative, though other interesting mechanisms
have also been proposed. Owing to their beneficial effect and low
toxicity, preparations containing extracts from H perforatum might furnish
an alternative to established therapy, especially among patients
concerned about stigmatization or less apprehensive of herbal
medication than of synthetic drugs.

Pharmacopsychiatry 1997 Sep;30 Suppl 2:117-124

Effects of the total extract and fractions of Hypericum
perforatum in animal assays for antidepressant activity.

Butterweck V, Wall A, Lieflander-Wulf U, Winterhoff H, Nahrstedt A

A commercially available extract of the aerial parts of Hypericum
perforatum, LI 160, showed pronounced activity in selected animal
bioassays. These include the forced swimming test (FST) and the tail
suspension test, used to determine antidepressant activity, and tests
indicating activity on the central nervous system, such as body
temperature and ketamine induced sleeping time. The counteracting
effects of drugs known to interfere with the central dopaminergic
system strongly suggested that dopamine mediated activity is important
for the activity of the extract. Dose-response experiments of the
total extract and of fractions rich in flavonoids and
napthodianthrones produced inverted U-shaped dose response curves.

Pharmacopsychiatry 1997 Sep;30 Suppl 2:113-116

Effects of long-term administration of hypericum extracts on
the affinity and density of the central serotonergic 5-HT1 A and
5-HT2 A receptors.

Teufel-Mayer R, Gleitz J

Extracts of St. John's wort, Hypericum perforatum L. (Hypericaceae),
are used as a phytotherapeutic antidepressant. A number of clinical
studies demonstrate that their antidepressive potency is comparable to
tricyclic antidepressants (TCA). Although the therapeutic effect of
hypericum extracts is well documented, very little is known about the
molecular mode of action. As the improvement of the depressive
symptoms with both TCA and hypericum extracts only occurs
significantly after a lag phase of 10 to 14 days, it is assumed that
the medication causes long-term adaptations within the central nervous
system. In this context, serotonergic (5-HT) receptors are of special
interest. Therefore, we investigated possible alterations in affinity
and density of 5-HT1 A and 5-HT2 A receptors caused by long-term
treatment of rats with St. John's wort. The brain without cerebellum
and brain stem of rats, treated daily for 26 weeks with a commercially
available hypericum extract (2700 mg/kg LI 160) were used for membrane
preparations. Affinity (KD) and amount (Bmax) of serotonergic
receptors were determined by employing receptor binding assays using 3
H-8-OH-DPAT and 3H-Ketanserin as selective radioligands for the 5-HT1
A and the 5-HT2 A receptors, respectively. We found that in
hypericum-treated rats the number of both 5-HT1 A and 5-HT2 A
receptors were significantly increased by 50% compared to controls,
whereas the affinity of both serotonergic receptors remained
unaltered. The data suggest an upregulation of 5-HT1 A and 5-HT2 A
receptors due to prolonged administration of hypericum extracts. These
results are consistent with a modification of the expression levels of
serotonergic receptors caused by synthetic antidepressants.

J Geriatr Psychiatry Neurol 1994 Oct;7 Suppl 1:S9-S11

Placebo-controlled double-blind study examining the
effectiveness of an hypericum preparation in 105 mildly
depressed patients.

Sommer H, Harrer G

One hundred and five outpatients with mild depressions of short
duration were treated in a double-blind study with either 3 x 300 mg
hypericum extract or placebo. The therapy phase was 4 weeks. The
effectiveness was judged according to the Hamilton Depression Scale
after 2 and 4 weeks. The values of the mean basic score in these
periods fell from 15.8 to 9.6 or 7.2 in the active group, and in the
placebo group, from 15.8 to 12.3 and 11.3. The differences between
active and placebo groups were statistically significant with P < .05
and P < .01 achieved after 2 and 4 weeks, respectively. In the active
group, 28 of 42 patients (67%) and, in the placebo group, 13 of 47
patients (28%) responded to treatment. Notable side effects were not

Anders Sandberg                                      Towards Ascension!                  
GCS/M/S/O d++ -p+ c++++ !l u+ e++ m++ s+/+ n--- h+/* f+ g+ w++ t+ r+ !y