Hypericum & Depression

Study 13

Pharmacological profile of hypericum extract: Effect on serotonin uptake by postsynaptic receptors

AU: Perovic-S and Mueller-W-E-G

SO: Arzneimittel-Forschung/Drug Research 45 (II), 11, 1145-1148(1995)

Description

Brains from adult rats were dissected on ice, cortices homogenized and centrifuged in an established way that results in a separation of postsynaptic membranes and an enrichment of postsynaptic receptors. This synaptosomes were then incubated together with hypericum extract LI 160 in different concentrations. Uptake was initiated by an addition of 5 micromol of radioactive serotonin and terminated by dilution on ice buffer and rapid filtration through glass fiber filters. The incubation period was 0-30 minutes. Radioactivity on filters was measured by liquid scintillation spectrometry. To correct for passive transport, the uptake at 0-4 degrees Celsius was measured.

Summary

• It was concluded that hypericum extract LI 160 inhibits serotonin uptake into rat synaptosomes in vitro, thus increasing the concentration of serotonin in the synapse.
• The reuptake inhibition shows an almost linear dose-response curve, with 20% inhibition at a hypericum concentration of 0.3 microg/ml, 50% at 6.2 microg/ml and 90% inhibition at a dose of 20 mikrog/ml.

Comments

The concentration necessary for a 50% inhibition was 6.2 microg/ml .This is equivalent to a concentration of hypericin of 6200 ng/m l (the dose in ngrams) x 0.25 mg (amount of hypericin in 300 mg extract) divided with 300 mg = 5.2 ng. That corresponds roughly to a fourth of the concentration measured in the brain after injection of 1 mg/kg hypericin in mice in the study by Chung et al. The blood level was 400 ng/ml in that same experiment. The mean steady-state concentration in blood for patients treated with 0,9 mg hypericin x 3 daily per os was measured to be 5.3 ng /ml, which is approximately 80 times lower than in the mice described above. This means that the probable level needed to get an immediate 50% reduction of serotonin uptake in the brain would be 80/4= 20 times that used in antidepressant treatment. What might be able to explain the possible effects is the accumulation of hypericin in the brain described in the study by Chung et al. For a final evaluation of Perovic and Mueller's findings, it is necessary to establish the concentration of hypericin in the human brain in patients treated with hypericum extract.

Treatment with high initial doses?

It might be intelligent to change the policy of antidepressive treatment, to start treatment with very high dosages initially in order to reach steady-state concentrations sooner. This could be a subject for future trials.

Accumulation in brain tissue as an explanation of benign side-effect profile?

The accumulation of hypericin in the brain over time might also explain why hypericum has such a benign effect-side-effect profile compared to other antidepressants. The slow accumulation in the brain leaves other areas in the body less exposed to possible effects on the serotonin metabolism in other parts of the body.

Clinical studies on long-term effect are needed

Due to hypericum's slow accumulation in the brain, we recommend studies on the long-term effects of treatment with hypericum.

Copyright © 1996 by Harold H. Bloomfield, M.D. and Peter McWilliams