Hypericum & Depression

Pharmaceutical Studies

Summary

Medical researchers tend to claim that they know more than they actually do. We really do not know how antidepressants work. There are still many black holes in our knowledge and there will certainly be many revisions about how they and hypericum exert their effect. For example, nobody has, as far as we know, yet come up with a good explanation for why it often takes so long for antidepressants to start working.

Hypericum was first thought to be a MAO-inhibitor, but today the most popular hypotheses are that hypericum works through cytokine modulation and serotonin and norepinephrine reuptake inhibition. We are quite sure this is not yet the end of the story. One hypothesis is that hypericum acts on many levels simultaneously, creating an accumulating effect by being both a MAO-inhibitor, serotonin-, norepinephrine-, and dopamine-reuptake inhibitor, a cortisol secretion inhibitor, etc. ("Many small streams create a great river.")

Is it possible that the different types of action harmonize together, to create a maximum amount effect at a certain point,with a minimum of side-effects, just like when the different rays from sunlight converge through a lens to create intense heat at the focus-point?

There are many studies documenting the clinical antidepressant effect of hypericum and it can be concluded that hypericum possesses an antidepressant effect of a magnitude similar to synthetic antidepressants, but with a minimum of side effects.

Hypericin accumulates in brain, stomach and skin tissue, but is more rapidly excreted in other tissues. This might be an explanation to its benign effect-side-effect profile and why its primary sites of action have been in the brain, skin and GI-system. (The most common side-effect complaints have come from these areas.)

• In a recent study Müller et al. have demonstrated a norepinephrine- and serotonin-reuptake-inhibiting effect of hypericum extract. It remains to be established whether this has clinical effect, as the concentrations of the active ingredients of hypericum in the human brain during antidepressive treatment has not been established.
  
  Another hypothesis is that hypericum acts on the CRH, ACTH and cortisol system by inhibiting the cytokine interleukin-6 and other cytokines excreted by cells of the immune-system.
• There are also interesting investigations on hypericum's effect on urinary secretion of catecholamine metabolites, light-induced and nocturnal secretion of melatonin and effects on benzodiazepine receptors.
  
  There are also interesting findings on the dopamine- reuptake inhibiting and prolactin-inhibiting effects of hypericum extract by Winterhoff et al.
• We will also report on the pharmacokinetics and pharmacological properties of hypericum extract in this section.

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

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