Pharmacodynamics of St. John Wort

Subject: Mental Health
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St. John’s Wort

Commonly known as Hypericum  perforatum, St. John’s Wort has been used to treat many ailments like hemorrhoids, neuralgia, and sleep disorders for centuries. However, it is best known for the treatment of mild and moderate depression (Gupta & Möller, 2003). St. John’s Wort is composed of several active ingredients including hypericin, protohpericin, hyperforin, cyclopseudohypericin, isohypericin, and other several flavonoids. Each of the active components has different levels of contribution to the antidepressant properties of the drug. On the other hand, it appears that there are different mechanisms linked to St. John’s Wort antidepressant effects. However, research has not been able to establish whether any of the effects influences another. As a result, there is a higher likelihood that the overall antidepressant effect culminates from the combination of the mechanisms and ingredients causing the effect.

Various mechanisms have been proposed regarding the treatment of depression using St. John Wort. One of the mechanisms is concerned with inhibiting the uptake of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) from the Synaptic cleft located in the interconnecting neurons (Gupta & Möller, 2003). The second mechanism regards the ability of binding gamma-amino-butyric acid receptors to the neuro-inhibitory receptor to prevent the binding of GABA. The reduction in GABA binding causes a decrease of depression in the central nervous system. The third mechanism is concerned with increasing the number of 5-HT2 in the brain’s frontal cortex. It is believed to be potentially beneficial in the treatment of depression. However, the available evidence to support this finding is from rats. The fourth mechanism is the ability of St. John’s Wort to inhibit the activity of COMT (catechol-O-methyltransferase) enzymes and MAO (monoamine oxidase) enzymes (Gupta & Möller, 2003). When active, the Central Nervous System (CNS) enzymes metabolize the precursors of dopamine into active compounds rather than allowing dopamine to be metabolized into norepinephrine in the brain. As a result, the inhibition of the enzymes favors NE formation in the CNS.

Of all the effects, there is no single one which appears to predominate the others. Therefore, the overall antidepressant effects are an amalgamation of different mechanisms. Research findings indicate that there is a possibility that the extracts of St. John’s Wort might affect the biologic impact because the concentration of the active ingredients might differ (Lawvere & Mahoney, 2005). Despite the effects on the CNS neurotransmitters, clinical data indicate that the benefits of the drug are minimal as they are limited to the mild and moderate depression. The lack of significant effects in the treatment of depressive conditions explains why the side effects of the drug are less than the antidepressants recommended in clinical practice.

Due to its availability as an herbal supplement, some people might tend to take St. John’s Wort without consulting the pharmacists. Therefore, it is likely to cause problems as there is a potential of having an herbal-drug interaction (Lawvere & Mahoney, 2005). For instance, it is expected to cause loss of efficacy due to the induction of drug metabolizing enzymes. Additionally, due to its different components of content, taking the drug could lead to potential toxicity or changes in efficacy. Moreover, there is a concern for patients that were initially on SSRIs and decided to add St’ John’s Wort. Such patients are likely to experience increased risks of serotonin syndrome manifested by symptoms like confusion, fever, agitation, nausea, coma, and diarrhea. Even though the drug is effective in the treatment depression, it might also present side effects due to herbal-drug interaction.

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  1. Gupta, R. K., & Möller, H. J. (2003). St. John’s Wort. European archives of psychiatry and clinical neuroscience, 253(3), 140-148.
  2. Lawvere, S., & Mahoney, M. C. (2005). St. John’s wort. Am Fam Physician, 72(11), 2249-2254.
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