Posted by Larry Hoover on November 5, 2002, at 9:02:35
In reply to Convoluted Post on St Johns Wort and other issues, posted by Alara on November 5, 2002, at 4:37:38
> 1. The writers suggest that St Johns Wort may be beneficial in conjunction with some SSRIs and the SNRI Effexor. I always thought that St Johns Wort was contraindicated against other antidepressants because there were fears about excess seretonin build-up. Have there been any conclusive studies?
I think you're misreading the statement. If you were to identify a sub-population of depressives, based upon their need for/responsiveness to the Effexor/Buspar combination, that sub-population might do well on SJW *as an alternative*, not as an augment.
There have not been, to my knowledge, any clinical studies done on SJW/SSRI combinations. Case reports do show that individuals have tried it. Mild serotonin syndrome seems to be the result.
Here are a couple of studies showing anxiolytic and anti-stress activity:
Indian J Exp Biol 2000 Jan;38(1):36-41
Anxiolytic activity of Indian Hypericum perforatum Linn: an experimental study.
Kumar V, Jaiswal AK, Singh PN, Bhattacharya SK.
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi 221 005 India.
The putative anxiolytic activity of 50% ethanolic extract of Indian Hypericum perforatum (IHp) was investigated in rats using various experimental paradigms of anxiety viz. open field exploratory behaviour (OFB), elevated plus maze (EPM), elevated zero maze (EZM), novelty induced suppressed feeding latency (FL) and social interaction (SI) tests. Pilot studies indicated that single dose administration of IHp had little to no acute behavioural effects, hence the extract of IHp was administered orally at different dose levels once daily for three consecutive days, while lorazepam (LR) (0.5 mg/kg, i.p.) was administered acutely. IHp extract (100 and 200 mg/kg, p.o.) showed significant anxiolytic effects on all the paradigms of anxiety. The results indicate that IHp and LR induced a significant increase in open field ambulation and slight increase in rearings and activity in centre, whereas grooming and fecal droppings remain unchanged. In EPM, significant augmentation of open arm entries, open arm/closed arm entries ratio and time spent on open arms was noted in IHp treated rats. In EZM test, significant increase in time spent on open arms and entries in open arms were observed, whereas slight increase in head dips and stretched attend postures were also observed. IHp and LR significantly attenuated the novelty induced increase in feeding latency. IHp treated rats also showed significant increase in social interaction in the novel environment. The IHp extracts showed consistent and significant anxiolytic activity in all the tests. The effects induced by 50% ethanolic extract of IHp were less marked than those of lorazepam were.
Indian J Exp Biol 2001 Apr;39(4):344-9Anti-stress activity of Indian Hypericum perforatum L.
Kumar V, Singh PN, Bhattacharya SK.
Department of Pharmaceutics, Banaras Hindu University, Varanasi, India.
Indian Hypericum perforatum (IHp) was investigated on a 14-day mild, unpredictable and inescapable foot shock stress (FSS) induced perturbations in behaviour (depression), suppressed male sexual behaviour and cognitive dysfunction in albino rats. Gastric ulceration, and adrenal gland and spleen weights, were also used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. FSS induced marked gastric ulceration, significant increase in adrenal gland weight with concomitant decrease in spleen weight. Chronic stress also suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests). All these FSS induced perturbations were attenuated dose dependently by IHp (100 and 200 mg/kg, po) and PG (100 mg/kg, po). The results indicate that IHp has significant anti-stress activity, qualitatively comparable to PG, against a variety of behavioural and physiological perturbations induced by chronic stress, which has been proposed to be a better indicator of clinical stress than acute stress, and may indicate adaptogenic activity.
The mechanism of action of SJW is still being worked out. They are quite sure that there's more to it than hypericin and hyperforin, as SJW extracts with those substances removed still have antidepressant activity. Here are a couple of summaries:
Pharmacopsychiatry 2001 Jul;34 Suppl 1:S56-60
St. John's wort extract Ze 117 (Hypericum perforatum) inhibits norepinephrine and serotonin uptake into rat brain slices and reduces 3-adrenoceptor numbers on cultured rat brain cells.
Kientsch U, Burgi S, Ruedeberg C, Probst S, Honegger UE.
Department of Pharmacology, University of Bern, Switzerland.
Despite almost forty years of widespread use, the mode of action of antidepressant drugs is still largely unknown. There is agreement that these drugs interact with central neurotransmission. Common findings are acute inhibitory actions on reuptake mechanisms for norepinephrine (NE) and for serotonin (5-HT) at presynaptic axons and chronic adaptive effects on neurotransmitter receptors on postsynaptic membranes. In particular, beta-adrenoceptor downregulation has been observed after chronic treatment with most antidepressants in vivo and in cell culture systems. We studied the effectiveness of Ze 117 (St. John's wort) extract (Hypericum perforatum) on NE- and 5-HT-uptake into rat brain slices. Potency and efficacy of the Ze 117 extract were compared with those of tricyclic (TCA) and selective serotonin reuptake inhibitor (SSRI)-type antidepressants. A dose-dependent inhibition was seen on NE and 5-HT uptake into brain slices. The Ze 117 extract was more selective for the uptake of NE than for that of 5-HT. The maximal extent of uptake inhibition by Ze 117 extract was comparable to that of imipramine (IMI), desipramine (DMI) or fluvoxamine for 5-HT, but lower for NE transport, than that of the synthetic antidepressants. Chronic exposure (8 days) of confluent C6-cell cultures to Ze 117 extract resulted in a dose-dependent beta-adrenoceptor downregulation equal to that induced by DMI, a potent TCA. None of these effects could be achieved with either hypericin or hyperforin alone in a relevant dose range. Our results indicate that the St. John's wort extract Ze 117 contains active, but as yet unknown antidepressant principles with effects comparable to those of TCAs.
Schweiz Rundsch Med Prax 2000 Dec 14;89(50):2111-21
[Mechanism of action of St. Johns wort extract]
[Article in German]
Muller WE, Singer A, Wonnemann M.
Pharmakologisches Institut fur Naturwissenschaftler, J. W. Goethe-Universitat Frankfurt.
Over the last few years St-John's wort preparations have been used in large quantities in Germany for treating mild to moderate depression. In the meantime the antidepressive action of these extracts has been proved in numerous placebo-controlled studies. Furthermore, a considerably lower adverse effect rate compared with classic antidepressants has been established. Analogously to other antidepressants, subchronic St-John's wort treatment of rats showed significant down-regulation of beta receptor density and a significant increase in 5HT2 receptors. The extract also exhibited antidepressant activity in animal pharmacological models of depression. Interest is now focused on identifying the underlying pharmacological mechanisms of action of this phytotherapeutic agent. Like other working parties, we were only able to identify a weak inhibitory effect of the extract and the pure substance hypericin on the monoamine oxidases A and B. Similarly to synthetic antidepressants, St-John's wort exerts marked inhibitory effects on synaptosomal uptake of serotonin and noradrenaline. However, dopamine and uptake and neuronal uptake of GABA and L-glutamate are also inhibited. These effects may mainly be attributed to the substance hyperforin contained in the extract. An additional, as yet unknown, pharmacological mechanism of action of St-John's wort extracts is beginning to emerge. Although hyperforin shows similar properties to classical antidepressants, there are indications of a novel mechanism of action. Our laboratory is currently investigating the means by which St-John's wort extract, or its constituent hyperforin, develops its antidepressant action.
> 2. The writers also suggest (elsewhere on the webpage) that St Johns Wort can reduce the effectiveness of oral contraceptive pills. I also read something like this on Psychobabble a few days ago. Can anyone point me towards any clinical trials which substantiate this claim?? I can NOT afford to get pregnant right now. lol.
You won't find anything in clinical trials. You'll find instances documented as case reports. SJW is an inducer of the liver enzyme P450 3A4. Anything that is normally acted on by that enzyme will be excreted in urine much faster than it would otherwise be. That includes natural substrates, like cortisol (one possible mechanism of the anti-stress activity), but also any drugs which are broken down by that enzyme. That includes synthetic birth-control hormones. At least, that's what the doctors believe is happening. Break-through bleeding and unwanted pregnancy have both been reported by women taking both medications. You're going to have to make a decision. You may want to include other methods of birth control, alongside the pill.
> 4. (This has nothing to do with the St Johns Wort issue.) In spite of having a mild depressive, high anxiety problem, I sometimes think I need a stimulant to get me out of bed in the morning. MAJOR CONFUSING PARADOX!! I sleep way too much to avoid anxiety, if that makes any sense. Many people on this board have tried to post useful suggestions to me in the past about medications that will help me to overcome my atypical depression, but I must admit that I stubbornly resisted, believing that I could conquer the world med free. Maybe I can. I'm going to give myself 2 more weeks to see how much the exercise and St Johns Wort help. But right now I'm still exploring the options.
Have you tried betaine or d,l-phenylalanine? Both have stimulant properties, and are therefore best taken in the morning.
> Does it make any sense to give a highly anxious person (who at the same time can't get motivated to get out of bed and go to work) an antidepressant and a stimulant? Will St Johns Wort help to augment the effects of the antidepressant with minimal effects on the heart and liver?If you're thinking of a combo (SJW and SSRI), there's no way to predict what will happen. The dose makes the poison.
> How much damage do these drugs really do to our heart, liver and kidneys anyway???That really depends on both your genetics and the effects of other environmental influences on your bodily functions. It's not predictable.
> Just concerned about my health.
>
> Sorry about being so long-winded as usual. Thanks for reading. :-)
>
> AlaraI like reading thought-provoking posts. Finding the answers keeps me abreast of the latest research.
poster:Larry Hoover
thread:126485
URL: http://www.dr-bob.org/babble/20021101/msgs/126499.html