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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by Maxime on December 26, 2003, at 13:16:55
Hello. I apologise if this has already been discussed here. But I was surprised to read that St. John's Wort was an MAOI! I currently take Parnate and MAOI. It's pooping out on me. Would it be safe to add St John's Wort to it?
Anyone know how to augment the effects of an MAOI?
I'm slipping hard and fast into a deep depression. I hope someone can help. I've been on so many meds with no results. I'm bipolar.
Maxime
Posted by linkadge on December 26, 2003, at 15:03:42
In reply to St John's Wort - An MAOI?, posted by Maxime on December 26, 2003, at 13:16:55
I would say definately not.
The actions of SJW are only partially explained by MAOI inhibiton. It also has reputake inhibiting properties for serotonin, norepinephrine and dopamine. The weakness of SJW as an MAOI can be seen by the fact that hypertensiver crisis have never been reported.
It is very easy to get Serotonin syndrome on SJW and and SSRI. I would advise against combining the two.
Posted by SLS on December 27, 2003, at 9:08:16
In reply to Re: St John's Wort - An MAOI?, posted by linkadge on December 26, 2003, at 15:03:42
Hi Linkadge.
> The actions of SJW are only partially explained by MAOI inhibiton.
What else does it do?
I remember reading that the few early studies indicating MAO inhibition were in error.
Thanks.
- Scott
Posted by NoMotic on December 27, 2003, at 13:35:36
In reply to Re: St John's Wort - An MAOI? » linkadge, posted by SLS on December 27, 2003, at 9:08:16
As I understand, it broadly inhibits the reuptake of glutamate, GABA, dopamine, norepinephrine, serotonin through affecting the sodium gradient. It doesn't actually block the reuptake pump or whatever like SSRI's. It indirectly leads to widespread reuptake inhibition across the board and this is responsible for its effects.
Also, it acts as a cytokine blocker (interleukin - 6). Some suspect this contributes to antidepressant action since cytokines can alter neurotransmitter levels.
Until they do more studies, it's hard to say exactly what is responsible for what effects. All they can do is assume and rule out certain reasons, and I guess they ruled out the MAO inhibition because of the lack of hypertension associated w/ its use.
Posted by linkadge on December 27, 2003, at 20:04:04
In reply to Re: St John's Wort - An MAOI?, posted by NoMotic on December 27, 2003, at 13:35:36
That is true about what you said with regards to the sodium transporter effect. However it really has been shown to have weak effects on MAO activity. Very little compared to standard MAOI's but still enough to be detectable in the rat brain. Another thing to consider, is that it may be a reversable inhibitor of MAO activity like the antidepressant Moclobemide. This drug effects MAO levels but has no dietary restrictions.
Many other plants have reversable MAO inhibition activity. Turmeric, Cinamon, Ginkgo, Kava, Tobacco, and others have varying effects on MAO activity.I had excellent responce to it. I thought that it made me dumb, but others say it really made them more attuned, weird.
Linkadge
Posted by tealady on December 28, 2003, at 0:33:12
In reply to Re: St John's Wort - An MAOI?, posted by linkadge on December 27, 2003, at 20:04:04
> That is true about what you said with regards to the sodium transporter effect. However it really has been shown to have weak effects on MAO activity. Very little compared to standard MAOI's but still enough to be detectable in the rat brain. Another thing to consider, is that it may be a reversable inhibitor of MAO activity like the antidepressant Moclobemide. This drug effects MAO levels but has no dietary restrictions.
>agree, I didn't notice any large increase in blood pressure either
>
> Many other plants have reversable MAO inhibition activity. Turmeric, Cinamon, Ginkgo, Kava, Tobacco, and others have varying effects on MAO activity.
>
> I had excellent responce to it. I thought that it made me dumb, but others say it really made them more attuned, weird.
I too had an excellent response..glad I tried it..although it took a while to kick in.
I'd never notice if it made me dumb, sigh...but I do feel more attuned ..I hadn't put it down to SJW , just to the lifting of depression in general...perhaps it was. I haven't taken it for 2 days now, so its easy to come off too, I think.Jan
Posted by tealady on December 28, 2003, at 12:43:03
In reply to Re: St John's Wort - An MAOI?, posted by tealady on December 28, 2003, at 0:33:12
>I haven't taken it for 2 days now, so its easy to come off too, I think.
>
> Jan
>
Correction :- I needed to restart on the 3rd day. I thought I was going so well, but I guess it was the SJW.Jan
Posted by linkadge on December 28, 2003, at 15:14:58
In reply to Re: St John's Wort - An MAOI?, posted by tealady on December 28, 2003, at 12:43:03
You're right, it certainly has an effect.
I had the worst withdrawl from it. But then again I was severly depressed when I started the stuff.
Linkadge
Posted by Larry Hoover on December 31, 2003, at 9:38:54
In reply to Re: St John's Wort - An MAOI?, posted by NoMotic on December 27, 2003, at 13:35:36
> As I understand, it broadly inhibits the reuptake of glutamate, GABA, dopamine, norepinephrine, serotonin through affecting the sodium gradient. It doesn't actually block the reuptake pump or whatever like SSRI's. It indirectly leads to widespread reuptake inhibition across the board and this is responsible for its effects.
Some of the effects, yes.
CNS Drugs. 2003;17(8):539-62.
Mechanism of action of St John's wort in depression : what is known?
Butterweck V.
Institute of Pharmacology and Toxicology, Universitatsklinikum Munster, Munster, Germany. butterv@uni-muenster.de
Extracts of Hypericum perforatum L. (St John's wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John's wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones. Although St John's wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John's wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, other in vitro binding assays carried out using St John's wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors. In vivo St John's wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John's wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John's wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John's wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John's wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids. This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John's wort and its active constituents with a large body of existing literature.
Life Sci. 2002 Sep 27;71(19):2227-37.
Inhibition of vesicular uptake of monoamines by hyperforin.Roz N, Mazur Y, Hirshfeld A, Rehavi M.
Sackler Faculty of Medicine, Department of Physiology and Pharmacology, Tel Aviv University, Tel-Aviv, Israel.
Hyperforin is the major active ingredient of Hypericum perforatum (St John's Wort), a traditional antidepressant medication. This study evaluated its inhibitory effects on the synaptic uptake of monoamines in rat forebrain homogenates, comparing the nature of the inhibition at synaptic and vesicular monoamine transporters. A hyperforin-rich extract inhibited with equal potencies the sodium-dependent uptake of the monoamine neurotransmitters serotonin [5-HT], dopamine [DA] and norepinephrine [NE] into rat brain synaptosomes. Hyperforin inhibited the uptake of all three monoamines noncompetitively, in marked contrast with the competitive inhibition exerted by fluoxetine, GBR12909 or desipramine on the uptake of these monoamines. Hyperforin had no inhibitory effect on the binding of [3H]paroxetine, [3H]GBR12935 and [3H]nisoxetine to membrane presynaptic transporters for 5-HT, DA and NE, respectively. The apparent presynaptic inhibition of monoamine uptake could reflect a "reserpine-like mechanism" by which hyperforin induced release of neurotransmitters from synaptic vesicles into the cytoplasm. Thus, we assessed the effects of hyperforin on the vesicular monoamine transporter. Hyperforin inhibited with equal potencies the uptake of the three tritiated monoamines to rat brain synaptic vesicles. Similarly to the synaptosomal uptake, the vesicular uptake was also noncompetitively inhibited by hyperforin. Notably, hyperforin did not affect the direct binding on [3H]dihydrotetrabenazine, a selective vesicular monoamine transporter ligand, to rat forebrain membranes. Our results support the notion that hyperforin interferes with the storage of monoamines in synaptic vesicles, rather than being a selective inhibitor of either synaptic membrane or vesicular monoamine transporters.
Psychopharmacology (Berl). 2002 Jul;162(2):193-202. Epub 2002 May 09.
In vitro receptor screening of pure constituents of St. John's wort reveals novel interactions with a number of GPCRs.Butterweck V, Nahrstedt A, Evans J, Hufeisen S, Rauser L, Savage J, Popadak B, Ernsberger P, Roth BL.
Institute of Pharmacology and Toxicology, Westfalische Wilhelms-Universitat Muenster, Domagkstrasse 12, 48149 Muenster, Germany. butterv@uni-muenster.de
RATIONALE: Hypericum perforatum L. (St. John's wort; SJW) is one of the leading psychotherapeutic phytomedicines and great effort has been devoted to clarifying its mechanism of action. OBJECTIVE: We have undertaken a comprehensive analysis of several pure compounds isolated from the crude extract to gain further insight into the molecular actions of various substituents of SJW. METHODS: We characterized the in vitro pharmacology of the naphthodianthrones hypericin and pseudohypericin, the phloroglucinol derivative hyperforin, and several flavonoids at 42 biogenic amine receptors and transporters using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. RESULTS: The biflavonoid amentoflavone significantly inhibited binding at serotonin (5-HT(1D), 5-HT(2C)), D(3)-dopamine, delta-opiate, and benzodiazepine receptors. The naphthodianthrone hypericin had significant activity at D(3)- and D(4)-dopamine receptors and beta-adrenergic receptors. With the exception of the D(1)-dopamine receptor, the phloroglucinol derivative hyperforin was less active than other SJW constituents tested on all screened receptors. CONCLUSION: Our present in vitro data clearly show that several pure substances in SJW are potential CNS psychoactive agents and may contribute to the antidepressant efficacy of the plant in a complex manner. Our data also reveal novel and heretofore unexpected interactions of pure compounds in SJW at a number of GPCRs, transporters, and ion channels. We hypothesize that additive or synergistic actions of different single compounds may be responsible for the antidepressant efficacy of SJW. These results and this general approach may impact our understanding of phytomedicines in general and H. perforatum specifically.
> Also, it acts as a cytokine blocker (interleukin - 6). Some suspect this contributes to antidepressant action since cytokines can alter neurotransmitter levels.
Yes, but....the evidence is contradictory, at least in so far as we understand the way things work. IL-6 is apparently necessary for at least one component of the antidepressant effect, but SJW potently inhibits IL-6 synthesis.
Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S8-10.
Interleukin-6 involvement in antidepressant action of Hypericum perforatum.
Calapai G, Crupi A, Firenzuoli F, Inferrera G, Ciliberto G, Parisi A, De Sarro G, Caputi AP.
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica Policlinico Universitario, Italy. gcalapai@unime.it
Hypericum, a plant widely used as antidepressant has been shown to interact with the immune system. We studied the effects of the administration of the Hypericum perforatum extract Ph-50, a Hypericum extract, standardized to flavonoids (50%) and containing 0.3% of hypericin and 4.5% of hyperforin in a forced swimming test and tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) diencephalic content using a high performance liquid chromatography method in male interleukin-6 (IL-6) knock-out (IL-6(-/-)) and wild type (IL-6(+/+)) mice. Hypericum extract (Ph-50; 500 mg/kg) oral acute administration reduced the immobility time of wild type, but not of knockout mice. Tryptophan content was not modified by Hypericum in all the animal groups. Serotonin and 5-HIAA diencephalic content was increased by Hypericum in both wild type and knockout mice. However, the increase observed in the wild type was greater than in knockout mice. These data indicate that IL-6 could be necessary to the antidepressant action of Hypericum, and that this cytokine (probably) mediates the effects of Hypericum through activation of the serotonin system.
Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S26-8.
Inhibition of substance P-induced cytokine synthesis by St. John's wort extracts.
Fiebich BL, Hollig A, Lieb K.
Department of Psychiatry, University of Freiburg Medical School, Germany. bernd_fiebich@psyallg.ukl.uni-freiburg.de
We tested the hypothesis that extracts from St. John's wort interfere with protein synthesis induced by substance P (SP), a neuropeptide which has been implicated in the etiopathology of depression and anxiety. Using human astrocytoma cells, which express functional neurokinin (NK)-1-receptors, we investigated whether extracts from St. John's wort are able to inhibit SP-induced synthesis of the cytokine interleukin-6 (IL-6). We found a potent and dose-dependent inhibition of SP-induced IL-6 synthesis by various extracts from St. John's wort. These results do not only give further evidence of the anti-inflammatory effects of St. John's wort, but also lend support to the hypothesis that the antidepressant effect of St. John's wort is, at least in part, a result of its inhibitory effects on SP-induced protein synthesis.
Planta Med. 1999 May;65(4):297-300.
Hypericin as a non-antioxidant inhibitor of NF-kappa B.
Bork PM, Bacher S, Schmitz ML, Kaspers U, Heinrich M.
Institute of Pharmaceutical Biology, Albert-Ludwigs University, Freiburg, Germany.
NF-kappa B is a transcription factor involved in immune and inflammatory responses. Here we show that micromolar concentrations of hypericin inhibited the PMA- and TNF-alpha-induced activation of NF-kappa B in HeLa and TC10 cells, respectively. In contrast, NF-kappa B activated by H2O2 was not influenced by hypericin, indicating a pathway-specificity of hypericin. Hyperforin and a Hypericum perforatum extract standardised on 0.15% hypericin and 5% hyperforin were not active at pharmacologically relevant concentrations. The PMA/TNF-alpha-induced transcription of a reporter gene, which is under the control of the NF-kappa B-dependent IL-6 promoter, was strongly reduced by preincubation with hypericin.
> Until they do more studies, it's hard to say exactly what is responsible for what effects. All they can do is assume and rule out certain reasons, and I guess they ruled out the MAO inhibition because of the lack of hypertension associated w/ its use.I can't find the abstract I wanted to quote here, but the study which first demonstrated MAO inhibition by SJW used doses which would be roughly equivalent to 300 times the dose commonly used in humans (I did the math, once upon a time). MAO and COMT inhibition are perhaps part of the puzzle, but they are of no clinical significance.
J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S57-9.
Inhibition of MAO by fractions and constituents of hypericum extract.
Bladt S, Wagner H.
Institut fur Pharmazeutische Biologie der Universitat Munchen, Germany.
The inhibition of monoamine oxidase (MAO) by six fractions from hypericum extract and three characteristic constituents (as pure substances) were analyzed in vitro and ex vivo to study the antidepressive mechanism of action. Rat brain homogenates were used as the in vitro model, while the ex vivo analysis was performed after intraperitoneal application of the test substances to albino rats. Massive inhibition of MAO-A could be shown with the total extract and all fractions only at the concentration of 10(-3) mol/L. At 10(-4) mol/L, one fraction rich in flavonoides showed an inhibition of 39%, and all other fractions demonstrated less than 25% inhibition. Using pure hypericin as well as in all ex vivo experiments, no relevant inhibiting effects could be shown. From the results it can be concluded that the clinically proven antidepressive effect of hypericum extract cannot be explained in terms of MAO inhibition.
Regards,
Lar
Posted by psychlover on January 5, 2004, at 22:31:51
In reply to Re: St John's Wort - An MAOI? » NoMotic, posted by Larry Hoover on December 31, 2003, at 9:38:54
Lar,
One of the studies you cited said this:
>With the exception of the D(1)-dopamine receptor, the phloroglucinol derivative hyperforin was less active than other SJW constituents tested on all screened receptors.
So why would you then recommend Perika hyperforin extract when the real effect seems to come from a combination of the various substances in SJW? Wouldn't it make more sense to take a whole-plant extract rather than just hyperforin?
Thanks!
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