4 replies to this topic

[Simeoni]

Im planning to do a trial on SJW. My interest is in upregulating the 5HT1A 5HT2A receptors. Im a bit cautious with this because there are some conflicting reports how SJW effect's your brain levels of glutamate. For example: According to this study ( https://www.ncbi.nlm...pubmed/20193678 ) the active component, hypericin, inhibits glutamate release in the cynapse. 

However, if we look at the info page on wikipedia, it says that the other active ingridient, hyperforin, has the  strongest re-uptake on glutamate:

"Hyperforin Serves as a TRPC6 and PXRagonist. Reuptake inhibitor of 5-HT (205nM), DA (102nM), NE (80nM), GABA (184nM), Glu (829nM), Gly and Ch (8.5μM). Angiogenesis, COX-1 (300nM), 5-LO (90nM),SIRT1 (15μM), SIRT2(28μM) and MRSA (1.86μM) inhibitor." ( https://en.wikipedia...um#cite_note-54 )

So my question is: What's the net effect of glutamate in the brain - when supplementing with SJW?

Reason I ask this, is because in my NutrEval my glutamate was in the high end of the normal range.

[gamesguru]

for Ki values, low corresponds to high inhibition.  so the NE uptake is strongest, and Glu is relatively weak.

 

if you read the study on hypericin (attached, Figure 1), you see it takes about 30 micromolar to reduce the glutamate release significantly.  in a 65 kg male, that's about (30*10^-6 mol/L)(504.45 g·mol⁻¹)(65 L) = 984 mg of pure hypericin.  which makes most supplements seem paltry (standardized to 0.3% hypericin), and honestly the uptake inhibition may be the more powerful effect, making this pro-glutamate.. bad for epileptics and schizophrenics.

 chang2010.pdf   489.05KB   2 downloads

Edited by gamesguru, 23 December 2016 - 02:45 PM.

[PeaceAndProsperity]

 making this pro-glutamate.. bad for epileptics and schizophrenics.

Don't you mean bad for epileptics but good for schizophrenics? Is there a high-glutamate hypothesis of schizophrenia?

[gamesguru]

Presynaptic Hypotheses

On the presynaptic level, the most obvious potential cause of NMDAR dysfunction would be a reduction in overall glutamatergic tone in the brain, leading to a global deficit in glutamatergic neurotransmission. However, while some findings of reduced CSF glutamate levels were reported (Kim et al, 1980), ultimately these were not confirmed (Javitt and Zukin, 1991), suggesting that more complex disturbances in glutamatergic function might be involved. In fact, over the last 20 years, it has been increasingly demonstrated that hyper, rather than hypo, glutamatergic function, potentially mediated through activation of AMPA receptors may be critical in schizophrenia, and that ideal treatment approaches may reduce rather than increase presynaptic glutamate levels (Moghaddam, 2003).

 

interestingly, riluzole, a glutamate release inhibitor, has shown great potential (monotherapy against treatment-refractory phenotypes) in treating OCD, schizophrenia, and even borderland (see attached study).

 

you can also connect the dots in an epigenetic context.  overmethylation accounts for three times as many cases as undermethylation[1].  and we find exactly that, hypericin likely excites DNMTs and further exacerbates the hypermethylated state.

 

but the lines of evidence converge from more sources (histamine, gamma interferon, and PKC), all suggesting st john's is utter rubbish for the schizophrenic, as are most SSRIs (they often cause suicidal thoughts and rarely address negative symptoms).  riluzole has roughly opposite relationships to these pathways as st john's

 Initial evidence of the beneficial effects of glutamatemodulating agents in the treatment of selfinjurious behavior associated with borderline personality disorder.pdf   141.29KB   5 downloads

[Galaxyshock]

Hyperforin from SJW is also antagonist of NMDA- and AMPA-receptors.