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Advice on a few supplements and herbs please?


Sam93
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Currently my HPPD 'stack' consists of a b vitamin complex, magnesium citrate, 1000mg omega 3 fish oil, and while these definitely help I've been looking for more.

What I was looking at are:

St. John's wort

Seems to be a mild SSRI with dopamine and norepinephrine reputake qualities as well. A member of the forum reported that it helped with his depersonalization so I thought I'd give it a 2 week trial.

Some info on its mechanism of action

Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort.[9] It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 μg/mL for all compounds, with the exception of glutamate, which is in the 0.5 μg/mL range.[10] Hyperforin also inhibits the reuptake of glycine[11] and choline,.[12] It appears to exert these effects by activating the transient receptor potential ion channel TRPC6.[13] Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake

So basically it inhibits the reputake of serotonin. Norepinephrine, dopamine, GABA, glutamate (not much) glycine and choline. Sounds quite good.

L-Theanine

While structurally related to the excitatory neurotransmitter glutamate, theanine only has weak affinity for the glutamate receptor on postsynaptic cells.[19] Rather, its primary effect seems to increase the overall level of the brain inhibitory transmitter GABA.[citation needed] Theanine also increases brain dopamine levels and has a low affinity for AMPA, kainate and NMDA receptors.[20] Its effect on serotonin is still a matter of debate in the scientific community, with studies showing increases and decreases in brain serotonin levels using similar experimental protocols.[5][21] It has also been found that injecting spontaneously hypertensive mice with theanine significantly lowered levels of 5-hydroxyindoles in the brain.[22] Researchers also speculate it may inhibit glutamic acid excitotoxicity.[20] Theanine also promotes alpha wave production in the brain.[10]

If you don't want to read all of that, it increases levels of GABA in the brain and increases levels of Dopamine in the brain, it may inhibit glutamic excitotocitiy and promotes alpha wave production in the brain (aren't alpha waves a problem in HPPD? I've took my weekly benzo so my cognition has reached somewhat of a decline.)

Passiflora

Passiflora as you probably know is a herbal sedative, not entirely sure how it works myself but in a study it was found as effective as Oxazepam with fewer side effects, source: http://www.ncbi.nlm.nih.gov/pubmed/11679026

Valerian root

I'm sure everyone knows what valerian root is, a pretty common herbal sedative which contains various chemicals that have affinity for the GABAA receptor, so a similar mechanism of action to Benzos.

Basically my HPPD responds exceptionally well to Benzos, and so herbs like these with benzodiazepine like mechanisms of actions may serve as a viable long or longER term treatment than Clonazepam. The study on passiflora being as effective as Oxazepam intrigued me.

Any thoughts on these? Thank you and have a pleasant and not too visually distorted day.

Sam.

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Hey Sam! I just wrote an absurdly long reply to the other supplement thread, so I'll try to keep this concise.
SJW: Haven't tried this myself, but the literature is definitely not convincing enough, and I'm not sure SSRI's are beneficial at all. You're referring to bpl who was taking several supplements concurrently, hence the improvements can't be isolated to SJW.

 

L-Theanine: My personal experience is that it is solely useful for mitigating caffeine jitters. Actually, I find it more stimulating than anxiolytic, though for some reason it takes the edge off of coffee whilst not being anxiolytic by itself. It can be really expensive though, so I'd advise to find the cheapest source of Suntheanine you can find (I'm really liking iHerb lately as a vendor, and I just looked; they've got 3 grams for 10 bucks, which is sufficient to experiment with). You know.. What the hell I'm gonna take 400mgs and see what happens right now. Haven't used it in a while. I'd say this one is a nice addition to your closet regardless. I take it sublingually as I enjoy the taste, or I add it to my drink.

 

Passiflora: Yes! My first experience with this was yesterday, and it was surprisingly awesome! Strangely enough I haven't been able to experience the effects again, even with thrice the dosage, so I'm wondering whether it may have been the strongest placebo ever or that something else in going on (idk maybe I should wait a few days and try again). Check out the "Treating Anxiety Safely and Effectively" thread and you'll read a little about it's GABA-mediated action, and that it's best avoided for long-term (daily) use. Using it as-needed won't be an issue, though you should be careful with the dosage (more than 15 grams and you might start hallucinating, or so it says on my box here.. hallucinations are of very mild nature though). In any case, the taste is pretty darn pleasurable and it makes a good tea!


Valerian: I've tried this in a period of high-anxiety before HPPD and it never did a thing, not even with insane dosages. In retrospect, it seems the product I was using might've been of bad quality though. Though the literature on Valerian isn't very convincing, and the general consensus is that it's very weak. Several of my friends and family have tried it and also found no effect to occur. If you are going to try it, I'd suggest you get an extract. In the aforementioned thread you'll also read that it's not the best idea for long-term use.

P.S. As for the alpha wave thing; alpha waves are reported to be faster in HPPD, thus increasing Alpha wouldn't be the best idea. Ideally, you want Theta activity IIRC, but I'm not that knowledgeable on this.

So much for being concise, haha! I could write much more than that though, so I guess it's relatively concise in this case.

All the best mate!

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Hey mate!

I still don't understand the stigma associated with SSRI's and HPPD, as I was under the impression there was nothing to suggest there was anything seretogenically going on with us, no overactive 5ht receptors and such, but I've not read much into the reports of SSRI's from our fellow trippers on the board. I was more interested in the dopamine reputake inhibition, and also noticed it inhibited the reputake of choline and to a lesser extent glycine.

Passiflora does sound great, especially the study suggesting it was as effective as Oxazepam as an anxiolytic, I've yet to try this but I think this is definitely one for the cupboard. Any reduction of visuals or dpdr with your experience?

As for valerian, I have found it to be a good anxiolytic and sleep aid in the past, pre hppd. It definitely works for me although my interest in valerian was mainly due to the search for a more herbal or natural replacement for benzodiazepines, maybe even a more sustainable treatment, but of course, I'm just weary of down regulation of my precious GABA A receptors.

Thanks for the info mate, hope all is well.

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Ohh I think I may have gotten that one wrong.. It upregulates GABA production, not receptors. Here's a study mentioning GABA A http://www.ncbi.nlm.nih.gov/pubmed/20108732.

As for the serotonergic stigma: I agree. Whilst indeed most HPPD is induced by serotonergic agonists, that needn't equate to serotonergic dysfunction being the cause. Even so, I wouldn't see the merit of SSRI's, for if mass serotonin influx induced a mass 5HT downregulation, then certainly 5HT upregulation would be more beneficial than SSRI activity. Conversely, if it is a case of 5HT2A hypersensitivity (as I believe is one of the theories I've read), then wouldn't it not be more beneficial do de-sensitize or antagonize these? In any case, SSRI's show no merit what so ever. Oh my bad, it appears to be "5HT2a hypoactivation" http://www.ncbi.nlm.nih.gov/pubmed/10721882. But even then, just read the study to get my point. And the case report of an SSRI improving symptoms was in concurrence of Olanzapine, which is essentially useless because of its widespread pharmacological action. So far there is very little if any evidence to show that HPPD is perpetuated serotonergically. As for SJW, yes definitely DRI activity sounds pretty nice, but higher DA levels could be achieved more effectively. Choline reuptake inhibition wouldn't improve anything, possibly even worsen symptoms I suspect. No idea about glycine though, haven't really looked in to that. I know, it's an essential part to neuroscience and all.. but that's the more complicated stuff I'd rather avoid until I feel cognitively more capable. Same goes for AMPA, haha.

Yes I saw that study as well.. Out of all the benzo's I've tried (only a few), I must say I found Oxazepam the best. Passiflora even better than that.
No visual improvements though, but definitely anxiolytic. As for DP/DR.. hmm I don't know I was just a lot less irritable which was a very welcome change. Certainly no repersonalization, but I was less bothered by the DP I guess? Wouldn't know how to describe it.

Why don't you see what herbal alternatives you can find that act on GABA B? Or maybe even a Positive Allosteric Modulator of the GABA A receptors? It would make your receptors more sensitive to their transmitters IIRC, which is not exactly upregulation but comes quite close to it, because both cause for an increased sensitivity to the neurotransmitter (in this case GABA). Makes sense I guess, though not sure: upregulation = more receptors = more sensitivity.
PAM = sensitizes receptors = more sensitivity.

By the way.. I found a source for L-Dopa the other day from a pretty massive botanical retail webshop. Not exactly on topic; just throwing it out there.

EDIT: Sorry, Bacopa Monnieri has GABA upregulation activity! My bad. PMID: 20153260

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So there's never really been a case of a SSRI improving symptoms to any clinically significant degree, I think I'll leave the St. John's wort then. I'd like to try these different things but there have been too many reports of permanent worsening of symptoms with reputake inhibitors, I know I read a members symptoms have been made permanently worse with Effexor, and Its quite clear Fluoxetine isn't beneficial to us.

As for Passiflora its interesting that you found it more effective than Oxazepam, passiflora contains some MAOI's I believe and I don't think I've read any reports on MAOIs being tested in us HPPDers which is something I'd like to see.

Yeah I was looking at positive alllosteric modulators, especially since Diclazepam is a PAM of GABA A, and while it is a benzo and not sustainable, it did relieve a lot of my symptoms and so this mechanism of action could only replicate that effect, albeit to a lesser degree, should I find any herbal remedies. I'm sure I read that kava kava upregulates GABA A, I'd love to be able to try it but unfortunately its illegal in the uk. Whether or not I could possibly get hold of some is a different story.

Ill have a search and see what gabaergic herbs I can find, I've yet to find one that works on GABA B, the only substance I'm familiar with that works on GABA B is Phenibut (infact I had a dream I took some phenibut last night, crazy), however i have been interested in GABA-Bs role in visual processing, there was a study I was looking at but I'm too tired to understand it as I've just woke up : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1159966/

An, nice find on the L-Dopa, would you not need some carbidopa for it to be effective?

Cheers.

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Good call on the SJW.


Yes indeed.. IIRC Passiflora also contains some nootropic compounds.. scopoletin I believe? This is also present in Brunfelsia (in higher amounts if I'm not mistaken), which I found interesting.

 

I've tried a MAOI.. But it was Selegiline which has Amphetamine metabolites, and I have a phobia for Amphetamines ever since that time it induced a psychosis in me. Suffice to say I didn't give it a long trial. Check out Rasagiline if you're going MAOI style though (I'd try it, but with recent discoveries it's descended on the list of priority). Considering Dr. Abraham's COMT inhibition findings, if anyone were to trial a MAOI, they should use MAO-B inhibitors. These are much safer (no tyramine interaction I believe), and though equally active in metabolizing Dopamine it is far more selective to DA than MAO-A. Check out this link if you're interested. It's been a while since I've read about it, so you might want to confirm it for yourself ;)

I didn't know that about Diclazepam.. I'd have to look into it more prudently, but I'm not up for that atm. I suspect that with perhaps once a week usage it might be beneficial? Yes Kava is awesome! I'll send you a PM about it in a few.

I'm also too fogged out to comprehend that study, but thanks for posting :) Phenibut.. glad I threw that stuff out!
As for Levodopa.. yes well I believe you would simply (I realize some people might find the word "simply" out of context here, haha) need a DOPA decarboxylase inhibitor. Carbidopa just happens to be that, but there are other compounds (I think it was ECGC or Quercetin or something) that have that property, which are easier to come by (though they might be less effective.. and might require a little tinker and play until you find the combination with which you don't vomit).

Cheers!

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Theanine is good for you!  It promotes alpha patterns in the brain and increases dopamine.  It also could be a good alternative to benzo's if you wanted to go the holistic route for treating anxiety. 

 

I used it primarily for sleep.  For me it didn't induce sleep, but made my sleep a LOT deeper and more restful. 

 

As previously stated works great for the caffeine jitters also...

 

The Japanese put it in a lot of "relaxation" drinks over there.  It's completely benign and I've read nothing about any adverse reactions.

 

It's expensive in it's pure form.  I recommend Suntheanine.

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