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How did Bilberry, Dandelion Root and Wobenzym N produce this effect?

G

Granite

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Sep 16, 2014
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I've had an HPPD-esque disorder for 17 years. At first it was just visual snow, tinnitus, tingling (circulation), and hives (cholinergic), but it developed into something worse years later. I woke up in a brain fog, with palinopsia (afterimages), chronic muscle contraction/tension, depression/suicidal feelings, disorientation/derealization, brain fog/memory issues, skin changes (thin skin permeability), paleness, digestive issues, dry sinuses/skin/mucous membranes, fatigue, felt dehydrated all the time and more...

I tried 100s of supplements, and most did not help and just made me feel worse, but I usually returned to baseline pretty quickly. However, 3 specific supplements had a profound effect on my condition -- Bilberry Root, Dandelion Root, and Wobenzym N -- that all produced the same instantaneous relief effect; and also the same exact rebound problem. Within 10 minutes of ingestion, I felt my chronic muscle tension/contraction totally relax, my mood lifted to happiness, digestive issues felt better, no tingling, no disorientation, no paleness (skin looked normal), and more energy.

I thought I had found the supplements that would treat me, but each one caused the same rebound effect after the supplement wore off. I noticed roughly 24 hours after taking the supplements, my mood shifted to extreme depression/suicide, the tingling returned harder, blood vessels looked swollen and dilated, my muscles tensed back up to horrible rigidness and pain that made it hard to breathe. It was devastating every time, and took anywhere from a couple days to weeks to return back to the baseline of my symptoms before I tried the supplement. Wobenzym was the worst, and gave me pressure headaches for weeks after; probably because I tried it two days in a row, whereas the others I tried half-doses only a single day.

Since then, I've been trying to figure out how these supplements were able to produce this profound effect. It's kind of seems like a benzo-withdrawal that happens rapidly; like neurotransmitters were released and cause some kind of hyperpolarization. That's my best guess, but I haven't a clue in all honesty and it's above my understanding of neurotransmitters. The only thing I could link between the 3 supplements is that they seem to be connected as flavonoids. None of the supplements were able to affect my visual symptoms, which I think tells me that it was still treating the problem at a level lower than the main cause, but they were still providing temporary relief for every other symptom I had.

Can anyone help me solve this mystery? It could help greatly in figuring out the mechanism by which my HPPD-esque disorder affects me.

TL/DR: Have HPPD-esque disorder. 3 supplements: Bilberry Root, Dandelion Root, and Wobenzym N all produced instant relief, but then caused massive rebound effect of symptoms. I am trying to figure out how these supplements were able to work on all my symptoms (except visual) temporarily before crashing back down.
 
Such broad and nonspecific negative symptoms are probably indicative of something a little more than HPPD. To my understanding, HPPD is simply when the sensory distortions of a drug seem to persist well afterwards... an overarching malaise, depression, and nonspecific negative physical symptoms are surely signs of something more complex than not being able to mentally process hallucinogen exposure.

This sounds silly, but Occam's razor would suggest that you're responding to placebo. None oo the supplements listed have major pharmacological action, nor do they share active components that would suggest a common etiology.

Dandelion root is effectively pharmacologically inert; it's prepared as an herbal tea or roasted as a replacement for coffee a la chicory root. Same with bilberry root, there's no evidence to suggest it has any major action in the body aside from having some mild antioxidants. As for Wobenzym N, it seems to be nothing more than a mixture of proteolytic enzymes - same thing you'd find in culinary meat tenderizer. The enzymes in question are extracted from papaya and pineapple plants, respectively, and are inactivated and destroyed in the gut. So none of these supplements share a common mode of action or anything.

Another thing pointing towards placebo: most compounds in food and drugs take much longer than 10 minutes to be completely absorbed and produce a systemic effect. Even on a totally empty stomach, it's normal for compounds to need between 20 minutes to 2 hours to be completely absorbed, depending on the nature of the compounds.

The nature of biologically based supplements means that their constituents are metabolized pretty rapidly, generally speaking, so it's also very strange that the natural polyphenols in bilberry root would be so resistant to degradation that they'd produce an effect lasting almost 24 hours. Even methamphetamine has a hard time topping that.

One final point to consider: If you've tried hundreds of supplements, would you not logically expect a placebo response from at least *some* of them? I'm assuming you're not taking the time to test each supplement against a placebo, are you? ;)

I'm sorry I can't really help aside from saying, maybe stop playing with supplements and see a doctor for a full physical if your issues are so wide-ranging and troublesome? And, if you know your physical body is fine, maybe examine your lifestyle and mental state. Hallucinogens do not simply trigger long periods of existential despair and physical malaise that don't go away for no reason entirely.
 
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Thanks for taking the time write such a thoughtful reply. It's true that my symptoms are broad, and HPPD itself is a disorder that had a broad classification, since the cause is not completely understood and the symptoms do seem to vary wildly from person to person. But, I do suffer with the core symptoms of HPPD, so at the moment it best encompasses my problems.

The case for placebo just isn't possible, and I can say this because of the dramatic effect it produces. It's a not simply, "Oh this kind of feels good, I think this helping sort of thing." When those supplements take action, it feels like breaking the lock off a chain. The most uncomfortable symptom I've had is this muscle tension/contraction that will not let up. It's a 24-hour a day thing. I've had MRI's and X-Rays confirm that my tendons, for example, are tight to the point that they sit high on my knees. So, the muscles are kind of locked, and when those supplements take action, my tendons just release and become like jelly. The problem affects my gastrointestinal track too, and I was diagnosed with pseudo-intestinal obstruction (which is viewable intestinal obstruction without evidence of a blockage), and the supplements were able to release the smooth muscle tension in the GI tract also and I could go to the bathroom immediately. This is not placebo possible stuff.

I understand your view, but I would ask if you could humor me then, and take a look at this possible thought. Maybe it has something to with an inflammatory pathway then? Aspirin works relatively quick (within 10-15 minutes), right? I did find this:

Dandelion leaves downregulate nitric oxide, prostaglandin E(2), and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and suppress the expression of iNOS and COX-2 by inactivating the MAP kinase signal pathway, making dandelion an anti-inflammatory agent
Click to expand...

Bilberry has been theorized to potentially drop blood pressure, based on preclinical evidence of vascular smooth muscle-relaxing properties
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Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for its purported effects in one series of women with dysmenorrhea (57). Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins
Click to expand...

Can you think of anyway I can safely test this without the rebound effect I experience? If this were to be the answer, what would explain why the rebound effect happens and my symptoms get worse? If a pathway like the MAP kinase signal pathway gets inactivated, does a build up of those inflammatory markers remain in queue for when the pathway gets reactivated?
 
The case for placebo just isn't possible, and I can say this because of the dramatic effect it produces. [...] This is not placebo possible stuff.
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It actually is: almost anything is possible with a placebo response. Placebo does not simply mean "mild positive response". It's part of why drugs are almost always compared against placebo as opposed to comparison against no treatment - just the simple act of treating a disease with placebo will cause some fraction of patients to experience total remission There's for instance a famous case where Alexander Shulgin was given orange juice he believed had morphine in it and was sent off to opioid dreamland - however it turned out to be simple juice alone. Some people given sham antidepressants respond equally as well to "real" antidepressants. The mind is a powerful thing.

Dandelion leaves/roots are not pharmacologically active to a significant extent in vivo, despite what some people may try to tell you. I've never heard of them being successfully used as anti-inflammatories, only as adjuncts to salads! As for anthocyanins, they are the major purple/red pigment in fruit and colored plants. Do you also respond the same way you do to bilberry extract as to blueberries, red cabbage, or to red leaf lettuce? How about taking some ibuprofen - a COX2 inhibiting anti inflammatory?


If you want to explore this more and convincingly rule out placebo, have someone conduct a blinded study where you are given either "active" pharmaceuticals, in your case e.g. dandelion root extract, or "inactives", say tapioca root, without you being informed which exactly you are taking. If you can differentiate the two with high success rate, then you know it's gotta be active.
 
^

And there are some people who would argue that all anti-depressants are sham anti-depressants.

But yes, yes, whatever works for 'you'.
 
OP, have you practiced mindfulness? Many people report a great relief of various symptoms when they do finally have a couple hours where they break the spell of constant mind chatter, where they really succeed at staying in the present moment.

I personally think a mindfulness-like state induced by placebo could account for a lot of your relief. The relief you can get from genuine mindfulness is going to be much longer lasting than a placebo induced version of mindfulness.
 
arent salads anti-inflammatory though?
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What gave you that idea? The salads I know of, even "exotic" ones, do not compare to the painkilling effects of ibuprofen or naproxen. They are in general pretty good for you though.

Strictly speaking you might be able to put willow bark in a salad (Salix spp. contains salicin, the glucoside of salicylic acid - the active metabolite of aspirin), but that would taste disgusting. Very bitter. And presumably you'd eventually poison yourself with salicylates if you ate too much bark.

The relief you can get from genuine mindfulness is going to be much longer lasting than a placebo induced version of mindfulness.
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Isn't mindfulness really just learning to quiet your thoughts and observe the moment more objectively? It seems to me that anyone practicing "placebo" mindfulness by just sitting quietly would be indistinguishable from the "authentic" means, then.
 
I would say that's a good description of mindfulness but I was thinking that a placebo induced mindfulness would require re-dosing of the drug and there could be a loss of effectiveness (and rebound symptoms from essentially placebo withdrawal, especially when one isn't understanding the goal of how to navigate their mind without altering the present moment actively).
 
Yes, even the immune system has, in a book I've been reading recently, been reportedly entrained, in animals, by pairing ciclosporin-A with a flavoured liquid. Eventually the flavour alone was sufficient to induce immunosuppression.
 
the thing with placebo and clinical research showing placebo can be just as powerful as meds is simply being, placebo is usually methelyne blue and reason for that is to cause piss discoloration confusing the person thinking they are on the actual drug. the problem with using methyline blue as placebo IS, its highly bioactive by itself and can mimic a lot of drugs out there kind of stupid for doctors in those researches now realizing it sooner hence why the placebo effect exists now days.
you can read more on this on the methyline blue wiki page ktnx
 
Methylene blue isn't used that often for placebos any more for that reason, most FDA trials use inert materials e.g. sugar/starch pills, or compare the new drug vs the old standard, e.g. comparing antidepressant efficacy to citalopram.
 
Methylene blue is an MAOI, IIRC.

That and your going to piss blue for a while=D

My evil side has always been tempted to screw open the shower head and insert a few gelcaps full into the shower, screw the head back on and wait for my old man to take his next couple of showers.

And aescin, that doesn't explain the results showing similar strong effects where the placebo was not methylene blue however. Such as the association (in an animal) between ciclosporin and a flavoured water resulting in immunosuppression.
 
i have no idea when Methylene blue has been stopped being used as placebo. but it could be that tons of trials have been screwed up because of it and that is rarely ever discussed and requires an article on

i just re-read what you said "not used that often anymore" wow so its still being used but its not the standard. very nice! maybe in 20 years people switch to another completely different placebo, one that in 40 years shows to also have bioactive action eventually BAM!
 
but it could be that tons of trials have been screwed up because of it
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The wiki article actually clarifies this, methylene blue is mostly used in informal settings when used as a placebo (e.g. a physician trying to placate a hypochondriac, not under the FDA's guidance). Despite popular rumor, the individuals who come up with, and run, official drug studies @ the FDA and/or NIH are not stupid, nor do they want to make their work harder than it has to be. Methylene blue is not the only acceptable placebo, nor was it mandatory to use it as one, nor it was the first thing anyone would reach for or think of when you say "placebo". It's just mentioned in the wiki because it can be used as one. Obviously in an actual drug trial, methylene blue makes a crappy placebo because it makes your urine, and eventually the sclera of your eyes going blue - and effectively every drug you could think to test would not tint your piss an azure hue. (For that same reason, it's hard to compare methylene blue versus placebo for efficacy at anything!) Placebos used in FDA studies are meant to be inert, yet be indistinguishable from the "real" drug in terms of presentation, and hence methylene blue wouldn't be appropriate. All placebos used for serious studies are identical-shaped, identical-mass dosage units (e.g. pills, tablets) that look identical yet contain no active ingredient.
 
For its MAOI properties. Since there are references to it being capable of causing serotonin syndrome, this obviously means it affects MAO-a, does it have any MAO-b inhibitor properties? and is it an irreversible inhibitor or a RIMA?

Been wondering if oral methylene blue could be used in combination with an e-fag in order to serve as a replacement for the beta-carboline alkaloids present in natural tobacco products but absent in the nicotine used to make up e-liquid or present in off the shelf e-liquids. Because E-fags are NOT the same, nicotine alone just doesn't fill that hole tobacco does. Especially after a shot of morphine or prope. After an IM/IV dose of morphine or some other opioids, (oxycodone being somewhat of an exception, presumably due to the KOR agonist properties of it lessening DA release in response to the MOR agonistic side of oxy) I always, always crave a rollup, whereas generally speaking I don't get that many episodes of craving as such for tobacco, despite being a smoker. A tobacco product serves this purpose just fine (after opiate administration) but use of an e-fag or transdermal nicotine base (carefully, mind you, since it is easily absorbed transdermally and in excess is pretty toxic stuff) just does not scratch the itch, so to speak (metaphorically, I do not mean to imply that it has any effect upon itching caused by opioid use)

And this could be tried straight away, whereas I'd have to wait, and do the extraction, not to mention pay for some yage' vine.
 
I don't think methylene blue is vaporizable, really: it's a charged compound.

Seems to me it'd be poor at crossing the BBB for the same reason?
 
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