Syntheso

I tried it a few times and don't remember anything that noticeable happening. I have some, maybe I'll experiment with doses. Cheers. Added some new bits.

reserved for anecdotes

Quite a few people have tried to create some 'stack' / supplement threads that haven't really taken off. I thought I would start one under some headings, and hopefully provoke some discussion in finding something that works quite well. This is a work in progress, so please excuse the current incompleteness (many hands make light work ). Let's work on it together. Please help me refine it with suggestions, studies, things I might have missed etc. Eventually it would be nice to end up with a concise list of supp's and optimal doses based on group research and anecdotes. Generally I am trying to go for something that is more than merely palliative. Some bits I have copied from around the forum, so thanks to whoever found them This is all theoretical/speculative. I am not a physician. Talk to your doctor before implementing any of these approaches. Objective things we know about HPPD which we can target; (I have copied this list from onedayillsailagain's Coluracetam hypothesis document). - Shortened latency of the P2 component in flash Visual Evoked Potential (VEP) test - Faster alpha rhythms - Widespread cortical inhibition in eyes-open state - Isolated and localized disinhibition of the occipital regions in eyes-closed state Onto some ideas; RESENSITIVE DOPAMINE RECEPTORS + INCREASE RECEPTOR DENSITY Sulbutiamine - synthetic derivative of thiamine (vitamin B1), crosses the blood–brain barrier more readily than thiamine and increases the levels of thiamine and thiamine phosphate esters in the brain - increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex - however decrease of the DA levels in the prefrontal cortex - modulatory effect of sulbutiamine on dopamernigic cortical transmission - possible withdrawal syndrome after long-term use / tolerance - "Sulbutiamine has additional effects at DA receptor subtypes other then the overall increase in D1 receptor density with chronic administration. It does improve mood and motivation, but this is transitory, with tolerance developing rapidly in contrast to the D1 receptor up-regulation. " - also appears to increase cholinergic signalling in the hippocampus (http://www.ncbi.nlm.nih.gov/pubmed/4059305) http://www.ncbi.nlm.nih.gov/pubmed/10996447 http://www.longecity.org/forum/topic/37804-sulbutiamine/ Summary: concerned about long term use of this. CDP-Choline - promotes partial recovery of the striatum dopamine and acetylcholine receptor function normally reduced with aging+ it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1908237/pdf/brjpharm00231-0009.pdf http://www.ncbi.nlm.nih.gov/pubmed/8709678 - - - - - - ALCAR - retards the decline in the number of Dopamine Receptors that occurs in tandem with the Aging Process and (more rapidly) with the onset of Parkinson's Disease. - enhances the release of Dopamine from Dopaminergic Neurons and improves the binding of Dopamine to Dopamine Receptors. - can prevent the destruction of Dopamine Receptors by MPTP (a neurotoxin capable of causing Parkinson's Disease via Dopaminergic Receptor death. studies to be quoted - - - - - - Inositol - increases D2 receptor density + "slight, albeit insignificant, increase in 5HT(2) receptor density" http://www.ncbi.nlm.nih.gov/pubmed/11267629 - - - - - - BDNF increase D3 receptor activity http://www.nature.com/nature/journal/v411/n6833/abs/411086a0.html - - - - - NMDA antagonists can upregulate D2 receptors. http://www.ncbi.nlm.nih.gov/pubmed/1382178 - - - - - Restricing Food Intake. http://www.sciencedaily.com/releases/2007/10/071025091036.htm DOPAMINE SUPPORT Given the apparent lack of dopamine in our system, ensuring the quality of our dopamine is as efficient as possible seems intuitive. This approach is not to do with increasing dopamine itself. L-Tyrosine Dopamine pre-cursor - - - - L-Phenylalanine Dopamine pre-cursor - - - - Folic Acid - helps increase dopamine levels in the brain "The scientists found that mice with low amounts of dietary folic acid had elevated levels of homocysteine in the blood and brain. They suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the substantia nigra, an important brain structure that produces dopamine. Loss of dopamine causes the nerve cells to dysfunction, leaving patients unable to direct or control their movement in a normal manner." "Folic Acid Deficiency May Increase Susceptibility to Parkinson's Disease." Alzheimer's Disease Education and Referral Center of the National Institute on Aging (January 14, 2002). www.nia.nih.gov/Alzheimers/ResearchInformation/NewsReleases/Archives/PR2002/PR20020114folicacidparkinsons.htm W. Duan, B. Ladenheim, RG Cutler, II Kruman, JL Cadet and MP Mattson, "Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons." J Neurochem (2002) 80: 101-10. "Folic Acid is a necessary cofactor to the enzyme, tyrosine hydroxylase, which converts tyrosine to L-dopa. Folic acid also serves as a methyl donor in a number of neurotransmitter pathways, including the conversion of norepinephrine to epinephrine." "Glossary of Ingredients." NeuroScience, Inc. www.neurorelief.com/index.php?option=com_content&task=view&id=158&Itemid=48 - - - - Uridine - modulates dopamine see; http://www.longecity.org/forum/topic/51802-gpc-choline-uridine-dha/ - - - - Fish Oil/EPA/DHA - Supports dopamine - Involved in visual parthway http://www.sciencedaily.com/releases/2007/11/071126110453.htm http://www.allaboutvision.com/nutrition/fatty_acid_1.htm - - - - Zinc Zinc regulates the dopamine transporter in a membrane potential and chloride dependent manner. The dopamine transporter (DAT), a membrane protein specifically expressed by dopaminergic neurons and mediating the action of psychostimulants and dopaminergic neurotoxins, is regulated by Zn(2+) which directly interacts with the protein. Herein, we report a host-cell-specific direction of the Zn(2+) effect on wild type DAT. Whereas low mumolar Zn(2+) decreased dopamine uptake by DAT expressing HEK293 cells, it stimulated uptake by DAT expressing SK-N-MC cells. Inhibition or stimulation was lost in a DAT construct without the binding site for Zn(2+). Also reverse transport was differentially affected by Zn(2+), dependent on whether the DAT was expressed in HEK293 or SK-N-MC cells. Pre-treatment of DAT expressing cells with phorbol-12-myristate-13-acetate, an activator of protein kinase C, attenuated the inhibitory effect of Zn(2+) on uptake in HEK293 cells and increased the stimulatory effect in SK-N-MC cells. Patch-clamp experiments under non-voltage-clamped conditions revealed a significantly higher membrane potential of HEK293 than SK-N-MC cells and a reduced membrane potential after phorbol ester treatment. Lowering chloride in the uptake buffer switched the stimulatory effect of Zn(2+) in SK-N-MC cells to an inhibitory, whereas high potassium depolarization of HEK293 cells switched the inhibitory effect of Zn(2+) to a stimulatory one. This study represents the first evidence that DAT regulation by Zn(2+) is profoundly modulated by the membrane potential and chloride. - - - - L-Arginine L-Arginine produces NO-independent increases in dopamine efflux in rat striatum THE effect of L-arginine (L-ARG; 10-100 mM) on dopamine efflux from rat striatum was investigated using in vivo microdialysis. L-ARG (50 mM-100 mM), but not D-arginine (100 mM) nor L-citrulline (100 mM), produced a biphasic effect on dopamine efflux with an initial small reduction, followed by a large sustained increase. The effect of L-ARG was not prevented by nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester or 7-nitroindazole monosodium salt. Efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was reduced by L-ARG (10-100 mM), D-arginine (100 mM) and L-citrulline (100 mM). These data suggest that changes in dopamine, DOPAC and HVA efflux produced by high concentrations of L-ARG occur independently of NO, and that the use of high L-ARG concentrations are inappropriate when investigating the role of NO in striatum. http://www.longecity.org/forum/topic/62663-alternative-ways-to-increase-dopamine-and-reduce-prolactin/ - - - - Resveratrol "Resveratrol may be useful to treat dysregulated dopamine neurotransmission, but it may enhance the risk of developing drug addiction." http://www.ncbi.nlm.nih.gov/pubmed/23499958 - - Manganese (?) - - There is a brand called Dopavite (http://dopavite.com/) which contains its own formula for optimising dopamine. INCREASING DOPAMINE (just palliative?) There have been numerous reports on the forum demonstrating the efficacy of L-DOPA (Sinemet) in alleviating HPPD symptoms, thus indicating a lack of dopamine in HPPD. Mucuna Pruriens - suggested that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted- reduced dyskinesias risk over synthetic source of L-DOPA http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1738871/ Concerns re increasing dopamine: Whilst presumably increasing dopamine will help initially, and make one feel better, dopamine will eventually be downregulated. I would only consider this approach if you are going to supplement to keep your dopamine receptors sensitivised. Might increase anxiety. COMT INHIBITION to prevent breakdown of dopamine (thanks Brendan) Rhodiola Rosea EGCG Oleuropein Quercetin Vitamin C tbc. NMDA Pregnenolone Sulphate (?) Interestingly, unlike pregnenolone, pregnenolone sulfate is a negative allosteric modulator of the GABAA receptor[5] as well as a positive allosteric modulator of the NMDA receptor.[6] In addition, it has been shown to activate the transient receptor potential M3 (TRPM3) ion channel in hepatocytes and pancreatic islets causing calcium entry and subsequent insulin release.[7] And here's another study: http://www.ncbi.nlm....pubmed/11861317. And I also suggest this one (pregnenolone administration increases PregS concentrations+ its effects in schizophrenia): http://www.sciencedi...30645221100786X. Piracetam http://www.karger.com/Article/Abstract/139100 - - - - Magnesium L-Threonate - protection / upregulation of NMDA receptor - - - - Magnesium Baths - - - - Sarcosine (?) increases the activity of NMDA receptors via the co-agonist glycine, both by inhibiting glycine transporter 1 and by acting as an agonist at the glycine site itself. - - - - NAC - antioxidant and NMDA properties - - - - UPREGULATE SEROTONIN RECEPTORS (?) St John's Wort - upregulates 5-HT receptors - other mechanisms http://www.ncbi.nlm.nih.gov/pubmed/12775192 Tianeptine (pharmacuteical) - SSRE. to be discussed. other mechanisms Cannabinoid receptor agonists - upregulate serotonin receptors http://www.researchgate.net/publication/233418515_Cannabinoid_receptor_agonists_upregulate_and_enhance_serotonin_2A_(5-HT(2A)_)_receptor_activity_VIA_ERK12_signaling NEUROGENESIS Promoting growth factors - NGF, BDNF, GDNF, etc. Bacopa Monneiri; http://www.ncbi.nlm.nih.gov/pubmed/23949198 also, epilepsy treatment use; http://gaia-health.com/gaia-blog/2012-02-28/common-herb-water-hyssop-reverses-epilepsy-treats-and-prevents-other-brain-disorders/ HIPPOCAMPUS GROWTH Creatine - supplies energy to cells - - - - Resveratrol GABA + ANXIETY Whilst benzos have given me the biggest symptom reduction, ever, and are helpful for many HPPD sufferers, I am not interested in agonising GABA receptors, as I fear for their downregulation and for the body to not recover fully. That said, we could try to increase receptor densities... Bacopa Monnieri - upregulates GABA/reverses epilepsy; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306740/ Theanine (see http://www.longecity.org/forum/topic/54028-treating-anxiety-safely-effectively/) - THEANINE could be a highly useful ANXIOLYTIC, since it DOES NOT function as a GABA RECEPTOR AGONIST but UPREGULATES THE PRODUCTION OF GABA within the brain, functions as a GLUTAMATE RECEPTOR ANTAGONIST, and enhances ALPHA-WAVE production within the brain. NEUROPROTECTION Taurine - protects against excitotoxicity by stabilising calcium homeostasis - increases GABA levels by acting as a gaba transaminase inhibitor. - also binds to glycine receptors. http://www.jneurosci.org/content/19/21/9459 http://www.jbiomedsci.com/content/17/S1/S1 GENERAL Vitamin C Vitamin B Complex Vitamin D3 (N.B; fat soluble, take with fish oil) much more to come...

Perhaps, then, you are histapenics (over-methylators) i.e low histamine levels. You could check doing a niacin flush test yourself, to get an idea. Might be useful to know. Remember, it is difficult to separate exactly what symptoms are specific to HPPD, especially more general ones (i.e 'feeling shit'). When I started correcting my histamine levels (in my case, histadelia), I started having an overall better sense of well-being, which made my whole 'HPPD' seem better. I have wondered if HPPD involves histamine imbalances or if histamine imbalance is a co-morbid disorder. Histamine imbalances are known to produce psychiatric symptoms. Carl Pfeiffer's book Nutrition and Mental Illness explores this.

I wondered if upregulating presumably downregulated serotonin receptors would help (i.e not thinking about agonising/antagonising, but repairing damaged receptors). CBD agonists appear to do this. Perhaps this has already been discussed.

The best thing to do, if you can be bothered, is to methodically work through them, trialing each for a few weeks. Perhaps at a megadose to really see what works. Then filter out the one's that didn't do much, and work out dosages for the ones that did.

Cool! I am tempted, but have spent a fair bit on different compounds lately. If it was cheaper, perhaps. I'll wait to hear your results. Please keep us informed! Good luck!

Sorry for the delayed response! I understand why the drug would theoretically help (except for the NMDA antagonism), but it just seems quite unspecific to HPPD, and not something particularly useful, to me. But, who knows? I'd be interested to hear a report... Thank you for reminding me about the stack. CILTEP sounds exactly like that kind of thing that needs to take place or that would help (to me). In fact, I ordered a four month supply. I share the same concern with you about overstimulation, but IMO, we do need to create the potential for our brain to develop. It is, of course, very important to resolve the disinhibition that HPPD presents, but you don't want to inhibit everything.. you need stimulation as well. Quiet down the parts roaring, and develop the parts that are hypoactive/damaged. Lots of people pack in Levetiracetam, Lamotrigine etc. saying it makes them even more depressed.. well, I'm not surprised if that's all that's going on. Almost like a global off switch to the brain, when you're already feeling shit. I have had success with Nefiracetam, an NMDA modulator/potentiater. I believe modulation is what needs to happen at this receptor; think 'modulating fear'. D-Cyloserine excites me lots. I have a bunch of other things that work at the NMDA receptor i.e Glycine, Pregnenolone, Sarcosine, but never got around to trying them. I personally don't see why it would be negative to supplement Pregnenolone, but that's just based on my own research.

Regarding NGF.. yes, ever since I heard about it, I just want to drop loads of that into my eyes! It is just so expensive Perhaps that is the answer to my question 'how do we get increased BDNF in the visual cortex without the cortical disinhibition'. Would increased NGF increase BDNF as well (edit; it seems so)? Time to find a NGF stack.

Cheers mate. My thoughts are the same as yours. On one hand, potentially helpful, on the other, not. This is why I mention that perhaps when someone's HPPD becomes less aggravated (when the brain gets better at inhibiting) it could be useful for a full recovery, or, if taken with something that is globally quite inhibitory (i.e AED's; thinking more along the lines of Levetiracetam and Lamotrigine), it could just be a good combo. Or maybe L-DOPA, as increased serotonin would decrease dopamine. How do we get increased BDNF in the visual cortex without the cortical disinhibition?! Maybe the 5HT2C antagonism is in part responsible for these effects.. But you've tried 5HT2C antagonists to no avail, right? Perhaps it is. But it seems more likely, given that 5-HT agonists have resulted in HPPD, that it is the access to serotonin that allows the visual cortex to be manipulated, not the blocking of it. I would be worried that giving more access to serotonin would just further manipulate the visual cortex in a destructive way. Though, plasticity/neurogenesis would be required reverse damage to that area. I do not have the motivation to do this now, but it would be worth seeing if any other SSRI's exhibit the same effects (Setraline, as noted above seems to have some clinical implications for HPPD). And if so, in what ways they differ, looking at binding affinities. I have read that there are lots of 5-HT receptors in the visual cortex, hence why agonising them produces such visual phenomena. You're right I did try Cyproheptadine, which I think binds to all/most 5-HT receptor subtypes + many other actions (inc. anticholinergic). I only managed it for two days though, because I had horrible nightmares which I just couldn't hack (which is strange considering it is used to treat nightmares). Given the upregulation/downregulation idea, chronic use probably would have been required to see results for that to work. I also thought perhaps there could be a serotonin syndrome (too much serotonin) in HPPD, which if were the case, presumably I would have seen immediate benefits. Though, maybe I would have needed inverse agonists for that. Idk... I'll read through those articles now. Hope you are well mate!

Ugh, sorry about the formatting.. bloody forum. Source: http://www.sciencemag.org/content/320/5874/385 full text Source: http://onlinelibrary.wiley.com/doi/10.1111/ejn.12206/abstract - - Illicit Drug Use and Palinopsia Patients with substance dependence often have perceptual abnormalities, and this is especially common in users of stimulants, cocaine, and hallucinogenics such as LSD, PCP, and marijuana.53 In addition, visual hallucinations have been reported after cessation of cannabis use.62 3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) caused palinopsia that persisted for two years, but eventually resolved with fluoxetine treatment.63 Sunness suggested that in her young palinoptic patient, an additive effect from several illicit drugs was the cause of palinopsia.64 Patient #4 presented with a history of multiple substance abuse, though based on his history, it seems most likely that his palinopsia was due to exclusively to LSD abuse. The most common natural hallucinogens are mushrooms and mescaline, and the most commonly abused synthetic hallucinogen is LSD.3 Approximately one fourth to one third of LSD users will experience some form of flashback phenomena.65 In a study of 123 prior LSD users, 44.3% experienced trailing phenomena.66 LSD exerts an inhibitory effect on the level of synaptic transmission in the brain.67 Patients often describe a “trailing phenomenon” or motion picture frames that remain frozen in space long enough to be perceived individually.66 Gaillard and Borruat concluded that LSD flashback phenomena rarely occur long after the last intake of LSD, though when it does occur, precipitating factors such as ethanol or medication use are often present.62Among other precipitating factors, Kawasaki and Purvin found LSD flashbacks associated with anesthetized tooth extraction and prolonged hot bathing.3 Trazodone and LSD both inhibit serotonin reuptake and interfere with the homeostasis of serotonin levels in the brain, though how the serotonin reuptake inhibitors are related to visual illusion has not been addressed.7 Source: http://apps.scco.edu/ceonline/courseview.asp?selclassid=10&selID=85&selOrderID=14 - - "Improvement of hallucinogen persisting perception disorder by treatment with a combination of fluoxetine and olanzapine: case report." - http://www.ncbi.nlm.nih.gov/pubmed/11386500 - - From the forum (mixed reviews) NEUTRAL ODISA "did nothing for me, neither positive or negative." + "Which are the most common SSRI's reported to have adverse effects? I did for a while, and I didn't experience any effects." NEGATIVE g29 DP/DR more intense and worsen visuals, specially halos around objects and trails. (I left the treatment in the second day)" jay "The only thing i had a big problem with was" + "First doctor I had (in England) just said I had depression and put my on, which turned into a nightmare. " Memnoth "Speaking with personal experience on both questions, (brand name Prozac) worsens visual snow permanently, after 5 days of treatment it increased my symptoms by 300%. Taking amphetamine while having visual snow appears to only worsen the symptoms during comedown, 5 years of sporadic amphetamine use have not worsened my symptoms permanently as far as I can tell. " Kellen "I took a 20mg dose of before bed and the next day I was fried. Like I was seriously tripping. I know 20mg is really low but why does it hit me so hard?" CONTEXT: Kellen talking about his sensitivity to drugs. Puppeteer "Was prescribed, had a bad reaction to it which may or may not have been related to HPPD" se7ven "have quit now, because the dp/dr got much worse." + started on 20mg 4 weeks ago and upped my dose to 40mg 3 days ago. it has only helped whit my depression. no wisual effected and a low effect anxiety. seriously feeling that im crazy all the time. suffering from bad dp/dr. considering to start klono to get my life quality back. 2muchmandy "I used to be on and it made me feel shiiit." + "only time I came close was on. It just killed all emotions I had, that stuff was horrible" Lucid "was on.... that turned into 4point restraints, suicide watch..." Emily "I tried once it brought on dp which made me have a panic attack." findacureformyson "We tried to increase his to 20m a few weeks ago and he freaked out, wanted to kill himself and harm others and had a major panic episode for three days." David S.Kozin (may be him quoting someone else's experiences from the old board) now since prozac in november of 2007 [/size]Major flaoters again. Colors brighter again. trails again.MAJOR DR again. and a lot of emotional instability, up and down, emotions are all over the palce. headaches. anxiety, major major major anxiety again. Insomnia again. Halo's around objects again. Slight afterimages (they are not as bad this time) -trails -weird street lights and car lights (when dark, especially in the morning, sometimes i see the light of cars stretch about double the car size with a transparent rainbow around, not overwhelming thou) -some color spots appear once in a while, mostly blue -conversations can be uncomfortable because my vision gets weird, sort of out of focus but its clear, damn hard to explain, makes me feel like i'm standing in a weird position or something. -some songs replay in my head, not only after hearing them anymore, reading the name of the song is enough now -irregular heartbeat(went to the doctor when i first got it, turns out i have 3 different heartbeats) -no anxiety -no panic attacks -looking down at my arms and hands, they look weird,arms are long, wrists are small and hands are big (saw a picture of that here, probably why i see it now) -bullshit dreams that don't make sense, at all POSITIVE/ Hannahb00 I am posting this to let you all know or anyone suffering from this that I am 22 now, have been totally clean and sober for one year (a little over) and am on Lamictal 50MG;; and my HPPD has seemingly disappeared." + "Im on PROZAC and LAMICTAL. 50MG. not using any ofther drugs and my HPPD has seemed to have dissapeared. I live a normal {for the most part lol} and productive life! I can go to work ! " 3rd_tour_of_duty "I've been on Prozac for 15 years, on clonazepam for 6 months which helps with the larger bouts of anxiety/dp/dr. Prozacs not very effective and I'm going to need a decent alternative soon but it keeps the wolf from the door in the depressive aspect of my condition." + "It helped me loads many moons ago mate. But everybody's different. " + "8 months after I first got it and I responded well not knowing what the hell was wrong with me, just that mentally I was far from 'normal'. With the Ssri and exercise I had it if not on the ropes then pushed back a fair bit. Allthough i was far from 100% life was bearable. Years later it caught up with me again though after a build up of stress and various other things, although I dunno if it was that or just the Prozac 'pooping out' on me as I've heard. " CMM "Once I took the, it was like the world came back. Colors were nice, I had hope inside of me and all the vision stuff went away. I was my old self again, well 98% to it. " + " I spoke with Dr Abraham through email and phone. He said nothing about the beta blocker. He also said prozac has never helped nor made hppd worse. " Chris "I'm considering going back on [fluoxetine]. It did nothing for me HPPD-wise, but I felt generally better on it. Definitely the best SSRI I have taken." pokeypup 'Success with prozac' http://hppdonline.com/index.php?/topic/1259-succes-with-prozac/?hl=prozac n.b didn't help visual symptoms - - Not Prozac, but another SSRI: Young, C. R. (1997). Sertraline treatment of hallucinogen persisting perception disorder. Journal of Clinical Psychiatry, 58(2), 85-85. [/size] Reports the case of a 22-yr-old man who presented with hallucinogen persisting perception disorder and symptoms of mild depression 6 mo after discontinuing the use of LSD. Antidepressant treatment was begun with sertraline, until a target dose of 100 mg was reached. Mild exacerbations of the LSD-like phenomena were noted for 2-4 days after each dosage increase. Within 1 mo of reaching the target dose the perceptual disturbances decreased until they had almost completely remitted, and the depressive symptoms also improved. It is hypothesized that hallucinogen persisting perception disorder is serotonergically mediated, and that sertraline initially exacerbates the perceptual disturbances, but attenuates them after chronic administration. - - Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096346/ Fluoxetine Method of Action Fluoxetine's mechanism of action is predominantly that of a serotonin reuptake inhibitor.%5B90%5D%5B91%5D Fluoxetine delays the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Fluoxetine may also produce some of its effects via its weak 5-HT2C receptor antagonisteffects.%5B92%5D In addition, fluoxetine has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine. However, the significance of this property is not fully clear.%5B93%5D%5B94%5D[/size] Molecular Target Fluoxetine Norfluoxetine SERT 1.0 19 NET 660 2700 DAT 4180 420 5-HT2A 200 300 5-HT2B ≥5000 ≥5100 5-HT2C 260 91 M1 870 1200 M2 2700 4600 M3 1000 760 M4 2900 2600 M5 2700 2200 - - I am tempted by this study that shows fluoxetine promoting visual cortex neurogenesis, but it seems risky business. My HPPD has calmed down quite a bit (I can function at 60-80% now), but I am by no means a full recovery. I wonder if the adverse reactions to Fluoxetine on the forum are because the trial was too short and/or perhaps the HPPD too aggressive at the time. Perhaps there is a way of targeting Fluoxetine more specifically or administering it with something else, i.e the positive report above of fluoxetine + lamotrigine, seems like an interesting pairing. I like the idea of something stimulating the brain and something inhibiting it at the same time, finding the correct cocktail, so to speak. Has anyone found any other substances that promote plasticity and neurogenesis in the visual cortex? Also, some other things to think about regarding serotonin (maybe not all that good for you): http://raypeat.com/articles/articles/serotonin-depression-aggression.shtml[/size] http://www.dannyroddy.com/main/things-are-getting-trippy-serotonin-and-lsd

Exercise - definitely going to be good in the long run (no pun intended). It might produce temporary exacerbation due to putting the body under physiological extremities like raising BP, more oxygen going to brain etc (e.g when I cough deeply these weird dots appear allover my vision which don't normally occur, but cease after about a minute). http://www.ncbi.nlm.nih.gov/pubmed/21282661

I fail to see why this might be particularly useful, perhaps you could explain? As I have posted more thoroughly elsewhere (admittedly this is quite ineptly written, I would like to re-write it now I have a better understanding), antagonising the NMDA receptor does not make sense to me, considering that the flow of calcium ions through it is required for LTP, memory formation, synaptic plasticity etc. and that its antagonism produces schizophrenic-like symptoms. Fear extinction, a process I believe needs to take place, requires this receptor to be open. It is my view that blocking this receptor might be palliative, but will not allow your brain to do the emotional processing required for a full recovery.

Absolutely. I feel like I have ADHD.

I got brain fog from bacopa monneiri the first couple of times. It antagonises the d2 receptor IIRC. But I remember that going away after a few days of taking it, then everything was good from then onwards. ODISA - Great! I was trying to get some d-cycloserine last night. Interested to hear how it goes. Where did you get it from?

I've been taking it for the last three months, full spectrum. I have noticed mild improvements from it with regards to cognition, maybe anxiolysis. It does seem to make me more clear headed. If I'm honest, I am continuing to take it due to its theoretical benefits as opposed to highly noticeable symptom relief. I am not sure I will buy any more when I run out, but it will be interesting to see if anything changes and how much, if so.

Everything will be okay, hang in there. Just a phase which will get better. Did you taper off the Klonopin?

Oh, hah! Silly me. How long did you try it for; Inositol/Ch Bitartrate + the NMDA agonism stuff? Cheers man let's hope it stays like this... Wishing you well, as always. I think what is interesting with the NMDA agonism is that no worsening of symptoms were experienced by either of us. And I definitely experienced positives, which might have been from the cholinergic mechanism of Nefiracetam, but nonetheless.. no obvious negatives from NMDA agonism. I agree with your first point. Well put. I have wondered that - if benzos hinder your brain fixing itself (or do they aid it in restoring the imbalances). Regarding that study. That is the kind of thing to me that seems really promising for HPPD. 'Modulating emotional memory' sounds exactly like the kind of process that needs to take place. And this drug works in the amygdala, that excites me. "7,8-DHF enhanced both the acquisition of fear and its extinction". I read this as, 'giving your brain the emotional plasticity to recover from trauma'. This disorder is not confined to the visual system; it involves fear circuitry as well. I believe we should do anything we can to allow this to be manipulated, positively. This includes doing things that move you; being with close friends, listening to music, crying, whatever.. all these things, I find, help. I haven't tried CDP-choline, hadn't really looked into it to be honest. It looks very promising at a glance. Have you tried it? Let me get back to you on that stack, I haven't looked into it. My experience with HPPD; around the age of 17, four years ago, I began experimenting with various drugs: LSD, mushrooms, MDMA, mephedrone, ketamine, methoxetamine, the 2c's, amphetamines.. many more. I was particularly interested in the psychedelics. I only smoked weed a bit when I was younger and it didn't agree with me so was never really part of my life. I did have a few terrifying experiences on it though during this 'phase'. I probably had around 20-30 big acid trips, 10-20 shrooms and a good few of the rest. I did a hell of a lot, basically. I don't remember having one bad trip (except for a couple on weed, which was rare). At this time of my life I also was deeply depressed due to breaking up with my first love. It took me around 1-2 years to get over fully. One day - I noticed things were still moving. My friend told me about HPPD. It went around three weeks later. Did some more stuff. It came back. At the time I wasn't making good decisions.. anyway, one day, it stuck permanently. Came and went a bit. But then it became really bad and more permanent, more towards the age of 18 (three years ago), and I realised how much it was affecting my life. The last two years up until the last few months were horrible. I hardly went into uni, spent days sleeping; painful to be awake.. you know the story. Visually, I have visual snow, pulsing in the dark, floaters, CEV's (sometimes), I have experienced things pulse in size dramatically back at the worse times, also seen things turn into things like a school of fish swimming towards my face. Used to have trails. I am not sure what else might be relevant.. if you have any questions, let me know Pretty sure I have read your experiences, but do send me a link.

HPPD'ers have found NMDA antagonism provides symptom relief. My current understanding of the NMDA receptor is that it is an important 'gate' that mediates long term plasticity and memory; the gate which probably mediates our long term modifications of neurochemistry. Blocking this gate might stop this long term damage 'feeding back' and producing symptoms. But, blocking this gate will, for sure, impact long term memory and NMDA antagonists e.g ketamine produce schizophrenic symptoms (hmm). There are loads of studies in that thread that show this. It depends on how bad your symptoms are, you might find it gives you valuable symptom relief that makes life just that bit more bearable. But, it might impact the ability to make beneficial long term adjustments to your brain. My proposal for treatment, 'chemically induced fear extinction', does not involve forgetting traumatic memories (e.g acid-like visuals) but creating new ones. They have shown in studies, which are in that thread, that this is how fear extinction works. So I suggest to leave this receptor as available as possible, for the sake of future neuroplasticity. In honesty, I am not quite sure about my theory until I understand things on a cellular level, but I think the reasoning based on the studies works. Many people have reported recovering largely from ignoring the visuals and just accepting them, keeping their mind occupied. I imagine this is a kind of fear extinction; learning how to deal with something that has marked your mind; like witnessing a death or being threatened. You don't forget this in PTSD recovery, but learn not to react whenever you see a body lying on the floor, or someone holding a knife. I did see that regarding d-cycloserine, but I would prefer something more pure. I cannot be sure how much of it is due to Keppra, but I am quite sure most of the recent developments are largely to do with it. Everyday, I take 2 grams vit c, a vitamin b complex, 450mg magnesium, 500mg calcium, 50mg manganese, 400-800mg ALCAR + 200-400mg alpha lipoic acid, 400mg SAMe (doctor's best), 500-1,500mg bacopa monneiri, I drink lion's mane tea and have magnesium baths. Notice some of my doses might seem quite high. Some of these supps were for lowering histamine levels, and seems to have helped my general feeling of well being (which is hard to separate from my 'HPPD'). I have wondered if there is a link between my HPPD and histamine levels. My noticeable histadelic symptoms began at the same time as I got HPPD. If you want me to discuss any of those things in particular, why I am taking them, let me know. It is worth mentioning that ALCAR seems to do a lot for me. Actually, anything that touches choline helps (ODISA ) I am not sure what happened to my introduction post.. I haven't been able to find it. Such a shame because I want to compare things to back then... Good luck man! I got some inositol in to trial but started something else first. What doses are you thinking of doing? The high 14-18g (IIRC) ? The only thing is consuming that much of it.. ugh. Have you looked into DMAE?

Puppeteer, using PTSD as a model for HPPD, I have quoted a few studies here that discuss hippocampal and amygdalal damage, size reduction etc. and more. I cannot quite remember all the points I made and if I still agree with them, but look at the studies! Which reminds me.. perhaps about time to try get some d-cyloserine. Sorry to here about Lamotrigine. I hope you are feeling better!

I got it done because I was generally interested to see what came up, and this did. From 23andMe if anyone is interested. Sinemet is probably my next shot depending how my Keppra trial goes. I am convinced my HPPD is particularly dopaminergic. I respond very well to Modafinil.

I have the A:A (met/met) polymorphism of this COMT SNP http://snpedia.com/index.php/Rs4680 I have not tried Sinemet.

You can get 10kg of Magnesium Chloride flakes for £40 on amazon. I wouldn't use the stuff that is made for oral consumption.

Lately I have been obsessed with thinking about magnesium, and how a nutritional deficiency in it is a likely factor in, if not the precursor to, HPPD. This is because, as you may know, magnesium is an antagonist of the NMDA receptor, it blocks, or 'protects', it, and balances the influx of calcium ions. Many psychoactive drugs are implicated in the NMDAR's, which play a role in addiction and long term memory. There is much to suggest that a magnesium deficiency leaves this receptor more vulnerable to stress, addiction, excitement, or, for example, the effects of LSD. Reading; http://evolutionarypsychiatry.blogspot.co.uk/2010/10/magnesium-and-brain.html http://jn.nutrition.org/content/131/9/2378.full http://www.ncbi.nlm.nih.gov/pubmed/2001142 http://www.magnezyum.info/images/stres_2.pdf This is a good book; Magnesium in the Central Nervous System - University of Adelaide. Section 3 most relevant, particularly Chapter 24 'Magnesium in drug abuse and addiction'. I got really excited about magnesium and came across transdermal magnesium therapy. As those who will have supplemented magnesium will know, over 450mg and you have diarrhea, magnesium being a laxative when administered orally. However, if you want to megadose magnesium, you can do so by putting quite a heap in the bath and rubbing it into your skin. I know ODISA has done this with Epsom bath salts, but based on my reading, you really can (and should) up the concentration of magnesium in the bath. I recommend bathing with magnesium chloride and putting 1.5kg in a tub with you and soaking for a while (also you can combine it orally, my choice is magnesium l threonate). This is safe and effective, 'Transdermal Magnesium Therapy', Sircus. Doing this over days will raise the levels of magnesium in your blood much more profoundly than orally, by which a small percentage of magnesium is actually absorbed. This has been confirmed by studies. I am also experimenting with magnesium eye drops. More on this another time. Current conclusion of megadosing transdermally... makes for a very relaxing bath and sure to relieve and muscle pain, perhaps anxiolysis, but didn't do much for the visuals. I wasn't really expecting it to. I believe magnesium deficiency to potentially be a factor allowing for HPPD conditions to follow, but not that correcting it can reverse the damage. To aid the excretion of histamine, I have started supplementing calcium. I considered how this might contribute to excitotoxicity (but then again, I haven't exactly been worried about activating my NMDA receptors). If anything, I have been feeling a bit more together since I started supplementing calcium. It got me thinking that perhaps excitotoxicity causes a calcium depletion and that this stops enough calcium getting to the places it needs. Calcium is a big player in the nervous system and a vital component of life. As Visual has noted above people tend to be dominant in either the sympathetic or parasympathetic nervous system and you can alter this with different minerals. Perhaps I was just slightly deficient in calcium. But a calcium depletion would make sense in excitotoxicity, in theory. I cannot find any study to back up that claim though, so just an idea.. There is also this claim; "Those who live in a fight-or-flight pattern much of the time are continuously losing calcium in their urine." http://www.drlwilson.com/articles/calcium.htm Would be interested to hear other reports of supplementing calcium to see if it relieves 'feeling shit' at all. Depletion in different minerals can produce psychiatric symptoms, the basis of Carl Pfeiffer's book, 'Nutrition in Mental Illness'. So this could be a factor. I would advise supplementing with magnesium first to make sure your NMDA receptors have the support they might need. Maybe an hour before so it has enough time to enter the bloodstream.

I don't know you, but I love you. I suffer with you. x