BigPapaChakra

Awesome, thanks for posting! I'm going to investigate this a bit. A couple questions before I dig in: Is it actually an anti-cholinergic, and if so, to what degree (i.e. a strong anti-cholinergic, mild, etc)? If it is, can its anti-cholinergic-'icity' be reversed/cancelled by cholinergic compounds or extra dietary choline? How long do the effects persist? What time of day do you use it? I could see its relaxing effects being good for sleep (as long as it doesn't largely mess with the different sleep 'waves'), yet, if it isn't sedating in any way, the decrease in DR and relaxation could be a good pair for stressful situations or 'bad days' (for me, when I have to go to class for a long time; I don't know why, but all my symptoms get wayyyy worse and fear rushes through my mind and I always make my stay as short as possible). Thanks!

I'd be interested in Emapunil, as well. It seems to have great potential. I'd advise against Valproic acid/Valproate, too. There is this private forum that is largely about peptides and epigenetics and there was a post about it there. A lot of people talked about it inducing psychotic-like epsiodes/symptoms, so instantly I was put off by it. Resistant Starch looks pretty awesome for modulating HDAC, LostFalco at longecity has spoken about it, and it makes sense since so many people claim they have an uplift in mood and energy when taking RS for a couple weeks. I'm weary, though, because 'bad' bacteria can also feed on RS and increase endotoxin/LPS, too. Molecular hydrogen formed via fermentation in the gut, or supplements (there are hydrogen supplements that some anti-aging physician recommend but I've never seen a clinical trial or experiment conducted on these products), seems pretty interesting.

You know, the Viagra idea may have merit - someone on this Facebook group I'm apart of posted dozens of studies on different ED drugs for different disorders because of their effects on cerebral blood flow; he has sleep apnea and was looking into things like that.. don't know if he actually tried them, though.

For my ideas, check out my rants at the thread Syntheso started, lol. I feel as though I'm babbling too much but I'm compiling essentially everything I think of, try, or research over there. I haven't investigated the hypotension, but your hypothesis sounds logical. IF your hypothesis is correct, or even partially correct, this creates some potential therapeutic options worth investigating such as: HBOT Altitude generators/hypoxic tents/living at altitude Intermittent Hypoxic Training (which has been shown to generate new mitochondria, too) concentrated oxygen oxygen generators inclined bed therapy (I have only tried this for at most 2 days in a row, so not a good experiment, but it has helped people with spinal cord injuries, parkinson's, etc) and perhaps: rebounding and/or vibration plates All of these increase either oxygen or carbon dioxide content (thus increasing oxygen utilization) of the body, as well as blood flow and lymphatic drainage/flow. Interestingly, these are things I have briefly looked into before simply for longevity and/or performance enhancing aspects, yet they seem to be very therapeutic for a variety of disorders. Check this out, some information by Yandell Henderson, Ph.D. on CO2 for various problems: "Catatonia.---Finally, mention may be made of the extraordinary observations reported by the late A.S. Lovenhart, in which he found that inhalation of carbon dioxide to cases of catatonia induced a temporary restoration of intelligence and mental responsiveness. The simplest explanation of the results in these cases is attained by postulating an habitual contraction of blood-vessels in the brain of the catatonic patient, similar to that in the heart and limbs of the cases discussed in the previous section. If this view is correct, the beneficial effects of the inhalation are due to improvement in the circulation in the brain under the influence of carbon dioxide upon the finer blood vessels."

Please lemme know if I should refrain from posting so much, lol. I just feel as though this thread has the potential to help a lot of people if we compile tons of info and experiences. On a side note, I feel terrible today . I have this nagging ringing in my ears, slight headache, my visual snow and eye floaters are worse than they have been for a longgg time, and ever other HPPD symptom is about the same as always (anxiety increased). Holding out on popping an etizolam (I've had em for over a week and still have not taken one... tryina be a trooper, lol). Some of my fears of CES have been shown to be unfounded, though, and therefore I'm pretty excited to start using CES daily, perhaps even many hours a day. Bob Beck is a physicist who developed an extremely efficacious electromedicine protocol that has actually cured people of their HIV and what not (I know someone on facebook who makes his own Bob Beck protocol devices and teaches people how; when I start feeling even slightly better I'm going to ask for instructions); one part of the protocol, primarily for those with neurological problems, is CES. Bob Beck had always recommended not running CES for over 30-40mins at a time due to the beneficial effects possibly decreasing over time - this seems not to be the case: Cranial Electrotherapy Stimulation Reduces Aggression in Violent Neuropsychiatric Patients "The study sought to determine if 3 months of daily cranial electrotherapy stimulation (CES) treatment reduced aggression in violent neuropsychiatric patients in a maximum security hospital.CES was used to treat 48 chronically aggressive neuropsychiatric patients in a maximum security psychiatric hospital. Retrospective chart review compared 3 months pre-treatment with 3 months of active therapy. Early patients had responded positively to CES with a 41% reduction in episodes of violence (P<.001), a 40% reduction in episodes requiring restraint (P<.001) and seclusion (P<.05), and 42% fewer as-needed emergency medications (P<.01). A subgroup of 10 treatment-resistant psychotic patients, who attacked without warning or apparent motivation and were designated as having sudden assault syndrome, were 48% less violent on CES (P<.001). CES has significant anti-aggressive effects in violent neuropsychiatric patients, who are often refractory to medication. This safe, easy-to-administer treatment can benefit long-term severely ill patients. (...) A comprehensive, annotated bibliography of CES detailing 126 human and 29 animal studies4 refers to cerebral spinal fluid studies showing a 150% to 200% increase in serotonin following CES treatment.5 The enzyme monoamine oxidase (MAO)-B rises with CES, indicating increased metabolism of dopamine and tyramine." (part of the study was a case report on one individual who had been extremely violent and psychotic for over 40 years, committing almost daily assaults, needing restraints, etc.) "CES was started at the .5 Hz setting, 1 hour twice daily and 15–45 minutes up to three times/day for her frequent agitated episodes. Compliance with CES improved after 2 weeks, and she began sleeping and eating better. Oxcarbazepine and ziprasidone were discontinued and a small dose of clozapine (200 mg/day) was added. Two weeks later the quetiapine dose was cut in half and she continued the escitalopram. In the first month of CES, she had only five aggressive episodes and required four restraints. PRNs dropped to 19. After 6 weeks of CES, the patient’s personality changed dramatically. She became outgoing, was no longer accusatory, and her grooming and hygiene became exceptional. Her assaultive behavior stopped altogether, as did the necessity for PRNs and other interventions. At the end of 3 months of CES she passed the dangerousness review board and was returned to the referring hospital. There was no recurrence of her illness on discontinuation of the CES treatments. Observers familiar with the patient from her years at both hospitals commented on what a different person she had become." Looks like it's time to start usin' this device ery day, lol.

I know the foc.us is pretty much for the PFC, but is there any way you can move it about and affect other areas? There are some spots that have seemed to help with associated disorders and some other severe ones like alzheimer's/schizophrenia; I actually spoke to a guy on longecity about tDCS and he had schizophrenia and severe depression. He only saw modest benefits after a few sessions but he said within a few weeks it worked better than any medication he had been on (he used a couple different spots).

Interesting: The use of visual feedback, in particular mirror visual feedback, in restoring brain function "This article reviews the potential use of visual feedback, focusing on mirror visual feedback, introduced over 15 years ago, for the treatment of many chronic neurological disorders that have long been regarded as intractable such as phantom pain, hemiparesis from stroke and complex regional pain syndrome. Apart from its clinical importance, mirror visual feedback paves the way for a paradigm shift in the way we approach neurological disorders. Instead of resulting entirely from irreversible damage to specialized brain modules, some of them may arise from short-term functional shifts that are potentially reversible. If so, relatively simple therapies can be devised—of which mirror visual feedback is an example—to restore function." To me, this makes very logical/intuitive sense when our problems were caused by various substances, many times psychedelics. Although I hypothesize I have damaged/downregulated receptors/areas of my brain, as others have as well, there's no way to be certain without extensive testing (EEG, qEEG, SPECT, neurotransmitter testing, etc).

Have been looking into Cerebrolysin, just out of curiosity depending upon my soon to be experienced trials with other things. This is an excellent review of the literature. Additionally, there is a private forum on peptides (both for body building purposes, as well as life-extension and intelligence enhancement), and the founder of the forum is a longgg time user of Cere. He has interesting takes on it, and I'm trying to compare it with the literature and see how Cere can be used again/improved by 'non-responders', for instance, odisa. "the way you use cerebrolysin is to dose a little and work the brain a lot, dose a little and work the brain a lot. The LIMITING FACTOR as far as I am concerned is not the dosage. 10ml will give you a neurochemical effect (which is responsible for happiness, horniness, agitation, anxiety, etc.) ... none of that "feel" has much to do with longer term synaptic formation or brain improvement. (...) None of this is WOW! Gee Wiz!! In fact I fully expect that the majority of people who try cerebrolysin will look for a "feel". They will dose high to get a "feel". They will report impressive things like better focus and calmness and all sorts of things to ooooh and ahhhh over. Maybe they will even notice the elements that make up the music from their earbuds... but they will likely not have any long term improvement because they will not study something that is difficult for them several hours a day, day in and day out. If one is not motivated to learn... if one is not madly curious about how things work... if one is easily bored... doesn't like to read... then cerebrolysin will not make one "smarter". This is not by any means directed at you but at those that believe that they can chemically induce intelligence same as chemically inducing muscle." He has used higher doses (like 10+ml) and in this post was experimenting with 1ml/day for a short period of time (like 5 days at a time). This leads me to three potential ways to non-chemically enhance Cere: partake in other potentially brain changing activities take Cere for a prolonged period of time take large doses (60ml has been used in the literature on people with no ill effects; it didn't have a better effect than 10ml, BUT more people responded (people who traditionally didn't get effects received benefits when drastically increasing the dose) So, what do I mean by potentially 'brain changing' activities. Well, for me personally, I'll be starting Z-Health next week, which has a lot of clinical literature on their site showing enhanced vision, better hearing, better sensory gating, increased intelligence (in certain aspects), when doing various forms of movement and visual exercises. It actually starts to re-shape areas of the brain, very similar to meditation's effects on the amygdala, hippocampus, white/grey matter, etc. So, maybe I could use Cere while doing weekly/bi-weekly Z-Health sessions, along side practice at home. Others could use Cere and take up a new practice that has potential to offer relief of a specific symptom of HPPD, say, HRV training for anxiety. The neurogenic effects of Cere could cause you to perhaps retain these new, therapeutic skills better. The author of that posted was using it to learn guitar and found that he both noticed the effects of Cere better while increasing his speed of skill acquisition. I could only imagine what would happen if you used Cere and, say, neurofeedback. Sorry for the rambling, though.

Looking forward to the update, hope it pans out well. Good luck!

Just emailed this clinic/treatment center. I'm amazed that I was never aware of them and I truly hope they reply to my email. The neuropsychiatrist that runs it has been trained in rTMS, multiple forms of TES, psychopharmocology, Vagal Nerve Stimulation, and more. They also offer HBOT, genomic testing, "pharmacogenomic" testing, brain SPECT scans, neurofeedback, and other nifty treatments. I'd do anything to do some HBOT and find a way (maybe converse with Dr. Peat on this) to use CO2 to enhance the effects. Sorry for the derailment! I'll discuss those other studies, compounds, etc. tomorrow!

Caprylic acid (C:8) is the most ketogenic mct - this is apparently the most pure caprylic acid on the market, though Dave Asprey sells an extremely pure one as well (but it's more expensive, as always, lol). I used to eat a ketogenic diet and my HPPD was much better, but stress hormones started getting the best of me (excessive fasting, excessive exercise, probable nutrient deficiencies such as selenium, etc). I'm going to attempt this again but with the knowledge I've gleaned from the likes of Ray Peat, Ph.D. and Hans Selye (endocrinologist who founded the idea of GAS - general adaptation syndrome). Time to grab some caprylic acid and more mct oil (and on the 21st.... KetoForce)!

It depends; even small amounts of coconut oil can potentially aid in thyroid health directly and indirectly, but for any significant effects (on brain health) it has to be copious consumption+mild to extreme carb restriction. Coconut oil is something like 58% "medium chain" (kind of a misnomer, actually) triglycerides, but there are a variety of MCT's. The ones that have the most pronounced effect on ketone levels, and thus neurological health, are the C:8 and C:10 (capric and caprylic acid). Paul Jaminet, Ph.D. recommends an modified ketogenic diet for people with severe neurological/psychological problems where people eat 10-14tbsp of coconut oil/day, in addition to eating only around 50g carb/day. If one were to take some mct oil, though, this could probably be pushed up to 75-100g/day. I'm actually listening to these podcasts with Dr. D' Agostino, and he claims he eats 50-100g of carbs per day and maintains high levels of ketones roughly 95% of the time and tracks it with breath ketone monitors which are very accurate. Ketone esters and/or salts would allow you to eat any amount of carbs while being put into an artificial state of ketosis for 3-4hrs; they're actually being investigated by the DoD/DARPA for use in the military to enhance wartime performance.

Oh, apparently KetoForce isn't necessarily a ketone ester, but some ketone salts. According to Dr. D' Agostino it is a "poor mans keto ester". People have still used em with great effects, though.

I'll now summarize what is relevant in the ketone ester diet, and make it much shorter than that^ mass of text, haha (sorry!). This study used two groups of rodents, one of which was fed ketone esters (KET) along with a slightly reduced carbohydrate diet (but there were still carbs in the diet coming from corn starch and sucrose); it contained BHB and a ketone precursor "®-1,3-butanediol)". To keep things simple - the rodents ingesting the KET diet showed decreased levels of anxiety, "superior cognitive performance" such as increased working memory, 'reverse' memory, etc, and they displayed less AB accumulation and Tau formation. You can view the graphs and such in the study and the differences were significant for the most part. I believe this could be helpful to us firstly because of the anxiolysis, but then again, some of us (myself included) could benefit largely from increases in general cognitive performance. I plan on learning more about this but right now I'm going to attempt: gradually increase coconut oil consumption gradually increase mct oil consumption (currently only taking a tbsp or so/day due to funds) experiment with caprylic acid (one of two fatty acids typically in mct oil, potentially creates more ketones and/or directly affects brain functioning more) experiment with different fasting protocols - bulletproof intermittent fasting, weekly ketogenic fasts, protein sparing modified fasts, IF, ADF, etc. potentially purchase ketone salts (KetoForce), though, this is terribly expensive ($80 w/o shipping); there are posts online from keto-advocates where KetoForce drastically increased BHB levels for 3hrs, with a peak increase at around 30-60mins - many use it for exercise (Dr. D' Agostino fasted for 7 days then did resistance training with only KetoForce in his body and broke his P.R. for deadlifts)

Okay, I'm going to try and make my way through the studies and write a summary of how they may be relevant to us. I'm going to start with the Buspirone+Melatonin study. One thing to point out, this study seems to be authored or funded by Brain Cells Inc - the creators of Coluracetam. I'm going to see if I can dig up any more studies this company has done because they seem to be of the opinion that a neurogenesis-based model of MDD/depression and mood disorders serves best to create efficacious treatments. "It has been demonstrated that neural stem cells in the adult human brain undergo neurogenesis, and that the resulting new cells are integrated into neural circuits that can become fully functional neurons (Eriksson et al, 1998). Several studies have specifically linked hippocampal function and neurogenesis to mood disorders." They then went on to reference a bunch of studies. Keep in mind this holds great relevance to NSI-189, which more or less activates neural stem cells which may then undergo neurogenesis, specifically in the hippocampi of those who ingest it. They also state that besides mood, things such as exercise and enriched environments can influence hippocampal neurogenesis. I've been interested in enriched environments for a couple months now, after reading a text (not one of his books) from Michael Hutchinson (check him out, he has tons of information on "mind machines" and smart drugs and combining the two). I'm just not certain how we can enrich our environment to enhance neurogenesis.... plants? Paintings? Scented candles, lol? I'm assuming it has to be novel, contain some form of interaction (for instance, you have to tend to plants), and be pleasing to all the senses (or as many as possible). Going forward, the authors state, "This drug combination demonstrated both enhanced neurogenesis in the pre-clinical neurogenesis-based in vitro assays, and antidepressant responses in the in vivo behavioral assays that were equivalent to a Serotonin Selective Reuptake Inhibitor (Fluoxetine)." I'm not certain if this could impact other aspects of HPPD such as DP/DR, but the enhanced neurogenesis sounds nice (I know that anti-depressants would technically induce this as well, but probably not to this degree with such a low dose). To keep from rambling too much (as I already have), I'll just conclude with the results. The study used 142 people - one group was given placebo, one given Buspirone, and one given Buspirone+melatonin (15mg IR Buspirone, 3mg ER melatonin). As the abstract from before alluded to, the combination group had the best results by far. Almost 60% of the people in the combination group were "CGI-I responders", and there were similar findings for CGI-S, IDS-C(30), and HAM-A. This was much better than Buspirone alone, which had essentially the same results as placebo. I wonder if this could offer a less intense (in terms of neurogenesis) alternative to NSI-189, or at least a neurogenesis-inducing combination that may be easier for us to acquire. I'll make sure my synopsis of the other studies are much shorter, lol.

I'll try and write up a summary soon; quick question though, could anyone elucidate MgT's effects on NMDAr's, please? On longecity I keep seeing people use it for NMDA-antagonism, then claim to have potentially increased their NMDAr density. I saw someone on Reddit write up something claiming that it's acute and chronic effects are different, both in its entirety and on NMDAr's specifically. From my preliminary knowledge it seems as though acutely it antagonizes NMDAr's, then chronically due to this inhibition/antagonism their density increases. I then found three studies that have further perplexed me, though have me highly interested in trialing MgT for a few months (as opposed to days/weeks): Enhancement of learning and memory by elevating brain magnesium. "(...) Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced." Ageing, hippocampal synaptic activity and magnesium. "One of general properties of magnesium at presynaptic fibre terminals is to reduce transmitter release. At the postsynaptic level, it closely controls the activation of the N-methyl-D-aspartate receptor, a subtype of glutamate receptor, which is critical for the expression of long-term changes in synaptic transmission." Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala. "In intact animals, elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, density of presynaptic puncta, and synaptic plasticity in the PFC but, interestingly, not in the basolateral amygdala. In vitro, elevation of extracellular magnesium concentration increased synaptic NMDAR current and plasticity in the infralimbic PFC, but not in the lateral amygdala, suggesting a difference in their sensitivity to elevation of brain magnesium." So, how does an antagonist cause upregulation/proliferation of the 'receptors' it antagonizes? Nonetheless, I want to calculate out the human equivalent dose (HED) and take that soon, every day, for a period of a few months. Perhaps that alongside pregnenolone could cause proper functioning of my (or anyone's) NMDAr's.

Didn't mean to do that, sorry. I tried taking out the links added from wikipedia so you could just see the ones I added, but just quoted the post, haha.

I will attempt to summarize the key points and potential relevance to HPPD/co-morbid disorders at some point today/tomorrow (I have to read them more thoroughly, take notes, etc). I'd like to quickly add some more compounds that may be beneficial to us and I haven't heard much of. I think it'd be cool if we did HPPD community wide group buys on novel, or even older compounds that have potential to help us. The group buys at longecity are for compounds with a far range of pharmacological activity, often times geared towards simply increasing working or long term memory (i.e. ISRIB, C16, etc). But, I don't know if that's allowed, and if it is, how many people would want to participate. Recent compounds I've found: Emapunil: from wikipedia, "is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO.[1][2] This protein has multiple functions, among which is regulation of steroidogenesis,[3][4]particularly the production of neuroactive steroids such as allopregnanolone in the brain.[5][6][7]" URB-597: from wikipedia, "In pre-clinical laboratory tests researchers found URB597 increased the production of endocannabinoids resulting in measurable antidepressant and analgesic effects.[3] URB597 is also known as KDS-4103. KDS-4103 is being developed by Kadmus Pharmaceuticals, Inc. for clinical trials in humans. Kadmus claims, on their website (linked below) that this class of compounds may have antidepressant, anti-anxiety, and pain-killing effects. Linopirdine: I found this when looking for studies on Coluracetam to educate myself more on the compound before potentially purchasing it; it was found in this study ameliorate cognitive deficits induced by atropine. From wikipedia, "in a murine model linopirdine is able to nearly completely reverse the senescence-related decline in cortical c-FOS, an effect which is blocked by atropine and MK-801, suggesting Linopirdine can compensate for the age related decline in acetylcholine release.[3]" THA (tetrahydroaminoacridine): I haven't looked into this too much but saw it in study comparing it to Coluracetam and Linopirdine; it's an anticholinesterase drug/compound. It seems to have some efficacy in diseases such as Alzheimer's.

I apologize for bogging down this thread, and also that the research/ideas/experiences I've been posting have been all over the place; I do think, though, that it's beneficial to look at things from multiple POV's. Perhaps we can incorporate some of this research into the original post by syntheso... I just found this paper, and it is definitely something I've been interested in since I first started messing around with diet/supp's for HPPD since I was 17 (and at that point I hadn't hypothesized I had HPPD): A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease Unfortunately it's not letting me copy an excerpt from the paper, but it's interesting (haven't read it in its entirety, yet, though). As I alluded to earlier, I have success with having Bulletproof Coffee as my breakfast in the morning, which I believe even if I have full liver glycogen stores, will still produce ketones due to a high dose of MCT's (I'd like to purchase a breath ketone monitor in the future to see if I can achieve this - 0.5mmol of beta-hydroxybutyrate while still consuming carbs every day). The paper is partially authored by Richard Veech, who is one of the most renown researchers in the field of ketones and keto-acids (keto equivalent of amino acids that hold therapeutic potential). Until I have purchased my home/DIY biology and chemistry labs and textbooks, along with college courses, and thus can make a more evidenced back opinion on oxidizing glucose vs. ketones, I'm going to start cycling in and out of ketosis again as a means to produce more ATP and increase oxygen utilization (or, derive more energy from less oxygen) in my brain.

Awesome, thanks again! Be prepared to have a full-time job finding full-text studies

GABA A receptor subtype selectivity underlying selective anxiolytic effect of baicalin. (full text again, haha?) "Baicalin, a naturally occurring flavonoid, was previously reported to induce anxiolytic-like effect devoid of sedation and myorelaxation in mice, acting through type A gamma-aminobutyric acid (GABA(A)) receptor benzodiazepine (BZ) site. The present study further expanded the behavioral pharmacology profile of baicalin and subtype selectivity was explored as a possible mechanism underlying its in vivo effects on mice. Baicalin was characterized using convulsion, memory, and motor function related animal tests; and its selectivity towards recombinant GABA(A) receptor subtypes expressed in HEK 293T cells was determined by radioligand binding assay and electrophysiological studies. In the picrotoxin-induced seizure, step-through passive avoidance and rotarod tests, the anticonvulsant, amnesic and motor incoordination effects commonly associated with classical BZs were not observed when baicalin was administered at effective anxiolytic doses, demonstrating a separation of the anticonvulsant, amnesic and motor incoordination effects from the anxiolytic-like effect. Although baicalin exhibited higher binding affinity for the alpha1-containing GABA(A) subtype compared with alpha2-, alpha3-, and alpha5-containing subtypes, this was not statistically significant. In contrast to the classical BZ diazepam, baicalin showed significant preference for alpha2- and alpha3-containing subtypes compared to alpha1- and alpha5-containing subtypes in whole-cell patch clamp studies (P < 0.01). Its subtype selectivity suggested that baicalin exerted its in vivo anxiolytic-like effect mainly through the alpha2- and alpha3-containing subtypes. Therefore, the present study revealed an underlying mechanism for the selective anxiolytic profile of baicalin, suggesting alpha2- and alpha3-containing subtypes were important drug targets for flavonoid-based anxiolytics." I have to review the studies I collected on Etizolam (I should make Anki spaced-repetition cards on this stuff!), but doesn't it act on the same GABA subtypes (I feel like it doesn't, but if so there may be synergy with etizolam, l-theanine, and a very pure, high absorption (which is the rate limiting factor in its efficacy) baicalin)?

Didn't see that you posted - awesome! Thanks!

Baicalein, a metabolite of the breakdown of Baicalin, enhances NMDAr-dependent LTP and memory: "Baicalein enhanced the N-methyl-d-aspartate glutamate receptor-dependent LTP in a bell-shaped concentration-dependent manner. Addition of the lipoxygenase metabolites 12(S)-HETE and 12(S)-HPETE did not reverse these effects of baicalein. Baicalein treatment enhanced phosphorylation of Akt during induction of LTP with the same bell-shaped dose–response curve. LTP potentiation induced by baicalein was blocked by inhibitors of phosphoinositide 3-kinase. CREB phosphorylation was also increased in the CA1 region of baicalein-treated slices. Baicalein-treated rats performed significantly better than controls in a hippocampus-dependent contextual fear conditioning task. Furthermore, baicalein treatment selectively increased the phosphorylation of Akt and CREB in the CA1 region of hippocampus, but not in the prefrontal cortex, after fear conditioning training." Baicalein attenuates impaired hippocampal neurogenesis and the neurocognitive deficits induced by y-ray radiation. Inhibition of 12/15-lipoxygenase by baicalein induces microglia PPARβ/δ: a potential therapeutic role for CNS autoimmune disease (appears to decrease the negative effects that PUFAs can have while inducing PPAR(delta) transcription factor activity, which interestingly makes the bodies fuel oxidation pushed more towards lipids, but it is also involved in myelination and to a degree, glucose metabolism) Chronic Administration of Baicalein Decreases Depression-Like Behavior Induced by Repeated Restraint Stress in Rats: "Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression."

Hey, I just posted this in the HPPD Stack thread, and it's highly relevant: "We used in vitro neurogenesis-based human neural stem cell (hNSCs) assays and rodent in vivo behavioral assays to identify potential novel antidepressants. A combination of buspirone and melatonin displayed antidepressant activity in these assays whereas neither buspirone nor melatonin alone showed any antidepressant-like profile. After evaluating numerous combination ratios, we determined that low dose buspirone 15 mg combined with melatonin-SR 3 mg yielded optimal antidepressant efficacy in our pre-clinical platform. The low dose of buspirone suggested that antidepressant efficacy might be achieved with only minimal adverse event liability. Based on these data, we conducted an exploratory 6-week, multi-center, double-blind, randomized, placebo- and comparator-controlled study of the combination of buspirone and melatonin in subjects with acute Major Depressive Disorder (MDD). The combination treatment revealed a significant antidepressant response in subjects with MDD on several measures (Clinical Global Impression of Severity and Improvement, Inventory of Depressive Symptomatology) compared to either placebo or buspirone 15 mg monotherapy. These preliminary findings have clinical implications and suggest that a platform of pre-clinical neurogenesis matched with confirmatory behavioral assays may be useful as a drug discovery strategy."