Alchemica
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Posts posted by Alchemica
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Thank you @cristop
I've done some microscope pictures, I'll work through what you've listed. Appreciate your time and help.
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Today's river adventure. I'm a total novice at plant ID so excuse me. Quite a few of these, want to see if it's worth grabbing seed? First thought it could be a Celastraceae of potential medicinal benefit? Heavily in flower, the blooms are heavenly in scent. Any input appreciated.
The Celastraceae at the botanic gardens have been calling me, including the Maytenus. If it is, the Celastraceae family is a source of important bioactive secondary metabolites. Among the compounds isolated from their species, triterpenes and triterpenoid quinonemethides are of great interest, due to the wide range of biological activities showed by those compounds. At the present time, great interest had been devoted to the study of the species of the family searching for new candidates or prototypes of drugs than could contribute to the fight against diseases like AIDS and cancer. The isolated compounds show mainly antimicrobial, cytotoxic, antitumoral, antiviral, antiinflamatory, hepatoprotective, antifeedant and insecticidal activities.
Exciting when you start to tune to the natural world around you with curiosity and spirit, want to inspire that in people.
Spotted some nice Dodonaea down at the river too.
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On 8/23/2017 at 10:12 AM, Halcyon Daze said:Sounds really cool but, what is a labyrinth to the heart exactly? Is it a maze with a tiny garden in the middle? That would be really pretty with natives.
I have recently seen a nice hedge made of salt bush, I don't even know which species it was but it hedged perfectly, they are very drought hardy, and easily grown from cuttings. Also the grey green foliage would make a nice backdrop for all the colourful flowers. They can also live for a really long time.
Dang, I might have to make one too LOL please elaborate on your ideas
For me, it a journey through the chakras. Dying to the ego and dominant mind, being born to the Heart. Dying to primal root chakra needs into activating higher love, spiritual love. Try and come up with some better explanations soon
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So if you were going to plant out a labyrinth to the Heart with Australian Natives, what would be some good plant additions? Looking at compiling a list. Eremophila, Boronia, Crowea and Lobelia and small Acacias are on my list. What are some high vibrational small native plants that you'd recommend? Any input welcomed.
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Found out the hard way rate of cacao fermentation STRONGLY ∝ to cacao concentration. Damnit! Now have cacao sludge going nuclear on me and overflowing. Be careful...
Like it seems you actually want to use a raw cacao that's maybe even gritty and planty and not overly fine, not the better tasting chocolate grade... first batch was fine using 200g/4L of the slightly more gritty raw organic product, this smoother chocolatey cacao isn't a good brewing one at 500g in the brew... -
10% is viable at my rate of consumption
They had me at 'dose-dependent improvements in cognition' in another study so I'm loaded on it... knocks my appetite way down, too... But if we can? go an oral rodent -> human dose equivalent, ie divide by ~12 we get something more achievable. I say it's possible -
Here's an interesting paper and some research I compiled:
Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants
Calamus oil: β-asarone produces an antidepressant effect, increases TH and could promote expression of GDNF, BDNF, and CNTF genes. β-Asarone functions as a neuroprotective effect in both in vivo and in vitro models of PD.α-asarone or β-asarone potentiated the NGF-induced neuronal differentiation.
The antidepressant-like effect of α-asarone could be mediated through both noradrenergic (α1 and α2 adrenoceptors) and serotonergic (particularly, 5-HT1A receptors) systems. α-asarone effectively modulates microglial morphological dynamics, this effect of α-asarone may functionally relate to its influence on neurogenesis. α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity in a mouse model of FXS.
β-asarone antagonised Aβ neurotoxicity in vivo and improved the learning and memory ability. β-asarone might be effective for the treatment of AD
Chamomile - anxiolytic: Bisabolol (α-(-)-bisabolol) is a sesquiterpene which is a part of the essential oil of a variety of plants, but its common source is German chamomile. It is a potent GABAAR modulator at the BZD site - the anxiolytic-like activity of bisabolol occurs via the GABAergic but not serotonergic transmission
Copaiba oil: Anti-inflammatory, analgesic, anti-addictive, antidepressant etc. ~50% β-caryophyllene. CB2 agonist, PPARγ modulator. Regulates μ opioid receptors increasing analgesic effects, alters expression of 5-HT2ARs, activates TrkA receptors mimicking NGF exerting antidepressant effects.
Frankincense: Contains significant quantities of α-pinine which is anxiolytic via GABAA BZD site modulation, antiinflammatory (PGE2) and memory enhancing via AChE. Also in rosemary EO. Also contains the psychoactive incensole acetate which is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like effects.
Jasmine: Contains methyl jasmonate. Antidepressant effects, established in animals, may be related to suppression of oxidative stress and release of TNFα.
Recently, it has been discovered to have anti-psychotic activity, suppressing pro-psychotic activity of dopaminergics and NMDA antagonists: MJ demonstrated antipsychotic-like property via mechanism related to its antioxidant property and interference with dopaminergic neurotransmission
It has strong anti-neuroinflammatory activity and suppresses memory dysfunction in mice. MJ also suppressed the expression of COX2, iNOS and NFκB. It has anti-amyloidogenesis-like effects.
Lavender - contains linalool and linalyl acetate etc: Anti-convulsant, analgesic, potent anxiolytic. VDCC blocker, GABAA modulator, DAergic, glutamate/ NMDAR modulator, 5-HT modulator (particularly altering 5-HT1AR binding). 80mg orally as efficacious as lorazepam and paroxetine for GAD. (-)-linalool to stimulates opioidergic, cholinergic M2 and dopaminergic D2 systems, as well as interacts with potassium ion (K+)-channels. The effects of (-)-linalool on pain responses are mediated, at least in part, by the activity of adenosine A1 and A2A receptors and by the reduction of nitric oxide (NO) production/release, probably through mechanisms involving opioidergic, cholinergic and/or glutamatergic systems. Reverses the effects of stress at the transcriptional level on inhalation, increasing things like oxytocin.
Lemon - limonene reversed increased immobility time in the FST induced by neuropathic pain in rats. The putative mechanism by which lemon oil produces antidepressant-like effects seems to be mediated by 5-HT and dopamine neurotransmission. The pretreatment with buspirone (5-HT1A partial agonist), DOI (5-HT2A receptor agonist), miaserin (5-HT2A/C receptor agonist), apomorphin (nonselective dopamine receptor agonist) and haloperidol (nonselective dopamine receptor antagonist), blocked the antidepressant effects of lemon oil. Moreover, the acute inhalation of this oil significantly increased dopamine contents in the hippocampus and 5-HT in the prefrontal cortex and hippocampus. As commented before, dopamine and 5-HT are intrinsically involved in the modulation of mood states, and hippocampus and prefrontal cortex are the main stages of this action. Thus, the antidepressant-like effects of Citrus limon oil might be mediated by limonene. Indeed, modulation of 5-HT and dopamine neurotransmission in brain areas highly involved with mood states could be on the basis of the antidepressant effects of lemon oil. Limonene also seems to have effects on adenosine receptors.
Oregano - contains carvacrol - antidepressant and antiinflammatory/ PPARα/γ dual agonist, TRPV3 agonist, modulates DA and 5-HT, decreases COX expression
Patchouli: Antidepressant. This aroma oil exposure may modulate the blood platelet serotonergic regulation through MAOA depending on the dose, duration, and conditions of exposure. Patchouli alcohol exerts antidepressant effects orally.
Piper: Piper species are considered to play a role in alleviating neuronal ailments that are associated with inhibition of acetylcholinesterase (AChE). Sesquiterpenes and phenylpropanoids were found to be rich in these EOs, of which asaricin, caryophyllene, caryophyllene oxide, isospathulenol, (+)-spathulenol, and β-bisabolene are the major constituents. The EOs from the leaves and stems of Piper austrosinense, P. puberulum, P. flaviflorum, P. betle, and P. hispidimervium showed strong AChE inhibitory activity with IC50 values in the range of 1.51 to 13.9 mg/mL. A thin-layer chromatography (TLC) bioautography assay was employed to identify active compound(s) in the most active EO from P. hispidimervium. The active compound was isolated and identified as asaricin, which gave an IC50 value of 0.44 ± 0.02 mg/mL against AChE, comparable to galantamine with an IC50 0.15 ± 0.01 mg/mL.
Spearmint (Mentha spicata) and caraway (Carum carvi) essential oils - sodium channel antimanics: Contain ®-(-)-carvone and (S)-(+)-carvone which prevent mania in animal models. (S)-(+)-carvone decreased spontaneous locomotor activity in sleep deprivation experiment, indicating a sedative effect while ®-(-)-carvone is not sedating
Some Australian Natives I love:-
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I've had a couple of sessions with this. It's potent heart medicine...
It is definitely strong but gentle heart medicine, it's an effect that builds for days after use, a slow resonance that grows, restores, in a healing way. I needed to have an energetic upgrade, two sessions with the yeasted cacao product tuned me deeper to the heart. Definitely feel the new actives are far more potent and efficacious than raw cacao as the plant offers directly. If you do DIY beer brewing, do a substitution with some cacao. Don't need to be fancy about how you do it, just add the resonance of the plant in good quantity! Use a bit of vitamin C to prevent oxidation of the polyphenols!
If anyone needs an initial R&D recipe, the one in the other thread works fine for a healing brew. The spirited aspect (methylxanthines, some of the flavonols/polyphenols, tetrahydro-β-carbolines, other biogenic amines including spermidine-like alkaloids) seemingly carries into the alcohol brew, the heart healing resonance seems to be retained to a large degree in the solids. If you can, don't decant off the solids from the brew when you bottle, keep them in the brew, just gently redisperse before a session!
I'll optimise this using greater doses of cacao and getting the alcohol percentage down, even though a bit is useful for preserving the product. Soon I'll move to kombucha cacao as it's likely the resonance that is more suitable for my healing work.
I find this interesting. How much of our mind dysfunction is immune-dysfunction? I find cacao enriching my diet restores my mind, maybe the immune system plays a role:
"The ability of cocoa to interact with the immune system in vitro and in vivo has been described. In the latter context, a cocoa-enriched diet in healthy rats was able to modify the immune system's functionality. This fact could be observed in the composition and functionality of lymphoid tissues, such as the thymus, spleen, and lymph nodes. Consequently, immune effector mechanisms, such as antibody synthesis, were modified. A cocoa-enriched diet in young rats was able to attenuate the serum levels of immunoglobulin (Ig) G, IgM, and IgA and also the intestinal IgM and IgA secretion. Moreover, in immunized rats, the intake of cocoa decreased specific IgG1, IgG2a, IgG2c, and IgM concentrations in serum. This immune-regulator potential was then tested in disease models in which antibodies play a pathogenic role. A cocoa-enriched diet was able to partially prevent the synthesis of autoantibodies in a model of autoimmune arthritis in rats and was also able to protect against IgE and T helper 2-related antibody synthesis in two rat models of allergy. Likewise, a cocoa-enriched diet prevented an oral sensitization process in young rats."
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Not only can this fermentation change from the main cacao catechins being NO/5-HT1A/opioid mediated effects to something else but also change how it acts on GABAARs. similarly to tea processing
I coupled a bit of L-theanine with my cacao sludge today to try and get my stress scores down a bit.
The same changes occurring in cacao brews happen in teas when they are formed. This process changes the polyphenols and the way they modulate GABAA receptors. Some of these compounds are also ligands for the GABAA receptor benzodiazepine site. the higher catechins like EGCG being PAMS at some sites. EGCG reversed the effects of GABAA receptor negative modulators and picrotoxin and methyl beta-carboline-3-carboxylate, EGCG and chlordiazepoxide fully generalised in substitution studies. The phenolic acids are also GABAergic, potentially at different GABAA subtypes. [see Flavonoid modulation of GABAA receptors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087128/]
Healthy properties of green and white teas: an update.
Polyphenols are the most relevant family of phytochemicals in terms of beneficial effects on human health. Within them, flavonoids constitute a very extensive group and are distributed in a great variety of vegetables. They have a common basic structure of (C6-C3-C6) diphenylpropane, which usually forms an oxygenated heterocycle. Flavonoids are usually bound to sugars (glycosides) and for that reason they tend to be water-soluble. Green and white tea are especially rich in flavonoids, specifically catechins. In this line, the consumption of green tea is considered the main source of catechins in the diet. The content in phenolic acids (gallic acid, benzoic acid, cinnamic acid, chlorogenic acid, caffeic acid), gallic esters of glucose (gallic tannins), quercetin and proanthocyanidols is also highlighted. Total polyphenols range between 10.60-25.95 g/100 g in white tea and between 13.7-24.7 g/100 g in green tea.
The most abundant catechins in green and white tea are (-) epigallocatechin gallate (EGCG), representing approximately the 59% of the total catechins; (-) epigallocatechin (EGC), whichaccounts for the 19%, (-) epicatechin gallate (ECG) in a proportion close to the 13% and (-) epicatechin (EC), around the 6% of the total. According to Hilal and Engelhardt and Carloni et al. catechin content in tea ranges from 9.89 to 17.00 g/100 g in green tea, from 7.94 to 16.56 g/100 g in white tea and from 0.74 to 10.00 g/100 g in black tea. Catechins content is consistent with the fermentation degree, since black, white and green teas are fully, slightly and non-fermented, respectively.10 Levels from 2.76 to 9.34g/100 g for catechins in white tea have also been reported. Regarding EGCG, the amounts change between 4.40-9.60 g/100 g in green tea and between 5.23-9.49 g/100 g in white tea. Cabrera et al. observed that the content of EGCG in green tea leaves was higher than 80 mg/g, whereas in black tea it did not exceed 30mg/g. Wu and Wei reported that one cup of green tea (2.5 g tea leaves/200 mL water) may contain 90 mg of EGCG and Johnson et al. estimated that the daily intake of 3-5 cups of green tea (720- 1200 mL) could provide up to 250 mg of catechins.
Polyphenols and L-theanine for stress:
Although green tea contains caffeine, its consumption produces a noticeable relaxation effect, which is attributed to the presence of catechins, L-theanine or both compounds. Furase et al. indicated that EGCG has sedative and hypnotic effects at the brain level, by acting partially at the level of GABA receptors moderating the response to the acute stress. In addition, a positive effect against anxiety in mice has been observed. The sedative effect is enhanced by the presence of L-theanine. This amino acid is considered as a neuroprotective agent that reduces psychological and physiological stress. However, the consumption of green tea does not induce sleep due to the caffeine content, which produces the opposite effect, stimulating the central nervous system and promoting wakefulness. Effects attributed to L-theanine also include promoting the secretion and functions of certain neurotransmitters in the central nervous system. For all these reasons, the consumption of green tea may be advisable in certain diseases associated with stress and anxiety.
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Yeah, makes up for all the healthy wild promiscuity I never got to have
I just had the unhealing drug sort
This brew sludge could be rich in B vitamins, too!
Things as simple as even basic B group vitamins at higher than RDI doses shouldn't be neglected as mood therapeutics...
Thiamine inhibited the upregulation of GSK-3β induced by stress, and reduced stress-induced behavioural changes in anxiety and exploration. Coincident, thiamine improved learning and extinction of contextual fear, and the acquisition of the step-down avoidance task. Our data indicate that thiamine has antidepressant/anti-stress effects that are associated with reduced GSK-3β expression and conditioning of adverse memories. Thus thiamine may modulate GSK-3β functions in a manner that is dependent on whether the contextual conditioning is adaptive or maladaptive.
The mood stabiliser lithium inhibits glycogen synthase kinase-3, maybe high thiamine supplementation may be protective against bipolar etc?
I feel more stable with higher dose B-groups on board in my diet, subtle but part of better health, particularly if you've fallen down to alcohol.
It's also the neuroprotective, antidepressant part rich in phenolic acids:
The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action
Not only is cacao brew spiritual but also way more likely to be healthy for you than plain neurotoxic and hepatotoxic alcohol brews: The flavonols are neuroprotective, cardioprotective, likely hepatoprotective and really healing healthy, so too the phenolic acids.-
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So I've fermented cacao, that was good according to taste testers. I had some of the alcohol free yeasted sludge from the bottom of the fermentation yesterday... it's a good healer.
Watch out ayahuasca... we have a new healer in town. This ones been yeasting for a bit now...
Fermented cacao solids, sans the alcohol part
For me it's a friendlier intelligence to work with. More heart-centred, less crazily spirited but intelligent and healing.
Tastes a hell of a lot better too.
Save some of the next batches for roasting
.Mmm active flavonols, phenolic acids, funky alkaloids... I bring you brewed cacao SLUDGE!
Got through half that, seems sufficient. It's maybe more an integration tool, not a vision ally, returning to heart, balancing energies, settling disturbances. Definitely a nice stabilising heart-resonance, definitely healing, cognitively clear with good emotional attunement.
I'd guess the spirited alkaloid constituents would carry into the ethanolic portion so that dimension wasn't overly prevalent, this remnant sludge is like the grounding, healing heart energy counterbalance. The two would be nice together. Given me good balanced healing with just this. Kind of the bit I need to work with at the moment, the yeasted polyphenol rich portion. Good relief from my issues from that, see how long it lasts.
If you brewed a strong cacao sludge you could get a dense alkaloid rich solution with minimal alcohol, too. Then roast. I'll play with that at some stage.
The other part of the traditional preparation involves roasting... why might that be important?
First the fermentation would increase both interesting bioactive/GABAergic polyphenols, including the parent serotonergic/opioid-active flavonols, and NMDA sperimidine alkaloids but also tetrahydro-β-carbolines (maybe even TIQs from the PEAs) and decent quantities of their precursor tryptamines! On roasting, Maillard-type reactions would occur and the remaining tryptamines form more tetrahydro-β-carbolines, possibly also undergoing decarboxylation to better levels of better actives...
Tetrahydro-β-carbolines
We have previously reported that several foods and fermented alcoholic beverages contain appreciable amounts of two of those THβCs found in chocolates, THCA and MTCA, reaching up to several mg/kg (Herraiz et al., 1993, Herraiz, 1996-2000). Interestingly, the concentration of THCA and MTCA in chocolate and cocoa is comparable to that of alcoholic beverages such as wine, beer, and liquor, which contain a relatively high amount of those compounds.
The origin of these tetrahydro-β-carbolines is a reaction involving L-tryptophan and aldehydes that are present or otherwise released during the processing of foods and beverages. Its chemical formation depends on the amount of precursors, storage time, pH, temperature, and processing conditions (Herraiz and Ough, 1993; Herraiz, 1996).
The same reaction is likely to occur in chocolates that suffer a fermentation from cacao beans and heating processes. Then, it is expected that serotonin, L-tryptophan, and tryptamine afford the corresponding THβCs (6OHMTHβC, MTCA, and MTHβC) through a Pictet-Spengler condensation with acetaldehyde
The biological significance of tetrahydro-β-carbolines and β-carbolines is related to their potential pharmacological actions on the nervous system, playing a role as neuromodulators via effects on monoamine oxidase (MAO), biogenic amine (serotonin) uptake/release, and benzodiazepine receptor binding. Then, these compounds exogenously supplied, or hypothetically produced in vivo, might become bioactive, exhibiting behavioral and/or toxicological implications. In this regard, it is very likely that part of the β-carbolines found in the human tissues and fluids have a dietary origin.
Tetrahydro-beta-carbolines, potential neuroactive alkaloids, in chocolate and cocoa.http://sci-hub.bz/10.1021/jf000508l
microRNA
One level cacao sludges likely work at is the epigenetic, particularly microRNA, level: on the short, non-coding regulatory RNAs. Their main, although not unique, function, consists in regulating the translation and/or degradation of so-called target messenger RNAs
Numerous studies have shown microRNAs to regulate fundamental processes, including muscle, cardiac, neural, and lymphocyte development, or the regulation of both the innate and adaptative immune responses. microRNAs are changed in a number of pathologies, such as metabolic, autoimmune, cardiovascular, mental and neuro-inflammatory diseases or cancers.
Strong anti-inflammatory/immunomodulating/protective/restorative effects of polyphenols found in cacao extracts have been noted with reduced levels of pro-inflammatory enzymes such as NF-kB, 5-Lipoxigenase (5-LOX), prostaglandin E2 (PGE2), reactive oxygen species (ROS), nitric oxide (NO), and TNF. They also likely get in at (IGF)-1/AKT/rapamycin (mTOR) pathway, by reducing the expression of IGF1 and Insulin receptor (INSR) genes, reduce the levels of Ribosomal protein S6 kinase beta-1 (p70S6K), activation of pro-survival PI3K/AKT pathway. and act at the ERK1/2-mTOR pathway. The break down flavonol polyphenols are also epigenetically active, modulating PKC, reducing pro-inflammatory cytokines, reduced apoptosis, reduction of vascular endothelial growth factor (VEGF) expression, and attenuated oxidative stress markers.
There is strong regulation of microRNAs related to the mind and things like NF-kB, AKT, and MAP kinase pathways
We really don't know how deep this goes!
Promiscuous Effects of Some Phenolic Natural Products on Inflammation at Least in Part Arise from Their Ability to Modulate the Expression of Global Regulators, Namely microRNAs.-
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Another aspect that has improved is with my N-acetylcysteine. I've obviously had a beneficial microbiome shift - the level of hydrogen sulfide production that I used to get from it has resolved.
This is interesting, H2S is extremely toxic, it's also a highly important neuroprotective, cardioprotective, immune modulating gaseous mediator. It's possible my high cacao diet (which modulates another gaseous mediator, nitric oxide) has shifted the microbiome away, through prebiotic effects from eating up my sulfur containing amino acids and is allowing them to do their job for health.
H2S has rapid neurorestorative, protective, antidepressant effects, if it is generated in the brain from donors like cysteine appropriately. Boosting endogenous production of protective hydrogen sulfide via supplementation with N-acetylcysteine is a novel way to promote health on the systems level. If your gut bacteria are making it toxic to you, that might be a different story...
That's a rather interesting model for neurodevelopmental, mood and psychotic illness. If cysteine metabolism is impacted by the microbiome, not only do you get epigenetic methylation problems, dysfunctional crucial H2S CNS signaling including AMPA-mTOR-BDNF signalling, dysfunctional immunomodulation, anti-oxidant through glutathione/redox problems, major glutamate problems and functional connectivity disorders including via astrocytes, potentially elevated homocysteine and more. If I've had something screwing with my sulfur containing amino acids for nearly 30 years, no wonder I was getting so sick! I used to get really bad H2S-like gas from any protein...
This could also extend to epilepsy etc - L-cysteine sulfinic acid, an agonist at a phospholipase D-coupled (Group I) metabotropic receptor. protects against epileptiform discharges. These cysteine and metabolites crucially regulate brain activity and connectivity through multiple mechanisms. Depends on the gut bacteria what is formed... http://jb.asm.org/content/188/15/5561.full
N-acetylcysteine also tackles autism in animal models through mGluR2/3s, OCD through the cystine/glutamate exchange system, and addictions similarly through the glutamatergic projection from the prefrontal cortex to the nucleus accumbens, where in addiction there is insufficient for normal mGluR2/3 activation, thereby increasing PFC-NAc glutamate release probability.
When I used to take N-acetylcysteine, I got really odd LFT results... -
Sitting with a functional blend at the moment. Cacao powder, bit of cinnamon metabolite, N-acetylcysteine and genistein. Don't want to add more for once.
I'm finding the combination of phytoestrogen ERβ agonism (pushed the dose for a bit, this stuff is friendly, now it seems to be kind of a PRN thing if I require a prosocial shift) with 2400mg/day N-acetylcysteine is tackling impulsivity, obsessive compulsive dimensions and coprolalia really well. Doing this while keeping mood good and cognition sharp. Restoring feeling in control. Giving me control over my life to reprogram it in a healthy direction.Most people don't understand this dimension at all. Always struggled with some dimensions of impulsivity but after my suicidal injuries, I started developing extreme addictions which just cascaded. Got to the point of more suicide attempts and more organic neuropsychiatric problems from such. From extreme obsessive compulsiveness, coprolalia, tics, impulsivity particularly on substance cues - it makes a vicious unescapable cycle happen if we don't appropriately target this therapeutically.
The ERβ agonism tapers down hyperactive mesolimbic dopamine while boosting mesocortical dopamine and allows a shift from seeking high reward, high risk things to a healthier state where executive function high order cognition starts to be restored. It also induces a prosocial shift, transcriptional oxytocin modulation etc, restores a loving energy. It also targets serotonergic aspects of obsessive compulsive and impulsive behaviours.
The N-acetylcysteine tapers down glutamate through the cystine/glutamate exchange system in things like the often damaged OFC. This helps prevents obsessive compulsive dimensions, improves the coprolalia too. It also reverses drug-induced metaplasticity and provides relapse protection.
Vulnerability to relapse is a cardinal feature of addictions, and the glutamatergic projection from the prefrontal cortex (PFC) to the nucleus accumbens core (NAc) has been identified as a potentially important neural mediator of relapse. In addiction, there is insufficient for normal mGluR2/3 activation, thereby increasing PFC-NAc glutamate release probability. N-acetylcysteine helps target this.
Through mGluR2/3s social deficits in autism spectrum disorders are also targeted.
A page on phytoestrogens as therapeutics: https://www.facebook.com/Phytoestrogens-as-therapeutics-126178541328922/ -
Well the feedback on cacao brew is really promising! I don't think it brewed to 10% alcohol but it's nicely spiritual and anxiolytic and sends you to a rather good place from the feedback I've received. Taste OK.
Not only is cacao brew spiritual but also way more likely to be healthy for you than plain neurotoxic alcohol brews: http://www.mdpi.com/2072-6643/9/5/477
So hypothetically, why does brewing cacao make it superior in spiritualness?
As I suspected, from looking at it, 4-hydroxybenzoic acid positively allosterically modulates GABA(A) receptors [http://waset.org/pdf/books/?id=38143&pageNumber=3]. It's likely the degradation of the cacao flavonols by yeast forms high concentrations of things like substituted 4-hydroxybenzoic acids.
Plain cinnamon metabolite, benzoic acid, is psychotropic. It, through CREB, BDNF etc is neuroprotective, antioxidant, pro-neurogenic etc, through DAAO modulates VTA dopamine and frontal cortical dopamine etc. The 4-methoxybenzoic acid, p-anisic acid, is said to be active: when p-anisic acid is locally perfused into the PFC, it induces DA and 5-HT release... I can't find anything for the activity of vanillic acid (4-hydroxy-3-methoxybenzoic). Maybe protocatechuic acid (3,4-dihydroxybenzoic acid) from flavonol yeast degradation does something cool, too
;)
Add the 5-HT1A-mediated, NO modulating effects of the parent flavonols and the hearty stimulant methylxanthines, plus ethanol and the synergism, spiritualness and anxiolysis just seems to cascade!
Then add the formation of biogenic amines, spermidine-type alkaloids that modulate the NMDA receptor and bioactive Trp/Phe metabolism alkaloids, that form when yeast acts on cacao and it's a party for your spirit!
For a similar guide on using lactic acid bacteria (the bioconversions should extend to yeasts) Bioconversion Using Lactic Acid Bacteria: Ginsenosides, GABA, and Phenolic Compounds https://www.ncbi.nlm.nih.gov/pubmed/28297748
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NLRP3 inflammasome activation mediates fatigue-like behaviors in mice via neuroinflammation.
Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions. We employed repeated forced swims to establish a model of CFS in mice. NLRP3 knockout (KO) mice were also used to explore NLRP3 inflammasome activation in the mechanisms of CFS, using the same treatment. After completing repeated swim tests, the mice displayed fatigue-like behaviors, including locomotor activity and reduced fall-off time on the rota-rod test, which was accompanied by significantly higher mature IL-1β level in the prefrontal cortex (PFC) and malondialdehyde (MDA) level in serum. We also found increased NLRP3 protein expression, NLRP3 inflammasome formation and increased mature IL-1β production in the PFC, relative to untreated mice. The NLRP3 KO mice displayed significantly moderated fatigue behaviors along with decreased PFC and serum IL-1β levels under the same treatment. These findings demonstrated the involvement of NLRP3 inflammasome activation in the mechanism of swimming-induced fatigue. Future therapies targeting the NLRP3/IL-1β pathway may have significant potential for fatigue prevention and treatment.
Some natural polyphenols target NLRP3: baicalin has antidepressant effect and its mechanisms likely related to the inhibition of NLRP3 inflammasome activation in rat prefrontal cortex. Quercetin might also be effective.
Natural compounds effecting NLRP3 inflammasome-mediated IL-1 production.
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Thanks for that feople.
Resonating on a stated %lauric coconut oil (51% lauric) to see how that feels with my cacao and genistein for breakfast. A bit cheaper than my 90% MCTs liquid coconut oil... I might have to look into some better MCTs one day. This is a cheap cooking coconut oil with stated LA%... it has no coconut taste but a pleasant creaminess. I felt better using coconut oil with my cacao so back to that. Should get the added goodness of the soy isoflavone, too.
It has a role in optimising brain energetics and elevating ketone bodies which exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential.
Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. LA reduces blood pressure in normotensive and hypertensive rats. LA increased PPARα transactivation and acts as a partial agonist at PPARγ and reverses adipose tissue insulin resistance. LA also activated the G protein-coupled receptor 84 (GPR84), regulating inflammation, and PI3K/Akt signaling pathway.
These oil constituents shouldn't be seen in isolation: octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment.
Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. -
Genes, Gender, Environment, and Novel Functions of Estrogen Receptor Beta in the Susceptibility to Neurodevelopmental Disorders.
It is proposed that perturbed estrogenic signaling in the fetal brain due to aberrant DNA methylation of the estrogen receptor β (ERβ) gene, and such methylation patterns, may be imprinted to future generations and could theoretically increase subsequent neurodevelopmental disorders such as ASD offspring risk. Exposure to endocrine-disrupting components in the environment and even pharmaceuticals, including hormonal contraceptives may increase the risk.
ERβ-/- mice display a defective migration and layering of cortical neurons as well as impaired spatial learning and increased anxiety behavior. Such behaviors have not been shown for ERα-/- mice, suggesting that ERβ is the main ER isoform in regulating neuronal development associated with cognitive and affective behaviors. ERβ is crucial in the developing brain. However, its mechanistic understanding here is far from clear. In adult rodents, it has been shown that ERβ is expressed in serotonergic neurons of the dorsal raphe nucleus, where it mediates E2-dependent tryptophan hydroxylase (TPH) production, the rate-limiting enzyme for serotonin synthesis, and maintenance of serotonergic neurons. ERβ is also the main ER isoform in dopaminergic (DA) neurons of the substantia nigra. It is well established that E2 promotes neuroprotection of these DA neurons. However, it is not clear if it is a direct effect of E2 on these neurons or if E2 exert its neuroprotective effect through oligodendrocytes, microglia, or astroglia. Interestingly, both oligodendrocytes and microglia express mainly ERβ. ERβ could rapidly alter transmission in the mPFC to alter PFC-dependent behaviors. ERβ opposes AR signaling and inflammation
New studies have suggested that ERβ may play a more important role during neuronal development, as well as having new functions in regulating temporal DNA methylation dynamics. Treatment with ERβ agonist causes a significant decrease in DNA methylation globally.
This strategy potently promotes remyelination (this has important implications for neuroprotective therapies that directly target oligodendrocyte survival and myelination - ERβ ligand therapy activates PI3K/Akt/mTOR signaling in oligodendrocytes and promotes remyelination)
See: https://www.ncbi.nlm.nih.gov/pubmed/28362134 for effect on male germline
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Back on track for an attempt with clean socialising just with a solid dose of genistein (2mg/kg) today.
Aim for catching up with a good friend if I can, otherwise I'll do something social. Challenge is to stay away from needing anything vicey detrimental in the way of anxiolysis.
That's pushing the dose but still not quite at the upper 3.7mg/kg human equivalent that was used as an antidepressant in one study. Content with the energy and working with it, no longer feels alien. It's soft energy but I like a bit of softness.
Been sticking with this long enough, just a couple of days, that I might be starting to get the neurogenic, systems level epigenetic, frontal cortical DA upregulation, pro-social 5-HT1A, oxytocin and vasopression transcription, upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB and neuroplastic shifts coming in slowly.While something was acutely notable, like a plasticity and cognitive shift for the better, the serotonergic effects were verified in mice at day 7. Considering I'm trying to medicate some heavy pathology beyond depression (though that comes with the terrain), not expecting rapid shifts on a heavily scarred brain.
ERβ, antidepressant responses, BDNF and 5-HT2A!
"...sex-unspecific regulation of ERβ by the stress and by antidepressants and its differential convergence with bioenergetics and apoptotic pathways in females and males implies its role as a vulnerability factor in the stress response and emphasizes mitochondrial ERβ-dependent pathways as an important gateway of ADs action, at least in females."
https://www.ncbi.nlm.nih.gov/pubmed/28716632
"ERβ agonism significantly enhanced BDNF/TrkB signaling and the downtream cascades involved in synaptic plasticity. Subsequent study in ERβ mutant rat models demonstrated that disruption of ERβ was associated with a significantly elevated level of 5-HT2A but not 5-HT1A in rat hippocampus, indicating ERβ negatively regulates 5-HT2A. Additional analyses in primary neuronal cultures revealed a significant association between BDNF and 5-HT2A pathways, and the data showed that TrkB activation downregulated 5-HT2A whereas activation of 5-HT2A had no effect on BDNF, suggesting that BDNF/TrkB is an upstream regulator of the 5-HT2A pathway. Collectively, these findings implicate that the disruption in estrogen homeostasis leads to dysregulation of BDNF-5-HT2A signaling and weakened synaptic plasticity, which together predispose the brain to a vulnerable state for depression. Timely intervention with an ERβ-targeted modulator could potentially attenuate this susceptibility and reduce the risk or ameliorate the clinical manifestation of this brain disorder."
Use of phytoestrogens/SERMs in psychotic spectrum illnesses
Well as desired, the behavioural preservation is slowly lifting, by either intent or phytochemical intervention, likely a combination. More open to the world around me.
My stress-induced coprolalia/obsessive compulsive symptoms (OCS) are there but diminished? These symptoms are considered highly treatment refractory and worsened by traditional pharmacotherapies. The current consensus is that it is a disruption of particularly serotonergic signalling, particularly 5-HT2A and pharmacological antagonism adds to it. However many phamacological therapies depend on D2/5-HT2A antagonist action to exert efficacy. That said, it appears targeting 5-HT2A through downregulation indirectly via estrogenic signalling could be a new, unexplored, therapeutic avenue. With such signalling, you also get the correct dopaminergic corrections, without antagonising anything!
This is highly prevalent and an unmet treatment need for a significant population of people with psychotic-spectrum illnesses. My psychosis may be organic and really well controlled (no positive symptoms!) but the OCS are debilitating: See https://www.ncbi.nlm.nih.gov/pubmed/28189922
"Although obsessive-compulsive symptoms (OCS) in schizophrenia have been conceptually controversial and clinically challenging, recent evidence suggests that schizophrenia with OCS may constitute a distinct schizophrenic subgroup. Recent epidemiological and clinical findings have shown that the subgroup obsessive-compulsive (OC) schizophrenia is associated with poor outcome and is more frequent than previously realized. Emerging biological evidence suggests that OCS in schizophrenia has more than one pathogenesis, with distinct mechanisms that may require different treatment interventions"
Genistein at high doses seems robustly healing as the current literature is discovering. In males and females. Why use synthetic SERMs when natural long-term safe options are provided by nature! This is a functional food option that can be titrated by the consumer!
It is intriguing to see that raloxifene as an adjunct to neuroleptics improves cognition and reduces symptom severity in men and women with schizophrenia even in treatmentresistant psychosis. A recent meta-analysis investigating symptom reduction reviewed numerous clinical trials and found that raloxifene adjunct therapy had a more profound effect on the negative symptoms and cognition than on positive symptoms. Because negative symptoms and cognitive impairments are more strongly linked with structural abnormalities in the brain than with positive symptoms, the findings that raloxifene improves cognition (information processing) and reduces negative symptoms in treatment-resistant psychosis may be a result of improved neuronal and synaptic density and connectivity that is disrupted in schizophrenia, particularly in the cortico-striatal region. Furthermore, because cognitive impairments are seen long before the onset of first signs of schizophrenia, (i.e., the positive and negative symptoms), early intervention with raloxifene in schizophrenia may produce more satisfactory results in terms of improving cognition, general psychopathology, and correcting the illness at an early stage.
The observations that raloxifene increases forebrain neurogenesis in the injured brain and enhances working memory and synaptic plasticity in the animal models of neurodegeneration suggest that it has potential brain- and behavior-reparative properties in addition to its potential anti-oxidant and anti-inflammatory effects. Oxidative stress and neuroinflammation exist and probably cause several neurodegenerative diseases including autism, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease; thus, raloxifene is worthy of intervention in these hard-wired brain diseases.
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Special moment. First bottle of Cacao Brew bottled...
How's it taste? Technically I can't tell you. I'm doing Dry July. Nonetheless, I tried ~10mL, a negligible dose of alcohol. You get a strong alcohol taste that is in between beer and wine, bit of beeriness with wine notes, followed by subtle cacao flavour. Interesting but I don't know? I always used to drink for effects...
Getting some friends to try it.
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First a recipe! Cacao based:
Cacao, coconut, rosehip, soy and lavender body butter attempt. Small scale.
10mL (2 tsp) coconut 90% MCTs [supermarket liquid coconut oil from the fancy cooking oils section]
10g raw cacao butter [Health food shops]
qs rosehip oil
Lavandula angustifolia essential oil [Thursday plantation lavender oil from the supermarket] or EO of choice
Pure genistein/cacao alkaloids - dose as required*
Over warm water, heat the coconut oil and add the genistein and/or cacao alkaloids. Stir to dissolve as well as possible, if you keep the dose low you should find it will mostly dissolve. I tried with 100mg and some of it remained in the oil at 5mL, better at 10mL. Add as many drops of lavender oil as your body needs, I did quite a few (500mg oil). Add the cacao butter to the warm oil while stirring. Add some drops of rosehip oil as desired (I used about 10).Allow to cool.
The coconut oil MCTs are called, when used this way, penetration enhancers. They help the actives penetrate the skin.
The Lavender modulates the autonomic nervous system and possibly has other health benefits. Inhalation modulates the transcription of deleterious stress effects on various brain chemicals, normalising the effects of stress. At 80mg orally it as as effective as lorazepam and paroxetine for generalised anxiety!
The genistein is a soy isoflavone that selectively modulates a special estrogen receptor - good for the body, mind, spirit and soul. Be cautious and don't use if you have breast cancer although evidence is not in anyway conclusive, it may actually be helpful. Doses of genistein should maybe be around 20mg in a serve of cream for women, higher for medicinal applications?
Cacao alkaloids up to 200mg/serve
This gives a butter that has a skin/warm roomtemp-ish melt in your fingersness
What's my thoughts on transdermal genistein? Hard to tell. @100mg If it's infusing into my bloodstream it's doing it a really nice gentle subtle way - could be useful. Until I can get solid evidence that it's reaching my brain I'm going to do dual application oral and transdermal. Split my doses. Infuse that HERβAL CNS healing into me both ways. Hopefully the transdermal should mellow out the peaks and troughs of oral administration all going well. This is just short-termish while I see how much this helps my brain along!
~~~So for anyone males wondering. Does genistein at mega doses acutely affect your primal manliness? Important for some, not so much me.
So far it doesn't seem to but I haven't fully experimentally verified that. Manly primal functions still there but it's less important to be even worried about sex or anything. Just interested in people and company and helping and love and all that.
It's a better state of manliness. You get your testosterone stuff as required, in the background awaiting loving use, plus a new social-emotional dimension which is way more fascinating and satisfying than a root...
I'll keep an eye on this dimension but yeah ERβ agonism is so far super man friendly. Just maybe don't try 1.8mg/kg too quickly.
In the name of science: Verified while I'm super HERβ'd on genistein, don't know if I'll be dosing to these doses again - No need for PDE5 inhibitors, more of a need to get in the state, adds some level of porn star duration dimensionality possibly through 5-HT? More emotional dimensions....
Using this in brain injury
Following brain injury, microglia and astrocytes assume a reactive-like state and secrete pro-inflammatory molecules that can potentiate damage. A therapeutic strategy that may limit this is of potential interest. In this context, selective estrogen receptor modulators, such as raloxifene and tamoxifen, are known to reduce microglia activation induced by neuroinflammatory stimuli. I'm doing it naturally.
There is strong observational evidence for estrogen enhancement of certain aspects of cognitive functioning
Estrogen has neuroprotective and neurotrophic actions that may be mediated by a variety of routes. Estrogen receptors (both alpha and beta forms) have been found in microglia and within reactive astrocytes. In addition, there is evidence that estrogen suppresses activation of microglia and astrocytes and thereby the inflammatory cascade. Circulating estrogen is critical to the health of some types of neurons. This has been clearly demonstrated for a subpopulation of dopaminergic neurons in the substantia nigra. It is not yet clear whether this effect on dopaminergic neurons is mediated via the intracellular estrogen receptor or by a plasma membrane receptor for estradiol, although the antioxidant actions of estrogen have been implicated.
The neuroprotective actions of estrogen have been convincingly demonstrated in animal models of ischemia, contusion, hypoxia, and drug-induced toxicity
Epigenetic effects!
(ERβ) is a ligand-inducible transcription factor regulating gene expression in response to the female sex hormone oestrogen. Previously, we found that ERβ deficiency results in changes in DNA methylation patterns at two gene promoters, implicating an involvement of ERβ in DNA methylation.-
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While we're at it, just modulate everything for me!
What known systems does ERβ agonism modify? In addition to the other aspects I've mentioned:
ERβ-mediated processes relate to regulation of transcription, translation, neurogenesis, neuromodulation, and neuroprotection
The alterations in transmitter signaling include the serotonergic; GABAergic; glutamatergic; adrenergic/noradrenergic; and cholinergic systems. In the case of peptidergic signaling mechanisms, the local production of CCK, cholecystokinin and PDYN, prodynorphin is influenced. Various peptide hormone receptors are also regulated. This group reflects changes in GAL, galanin; GnRH, gonadotropin-releasing hormone; POMC, pro-opiomelanocortin; PRL, prolactin; CRH, corticotropin-releasing hormone; ANG, angiotensin; PACAP, pituitary adenylate cyclase-activating polypeptide; and BK, bradykinin neurotransmission/modulation. Growth hormone and trophic factor production is also highly targeted. A strong regulatory effect is exerted upon certain potassium channels. Synaptic vesicle proteins are also regulated. Transcription factors show altered expression accompanied with modification of RNA processing, translation and protein synthesis. These complex mechanisms may regulate neurogenesis and synaptic plasticity
This includes genes encoding growth factors (Igf2, Igfb2, Igf1r, Fgf1, Mdk, Ntf3, Bdnf), transcription factors (Otx2, Msx1), potassium channels (Kcne2), neuropeptides (Cck, Pdyn), peptide receptors (Crhr2, Oprm1, Gnrhr, Galr2, Sstr1, Sstr3), neurotransmitter receptors (Htr1a, Htr2c, Htr2a, Gria2, Gria3, Grm5, Gabra1, Chrm5, Adrb1), and vesicular neurotransmitter transporters (Slc32a1, Slc17a7).
See: http://journal.frontiersin.org/…/10.3…/fncel.2016.00149/full
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Another aspect I'm interested in seeing resolve is my sleep difficulties. It's a huge issue and I've tried everything. Now I just use a sedating antihistamine dose when I need but it would be nice to not need that. Sick of having poor quality sleep.
While androgens drive DA/NE arousal systems, I'm adding a bit of mellowness to that. It feels calming! Had a nap on the 1.8mg/kg...
It appears that the hormones estrogen, progesterone, and testosterone play a role in the regulation of circadian rhythm in animals.
Gonadal steroid receptors are expressed in almost every site that receives direct SCN input and cause differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal-pituitary (HPA) axis, and sleep-arousal systems. Disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease.
Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity.
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Up to cacao + 1.8mg/kg genistein, mixed in coconut MCTs and administered orally.
Contrary to beer which contains a potent phytoestrogen which attaches preferentially to ERα and is physically feminising, genistein is different. Beer drinkers are upping the physical/sexual feminisation, I'm upping the beneficial ERβ activity.
Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects
Coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders.
Particularly useful for the mind are HERβAL ERβ agonists!
So what's a genistein dose like? You can get soy isoflavone caps which have like 50 or 60 mg of isoflavones with sometimes only 2-20mg genistein in them. I'm going deep to suss this one out... 15 or 45 mg/kg, p.o. exerted dose-dependently antidepressant-like effect in mice while 2-8mg/kg was injected intraperitoneally for anxiety in traumatised PTSD rats and 10mg/kg to prevent seizures. Many anti-carcinogenic effects of genistein are seen in the range of 10-20mg/kg I'll eventually work up to 3.7mg/kg going on the oral doses converted roughly to human equivalents, seeing how I go.
If you take it orally, it's suggested in the literature to take it with a prebiotic to prevent its degradation by gut bacteria - this one doesn't seem to form equol-type desired breakdown products so you want to divert away from genistein degradation.
ERβ is a key requirement for activation of mechanisms that underlie estrogen-inducible neuronal morphological plasticity, brain development, and cognition. ERα, on the other hand, is more predominant in mediating the sexual characteristics of estrogen effects in the reproductive organs such as breast anduterus. ERβ is a pharmacological target to promote memory function and neuronal defense mechanisms against age-related neurodegeneration such as Alzheimer’s disease (AD) and psychiatric disorders, while avoiding activating untoward estrogenic proliferative effects in the breast and uterus, although this might be at the cost of lower efficacy due to the lack of activation of ERα in the brain. Other potential therapeutic advantages associated with ERβ include regulation of estrogen vasculoprotective action and development of interventions targeting diseases such as depression, colon cancer, prostate cancer, obesity, leukemia, and infertility.
However, a potential disadvantage of an ERβ-selective ligand is the lack of activation of ERα in bone, as ERα has been demonstrated to mediate estrogen regulation of bone density.
Genistein has high selectivity for ERβ with strong serotonergic effects.
MalesA 2010 meta-analysis of fifteen placebo-controlled studies said that "neither soy foods nor isoflavone supplements alter measures of bioavailable testosterone concentrations in men." Furthermore, isoflavone supplementation has no effect on sperm concentration, count or motility, and it leads to no observable changes in testicular or ejaculate volume. A 2010 review suggested that the sperm count decline and the increasing rate of testicular cancers in the West could be linked to a higher presence of isoflavone phytoestrogens in the diet, even if this is not proved and must still be debated.
FemalesIt is unclear if phytoestrogens have any effect on the cause or prevention of cancer in females. Some epidemiological studies have suggested a protective effect against breast cancer. But a recent in vitro study concluded that females with current or past breast cancer may risk of tumor growth by consuming soy products, since they can stimulate the growth of estrogen receptor-positive cells in vitro. Low levels of genistein and daidzein, the phytoestrogens in soybeans, showed the potential to stimulate tumors, while protective effects were found at larger concentrations of the same phytoestrogen. A 2006 review article concluded that not enough information is available on the effects of phytoestrogens to justify drawing conclusions. While preliminary in vitro results suggest that isoflavins inhibit tumor growth, more research is needed to evaluate how isoflavones affect breast tissue in females at high risk for breast cancer. A more recent epidemiologic study argued that consumption of soy estrogens is safe for patients with breast cancer and that it may in fact decrease mortality and recurrence rates. Thus, even review studies have failed to produce consensus on the relationship between phytoestrogens and breast cancer.
It also remains unclear if phytoestrogens can minimize some of the deleterious effects of low estrogen levels (hypoestrogenism) resulting from oophorectomy, menopause, or other causes. A Cochrane Review of the use of phytoestrogens to relieve the vasomotor symptoms of menopause (hot flashes) concluded that there was no conclusive evidence to suggest any benefit to their use, although genistein effects should be further investigated. Another study reported that phytoestrogens such as genistein may help prevent photoaging in human skin and promote formation of hyaluronic acid.
Modulate DA
I've always wanted a way to drop mesolimbic DA activity while boosting mesocortical DA. Hypothetically part of a perfect strategy for me.It wasn't long ago, being a bit of a big pharma-posessed person, I thought to go a SGA+dexamphetamine. Now I'm resonating with ERβ-selective phytoestrogens as a potentially great tool to healthily modulate DA nicely while at the same time boosting hippocampal-dependent functions, neurogenesis, neuroplasticity and providing neuroprotection - genistein adding serotonergic + other beneficial activity to boot.
ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopamine content of the PFC. Large increases in both dopamine and 3,4-dihydroxyphenylacetic acid content of the PFC are seen with modification of this system.
ERβ agonists prevent amphetamine induced PPI disruptions, likely by preventing mesolimbic DA hyperactivity.
There are sexually dimorphic aspects but it seems ERβ benefits are more conserved between the sexes? See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793919/
Maybe I can instill better long-term goal directed behaviour through ERβ modulation?
Disorders of the dopamine system, such as schizophrenia or stimulant addiction, are associated with impairments in different forms of cost/benefit decision making. The neural circuitry (ie amygdala, prefrontal cortex, nucleus accumbens) underlying these functions receives dopamine input, which is thought to have a central role in mediating cost/benefit decisions. Estradiol modulates dopamine activity, and estrogen receptors (ERs) are found within this neurocircuitry, suggesting that decision making may be influenced by estradiol.
Agonists modulate cost/benefit decision making, whereby concomitant activation of ERα and β receptors shifts the decision criteria and reduces preference for larger, yet more costly rewards.
Oxytocin and Vasopressin - Social dimensions
I never responded with benefit on the whole in any way to potent therapeutic and supra-therapeutic doses of oxytocin via multiple RoAs. Always felt it was a missing dimension for me endogenously. Why was this 'miracle cure' so crappy for me?
Oxytocin (OT), has gained widespread attention as a potential therapeutic agent in a myriad of disorders, including autism spectrum disorder, schizophrenia, and addiction.
Yet results are so variable. What if I simply need to induce some of the good stuff a different way? Maybe ERβ agonist phytoestrogens that also have strong effects on serotonergic systems, including 5-HT1ARs, are potently useful as a pro-social tool? I aim to test that a bit!
Maybe I can get these pro-social systems cranking another way: Steroid hormones differentially modulate stress responses and alter OTR expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase OT peptide transcription, suggesting a role for OT in this estrogen receptor β-mediated anxiolytic effect. ERβ activation plays a critical role in estrogenic regulation of OT and AVP gene expression in the PVN.
Weight lossHaving a bit of belly fat I want to slaughter, I might get around to applying this cream... these ERβ ligands reduce obesity and metabolic diseases in mice by converting bad fat (white fat) to good fat (brown fat). This is significant as brown fat increases metabolism and may facilitate weight loss. Don't need new agonists when nature provides them!
Animals fed a high-fat diet showed a significant increase in body weight, and this weight gain was attenuated by ERβ ligands. High-fat diet-mediated increases in serum cholesterol, leptin, glucose, and fat accumulation in organs were also reduced by ERβ ligands. In addition, MRI scanning indicated that ERβ ligands altered body composition by reducing fat mass and increasing lean body mass. Organ weights and gene expression analyses demonstrated that adipose tissue is the center of action for ERβ ligands, and the reduction in body weight is likely due to increased energy expenditure. In vitro and in vivo mechanistic studies indicated that the anti-obesity effects were due to indirect peroxisome proliferator-activated receptor γ
Impairment of insulin and glucose metabolism by ERβ may have significant implications for our understanding of hormone receptor-dependent pathophysiology of metabolic diseases, and may be essential for the development of new ERβ-selective agonists.
More infoIn premenopausal women (20 to 43 y) administered 0.4 - 0.8 mg/kg:
Serum concentrations of [13C]genistein and [13C]daidzein peaked after 5.5 and 7.4 h, respectively. The systemic bioavailability and maximum serum concentration of [13C]genistein were significantly greater than those of [13C]daidzein. The bioavailability of both isoflavones did not increase linearly when the dietary intake was doubled. The mean volume of distribution normalized to bioavailability (Vd/F), clearance rate, and half-life of [13C]daidzein were 336.25 L, 30.09 L/h, and 7.75 h, respectively; the corresponding values for [13C]genistein were 258.76 L, 21.85 L/h, and 7.77 h. The average recovery of [13C]daidzein and [13C]genistein in urine was 30.1% and 9.0% of the dose ingested, respectively.
The value for AUCinf for [13C]genistein was significantly greater (P < 0.05) when the isoflavone dose was increased to 0.8 mg/kg body wt. Like [13C]daidzein, however, the mean values for the bioavailability of [13C]genistein did not double with a doubling of the intake of isotope [6.33 (moderate dose) compared with 9.77 (mean for the low dose and low dose repeat) μmol · h/L]. Cmax also significantly increased in 2 of the low-dose regimens compared with the moderate dose (P < 0.05). The values for Cmax and AUCinf were unaffected by prior exposure to isoflavones (low dose after food). For AUCinf, the mean was slightly lower, but the difference was not significantly different from the values for other low-dose regimens. The calculated t1/2, CL, and Vd/F were not significantly different among the dosing regimens.
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I did see that at the Central Markets. Maybe next time I'm there I'll grab a bag for a batch. Thanks for that tip!
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So in addition to this, as mentioned in the phytoestrogens thread, later this week I'll get healthy doses, low doses, of genistein into me. I'll keep rolling with the oils and cacao - I'm happy that I'm getting some new found frontal cortical stuff happening particularly with the help of flavonols, Cacao is nicely cerebral, but to me, my hippocampal-dependent stuff seems less well intact. Genistein is a cheap thing to add to see what's recoverable.
I'm using genistein as it's a potent ERβ agonist and serotonergic - antidepressive, neuroprotective and even has possible use in things like PTSD. Other benefits include anti-carcinogenic effects which are seen in the range of 10-20mg/kg bodyweight a day but I'll start low. As an added benefit, genistein appears to inhibit adipogenesis as well as induce fat cell apoptosis via AMPK
Estrogens through ERβ improved many aspects of deleterious effects of brain injury on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. E2 has therapeutic potential for both prevention and intervention of induced brain damages.
Modulating this system improves attention, memory, learning and the associated brain activity in chronically ill men and women with psychosis-spectrum disorders.
In addition:
So since I've recently drastically cut dairy just as I haven't felt like having it, I may need to supplement calcium or get back into something calciumy? I'm getting good doses of magnesium now through cacao which I really like and Mg is getting backing in the recent literature for depression and anxiety but dropping calcium is not good - low calcium levels can affect your sense of well-being and cause changes in your behavior. Again, lethargy, anxiety, jitters, depression and irritability are common.
Calcium and magnesium have a complicated relationship that is not fully understood. The human body needs adequate levels of magnesium in order to properly use calcium, and magnesium deficiency affects calcium metabolism and alters levels of certain hormones that regulate calcium in the body. The two minerals may also compete with other and interfere with the other's function. For example, magnesium may prevent calcium from properly contracting muscles when the ratio of magnesium to calcium is incorrect.
Seeing I get a couple hundred milligrams Mg a day from Cacao alone, definitely worth putting some 333mg Ca +D tablets in and seeing what that does. RDI for me for Mg is 400 mg/day and Ca about 1,000mgI'll start upping my calcium today.
Essential oils I've Known and Loved - add yours
in Pharmacology, Chemistry & Medicine
Posted
It's a risky one. Personally I love a few drops in soy milk but I'm taking an informed risk
Love Acorus spiced soy milk acutely. A few drops in the milk. Tasty and 'grounding/centreing'. As it's rich in asarones, it should only be seen as a short term addition and a low dose thing, just wanted to connect and appreciate the essence of the plant. Longer term it's potentially carcinogenic [https://examine.com/supplements/acorus-calamus/]. Calamus is used as a symbol of love, lust, and affection. For acute ingestion, β-asarone and Acorus calamus appear to be quite beneficial and protective. Over the long term, it is potentially carcinogenic and causes organ damage. Remember it shouldn't be used therapeutically and is sometimes sensitising...
"I probably know calamus more deeply than any other plant I’ve worked with, yet in spite of that (or perhaps because of it…) I find it most difficult to capture what I know of it in a way that adequately conveys its essential nature; its medicine. Perhaps this is because calamus is not a plant that facilitates “capturing” on any level, but rather teaches us to yield to the flow of things and let go of our needs for stark outlines and delineations. Still, this plant has clearly offered itself to me not only to learn from, but to share, and so that I’ll try to do here…
...some words to describe the effect of Sweet Flag: Calming. Centering. Perspective. Joyce Wardwell once used the word “Resolution”… that’s a good one. It’s tempting to say that it instills “focus”, but focus isn’t quite the right word. “Focus” implies fixing the perception on a certain aspect of something, and Sweet Flag tends to open one’s awareness so that they’re able to take in what’s going on around them (or within them) with great clarity, without singling out any one aspect. So perhaps saying it instills clarity of perception is more accurate. I like to use borrow the concept of "depth of field" from photography... a narrow depth of field implies a narrower range of focus; broad depth of field a broader, more inclusive focus... this isn't meant to imply a purely or predominantly visual effect; I think of calamus as increasing one's perceptual depth of field.
Sweet flag also seems to put your energy into balance, and get you energetically resonating as a whole. I like to say it "unscatters" energy. For this reason it excels as a treatment for panic and anxiety attacks, not only for full-fledged episodes, but for the "little daily anxiety attacks" that most of us can relate to. It is especially good when an intense/traumatic situation occurs, and you handle it excellently, but after its over you're all strung out and a nervous basketcase. I find it works best when a bit is chewed as soon as the onset of an attack is perceived... often I've heard that once the attack starts, it's not that it doesn't work as well, but that it's hard to remember to use it. Again, I think of that shuddering bitter quality; I visualize the shudder as the "freaking out" person getting a good shake: "Get a hold of yourself! Come back here, into your body!".
(Incidentally, I feel this affect on anxiety is the reason why it was used for quitting smoking: not just because it causes a "distaste for Tobacco" (it has been smoked with Tobacco for treating headaches; although I personally don't think the two blend together that well... like chocolate and tomatoes, if you had one, would you really want the other?). The intense anxiety associated with "Nicotine fixes" is very much like the anxiety picture that Sweet Flag is good for. However, it should not be assumed to be a magic bullet for the Tobacco habit, but rather an effective tool to supplement and enhance determination and will power. Quitting smoking requires… well, a long write up of its own.)
I've used the plant quite a bit with people suffering from trauma, including post traumatic stress disorder, chewed to push away the flashbacks, quell the panic, and return to the present moment. Feelings of dizziness, nervous queasy stomach, "leaving the body", panic, looks like a scared animal in the headlights, doesn't know which way to go, frozen by fear, wants to run, but which way?, disassociated... all these are good indications. Have the person chew on Calamus and breathe deeply, fully and slowly and often the anxiety and panic will fade. It's an another option to consider alongside excellent remedies such as anemone, or indian pipe.
In Ayurvedic medicine, calamus is called vacha, which means "to speak"... not only a restorer of the voice in a strictly auditory manner, it is said to connect the heart to the voice, to allow people to speak clearly, to speak truth. One client with PTSD would chew on it before or bring it with her to therapy sessions, as she felt it helped her let out things she felt she was holding in, fearing to speak aloud, to have "out there". Herbalist and Naturopath Anne Hill offers some eloquent insights: "Intuitively and thru some playing around with calamus I have come to regard it as an herb for when people are in stuck mental states, like spiritual emergence type of situations where a layer of fear becomes prominent and inflamed almost and is ready to unfurl itself and fall away so that the person can move to another working level. I think calamus helps by thinning the veil between ego and spirit as well as spirit and Universe (or ____________ please insert deity name of choice here). When one has a glimpse or feeling of universal love, that fear can be more easily released... My understanding of being in fear is that it is so all inclusive that it barricades itself in so that no new or different perspectives or information can be obtained to help one move outside of that fear."
K.P. Khalsa tells a very moving story in a presentation he offered on herbal remedies for autism (that link goes to a recorded presentation; calamus is discussed at 45:45) that illustrates the immense potential of vacha: "I was talking to someone the other day whose child [is] 16... he's been essentially nonverbal his entire life. He's said a couple of things here and there, but really he doesn't communicate verbally. She was telling me that recently they were sitting in their living room watching TV and mom and dad were sitting on the sofa behind the child... he was sitting a few feet from the TV on the floor watching his favorite TV show... and he'd never said a word to them in their entire life. He had started taking calamus from their therapist about 2 weeks previously, and in the middle of his favorite TV show, he turned around, looked at both of them on the couch, and said "Mom and dad, I love you."
http://www.herbcraft.org/calamus.html