Alchemica

I can do you a turmeric and a un-ID'd galangal if you cover postage? Also Alpinia zerumbet. They're all shoots off the main plant. A. zerumbet is truly a multi-purpose ginger plant with promising medicinal properties." [1] "Shell ginger is an exceptional multi-targeted plant for human use, considering various organs, diseases, and mechanistic actions. As it presently stands, the plant’s potential for human life is likely underestimated." Apparently, Alpinia zerumbet has leaves that make a tasty tea. I've tasted a little bit of rhizome, got quite a refreshing taste, the tea from the leaves is personally quite mild in flavour but pleasant. Leaf extracts of A. zerumbet and A. zerumbet ‘Variegata’ ranked first and second among five Alpinia species screened for phenolic contents and antioxidant activities There was some interest on kava forums with regard to it, even though the kavalactones might not be the more renowned 'euphoric' ones. Alpinia zerumbet has anti-hypertensive, anti-obesity, anti-diabetic and sedative etc properties. The major bioactive phytochemicals are dihydro-5,6-dehydrokawain 0.41% in leaves and 0.35% in rhizomes and 5,6-dehydrokawain [Desmethoxyyangonin], and essential oils, phenols, phenolic acids, and fatty acids. Kava is able to increase dopamine levels in the nucleus accumbens and desmethoxyyangonin likely contributes to this effect. Literature now suggest that culinary shell ginger may contribute to longevity [2] The kavalactones are found in fresh leaves, stems and rhizomes range from the highest amounts of dihydro-5,6-dehydrokawain per fresh weight were detected in leaves, followed by rhizomes, and stems, whereas the reversed constellation was found for 5,6-dehydrokawain with the highest contents in rhizomes and lowest ones in leaves. Leaves, at higher doses, exert antidepressant effects through the dopaminergic and/or noradrenergic system, with antioxidant and anxiolytic-like effects [3]. It also contains labdane-type diterpenes and leaves contained considerable amounts of total polyphenols. The 'Variegata' is an aromatic medicinal plant, its foliage producing an intense, unique fragrant odour due to 1,8-cineole, p-cymene, humulene, camphor, linalool, (E)-methyl cinnamate, gamma-cadinene, humulene oxide II and a-terpineol. [1] https://www.researchgate.net/…/321396609_Alpinia_zerumbet_a… [2] https://www.ncbi.nlm.nih.gov/pubmed/29385084 [3] https://www.ncbi.nlm.nih.gov/pubmed/25885936

Have some more Morning Glory (white seeds) light blue and purple flowers if anyone is interested. Can do three people free. Post here and then shoot me a PM. .

What doses of Salvia guarantitica are people finding active? Even though my interest in sedative plants has declined recently, on the contrary I now need pep... There were questions as to how effective Salvia guaranitica would be: . That said, I want to find exactly what the "high concentrations" of cirsiliol are in the plant, I can't spot anything? It may be feasible to get 2mg/kg (active i.p dose in mice), which is quite low in human equivalence - that said, It does seem odd to me that a flavonoid is reasonably potent with it's low affinity? Salvia guaranitica is used as a traditional medicinal plant used in Latin America as sedative. Studies demonstrated the presence of cirsiliol in its extracts and found that this flavonoid is a competitive low affinity benzodiazepine receptor ligand. Sedative and hypnotic properties of the ethanolic extracts of S. guaranitica (Medina et al., 1989) have been associated with the presence of high concentrations of the flavonoid cirsiliol and caffeic acid ethyl ester (Mader et al., 1996). Cirsiliol 2 mg/Kg, i. p. significantly decreased the number of head dips and rearings in the holeboard test, which indicates sedative action (Wolfman et aI., 1994). Moreover, cirsiliol at a dose of 4 mg/Kg, i. p., exerted hypnotic effects [1] Salvia guaranitica extracts and its active principle cirsiliol, possess sedative and hypnotic properties at a dose equivalent to 3g of the fresh leaf; cirsiliol produces these effects probably acting on the benzodiazepine receptor. [2] It also contains caffeic acid ethyl ester, also with affinity for GABAARs. The paper states: "additional active principles present in Salvia guaranitica and possessing synergistic action with cirsiliol can not be totally ruled out" Saw a great initiative from beyondblue - they've released a Salvia guaranitica - 'Black and Bloom'. Not only do you get a pretty plant but a traditional medicine plant. As I'm finding, these plants are tough as seem to thrive. Proceeds from the sale of Black and Bloom go to the beyondblue foundation. Hopefully more plant retailers start to sell these, first time I've spotted them. With a hardly responsive GABAergic system and having a baseline of a really low mood, they seem mild. Plants are relatively small but some oral experiments, in conjunction with some healthy dietary modification: "Amistad": At 4g fresh younger leaf, easily a placebo, nothing really noted other than possible very mild relaxation "Black and Bloom" At 4g fresh mature large leaf, it seemed very mildly calming, easily placebo. At 8g still relatively mild, easily placebo. "Black Cobalt" mature large leaves, jumped in at 10g and this one seemed possibly more active but it was more likely I was having a slightly better day @ 7g spent morning in the garden and felt OK, easily placebo

I've been continuing this quite awhile hoping it would make a standalone anti-depressant option for me. The seasonal shift has been intense for me. If anything, it's brought some stability but actually confronted me with new levels of existential distress That classic K10 question "how often did you feel worthless" so pressing... this scary crushing sense of my mortality imbuing this impetus to do things worthwhile and positive even when things are a struggle. Normally, I'd be in quite a suicidal state, where you're actually encouraging that process of death to hurry up but when you start seeing the bigger picture, in a more clear-headed and less pathological state of mind... Coming out of that seemingly super-inflammatory state - I strongly believe inflammatory mediators, as research suggests, strongly promote a general trade-off towards focusing on immediate (often maladaptive) versus delayed (often more eudaimonic) outcomes while leading from everything to mood issues, anger problems to impulsivity - has been strange, not being pepped pathologically, forcing me to be reconsidering what the hell I'm doing with life. It's not easy finding that meaning, purpose and contribution when you're not feeling the greatest but I'm trying to make small positive vibrational shifts. Probiotic turmerics, even with saffron, is not providing good stable uplift - Been sticking with it, hoping the mood support would be adequate.. It's easing some symptoms but the mood has been incredibly 'sanely depressing'. Been trying to give the anhedonic, anergic, apathetic moods a kick in the arse by keeping up exercise (it's reduced in vigour as I'm just so drained), gardening and exerting meaning and purpose but it's not working very well. Been chipping away at incremental meaningful stuff but plagued by quite an intense and anergic dysphoria, at best anhedonia - what I was trying to keep on top of and had slight success for a bit... Been painfully fighting the inner death drive with lots of potting up plants for others and propagating things that will hopefully cope with the weather, sounds small but all I can manage. The "life output" trays are filling up again, trying to give the barrage of morbid looping thoughts the finger but it's a battle. Trying to assert some simple meaning and break my mind from the loops of depressogenic thoughts, maintain some behavioural activation even though it's so energetically hard, haven't had a energetic shift like this in a long time. Been a long time without my serotonin transporters occupied and continual serotonergics... finding aiming for the social can amplify things the wrong way at the moment, yet trying to not get extra disconnected.

Yeah I sort of came to the conclusion it probably needs longer term dosing over acute. At 3g I got mild effects improved sleep quality (with atypical vivid dreams) but I'm not the best test subject. I don't know how stable the galphimines are thermally but I probably wouldn't smoke, if anything "The plant’s dried leaves and flowers are macerated in alcohol and shaken by hand to obtain the required potency." [1] That said, I had someone with diagnosed GAD try it and they found it gave them an early sleep and said "Definitely find it calming". Maybe if there's nothing too pathological, like hyper-excitability etc, it's not too effective?

I'll sort out the above. No problems @mole. OK we'll leave it there. If anyone gets desperate for some seed, let me know, otherwise it's available other places, let me know if you can't find others.

Can spare a few people some free seed [and/or smallish quantities of research material (in exchange for an opinion in a thread)]. I'll say the first three people? Can probably do more if someone's really keen, just keeping some seed for plant meets etc. Post here then shoot me a PM. "Best time to sow is late autumn and winter in good quality seed raising mix, cover lightly as seeds need light to germinate. Place in a warm sunny position. Don't plant out until late spring/early summer, keep moist on transplant. Don't overfeed - likes impoverished soil" High-quality evidence was found to exist for the use of Galphimia glauca (galphimia) for anxiety disorders [1] Dose: Dried herb 0.6–1 g per day standardized to 0.175–0.348 mg of galphimine B Clinical trials showing equivalence to synthetic anxiolytics No adverse reactions found in studies Generalized anxiety, GAD While emerging data is encouraging, further placebo-controlled studies are needed. Galphimines have been identified as active compounds in galphimia, with the nor-secotriterpenes galphimine A and galphimine B, being shown to have the strongest anxiolytic activity. Galphimine B has been considered the primary active constituent for galphimia’s anxiolytic and sedative effect, and is the constituent standardized for clinical trials. Galphimine B has been shown to interact with serotonergic transmission in the dorsal hippocampus in rats. This occurs by increasing the frequency of neuronal discharge in CA1 cells, resulting in activation of 5HT(1A) receptors. One study in mice demonstrated that galphimines cross the blood–brain barrier, with galphimine A found to have an effect on the central nervous system. 2.5.3 Evidence of Efficacy 2.5.3.1 Preclinical A number of galphimine constituents, including galphimine B, were evaluated for their anxiolytic effects in mice using the EPM. Mice were intraperitoneally administered 15 mg/kg of a galaphimine derivative 1 hour before testing. An anxiolytic-like effect in the mice was found for both galphimine A and galphimine B, with a significant increase in the time spent in and number of entries into the open arm in the EPM. A second study on mice used a methanolic extract (standardized for galphimine B, 8.3 mg/g) at different doses (125, 250, 500, 1000 and 2000 mg/kg), which were orally administered at three different times (24, 18 and 1 hour before the test). Significant anxiolytic-like effects were found in the light–dark paradigm test and the EPM, but not the forced swimming test. 2.5.3.2 Clinical Two clinical trials have found galphimia to be an effective anxiolytic. The first was a 4-week, positive-controlled double-blind RCT, with a cohort of 152 patients with a DSM-IV diagnosis of GAD and HAMA scores ≥19 . The two groups received either galphimia aqueous extract (310 mg standardized to 0.348 mg of galphimine B), or the benzodiazepine lorazepam (1 mg). Each treatment was administered in capsule form (identical in appearance) twice daily. Both groups demonstrated a significant reduction in anxiety symptoms. There were no significant side effects reported in the galphimia group, which contrasted with the lorazepam group, in which over 21 % of people reported excessive sedation. https://neupsykey.com/herbal-anxiolytics-with-sedative-actions/ "0.175 mg of galphimine-B and administered for 15 weeks to patients with generalized anxiety disorder, showed greater anxiolytic effectiveness than that obtained with lorazepam, with high percentages of therapeutic tolerability and safety." [2, 3] Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases, particularly nervous hyperexcitability disorders. This plant contains galphimines which have been shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the Ventral tegmental area [4]. Galphimine-B appears to be an allosteric modulator of 5HT1A receptors [5] It was capable of blocking positive and cognitive symptoms associated with psychosis induced by ketamine [6] Anti-inflammatory activity and chemical profile of Galphimia glauca. [1] https://www.ncbi.nlm.nih.gov/pubmed/29575228 [2] https://www.ncbi.nlm.nih.gov/pubmed/22828921 [3] https://www.ncbi.nlm.nih.gov/pubmed/17562493 [4] https://www.ncbi.nlm.nih.gov/pubmed/12567277 [5] https://www.ncbi.nlm.nih.gov/pubmed/21742023 [6] https://www.ncbi.nlm.nih.gov/pubmed/29710504

I'm not sure about how long SSRI medications induce changes to 5-HT2ARs particularly with relevance to being 'constitutionally right' for tryptamines, mindperformer is likely more versed, but there are some imaging studies with regard to depression. I'd say a lot of the binding potentials change depending on the course of the illness, too? A remitted depression etc being different. More so, binding pattern for 5-HT1A/2A seems to change in depression and might be long term ...findings should be considered preliminary but suggest that recovered subjects with a history of recurrent major depression have elevated binding potential of cortical 5-HT2A receptors. The correlation of increased 5-HT2A receptor binding potential with increased scores on Dysfunctional Attitudes Scale" [1] Higher 5-HT1A receptor binding potential has been found in major depressive disorder (MDD) during and between major depressive episodes. [2]

Thanks for your awesome contributions @mindperformer Appreciate the directions to look into and the plants you mention One I'm currently interested in, drying a bit of material can probably spare some for bioassays Galphimia (Galphimia glauca) Dried herb 0.6–1 g per day standardized to 0.175–0.348 mg of galphimine B Galphimine B Clinical trials showing equivalence to synthetic anxiolytics No adverse reactions found in studies Generalized anxiety, GAD While emerging data is encouraging, further placebo-controlled studies are needed. Galphimines have been identified as active compounds in galphimia, with the nor-secotriterpenes galphimine A and galphimine B, being shown to have the strongest anxiolytic activity. Galphimine B has been considered the primary active constituent for galphimia’s anxiolytic and sedative effect, and is the constituent standardized for clinical trials. Galphimine B has been shown to interact with serotonergic transmission in the dorsal hippocampus in rats. This occurs by increasing the frequency of neuronal discharge in CA1 cells, resulting in activation of 5HT(1A) receptors. One study in mice demonstrated that galphimines cross the blood–brain barrier, with galphimine A found to have an effect on the central nervous system. 2.5.3 Evidence of Efficacy 2.5.3.1 Preclinical A number of galphimine constituents, including galphimine B, were evaluated for their anxiolytic effects in mice using the EPM. Mice were intraperitoneally administered 15 mg/kg of a galaphimine derivative 1 hour before testing. An anxiolytic-like effect in the mice was found for both galphimine A and galphimine B, with a significant increase in the time spent in and number of entries into the open arm in the EPM. A second study on mice used a methanolic extract (standardized for galphimine B, 8.3 mg/g) at different doses (125, 250, 500, 1000 and 2000 mg/kg), which were orally administered at three different times (24, 18 and 1 hour before the test). Significant anxiolytic-like effects were found in the light–dark paradigm test and the EPM, but not the forced swimming test. 2.5.3.2 Clinical Two clinical trials have found galphimia to be an effective anxiolytic. The first was a 4-week, positive-controlled double-blind RCT, with a cohort of 152 patients with a DSM-IV diagnosis of GAD and HAMA scores ≥19 . The two groups received either galphimia aqueous extract (310 mg standardized to 0.348 mg of galphimine B), or the benzodiazepine lorazepam (1 mg). Each treatment was administered in capsule form (identical in appearance) twice daily. Both groups demonstrated a significant reduction in anxiety symptoms. There were no significant side effects reported in the galphimia group, which contrasted with the lorazepam group, in which over 21 % of people reported excessive sedation. High-quality evidence was found to exist for the use of Galphimia glauca (galphimia) for anxiety disorders [1]. "0.175 mg of galphimine-B and administered for 15 weeks to patients with generalized anxiety disorder, showed greater anxiolytic effectiveness than that obtained with lorazepam, with high percentages of therapeutic tolerability and safety." [2, 3] Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases, particularly nervous hyperexcitability disorders. This plant contains galphimines which have been shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the ventral tegmental area [4]. Galphimine-B appears to be an allosteric modulator of 5HT1A receptors [5] It was capable of blocking positive and cognitive symptoms associated with psychosis induced by ketamine [6] The plant yields approx. 0.26% galphimines by the looks of it [1] https://www.ncbi.nlm.nih.gov/pubmed/29575228 [2] https://www.ncbi.nlm.nih.gov/pubmed/22828921 [3] https://www.ncbi.nlm.nih.gov/pubmed/17562493 [4] https://www.ncbi.nlm.nih.gov/pubmed/12567277 [5] https://www.ncbi.nlm.nih.gov/pubmed/21742023 [6] https://www.ncbi.nlm.nih.gov/pubmed/29710504

I put myself on daily probiotic turmeric. Been doing that for a while now. Anyone use it as a brain tonic? I whip up a couple of strong (20g) turmeric, ginger, black pepper and occasionally saffron probiotic sludges a day The more probiotic turmeric combos I get into me, the more I see how much I was probably running on likely extreme neuroinflammation. It's a robust shift, some really positive glimpses at something when I mega dose, some days not always feeling wonderful but on the whole small steps that are generally positive, using pretty much all the polyphenol classes and including the turmeric concoctions at a high dose in a good diet. I'm sticking with this, hoping an antidepressant effect becomes apparent.. So far, the most robust improvement I've had is in self-regulation (which was in tatters) buffering to better levels, along with getting sleep (quite a bit of sleep debt built up), more so than mood. Quite profound is the way these probiotic turmeric combos seem to be modulating aberrant reward related stuff. It's very anti-addictive but at the same time I'm stopping so many locked in behavioural loops that nothing at all left seems rewarding anymore. Push through it, hope I can write some new eudaimonic pathways Inflammation and mental health: Research indicates that mood disturbances and psychiatric disorders are closely related to CNS or whole body inflammation [1]. The prevalence of inflammation, measured by one marker only, in the diagnostic groups of psychotic disorders, mood disorders, neurotic disorders and personality disorders was 32%, 21%, 22% and 42%, respectively [2]. ' Inflammation was consistently found to affect basal ganglia and cortical reward and motor circuits to drive reduced motivation and motor activity, as well as anxiety-related brain regions including amygdala, insula and anterior cingulate cortex, which may result from cytokine effects on monoamines and glutamate [3]. Higher levels of inflammation are associated with longitudinal changes in brain function in regions important for cognition [4]. Increasing evidence points toward an involvement of the immune system in MDD pathogenesis. Inflammation can affect monoaminergic and glutamatergic neurotransmission [5]. Negative symptoms of schizophrenia are associated with increased inflammation [6]. Inflammation may at least partly mediate resting state functional connectivity via effects on mesolimbic and mesocortical dopaminergic systems [7]. Inflammatory measures were positively related to striatolimbic resting-state functional connectivity but negatively related to corticostriatal resting-state functional connectivity Chronically elevated levels of inflammatory markers, for example, are associated with clinical depression, post-traumatic stress disorder (PTSD) and many other psychological and behavioral issues and likewise these conditions often have elevated impulsivity. Inflammatory mediators promote a general trade-off towards focusing on immediate versus delayed outcomes. Inflammation is particularly influential on impulsivity - higher active inflammation – as quantified by plasma levels of IL-6, TNF-α, and white blood cell count – predicted more impulsivity. The relationship remained significant when controlling for factors known to covary with both inflammation and impulsivity [8] "Better understanding of the outcomes associated with impulsivity of inflammatory origins may yield low-cost interventions that can ameliorate behavioral problems notoriously resistant to current treatment strategies. For example, anti-inflammatory medications may be helpful as adjunct treatments for behavioral disorders related to impulsivity, such as substance abuse or certain mental illnesses." [1] http://www.dailymail.co.uk/…/Cambridge-psychiatrist-claims-… [2] https://www.ncbi.nlm.nih.gov/pubmed/29544672 [3] https://www.ncbi.nlm.nih.gov/pubmed/29173175 [4] https://www.ncbi.nlm.nih.gov/pubmed/29304217 [5] https://www.ncbi.nlm.nih.gov/pubmed/29604382 [6] https://www.ncbi.nlm.nih.gov/pubmed/29499967 [7] https://www.ncbi.nlm.nih.gov/pubmed/29689344 [8] https://repository.tcu.edu/handle/116099117/20630 More on neuroinflammation Mental illnesses and ASD seem to be strongly related to neuroinflammation, activation of inflammation in animal models leads to behavioural abnormalities. That said, it is suggested to be at best one cause of depression [1]. Schizophrenia and autism spectrum disorders share core symptoms and overlap in many ways pathologically, mainly by extensive microglial activation and similar behavioural attributes, this microglial activation also extends to brain injuries. The neuroprotective effect of curcumin is mainly mediated by blockade of microglial cell activation [2]. Psychological stress activates inflammation and that this activation would be found to predict the later development of pathology. Social isolation/feeling lonely is associated with systemic inflammation. There is evidence that a range of psychosocial stressors lead to elevated microglial activity [3]. Neuroticism has also been associated with higher levels of inflammatory markers while conscientiousness has been associated with lower inflammatory markers [4]. Chronic neuroinflammation and the loss of neurotrophic factors promotes 'locked in' behavioural inflexibility and promotes the pathogenesis of disorders such as addictions and feeds antisocial personality traits [5]. A multitude of studies support the notion that inflammatory processes form an integral part of the mechanisms precipitating addictions [6]. It appears elevated neuroinflammation is important throughout the cortico-striato-thalamo-cortical circuit of obsessive compulsive disorder, too [7] See Resident evil: Inflammation and depression [1] http://www.psychiatrictimes.com/special-reports/introduction-inflammation-connection [2] https://www.ncbi.nlm.nih.gov/pubmed/18214347 [3] https://www.ncbi.nlm.nih.gov/pubmed/26847047 [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544833/ [5] https://www.ncbi.nlm.nih.gov/pubmed/28810156 [6] https://www.ncbi.nlm.nih.gov/pubmed/29054292 [7] https://www.ncbi.nlm.nih.gov/pubmed/28636705 Microglial activation - a pathological player? Activated pro-inflammatory microglia trigger anxiety- and depressive-like behaviours, mainly by increasing the expression of pro-inflammatory mediators and neurotoxins in stress-sensitive brain regions. Injury, stress, toxic exposures and social stress can induce microglial over-activation [1] It is proposed M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases [2]. While activated M1 microglia may exacerbate injury by producing neurotoxic substances when overactivated for prolonged times, activated M2 microglia (the anti-inflammatory and tissue-reparative phenotype) protect neighboring cells by removing cell debris and releasing trophic factors for brain repair. Curcumin promoted microglial M2 polarisation and inhibited M1 polarisation. Long-term depression is a progressive disease and elevated microglial activation and inflammation play a role, it is suggested targeting the inflammatory process is needed to prevent neuroprogression [3]. Our gut microbiota is critical for modulation of the HPA axis and thus the stress response and brain processes such as myelination, neurogenesis and microglial activation and can effectively modulate behaviour and influence psychological processes such as mood and cognition. The gut microbiota is essential for the maintenance of microglia in a healthy functional state, which is necessary for the prevention of neurodevelopmental and neurodegenerative disorders [4]. Microglia have more recently emerged as key players in regulating neuronal network excitability [5] and reward. Activated microglia within reward circuitry result in disruption of dopaminergic signaling and reward behaviour. Activation of microglia by addictive drugs or other causes results in a proinflammatory dominance of the innate immune system, which is then critically synergise on the neurocircuit of reward and dependence [6]. Repeated drug-induced microglial activation produces progressive increases in microglial reactivity, further potentiating the neurobiological consequences of chronic drug use [7] Even acute inflammation impairs 'theory of mind' (ToM) explaining social-cognitive deficits in people that exhibit low-grade inflammation [8]. Inflammation, Self-Regulation, and Health: An Immunologic Model of Self-Regulatory Failure Exposure to stress, infection, and disease in early life increases proinflammatory cytokine activity, which decreases an individual’s self-regulatory ability. Poor self-regulation and poor health behaviours, which lead to greater exposure to stress and disease. As these dynamics continue over childhood and adolescence, compounded by social stressors, more stable differences in brain structure and function can develop that ultimately produce persistent impairments in self-regulation in adulthood. Dysregulated or enhanced neuroinflammation is argued to facilitate the etiology of mental disorders. Immune system activity — especially components of the immune system involved in inflammation — appear to impair numerous facets of self-regulation: inflammatory activity can impair both cognitive and emotional self-regulation. Markers of systemic inflammation have been associated with brain alterations that negatively impact executive function in humans: higher levels of proinflammatory cytokines at baseline predict lower executive function. Acute inflammatory challenges alter DLPFC response when individuals engage in tasks that require self-control, reduces resting glucose metabolism in the ACC in humans, which is a brain region critically important in self-regulation and reduces functional connectivity between the medial PFC (mPFC) and brain regions involved in mood and emotion. Inflammatory activity impairs sensitivity to reward. Inflammatory activity may impair self-regulation by reducing motivation and may either help or hinder self-regulation by decreasing sensitivity to reward. Inflammation may modulate mesolimbic and mesocortical dopaminergic systems. "Prolonged or severe stress exposure disrupts homeostatic or ‘healthy’ communication between the CNS and peripheral immune system, shifting immune signaling toward a proinflammatory state. Part of this response includes elevated and prolonged proinflammatory signaling in the CNS that is argued to be linked with stress-related psychiatric disorders." There is mounting evidence that social stress activates microglial cells in the central nervous system. Microglial activation is positively correlated with psychiatric disorders. Pro-inflammatory cytokines including IL-1β and TNF-α, can reduce the availability of serotonin, dopamine and noradrenaline by increasing the expression and function of reuptake transporters, reducing synthesis or decreasing monoamine precursors and also act on the glutamate pathway and together with astrocytes stimulate the increased release of this neurotransmitter and decreased brain-derived neurotrophic factor, which ultimately leads to excitotoxicity [9] Elevated pro-inflammatory cytokine levels caused by microglia activation, often induced by social stress, contributes to the development and persistent anxiety-like behaviour [10] [1] https://www.frontiersin.org/articles/10.3389/fnbeh.2017.00207/full [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276905/ [3] https://www.karger.com/Article/Abstract/470805. [4] https://www.wjgnet.com/1007-9327/full/v23/i30/5486.htm [5] https://www.hindawi.com/journals/np/2013/429815/ [6] https://www.ncbi.nlm.nih.gov/pubmed/22707932 [7] https://www.colorado.edu/lab/bachtell/research/neuroinflammation-and-addiction [8] https://www.ncbi.nlm.nih.gov/pubmed/29742460 [9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660717/ [10] https://www.nature.com/articles/npp2016102 Why turmeric? Turmeric, a source of curcuminoids, including the essential oil containing ar-turmerone [1] is a neuroprotective and neuropharmacological drug. It may be used in neurodegenerative disorders [2] including MS [3], depression etc. Curcumin may be used as an effective and safe modality for treatment in patients with depression, with a better tolerability profile and safety than SSRIs [4]. Patients receiving curcumin showed increased levels of BDNF relative to baseline, whereas patients receiving placebo showed declines relative to baseline but results did not show more distal effects on cognition or clinical symptoms for patients with schizophrenia [5] Curcumin may increase the concentration of monoamines available to interact with receptors, alleviating depression Curcumin strongly inhibits inflammatory cytokines like nuclear factor-kappa B, NLRP3 inflammasome, and interleukin-1B. this may help explain its antidepressant activity. There's suggestion that curcumin may be useful for treating human motivational symptoms The study findings that epigenetically, cooking with/using whole turmeric is superior to using turmeric extract preparations seem to match my experiences - those 'bioavailability enhanced commercial products' or curcumin extracts (even with piperine) just don't personally compare to solid dose of whole turmeric etc IMO. Something about it fermenting in the gut, activity of the volatiles, or high volume of dispersion/absorption of the curcuminoids through using the actual powder, I'm not sure? Particularly fermented with quality probiotics. Even a curcumin free water turmeric extract has effects on mood . At least 235 compounds, primarily phenolic compounds and terpenoids, have been identified from C. longa. What's interesting about using whole turmeric is curcumin-free turmeric components such as those in a possess numerous biological activities, including neuroprotective, anti-inflammatory, anticancer, and antidiabetic activities. Volatiles like aromatic-turmerone exerts beneficial effects on the brain - inhibiting microglial activation, preventing brain damage caused by neuroinflammation and increasing neural stem cell proliferation . Bisacurone has been identified as another of these components, also with anti-inflammatory effects. [1] a) https://www.ncbi.nlm.nih.gov/pubmed/28849618 b ) https://www.ncbi.nlm.nih.gov/pubmed/25928248 [2] https://www.ncbi.nlm.nih.gov/pubmed/22742420 [3] https://www.ncbi.nlm.nih.gov/pubmed/29079885 [4] https://www.ncbi.nlm.nih.gov/pubmed/23832433 [5] https://doi.org/10.1016/j.schres.2017.09.046 The effect of curcumin on serotonin appeared to be dose-dependent, at high doses curcumin also increased dopamine and to a lesser extent noradrenaline. Additionally, the effect of curcumin on the serotonergic system was possibly related to its interaction with 5-HT1A/1B and 5-HT2C receptors. In studies, regarding behavioural changes; the effect of curcumin was more pronounced than fluoxetine. Curcumin raised brain GSH and reduced brain MDA, TNF-α and IL-6 contents Importantly, curcumin normalises the levels of dopamine in the frontal cortex of rats and exerts biochemical and morphological effects of the on the PFC and hippocampus. Curcumin enhances the level of neurotrophic factors such as brain derived neurotrophic factor (BDNF) There have been signs of antidepressant properties through an interaction of curcumin with dopamine receptors and an increase in brain dopamine levels. Supplementation of curcuminoids to standard antidepressants showed a significant reduction of anxiety and depression in patients with major depressive disorder Moreover, curcumin extracts significantly improved depressive symptoms and demonstrated anxiolytic effects in patients with atypical depression. There was a significant improvement of sustained attention, working memory tasks, and mood after curcumin treatment. Curcumin showed a significant reduction in SGA‑induced body weight gain on the rats. It exerts hypoglycemic, antioxidant, antitumor, and anticarcinogenic activities. It also prevents tardive dyskinesia Why probiotic? Influence of gut microbiota on neuropsychiatric disorders Got a broad spectrum of probiotics gong on. Along with things like L. plantarum which significantly reduced anxiety-related behaviour and altered GABAergic and serotonergic signaling in the brain, it also ameliorated cognition deficits but also restored ACh and the histopathological features to control group in an AD model, I'm using a lot of L. rhamnosus rich food which has anxiolytic and mood effects: Lactobacillus rhamnosus, can dramatically alter GABA activity in the brains of mice. It reduces stress-induced elevation in stress hormones. Enriching food with Bifidobacterium longum which decreases anxiety and may improve mood among anxious animal models. Lactobacillus casei which cultures appeared to improve mood among those only with a low/depressive mood at baseline. Bifidobacterium animalis which scavenged free radicals and decreased MAO activity. "The development of the forebrain, esp. the neocortex, in social mammals and ultimately primates and humans depends on correct and timely signals from microbial symbionts—which is disturbed, when the microbiota is absent or disturbed. Likewise when the microbiome is disturbed, there is evidence of increased hypothalamic–pituitary–adrenal (HPA) axis activity in response to acute stress. The immune pathway within the brain–gut–microbiome axis may be a plausible mediator of the effects of this axis on social behaviour" Recent data provide evidence that related bacterial species can interact specifically with a variety of different neuronal populations. For example some bacteria affects the functioning of CNS neurons in the hippocampus and amygdala, and alter PFC funtioning. They can alter vagal tone, HPA axis activity, neuroinflammation/microglial activation, alter serotonergic transmission, levels of brain-derived neurotrophic factor, NMDA receptor subunit expression, GABAergic signalling and receptor expression etc [ref] There are also links to a role for oxytocin. Altering the microbiome has been shown to do things like: -improve mood, but only in those who have poorer mood at baseline and alter anxiety related measures -reduce cortisol output in response to an acute stressor -alter brain activity when processing information related to emotional facial expressions -improvement in sustained attention in healthy older adults The first clinical trial of probiotics in bipolar disorder found probiotics lowered the rate of rehospitalisation, building on previous research that has found promise for these in depression, anxiety, cognition, and autism Supplemental probiotics to combat brain-related dysfunction offers a promising approach [1]. Evidence suggests [2] that chronic administration of Lactobacilli and Bifidobacteria strains can have effects on areas of the brain related to emotion, mood, memory, and somatosensory processing - probiotic ingestion attenuates emotional reactions and decreases activity of certain brain regions when measuring brain responses to emotional stimuli Along with improved depression, anxiety, anger, and anxiety in adults [3], probiotic intake for 4-6 weeks altered neural activity in brain regions that control central processing of emotion and sensation in healthy women but no change in gut microbial composition was detected [4]. In a more recent study, a slight change was detected in the microbiome and [5]: Probiotics improved self-reported behavioural measures of positive affect and cognitive reactivity Probiotic administration influenced the behavioral scores for depression and anxiety questionnaires, significantly increasing positive affect and blunting vulnerability to depression in terms of hopelessness and risk aversion Probiotics improved memory performance and altered brain activation patterns Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks In major depression, probiotic (Lactobacillus helveticus and Bifidobacterium longum) resulted in an improvement in BDI score compared with placebo whereas no significant effect of prebiotic supplementation (galactooligosaccharide) was seen [6] “The Social Network” – How the Gut Microbiome Governs Our Social Behaviour [1] https://www.ncbi.nlm.nih.gov/pubmed/29701810 [2] https://www.ncbi.nlm.nih.gov/pubmed/29698377 [3] https://www.ncbi.nlm.nih.gov/pubmed/20974015 [4] https://www.ncbi.nlm.nih.gov/pubmed/23474283 [5] https://www.tandfonline.com/doi/abs/10.1080/19490976.2018.1460015 [6] https://doi.org/10.1016/j.clnu.2018.04.010 There seem to be changes in the microbiota that are associated with substance use [1] across an array of SUDs and eating disorders [2] Ethanol drastically changes the microbiome and increase in gut permeability and induces a pro-inflammatory responses. Microbiome alterations were shown to be correlated with alcohol use disorder-related symptoms, i.e. craving, depression and anxiety and manipulations in the gut microbiota may affect cocaine-related behaviors (Animals with reduced gut bacteria showed an enhanced sensitivity to cocaine reward and enhanced sensitivity to the locomotor-sensitising effects of repeated cocaine administration [3]) and methamphetamine [4]. There is a strong negative influence of alcohol dependence on gut microbiota [5] and "Intestinal flora between cocaine users and non-cocaine users and have found that cocaine users have a higher mean relative abundance of Bacteroidetes and a lower abundance of Firmicutes than non-users; are more likely to smoke; have a lower mean percentage of body fat; and consume more alcohol than non-users." Phytonutrients impact the microbiome “eat the rainbow” AND eat prebiotic and probiotic foods" so to do omega-3's: Some of the health-related benefits of omega-3 may be due, in part, to increases in butyrate-producing bacteria. You can shift the microbiome with probiotics. Some of the other non-LAB are also now available as supplements. Probiotic intake induced an increase in Proteobacteria and in the Clostridiales spp. Patients taking probiotics had an increased numbers of butyrate-producing bacteria, especially Faecalibacterium and Clostridiales spp. Probiotic intervention modulated the fecal concentrations of butyrate in a manner dependent on the initial levels of short-chain fatty acids (SCFAs) [things like live B. bifidum cells affected the relative abundance of dominant taxa in the fecal microbiota and modulated fecal butyrate levels] [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472629/ [2] https://www.ncbi.nlm.nih.gov/pubmed/28482009 [3] https://www.ncbi.nlm.nih.gov/pubmed/27752130 [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575146/ [5] https://microbiomejournal.biomedcentral.com/.../s40168... Black pepper - more than a spice and bioavailability enhancer... "During the time of Hippocrates the pepper was used as both a spice for food and as a medicine. The Asian world has long considered black pepper to be an important spice for detoxifying and as an anti-aging compound. It is widely used in different traditional systems of medicine like Ayurvedic and Unani System of medicines" Black pepper is itself used as an analgesic, antiinflammatory, anticonvulsant, antioxidant, antidepressant and cognitive-enhancing agent. It contains 5-10% pungent acid-amides, with piperine as its main compound and several others, such as the N-isobutylamide guineensine which is a nanomolar inhibitor of cellular uptake of the endocannabinoid anandamide. Recent studies on the pharmacological actions of piperine have demonstrated its antioxidant activity, antiinflammatory [1] and cognitive-enhancing effect following long-term oral administration. It performed as well as memantine in an Alzheimer's model [2]. It reduces cholinesterase levels and amyloidal plaque formation [3]. It is a potent anti-inflammatory [4]. The antidepressant-like effects might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake, along with inducing BDNF promoter, increasing brain-derived neurotrophic factor expression in the hippocampus and promoting neurite outgrowth [5,6]. It predominately seems to be mediated via the serotonergic system by enhancing 5-HT content [7] It exerts anxiolytic effects by GABAergic and nitrergic systems [8] It exerts anticonvulsant effects [9] due to antioxidant actions, as well as TNF-α reduction, along with effects on inhibitory amino acids and on the GABAergic system [10] and analgesic properties dependent on the opioid system [11] Piperine pre-treatment time-dependently improves the bioavailability of poylphenols, including flavonoids/green tea catechins and curcumin, through the reversible and selective inhibition of UGTs and SULTs. It also increases the bioavailability of things like ashwagandha, rosmarinic acid and a variety of drugs [12]. Enzymatic inhibition by piperine resulted in increased bioavailability of many drugs and nutrients e.g. amoxicillin, ampicillin, acefotaxime, carbamazepine, ciprofloxacin, norfloxacin, metronidazole, oxytetracyclin, nimesulide, pentobarbitone, phenytoin, resveratrol, beta-carotene, curcumin, gallic acid, tiferron, nevirapine, and sparteine by different types of mechanisms. Curcuminoids and piperine could inhibit drug metabolism but is "unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes." [1] https://www.ncbi.nlm.nih.gov/pubmed/28185326 [2] https://www.ncbi.nlm.nih.gov/pubmed/28939403 [3] https://www.ncbi.nlm.nih.gov/pubmed/26023568 [4] https://www.ncbi.nlm.nih.gov/pubmed/28185326 [5] https://www.ncbi.nlm.nih.gov/pubmed/29063362 [6] https://www.ncbi.nlm.nih.gov/pubmed/17701559 [7] https://www.ncbi.nlm.nih.gov/pubmed/21477634 [8] https://www.ncbi.nlm.nih.gov/pubmed/25149996 [9] https://www.ncbi.nlm.nih.gov/pubmed/28352353 [10] https://www.ncbi.nlm.nih.gov/pubmed/23313550 [11] https://www.ncbi.nlm.nih.gov/pubmed/24388894 [12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458266/ Ginger: This itself functions as a bioavailability enhancer. Ginger has also a broad anti-inflammatory properties and may be useful in auto-immune conditions including MS. Ginger and its constituents, such as 6-gingerol, 6-shogaol, 6-paradol, zingerone, and dehydrozingerone, are effective for ameliorating the neurological symptoms of neurodegenerative conditions. Ginger and neurodegenerative disorders:

I had an interest in the minerals awhile ago, sorry it's not well referenced, these were just my notes: Didn't get to boron... A good article from 2007, so it's a bit dated, that covers vitamins and minerals. For zinc, see https://www.psychologytoday.com/…/201309/zinc-antidepressant It is an effective SSRI augmentation strategy. In addition, chronic zinc treatment induced increases in both 5-HT1AR protein levels and density of 5-HT1A receptor binding sites, it also increased tissue levels of serotonin metabolite and turnover. On the other hand, DA, DOPAC, HVA tissue levels increased while DOPAC/DA and 3MT/DA decreased in the PFC of rats after chronic zinc treatment. Acute treatment induced increases only in tissue levels of DOPAC, and DOPAC/DA - the antidepressant effects of zinc are mediated in concert with the modulation of the serotonergic system including postsynaptic 5-HT1ARs and allude to a possible involvement of dopaminergic neurotransmission in this action. Magnesium is a treatment option that may offer great potential for patients with MDD and treatment-resistant depression based on prior work in animals and humans. Combined magnesium and vitamin B6 supplementation reduced anxiety but had no effect when used in isolation. A very small study found benefit from a combination probiotics/magnesium orotate formulation adjuvant administered with SSRIs for treatment resistant depression. See http://evolutionarypsychiatry.blogspot.com.au/…/magnesium-a… and Magnesium and depression: https://www.ncbi.nlm.nih.gov/pubmed/27910808 Selenium Accumulation of reactive species generated during the normal course of metabolism is highly toxic to biological macromolecules and is a major concern in the pathogenesis of chronic diseases and a significant factor for cognitive decline. The preferential retention of selenium in the brain suggests that it plays important functions. To date mood is the clearest example of an aspect of psychological functioning that is modified by selenium intake. Five studies have reported that a low selenium intake was associated with poorer mood. The underlying mechanism is unclear although a response to supplementation was found with doses greater than those needed to produce maximal activity of the selenoprotein glutathione peroxidase. Although the functions of many selenoproteins are unknown some play important roles in anti-oxidant mechanisms. Selenium likely plays a role in normal aging, schizophrenia, Parkinson's and Alzheimer's disease. Selenomethionine enhances stress resistance, is effective in promoting neurogenesis, ameliorates aging indicators, improves the cognitive function of AD mice (rescues spatial learning and memory impairments in aged 3xTg-AD mice via decreasing the level of tau protein and tau hyperphosphorylation) and may be a promising therapeutic option for AD as it decreases the deposition of Aβ and tau hyperphosphorylation. Selenium affects the cells of the nervous system, and, thus, affects mood: neurotransmitters do not turnover as quickly in Selenium deficient individuals Low Selenium levels are correlated to depression, anxiety, confusion, and hostility. Supplementing for 5 weeks with 100 mcg of Selenium, lessened anxiety among patients who participated in a clinical trial. Hospitalized elderly, cancer, and/or HIV patients reported less anxiety after Selenium was added to their diets • Even though every aerobic cell is at risk of oxidative damage, the brain is especially vulnerable and this condition is a significant factor for cognitive decline. • Selenium compounds and selenoproteins exhibited a strong antioxidant role Selenium deficiency or altering the structure or deletion of selenoproteins is associated with severe brain injury. • Maternal Se status is associated with cognitive ability of the new born. However, the relationship between maternal Se and cognitive ability is not linear (inverted “U”) suggesting both deficiency and excessive Se intake may result in adverse neurobehavioral outcomes. • Selenium nutrition in the elderly prevents the progression of Alzheimer’s disease, cognitive decline, mood disorder, and depression. However, Se supplementation to healthy individuals with adequate baseline Se with no symptom of mood disorder has not been shown to improve mood Selenium has potential antidepressant- and anxiolytic-like effects and "Se is capable of alleviating inflammatory signaling pathways. Obesity is associated with chronic low-grade inflammation. Depression is also defined as an inflammatory disorder. Inflammatory mediators such as tumor necrosis factor-alpha (TNFα) participate in the progression of depression. They are also obesity-associated parameters. Due to TNFα induced depressive-like behaviors and the positive association between this proinflammatory cytokine and obesity, TNFα-activated signaling pathways and those inhibiting them have recently gained importance as potential targets and therapeutic tools, respectively. More studies are necessary to develop compounds with therapeutic nature against depressive disorders and obesity. PPARγ is an important signaling pathway that occurs at the crossroads of depression and obesity. Se, aside from its anti-inflammatory, anticarcinogenic and antioxidative nature, affects also the way of PPARγ action. Se supplementation or fortification ... will be promising approaches for future hope during the treatment of these diseases." Chromium Chromium is antidepressive and may help regulate blood sugar. Chromium supplementation for glucose regulation has shown mixed, modest-sized effects in patients with type 2 diabetes (T2DM). Chromium has the potential to improve insulin, dopamine, and serotonin function, The antidepressant activity has been linked to a major role of the AMPA receptor and participation of NMDA glutamatergic and 5-HT1 and 5-HT2A/C serotonin receptors. Chromium treatment decreases the sensitivity of 5-HT2A receptors Plasma chromium concentrations were inversely associated with T2DM and pre-DM in Chinese adults [1]. A moderate dose of Cr was associated with improved glycemic control whereas a high dose, while showing some improvement, was not better [2]. Combined chromium and magnesium decreases insulin resistance more effectively than either alone [3]. Cr supplementation showed beneficial effects on blood markers of vascular inflammation, insulin resistance, and oxidative stress compared to placebo [4]. What's the difference between the nicotinate and picolinate? "In a recent investigation conducted at the University of Texas at Austin, a group of healthy, sedentary, obese women was given either chromium picolinate or chromium nicotinate (200 mcg twice a day) for nine weeks, The subjects were divided into four groups: 1) chromium picolinate, 2) chromium picolinate with exercise, 3) chromium nicotinate with exercise, and 4) exercise Plus placebo. Twice-a-week exercise was extensive, involving step aerobics, cycling for 30 minutes and resistance training. Supplementing with chromium picolinate resulted in statistically significant weight gain (+2.9%), caused by a gain in fat-free mass with a slight gain in fat mass. Exercise plus chromium nicotinate caused a significant reduction in bodyfat (-1.6%) and a lowered insulin response to an oral glucose load. Exercise by itself or with chromium picolinate didn't significantly affect bodyweight, fat mass or fat-free-mass levels. This is the first study to show that chromium nicotinate plus exercise can cause a significant decrease in bodyweight with a slight gain in muscle, but study authors didn't suggest a mechanism for this effect. Nonetheless, it would seem that giving chromium picolinate to healthy, obese women is contraindicated for weight loss. Using chromium nicotinate plus exercise, however, may increase the weight loss that normally occurs with regular exercise." [1] Inverse Association of Plasma Chromium Levels with Newly Diagnosed Type 2 Diabetes: A Case-Control Study. https://www.ncbi.nlm.nih.gov/pubmed/28304331 [2] A Double-Blind, Randomized Pilot Trial of Chromium Picolinate for Overweight Individuals with Binge-Eating Disorder: Effects on Glucose Regulation. https://www.ncbi.nlm.nih.gov/pubmed/27835050 [3] Combined chromium and magnesium decreases insulin resistance more effectively than either alone. https://www.ncbi.nlm.nih.gov/pubmed/27702717 [4] Impact of chromium dinicocysteinate supplementation on inflammation, oxidative stress, and insulin resistance in type 2 diabetic subjects: an exploratory analysis of a randomized, double-blind, placebo-controlled study. https://www.ncbi.nlm.nih.gov/pubmed/27687012 For a review, see: Selenium, Vanadium, and Chromium as Micronutrients to Improve Metabolic Syndrome.https://www.ncbi.nlm.nih.gov/pubmed/28197835

The taurine is seemingly really useful for the impulsiveness and "feeling in control again" at high doses. It seems to settle the pathology. It does seem to modulate aberrant dopaminergic subcortical stuff subjectively for me, the tics etc. Added a bit of creatine from today... used it before, mainly with things not so great for mental health. Stick with this, the energetics of my brain seems very disturbed. Creatine and the Brain Creatine as a treatment for people with SSRI-resistant MDD is suggested [1]. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy [2]. It targets similar pathways to ketamine [3]. Even a single treatment of creatine or exercise has partial effects as an antidepressant in mice with chronic mild stress-induced depression [4]. Combined creatine and exercise has synergic effects and is more effective than a single treatment. Dietary supplementation with creatine can improve learning, memory, and mitochondrial function and have important implications for the treatment of diseases affecting memory and energy homeostasis [5]. Supplementation with creatine for 6 weeks is associated with improvement in verbal fluency tests in bipolar disorder [6]. "Oral creatine administration may improve short-term memory and intelligence/reasoning of healthy individuals but its effect on other cognitive domains remains unclear. Findings suggest potential benefit for aging and stressed individuals. Since creatine is safe, future studies should include larger sample sizes. It is imperative that creatine should be tested on patients with dementias or cognitive impairment." [7] ' [1] https://www.ncbi.nlm.nih.gov/pubmed/26907087 [2] https://www.ncbi.nlm.nih.gov/pubmed/26822799 [3] https://www.ncbi.nlm.nih.gov/pubmed/26660117 [4] https://www.ncbi.nlm.nih.gov/pubmed/27757384 [5] https://www.ncbi.nlm.nih.gov/pubmed/29339557 [6] https://www.ncbi.nlm.nih.gov/pubmed/27890303 [7] https://www.ncbi.nlm.nih.gov/pubmed/29704637

I'm guessing this is in reference to non-alkaloid constituents only. Don't have any experiences to add but please keep it to legal soap ingredients Here's some info on what alcohol could potentially pull in the way of non-alkaloid constituents "Acacia was referred to as ‘the tree of life’, reflecting its healing nature. Early colonial botanists described medicinal attributes of Acacia species that were known by indigenous Australians" It is said the biological activities of the Australian Acacia gums were similar to those of Gum Arabic, rich in complex polysaccharides, and that these gums may have potential value as functional human food ingredients. They act as quite effective prebiotics. Neuroprotective effects of Gum Arabic have been established in the ageing brain and ingestion causes significant reduction in BMI and body fat percentage among healthy adult females. Barks and leaves are the most commonly used parts in all cultures (Australian Aboriginal, African, Asian and Arabs). Other parts used, in decreasing order, are: seeds ≥ gum˃ pods˃ roots ≥ woods˃ flowers ≥ twigs. Many Australian Acacias are potentially useful in the "treatment of diabetes and neurodegenerative disorders. These Acacia species are rich sources of phenolic antioxidants" but I can't see the phenolic content of the gum [1] Phytochemical and pharmacological investigations of Australian Acacia: An ethnomedicine-guided bioprospective approach https://researchoutput.csu.edu.au/files/9318404/88453

“The Social Network” – How the Gut Microbiome Governs Our Social Behaviour As I continue, I'm quite a bit into my fermented probiotic, polyphenol laden, omega-3 rich, veggie/herb/greens, vitamin and mineral rich and quality plant protein food and beverage bender with exercise (which includes fermented soy, fermented turmerics etc, most beverages are lacto-fermented etc), The fermented cabbage intake wasn't enough, nor caps of probiotic, nor more prebiotic food, this time I'm going balls to the wall. One thing I'm keen to observe as I shift the bacteria laden food I'm consuming is not just mood, cognition and anxiety parameters but if it shifts social engagement etc. I'm noting a few subjective things: - I feel way less perma-stressed, little less anxious, less fragmented with stress hormone pep. Much less emotional dysregulation - mood is more stable. More functionally grounded. Feels a bit literally soothing without needed to use soothing plant meds. I'm not chasing non food things to lift my mood. Even caffeine use is less tempting, not so much pep required to lift mood. - Hunger is down -people aren't giving me the typical annoying 'bloody humans' feelings that normally arise, normally a large portion of the population tends to give me the sh*ts. There's an emotional approach that feels softer. Not quite prosociality but tending that way Both urbanisation and social isolation may alter the microbiome to pathology "Urbanization is on the rise, and environments offering a narrow range of microbial exposures are linked to an increased prevalence of both physical and mental disorders." Urban environments are linked to immunoregulatory deficits - "prospective human and mechanistic animal studies strengthen the idea that an exaggerated immune (re)activity plays a role in the development of mental disorders" A normal, healthy, and rather non-parasitic microbiota may provide developmental cues that facilitate social behaviour. Socially shared microbiomes could drive the evolution of population-specific mating signals and it has been established common group membership and dietary intake can influence and predict gut microbiota composition. More complex socially driven behaviors can modulate microbiota populations [1]. Animals with an altered microbiome spent significantly less time with a conspecific and did not show the typical preference for a novel mouse when given a choice between a familiar and a novel interaction partner. A "possible mechanism predisposing those with an urban upbringing, relative to those with a rural upbringing, to develop mental disorders in which inflammation has been identified as a risk factor, is an exaggerated inflammatory response following psychosocial stress exposure. Increased inflammation in urban environments may be due to impaired immunoregulation, which is thought to be dependent, at least in part, on reduced exposure, especially during early life, to microorganisms with which mammals coevolved, as has been proposed by the “biodiversity” hypothesis, “missing-microbes” hypothesis, or “old-friends” hypothesis, which all have been evoked to explain the epidemic of inflammatory disease in urban environments." [2] We may be so removed from old-friends that it is altering social behaviour and as we spread our urbanicity, be spreading pathology: "social behavior affects the composition of the microbiota and vice-versa and differential expression of RNAs has been observed in cognitive disorders that are associated with altered social behaviour. It is well-documented that microbes can directly target the host's transcriptional regulatory machinery. There are several potential routes for microbes to interact with host cellular function and even behavior and some of these may be mediated by alterations of the epigenetic gene regulation in the brain." [3] "The development of the forebrain, esp. the neocortex, in social mammals and ultimately primates and humans depends on correct and timely signals from microbial symbionts—which is disturbed, when the microbiota is absent or disturbed. Likewise when the microbiome is disturbed, there is evidence of increased hypothalamic–pituitary–adrenal (HPA) axis activity in response to acute stress. The immune pathway within the brain–gut–microbiome axis may be a plausible mediator of the effects of this axis on social behaviour" Recent data provide evidence that related bacterial species can interact specifically with a variety of different neuronal populations. For example some bacteria affects the functioning of CNS neurons in the hippocampus and amygdala, and alter PFC funtioning. They can alter vagal tone, HPA axis activity, neuroinflammation/microglial activation, alter serotonergic transmission, levels of brain-derived neurotrophic factor, NMDA receptor subunit expression, GABAergic signalling and receptor expression etc [4] There are links to oxytocin with some Lactobacillus. Altering the microbiome has been shown to do things like: -improve mood, but only in those who have poorer mood at baseline and alter anxiety related measures -reduce cortisol output in response to an acute stressor -alter brain activity when processing information related to emotional facial expressions -improvement in sustained attention in healthy older adults [1] http://www.microbiomeinstitute.org/…/social-constructs-and-… [2] http://www.pnas.org/content/early/2018/04/24/1719866115 [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212686/ [4] https://academic.oup.com/…/doi/10.1093/nutrit/nuy009/4985887 The microbiome in addictions What's also interesting to me particularly is how alterations in the gut microbiota affect pathological reward-related behaviour like the intake of drugs of abuse/alcohol and food etc. There seem to be changes in the microbiota that are associated with substance use [1] across an array of SUDs and eating disorders [2] Ethanol drastically changes the microbiome and increase in gut permeability and induces a pro-inflammatory responses. Microbiome alterations were shown to be correlated with alcohol use disorder-related symptoms, i.e. craving, depression and anxiety and manipulations in the gut microbiota may affect cocaine-related behaviors (Animals with reduced gut bacteria showed an enhanced sensitivity to cocaine reward and enhanced sensitivity to the locomotor-sensitizing effects of repeated cocaine administration [3]) and methamphetamine [4]. There is a strong negative influence of alcohol dependence on gut microbiota [5] and "Intestinal flora between cocaine users and non-cocaine users and have found that cocaine users have a higher mean relative abundance of Bacteroidetes and a lower abundance of Firmicutes than non-users; are more likely to smoke; have a lower mean percentage of body fat; and consume more alcohol than non-users." Phytonutrients impact the microbiome “eat the rainbow” AND eat prebiotic and probiotic foods" so to do omega-3's: Some of the health-related benefits of omega-3 may be due, in part, to increases in butyrate-producing bacteria. You can shift the microbiome with probiotics. Some of the other non-LAB are also now available as supplements. Probiotic intake induced an increase in Proteobacteria and in the Clostridiales spp. Patients taking probiotics had an increased numbers of butyrate-producing bacteria, especially Faecalibacterium and Clostridiales spp. Probiotic intervention modulated the fecal concentrations of butyrate in a manner dependent on the initial levels of short-chain fatty acids (SCFAs) [things like live B. bifidum cells affected the relative abundance of dominant taxa in the fecal microbiota and modulated fecal butyrate levels] [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472629/ [2] https://www.ncbi.nlm.nih.gov/pubmed/28482009 [3] https://www.ncbi.nlm.nih.gov/pubmed/27752130 [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575146/ [5] https://microbiomejournal.biomedcentral.com/.../s40168...

Thanks for the input. The Galbulimima bark is one I'm yet to try. I went away from BCAAs and now for brekky have fermented soy protein. It seems good so far, most mood stabilising protein meal I've noted to get exercise done without needing to get pepped and has the satiating/whole body beneficial proteins and hypothetically the encrypted proteins with antidepressant, opioid and cognitive benefits etc with a good level of free aromatic aminos. Occasionally have a bit of acetyl-L-carnitine. Found my stress responses have gone down since I upped the probiotic food and such seems just as good a stress buffer, to the point where L-lysine/arginine blends weren't needed. Went back to taurine - why? Taurine and the brain, does it help give you those wings? - I've wondered why they put it in energy drinks etc? There's some suggestion taurine enhances exercise performance, supporting healthy VO2 max, exercise time to exhaustion and maximal workload but does it have much effect on the mind without heaps of caffeine in the mix? I've tried supposedly 'more active' homotaurine derivatives which are supposedly CNS active to not much effect. How much does this often considered to be pretty inert and boring compound do in the brain at high doses, for a reasonable time? Particularly, does it have therapeutic applications? Seeing it's such a cheap, safe thing that's found to have good effect in psychiatric conditions in some studies [1,2], I've been heaping taurine into my diet, not expecting really anything. There's something very 'modulatory' about it at high dose. I always dismissed it as pretty inert but they're even suggesting it as an option for ADHD. I stopped for a bit and things went a bit downhill. Taurine effects include: neuromodulatory, osmoregulatory, membrane stabilisation, and antioxidant action coupled with neuroprotective (taurine is a potential therapeutic agent for neurodegenerative diseases, promoting neuronal proliferation, stem cell proliferation, and differentiation, via several mechanisms), anti-diabetic (it improved glucagon activity, promoted glycemic stability, modified glucose levels, successfully addressed hyperglycemia via advanced glycation end-product control, improved insulin secretion and had a beneficial effect on insulin resistance) and anti-depressive effects (regulation of hypothalamic-pituitary-adrenal (HPA) axis and the promotion of neurogenesis, neuronal survival and growth in the hippocampus). "Dysregulation of dopamine (DA) level has been associated with various psychiatric disorders... Taurine is a ubiquitous β-amine acid in mammals, which is involved in a variety of physiological and biological processes such as cell membrane stabilization, osmoregulation, detoxification, immune regulation, antioxidation, and neuromodulation. In recent decades, considerable attention has been paid to the role of taurine in the central nervous system. Notably, various evidences have shown that taurine is a neurotransmitter. Taurine has neuroprotective effects and a taurine additive has been suggested as a potential candidate for neuroprotectants. Recent results reported that high-dose taurine improves hyperactive behaviour and brain functional signals Low-dose taurine favors impulsive behavior and striatal dopamine uptake whereas high-dose taurine improves spatial learning, memory and striatal dopamine uptake. Supplementation of taurine could be a remedy for ADHD. Since high-dose taurine is non-toxic to humans and has been clinically used to treat various disorders, the findings in this study by using high-dose taurine (560 mg/ 100 g diet) did provide a rational suggestion for high-dose taurine on ADHD treatment. Notably, much evidence indicates that taurine strengthens the effects of dopamine and has a synergistic effect with dopamine in the brain, inhibiting the reduction of sucrose consumption and improving the learning ability and spatial memory of rats that are exposed to chronic unpredictable mild stress (CUMS)" [3] Taurine is a psychopharmacologically active compound with potential for "a variety of therapeutic uses including as a neuro-protective, anti-cataleptic, anti-addicting, and analgesic agent." With regard to the dopamine elevating properties of alcohol, raised levels of taurine in the nucleus accumbens (nAc) is pivotal. Acute or chronic administration of psychotropic drug cocaine may increase extracellular release of endogenous taurine [4] [1] https://www.ncbi.nlm.nih.gov/pubmed/29561067 [2] https://www.ncbi.nlm.nih.gov/pubmed/27835719 [3] https://www.ncbi.nlm.nih.gov/pubmed/29694913 [4] https://www.ncbi.nlm.nih.gov/pubmed/23392920