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Alchemica

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Everything posted by Alchemica

  1. Alchemica

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    From the album: Healing in the gardens

  2. Alchemica

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    From the album: Healing in the gardens

  3. Alchemica

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    From the album: Healing in the gardens

  4. Alchemica

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    From the album: Healing in the gardens

  5. Alchemica

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    From the album: Healing in the gardens

  6. Alchemica

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    From the album: Healing in the gardens

  7. Alchemica

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    From the album: Healing in the gardens

  8. Alchemica

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    From the album: Healing in the gardens

  9. Alchemica

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    From the album: Healing in the gardens

  10. Ketosis as therapy Heard of a few people doing this, feel free to share your experience We're often centric on putting something in to remedy disease. Taking things out is often less favoured and easy. The nice thing about a diet change is you regain choice of, and gain discipline of what you put into your body and hopefully a health outcome out of it. The second is you can often address the issues of poor health Finding a diet and lifestyle that delivers improvements puts a feeling of health back in your conscious control. I thought, what am I like with very low carbs? I tried exogenous ketones, looking for a fix. What happens with using willpower for better health? I'm still using thiamine but now as a B150 complex and keeping balance in micronutrients including trace elements... my macronutrient profile was not delivering - I was perma-hungry on my relatively planty but carb-loaded diet... keeping up exercise and gardening but so up and down and moody, push through it I tried.... Why not change diet a bit/have another crack at nutritional ketosis? It's "trendy" but also interesting on paper. "...changing diet triggers a deeper consciousness about you" Allowing you to "align your new eating habits with your other new ones in general" Mice on higher glycaemic food showed more autistic behaviors, such as reduced social interactions and activities that seemed to serve no purpose, according to the study, while the low glycaemic mice saw their behaviours improve "Dietary lifestyle changes can have a positive impact throughout the lifespan and appear to not only reduce the risk of acquiring cognitive impairments, but can also attenuate existing impairments: a recent study showed that a 4-week low-saturated fat/low-glycaemic index (GI) diet resulted in improved memory performance and insulin metabolism in adults with amnestic mild cognitive impairment In a healthy young student population those with better glucose regulation perform better on tests of memory, vigilance, planning and dichotic listening compared with those with poorer glucose regulation. A higher-glycemic load diet was associated with higher depression symptoms, total mood disturbance, and fatigue compared to a low-glycemic load diet especially in overweight/obese, but also otherwise healthy, adults" [ref] In ASD, all subjects on the KD had increased BHB, only 50% of subjects demonstrated significant improvements in some studies, some being super-responders with dramatic improvements in social affect. There have been improvement in case studies in hyperactivity, attention span, abnormal reactions to visual and auditory stimuli, usage of objects, adaptability to changes, communication skills, fear, anxiety, and emotional reactions In more serious mental illness, evidence against the role of calorie restriction the mechanism of action of improvement in models, it seems to be more related to ketone bodies I got into meal skipping first. Then low GI, then super carb reduction, then ketotarian. Eventually I was in measurable ketosis, over 1.5mmol/L. Even just getting to breakfast skipping was hard enough without mood going way too low and symptoms initially. Ketosis, it's nice for some conditions on paper but what's it like in reality? "...many people with certain mental disorders find it especially difficult to maintain thanks to the very symptoms they’re looking to manage". "...amid the excitement about the ketogenic diet, I think it’s important to point out its drawbacks as a psychiatric tool." I agree, if you're looking to use a more extreme diet for mental health "wait until your brain is relatively stable before any kind of diet change". I tried getting into ketosis with extreme distress as a baseline once, even helping it along with BHB and I don't recommend it. It didn't work and made things worse. "...after two days of eating fewer than 30 grams of carbs, it hit — a period of low energy and weakness I woke up achy and sluggish, confused and depressed. I was simply too tired to be nervous about anything. But my depression had deepened, sending me into a dull blue fog. Then ten days, each of them torturous." 1. Caloric restriction increases longevity, memory, quality of life and reduces risk factors for neurodegenerative and psychiatric diseases "We suggest that switching between time periods of negative energy balance (short fasts and/or exercise) and positive energy balance (eating and resting) can optimize general health and brain health The increase in autism tracks remarkably closely with the increase in childhood overweight or obesity during the same time period (data from autismspeaks.org and the US Centers for Disease Control), suggesting a causal link between lack of metabolic switching and autistic behaviours, potentially through BDNF expression and excessive mTOR pathway activation" [1] "...metabolic programs relying on efficient fatty acid and ketone body oxidation are most of the time shut off in the modern lifestyle and have to be reintegrated in order to overcome the obesity epidemic – widely known as the breeding ground for most of the Western diseases" The modern lifestyle promotes continuous fueling of adipocytes - most authorities in the Western world recommend at least 50% of the daily caloric intake as carbohydrates but we're losing metabolic flexibility. We have an environment of energy abundance, prolonged psychosocial stress and physical inactivity. It is suggested that "...that the strong increase of diseases related to metabolic abnormalities is largely based on a deficit in metabolic flexibility induced by things like psycho-emotional stress, high meal frequency, physical inactivity etc" It's suggested we need to get used to "periodic fasting or calorie restriction, occasional meal skipping, ketogenic diets and of course exercise. Intermittent fasting and longer-term caloric as well as carbohydrate restriction are parts of our genetic heritage" [ref] There is abnormal hedonic behaviour displayed by diets with high-glycemic carbohydrates - today modern humans are surrounded by a plethora of rewarding stimuli in a nearby environment and through food, we are blunted to the point of reaching reward hyposensitivity What happens with strict carbohydrate restriction to induce adaptation to ketosis? - Improved memory function with a medium effect size in individuals with impairment in response to a relatively brief period of carbohydrate restriction designed to reduce insulin levels and induce ketone metabolism. Improved memory performance, potentially by regulating hippocampal function - Upregulation of GABAergic tone, regulation of glutamatergic transmission (changes the ratio of GABA:glutamate in favor of GABA), dopaminergic and serotonergic modulation along with changes in kynurenine metabolism. Enhanced the availability of brain tryptophan and serotonin, later releases of endogenous endorphins - greater satiety and reduced overall consumption - improved central insulin sensitivity - enhanced cerebral blood flow and blood–brain barrier function - reduced mammalian target of rapamycin (mTOR) expression, similar to the effects of the antidepressant ketamine - dramatic up‐regulation in neuronal autophagy (sometimes referred to as cellular cleansing) - may moderate the pathogenic relationship between stress reactivity and brain in limbic and prefrontal regions - β-hydroxybutyrate increases the frequency of gamma oscillations and has a protective role in executive function in serious mental illness - anti-oxidant/anti-inflammatory action - increases the activity of a family of transcriptional repressors known as sirtuins and broad epigenetic regulatory activities at physiological concentrations, these may alter seeking behaviour, preventing excessive ethanol intake and relapse and facilitate extinction. Enhance GABAergic and glutamatergic plasticities in DA neurons and normalise hyposensitivity to GABA. - activated brain PPARα: through this is likely to regulate expression of many genes encoding enzymes of amino acid/neurotransmitter metabolism and stimulation of PPARα improves cognitive function (reducing cognitive inflexibility, perseveration etc) in models of impaired cognitive function The beneficial effects of caloric restriction may require only a short‐term reduction in caloric intake Some of the things that temporarily flared up were transient worsening of AVHs and not enough energy to want to bother trying to socialise. I was temporarily in quite a negative mindset and not interested in much of anything. Now there are a few elements: 1. Stability of mind, quite a notable difference in consciousness and anxiolysis. A calm, centred softness. Consciousness is becoming clear and slowly expansive again. Still struggling with my memory, eg ingraining things but we'll see how that goes. Normally I struggle with extreme perservation, feel "locked in" to loops, like I'm not in control, "driven" and akathisic. There feels like a liberating sense of me driving choice again. Even social interaction was a relatively normal experience without aberrant emotionality and odd stress responses 2. Lack of hunger and better sleep 3. Clean energy as needed and less inner mind chatter. Normally I feel heavy in body, mind and spirit but today I felt like having an unco grove to music to unwind a bit, just to loosen up a bit 4. A spiritual element. Feeling generally satisfied as I am with a clear horizon. Normally I'm on the chase for something... and then another thing. While I'm trying to put minimal kJ in, it's interesting being in a state where you're burning and using fats, either what you put in, or your own, for energy. Instead of spiking blood glucose, you can get a feel for different fats and their uses. MCTs are nice for a quick boost and adapting to ketosis [1] and the initial stage but soon enough, you want to be running on healthier fats. That said, MCTs are the 'crack of fats' increasing BHB in a linear, dose-dependent manner and increasing total brain energy metabolism by increasing ketone supply [2], having positive effects on verbal memory and processing speed in patients with impairments [3] and exerting anxiolytic and social effects [4]. Coconut oil may improve brain health by directly activating ketogenesis in astrocytes [5] and has beneficial effects on neuron survival [6] If you want an interesting combo, try a carnitine source with your longer chain fats. Long-chain fatty acids (LCFA) require L-carnitine as a transporter into the mitochondrial matrix, while the MCTs do not. While most patients do not require carnitine supplementation [7], Carnitine helps shuttle fatty acids across cell membranes to be oxidized by mitochondria, covering an important role in lipid metabolism, acting as an obligatory cofactor for β-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial membrane as acylcarnitine esters. Oleic acid sources do seem to curb hunger nicely. There is reduced food intake in an oleate-specific manner [8].There is a hypoglycemic effect of oleic acid and the probable dependence of glutathione [9] Watch out for saturated fats: these increase brain inflammation and activates the hypothalamic-pituitary-adrenal axis Dietary lecithin may increase the efficacy of omega-3 supplementation when their intake is combined [1] https://www.ncbi.nlm.nih.gov/pubmed/29951312 [2] https://www.ncbi.nlm.nih.gov/pubmed/29914035 [3] https://www.ncbi.nlm.nih.gov/pubmed/30367958 [4] https://www.ncbi.nlm.nih.gov/pubmed/29908242 [5] https://www.ncbi.nlm.nih.gov/pubmed/27430387 [6] https://www.ncbi.nlm.nih.gov/pubmed/28126466 [7] https://www.ncbi.nlm.nih.gov/pubmed/11879348 [8] https://www.ncbi.nlm.nih.gov/pubmed/27654062 [9] https://www.ncbi.nlm.nih.gov/pubmed/28214972
  11. Alchemica

    Ketosis as therapy

    What have I noted about running on low intakes of carbohydrates? I've been running low carbs. To the point most fruit sounded scary and I got very selective with fruits and anything carbs - occasionally a few chickpeas was my limit. I've only just started putting them back in significantly ie some brown rice - I don't have bread, cereal. pasta etc. I was very hesitant to start putting in significant carbs again as they do seem to significantly impact weight aspects for me but I was getting totally dysfunctional Why the sourpuss? Maybe it's your low carb diet In direct contrast to what advocates of low-carbohydrate diets promise—an end to mood swings and fatigue, low-carb diets can lead to pronounced feelings of depression and sadness, even rage. "People feel very angry, and their antidepressants don't work well, either" Low-carb diet may particularly have an adverse effect on those prone to low moods. “If you’ve cut our carbs and experience anxiety or depressive feelings as a result, you’re actually less likely to exercise, eat well and take care of yourself. "...the low-carbohydrate diet may have had detrimental effects on mood that, over the term of one year, negated any positive effects of weight loss" [1] Restricting carbohydrates could make it hard for you to fall and stay asleep. [2] As I mentioned in the sleep bit: Also, fasting blood glucose results have been persistently somewhat elevated causing concern. Can being low on carb intake paradoxically potentially do that kind of blood glucose dysregulation? It seems it can... “Why is my fasting blood glucose higher on low carb?” I hadn't heard of “adaptive glucose sparing” [3] My cognition was crap, probably from the months of sleep deprivation too. Persistent odd states of consciousness, too. Despite a growing body of clinical evidence suggesting that low-carbohydrate diets can be helpful for people with brain problems, including neurological, psychiatric, and cognitive disorders such as Alzheimer’s disease, a low-protein, high-carb diet may be an easier alternative to calorie restriction for people looking to preserve brain health and prevent cognitive decline [4]. These findings have been critiqued "There is a strong consensus that a diet rich in carbohydrates and fiber is crucial for brain health and Alzheimer's prevention." (along with associated fiber deficiencies also harm our guts and subsequently our microbiome, which can also pose negative long-term effects on the brain and incite brain fog, confusion, and even anxiety). ...the low-protein, high-carbohydrate diet appeared to promote hippocampal health and biology in the mice, on some measures to an even greater degree than those on the low-calorie diet [1] https://www.sciencedaily.com/releases/2009/11/091109173614.htm [2] https://www.livestrong.com/article/482729-i-cant-sleep-on-a-low-carb-diet/ [3] https://www.dietdoctor.com/low-carb/fasting-blood-glucose-higher [4] https://www.medicalnewstoday.com/articles/323772.php
  12. Alchemica

    Free Galphimia glauca

    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
  13. This plant was once of interest at the forums and on and off of interest to me but I've not heard much of people's positive experiences with it. If you have anything to share, feel free. Radix puerariae is one of the most widely used ancient traditional Chinese medicines and is also consumed as food. Kudzu is now considered for the treatment of many kinds of addictions, metabolic conditions, pain and for it's CNS therapeutic potential. The most abundant isoflavone of kudzu root is puerarin, but it also contains daidzein, daidzin and other isoflavones It selectively suppresses ethanol intake and inhibits mitochondrial aldehyde dehydrogenase (ALDH-2, an enzyme involved in serotonin (5-HT) and dopamine (DA) metabolism and alters monoamine levels. It "specifically targets unique drug related episodic surges in dopamine, a pathophysiologic mechanism that appears to underlie much of drug-seeking behaviour." [1] " a single dose of kudzu extract (active isoflavone content of 520mg) quickly reduces alcohol consumption in a binge drinking paradigm. These data add to the mounting clinical evidence that kudzu extract may be a safe and effective adjunctive pharmacotherapy for alcohol abuse and dependence. " [study] It's intriguing as puerarin is also a promising rapid-acting antidepressant compound through AMPAR-mTOR signaling pathway activation and increased BDNF [2], exerts anxiolytic-like effects, which may be "associated with normalisation of 5-HT levels and biosynthesis of allopregnanolone in brain" [3] and alleviated the behavioural deficits induced by chronic stress [4] and may be a "potentially valuable preventative therapeutics for memory-related nervous disorders" [5]. It also possibly acts through opioid system. Available evidence from animal models shows that antioxidant and antiapoptosis activities of puerarin protect neurons against damage in dementia and Parkinson's (partially prevents the chemically-induced DA neurodegeneration in mice and rats, and stimulates striatal GDNF) and puerarin has been shown to decrease the morbidity of ischemic stroke [6]. It is neuroprotective and there are therapeutic application of puerarin-related compounds in neurodegenerative diseases It has been called a "potentially valuable preventative therapeutic for brain disorders due to their abilities to promote the neuronal cytoarchitecture and the synaptic functionality" "The antidiabetes activity of puerarin includes reduced body weight gain, improved blood glucose control, and improved glucose tolerance. R. pueraria has been used to treat diabetes for thousands of years, and Puerarin can reduce blood sugar and increase insulin receptor sensitivity in patients with type 2 diabetes". - Acute administration of puerarin significantly improves glucose tolerance in animal models and is promising in humans: - Chronic kudzu root supplementation improves glycaemic control, insulin sensitivity in animal models Kudzu root in the diet in animals is associated with a decrease in fasting glucose and improvements in both glucose tolerance (oral glucose tolerance test) as well as insulin tolerance (indicative of insulin sensitivity) - Isoflavones act as antidiabetic agents [7] and decreased food intake and body weight gain [8] and Pueraria lobata could interfere with antipsychotic-associated insulin resistance and revert overexpressed IR-related proteins [9]' -Paradoxically, there is "evidence for the role of phytoestrogenic compounds in improvement of sexual function and testosterone production in male animals" These isoflavones have been linked to "significantly improved androgenic and sexual behaviour parameters. There was also an increase in serum concentration of FSH and improvement in serum testosterone level" [10] However, like other isoflavones, puerarin, kudzu and its other phytoestrogenic components act in part as selective estrogen receptor modulators displayed preferential affinity for ERβ and altered sperm parameters [11] There are hints that they may be negative as removing dietary isoflavones in adult male rats causes obesity and diabetes in some models [12] and long-term consumption of a diet rich in soy isoflavones can have marked influences on patterns of aggressive and social behaviour [13]. This is coupled with dysregulation of the HPG-axis and thyroid function Isoflavones definitely seem like a bad idea developmentally as they "...produced a delay on the onset of puberty and "at high doses of isoflavones ... prevent the stimulation of the secretion of pituitary hormones and the production of T abolishing the onset of puberty" [14] There is possible for interactions [15] [1] https://www.ncbi.nlm.nih.gov/pubmed/26022266 [2] https://www.ncbi.nlm.nih.gov/pubmed/30284466 [3] https://www.ncbi.nlm.nih.gov/pubmed/29101599 [4] https://www.ncbi.nlm.nih.gov/pubmed/28740098 [5] https://www.ncbi.nlm.nih.gov/pubmed/28734961 [6] https://www.ncbi.nlm.nih.gov/pubmed/30693344 [7] https://www.ncbi.nlm.nih.gov/pubmed/30958562 [8] https://www.ncbi.nlm.nih.gov/pubmed/30402623 [9] https://www.ncbi.nlm.nih.gov/pubmed/30946280 [10] https://www.ncbi.nlm.nih.gov/pubmed/24489512 [11] https://www.ncbi.nlm.nih.gov/pubmed/22278629 [12] https://www.ncbi.nlm.nih.gov/pubmed/27469930 [13] https://www.ncbi.nlm.nih.gov/pubmed/15053944 [14] https://www.ncbi.nlm.nih.gov/pubmed/30924551 [15] https://www.ncbi.nlm.nih.gov/pubmed/24710899
  14. Alchemica

    Free Galphimia glauca

    Did you have luck germinating this @Glaukus? As one of my first attempts with seeds, I may have been too hasty collecting seed. Revisiting this, from the latest study, it seems to be a rather cumulative effect, not so much acute effects. A gradual improvement was observed in GAD - 68.1% of the patients were completely asymptomatic at the end of the administration of the experimental treatment, and 92.0% of patients were considered with therapeutic success. It managed to progressively improve the activities of patients in daily life, as well as provide palpable improvements regarding their tranquility and their perception of anxiety and depression. https://www.ncbi.nlm.nih.gov/pubmed/30834253
  15. Alchemica

    Tagetes lucida

    First lots have been sent out and received with a couple of people trying the herb too. If they have any experiences with the plant feel free to let us know. Sorry to be a pain @Humbolt but I'm not comfortable sending to Tas/WA these days (thought I put that in but must have not) So @Paradoxical I'll send some seeds for you More on the plant: In traditional medicine, it has been said the herb "alleviates crazy people and those astonished and frightened by thunder". While a simple tea was claimed not to work, 2g dried and powdered, administered with juice was found effective, or a fresh alcohol tincture (Lazar, 2002 via The Garden of Eden) In other sources " The infusion of one bundle with water makes two to three cups of an aromatic tea, a sufficient dosage to produce profound stimulating and aphrodisiac effects" [1] It has featured in snuff blends "...the Tagetes herb clears thinking, relieves tension, aids emotional control" and a fermented tea, which is prepared the same way Sinicuichi (Heimia salicifolia) is prepared [2]. May have more seeds too soon
  16. Sprouts featuring in recent news Johns Hopkins Medicine researchers say they have further characterized a set of chemical imbalances in the brains of people with schizophrenia-related to the chemical glutamate. And they figured out how to tweak the level using a compound derived from broccoli sprouts. They say the results advance the hope that supplementing with broccoli sprout extract, which contains high levels of the chemical sulforaphane, may someday provide a way to lower the doses of traditional antipsychotic medicines needed to manage schizophrenia symptoms It’s possible that future studies could show sulforaphane to be a safe supplement to give people at risk of developing schizophrenia as a way to prevent, delay or blunt the onset of symptoms Further research is needed to learn whether sulforaphane can safely reduce symptoms of psychosis or hallucinations in people with schizophrenia. They would need to determine an optimal dose and see how long people must take it to observe an effect. ” https://neurosciencenews.com/broccoli-sprout-schizophrenia-13051/
  17. Some experiments trying to get better sleep, rough notes I kept while I was quite struggling so excuse the poor referencing, I'm still struggling getting sleep at times. I get some effects from Jujube/Zizyphus seed. It's worth a shot for people. Finally got around to trying some Jujube seed extract. Didn't get much from the fruits. I like it, initially I blended it with a bit of Ashwagandha. I don't get worthwhile kava effects anymore but this is quite nice at a decent dose. I'll likely use it for sleep (wasn't expecting it to be strong enough to consider using for sleep) It has been also traditionally used for psychiatric disorders in Chinese and Korean medicine. Traditionally, one of the main functions of jujube, as described in herbal medicine, is to benefit our brain by calming down the mind and improving quality of sleep. Jujube possesses neuroprotective activities, including protecting neuronal cells against neurotoxin stress, stimulating neuronal differentiation, increasing expression of neurotrophic factors, and promoting memory and learning. The plants secondary metabolites modulate GABAergic activity and the serotonergic system, interestingly the postsynaptic 5-HT1A receptors. Intriguingly, it exhibited significant effects on both the expression and activation of GABAA receptors. It improves memory impairment through BDNF/TrkB signaling and is suggested to have a protective effect against chronic depressive disorders The Zizyphus seed/hops/chamomile is nice, more chill than sleep for me but last night I added valerian and lemon balm. Once again, for someone who has severe GABAergic dysregulation/tolerance and sleep issues, it's quite anxiolytic but not so pronounced in it's sedative action for me. I'll get there eventually. "This clinical investigation on safety and effectiveness of a herbal compound made of valerian, hop, and jujube opens interesting perspectives on usage of herbal compound to manage primary insomnia." https://www.ncbi.nlm.nih.gov/pubmed/28603433 Explored some valerian by itself as a sleep aid for a bit. Once again, anxiolytic, not exactly sleep promoting for me. Added things like lemon balm etc. They're something you can tune to. Interestingly, the use of combined valerian and lemon balm phytomedicine extract provides a viable treatment option for hyperactivity, attention deficits, and impulsiveness, in addition to nutritional and lifestyle modifications Valeriana officinalis extract is a popular herbal medicine used for the treatment of anxiety and sleep disorders. The anxiolytic and sedative effects are mainly attributed to the modulation of GABAergic transmission but the selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant. Binding affinities could also be demonstrated at some of the screened melatonin (ML1 and ML2) and serotonin (5-HT4e, 5-HT6 and 5-HT7) receptor subtypes. A single oral dose of valerian modulates intracortical facilitatory circuits. While none of the valerian extracts displayed sedative effects, they did produce pronounced anxiolytic and antidepressant effects in one study. Valerian root extract may reduce emotional, physical, and behavioral symptoms of premenstrual syndrome. Its pharmacological activity may result from interactions among multiple constituents rather than any one compound or class of compounds. The primary active constituents include valerian’s essential oil and its corresponding sesquiterpenes (valerenic acid), the iridoid esters (valepotriates) Throughout history, lemon balm has been used medicinally to heal wounds, prevent and treat cold sores, soothe nerves, improve sleep, and strengthen the memory and the mind. The ancients are known to steep lemon balm in wine, a traditional medicinal dosage form, for fevers and to uplift the spirits. Lemon balm contains more than 100 chemicals including the flavonoids (quercitrin and rhamnocitrin), which have an antioxidant effect; phenolic acids and tannins, primarily rosmarinic acid; the 7-glucosides (apigenin, kaempferol, quercetin, and luteolin); caffeic and chlorogenic acids; triterpenes; and volatile oils citral a, citral b, (10%-30%), and citronellal (30%-40%) that render its lemony flavor and aroma. Some evidence indicates that valerian preparations may have a mechanism of action and clinical characteristics that differ from the benzodiazepine-related sedative/hypnotics, making them more suitable for long-term use. A one-time valerian 1600mg dose, often used to treat insomnia, does not appear to impair driving simulator performance after acute ingestion. How a few things impact at the EEG level: "Under diazepam the power in the theta frequency band decreased while it increased in the beta band. In contrast, some plant extracts showed an increase of power in the theta frequency band, but no increase in the beta frequency range. Valerian extract, which was administered in both studies, displayed an increase of power in the delta and theta band and a decrease in the beta band. Kava-kava preparation caused a decrease of relative alpha power in the vigilance controlled EEG. This effect was more pronounced 6 h than 2 h after drug administration. In a polygraphic sleep study two dosages of a Kava-kava preparation, given for one night, did not alter the sleep stage distribution significantly, while the sleep spindle density was increased.The most consistent single effect was a power increase in the theta band. Fronto-centrally a decrease in power in the high frequency beta band was also observed 180 minutes post administration Valerian Absolute power in the theta frequency band increased 120 minutes post administration Power increases were also observed in the neighbouring delta and alpha bands Total power remained unchanged under Lavandula extract 120 minutes post administration, and there were only very few changes in the different frequency bands. 180 minutes post administration total power decreased in the fronto-centrallead under RT and RS conditions. This power decrease could also be seen for absolute power in all frequency bands Total power increased 120 minutes post intake of Passiflora extract in the occipito-temporal lead. Other changes were essentially restricted to an increase in theta power 120 minutes post Lemon Balm administration total power increased fronto-centrally under resting conditions (RS). At this time point power increases were observed with a maximum in the delta, theta and slow alpha band occipitotemporally. For the fronto-central lead these power increases extended from the theta to the beta frequency band. Californian poppy: 120 minutes post administration absolute and relative power increased mainly in the theta and alpha frequency bands'"
  18. I've been revisiting this trying to improve sleep by changing macronutrient profiles a bit. I was finding restricting carbs with higher protein intake was seemingly messing with sleep even more. Dietary intake habits (affecting the state of nutrition) are perceived to be one of the factors predisposing, causing and consolidating sleeping disorders When it came to one study [1], two thirds of the subjects with sleep difficulties were characterised by an inappropriate state of nutrition. Sleep disorders could have been influenced by the low energy value of the subjects’ diets, as it has been shown that lowering the energy intake significantly decreases melatonin, a low intake of assimilative carbohydrates could have an influence on pinealocytes and the sleep-wake cycle. Similar results were seen in [2] where beans/carbohydrates and dairy were associated with improved sleep quality. "It was ascertained that, despite the insufficient energy value of the subjects’ diets, too much energy came from proteins [they] showed insufficient energy value, insufficient intake of assimilative carbohydrates, fibre, K, Ca, vitamin D3 and water with simultaneous excessive intake of Na, P, Fe, Zn, Cu and vitamins: A, B2 , B6, B12, PP, and C" Inbalanced intake of energy and nutritive value could have affected the proper synthesis of neurotransmitters regulating sleep-wake cycle and melatonin hormone. https://www.ncbi.nlm.nih.gov/pubmed/29265779 https://www.cureus.com/articles/16904-influence-of-dietary-intake-on-sleeping-patterns-of-medical-students
  19. Sounds good, hope the terpenes help - keep us updated! Sorry to hear you're being troubled with more struggles, that's no fair
  20. Saw this and thought of your post @FancyPants Protein Kinase C: Targets to Regenerate Brain Injuries? "Recent reports describe several non-tumorigenic diterpenes isolated from plants of the Euphorbia genus, which specifically modulate the activity of PKC isozymes promoting neurogenesis." There's lots of attempts to use pro-neurogenic plant compounds for example Ar-turmerone from turmeric essential oil Other molecules include: Eg TrkB (BDNF) 7,8-Dihydroxyflavone (Present in several plants such as Tridax procumbens L., Godmania aesculifolia (Kunth) Standl. and Primula sp. Huperzine A (Huperzia serrata (Thunb.) Deoxygedunin (Azadirachta indica A. Juss) Hyperforin (Hypericum perforatum L) and other polyphenols etc See more botanicals here Eg TrkA (NGF) β-caryophyllene Lion's mane etc GDNF Ibogaine β-Asarone (promotes expression of GDNF, BDNF, and CNTF genes)
  21. How do you modulate your serotonin system with dietary factors? I wanted to try and address persistent issues at the most fundamental dietary level possible - amino acids, vitamins. I tried some challenge doses with tyrosine and tryptophan and the later seemed to provide the most robust improvements. I keep on top of B-vitamins but assumed tryptophan in dietary protein was going to be enough... I've been abstinent from deleterious things for a long time now but it didn't mean health was improving. I couldn't shift a worsening phenotype of persistent emotional and mood dysregulation, cognitive decline, multiple night time awakenings and poor sleep quality, uncharacteristic uncontrollable verbal aggression (to the point of coprolalia), impulsiveness, intrusive thoughts, obsessiveness and plain dysphoria. SSRIs alone were not getting at the issue sufficiently. Diet, exercise and meaningful activity wasn't stopping the roller-coaster. Studies have found disturbances of tryptophan metabolism and their association with depression in alcoholics. Particularly, a decreased tryptophan ratio to other amino acids competing with tryptophan for brain entry has been investigated - diminished supply of tryptophan would lead to serotonin deficiency and thus contribute to depression in alcoholics Depressed alcoholics had significantly decreased ratios of plasma tryptophan to amino acids sharing with it the same transport carrier into the brain (tryptophan ratio). This ratio has been shown to predict the brain serotonin concentration. It is not presently known whether amino acid modifications disappear after a period of abstinence or persist [1]. Patients who had exhibited violent behavior were observed to have tryptophan ratios lower than patients with no history of violence. Research has demonstrated a robust response to increasing plasma Trp/LNAA ratio, stimulating a significant affective response. Unexpectedly Trp supplementation not only improved central serotonergic functioning but improved the profile of tryptophan metabolism [2]. [1] http://grantome.com/grant/NIH/R01-AA006510-02 [2] https://patentimages.storage.googleapis.com/50/94/8b/2fef42545c61d4/WO2005049012A2.pdf Using the amino acids is not just addressing pathology but providing some vital things: A source of believable hope, when things feel hopeless A source of day-to-day stability and connection to something when other sources of connection are non-existent or volatile A sense of being in control, when things feel out of control A secure quasi 'attachment relationship' to something when these might not elsewhere exist A safe displacement onto healthier behaviours for residual impulsivity and craving A placebo effect synergistic with added active effects. Placebo effects themselves can be potent medicine, as seen in many illnesses, from depression to Parkinson's. Sure it's better to find these things in other ways but it's often the most stable, permanent connection in times of illness and volatility one can find In recovery: “Glutaminergic-Dopaminergic Optimization Complex Therapy”, has been well-researched in many clinical trials and shown to provide gentle activation of dopamine across the brain reward circuitry in abstinence. Additionally, significant increases in resting state functional connectivity have been demonstrated in human and animal models using state of the art resting state fMRI measurements [1] Amino acid based therapies have led to: Improved Physical and BESS (behavioural, emotional, social and spiritual) Scores Reduced craving, relapse rates and enhanced recovery Stress reduction lead to improved sleep, enhanced energy, and improved focus and performance, reduced appetite, loss of unwanted weight, decreased body inches, and enhanced well-being Cognitive processing speeds were enhanced Significant results were observed for weight loss, sugar craving reduction, appetite suppression, snack reduction, reduction of late night eating, increased energy Research is needed regarding the potential for return of well-being in recovery by the gentle induction of “dopamine homeostasis;” balancing serotonergic, endorphinergic, cannabinergic, glutaminergic, dopaminergic mechanisms and restoring healthy brain function and connectivity. While I'm just using simple aminos and vitamins, one such version that has been extensively researched is KB220Z which is composed of the following ingredients: 10 mg (500%) vitamin B6, 15 mg (1,033% of daily value) thiamine, 200 mcg (166%) chromium poly nicotinate, and a fixed dose of synaptose. Synaptose is a combination of amino acids and herbs. The amino acids include L-tyrosine, DL-phenylalanine, L-glutamine, and 5-hydroxytryptophan. The herbs include passionflower extract and a complex containing astragalus, arabinogalactans, N-acetylglucosamine, aloe vera, white pine bark extract, frankincense resin, Spirulina, Rhodiola [1] https://dx.doi.org/10.1080%2F10826084.2016.1244551 What if the serotonergic dimension needs more urgent addressing? I tried L-methylfolate 15mg/day (+B12 1mg) with slight improvements for a short time, then also added some tryptophan [1] to the diet. A few days into adding the Trp and the coprolalia waned, emotional regulation started to return. I started to get malleable non-intrusive thinking again. Mood started to improve. See what happens longer term Folate for Depression, Schizophrenia and Dementia: Folate supplementation may be beneficial for severe mental health problems Folate deficiency seems to be an important contributor for the onset and progression of neuropsychiatric diseases [2]. L-methylfolate addresses hyperhomocysteinemia, lower methylation reactions and tetrahydrobiopterin levels [3]. Brain folate abnormalities causes diminished production and availability of tetrahydrobiopterin (BH4) which is a critical cofactor for the rate-limiting enzymes involved in the synthesis of the monoamine neurotransmitters and may be targeted by L-methylfolate. L-methylfolate should cause, in an over-simplistic framework: -Activation of tryptophan hydroxylase initiates a cascade that leads to the synthesis of serotonin, and -Activation of tyrosine hydroxylase initiates a cascade that leads to the synthesis of dopamine and norepinephrine [1] http://journals.sagepub.com/doi/abs/10.1177/0269881111430744 [2] https://www.ncbi.nlm.nih.gov/pubmed/25939915 [3] https://www.ncbi.nlm.nih.gov/pubmed/27068282 Why L-methylfolate? Many users find it quite effective - some users get quite rapid responses "Within 1 day, I felt like my internal motor that had been idling along at a 5 out of 10 had been turned up to a 10 for the first time in a long time. I had more energy, clearer thoughts, happier disposition..." "I felt better the first day. I feel like normal people feel. I have hope, motivation, freedom. I am completely happy." "Within just days of my first dose, I could fell a huge, positive difference. My mind and speech were clearer, my anxiety was nearly unrecognizable, and I was just plain happy." "...my lows vanished within first week on 15mg/day." "Within one week of taking L-methylfolate, I had absolutely NO anxiety. It was so quiet in my soul that I almost felt anxiety about not having anxiety! It was foreign to me; the steady drip, drip, drip of adrenalin rushing through my system was shut off." "Within 10 days, I felt more alive, motivated, energetic, and at peace then I had EVER felt in my life. " 15 mg eight days ago and I feel absolutely wonderful. Mood is great, anxiety has improved significantly, and I feel so peaceful. My energy level is up, and I feel hopeful and full of life again. I am so relieved and happy I could cry." I am able to finally really smile and laugh. I have not been able to find humor in things for years. I have more of a sense of well being I have more serenity I have an increased amount of time I feel better emotionally and mentally There is some support for the efficacy of both standard folic acid and L-methylfolate as an augmentation agent for depression [1]. The lowest dose of MTHF studied in depression to augment antidepressant treatment is 7.5 mg, roughly equivalent to 52 mg of folic acid. Synthesis of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine is regulated by L-methylfolate, which can cross the blood brain barrier. "Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs" [2]. It shows promise against negative symptoms in psychotic illness [3]. "Clinical improvement in depressed patients treated with an SSRI and l-methylfolate (0.5 to 1 mg) was 30 percent greater than that in matched patients treated with an SSRI only. A systematic review of controlled studies (total N = 247) concluded that folate augmentation (1 to 15 mg per day) enhanced the efficacy of conventional antidepressants." "Does folate supplementation relieve symptoms of depression? A ten-week trial of 127 participants compared 0.5 mg/day folic acid (standard folate) augmentation of fluoxetine to placebo augmentation, and found that folic acid significantly outperformed placebo in terms of treatment response rate (38% vs. 18%) and overall improvement on the Hamilton Depression Rating Scale. However, the advantages for folic acid were not seen until ten weeks into treatment. In a smaller trial, patients with depression or schizophrenia were given either 15 mg methylfolate (equivalent of 7.5 mg L-methylfolate) or placebo in addition to their existing medication regimen. Though hampered by a small sample size (24 depressed patients and 17 patients with schizophrenia), there was a statistically significant benefit on a general clinical outcome scale and there were trends toward a significant benefit on other outcome measures in the six-month study" Administration of MTHF may have significant advantages over administration of folic acid to augment antidepressants in depressed patients who do not respond adequately to their antidepressant treatment. Such patients may or may not be folate deficient, may or may not have the inefficient form of the genotype. "Biomarkers associated with inflammation or metabolism (higher BMI) and genomic markers associated with L-methylfolate synthesis and metabolism may identify patients with SSRI-resistant depression who are responsive to adjunctive therapy with L-methylfolate" [4]. "Patients with schizophrenia who take daily folic acid in the form of methylfolate 15 mg together with an antipsychotic may have fewer positive symptoms (e.g. hallucinations and delusions) and fewer negative psychotic symptoms (paucity of thought, social withdrawal) and may respond more rapidly" [5] [1] https://pro.psychcentral.com/l-methylfolate-for-depression-the-real-deal/ [2] https://www.ncbi.nlm.nih.gov/pubmed/23212058 [3] http://www.schizophreniaforum.org/news/l-methylfolate-shows-promise-against-negative-symptoms-schizophrenia [4] https://www.ncbi.nlm.nih.gov/pubmed/24813065 [5] https://www.psychologytoday.com/us/blog/integrative-mental-health-care/201709/folate-depression-schizophrenia-and-dementia Addressing homocysteine and potential B9/B12 deficiencies While I keep on top of B-vitamins generally... Stress can increase homocysteine levels (HCy). Higher levels of hostility were associated with higher levels of homocysteine [1]. People high in hostility are known to report more life stress, it is possible that homocysteine concentrations are elevated among these individuals due to increased stress [2]. Elevated levels of homocysteine have been associated with major depressive illness (and positively correlated with anger and length of depressive episode), bipolar disorder (both during manic and depressive episodes and in euthymic state) and various other mental conditions. "Studies of subjects with a wide range of cognitive functions showed increased plasma Hcy and decreased serum folate and enzymatic cofactors involved in methionine and Hcy metabolism are associated with the risk of cognitive dysfunction" Supplemental use of these vitamins has shown a slowing cognitive decline and also improvement in clinical status in patients with cognitive impairment, particularly in those with high baseline levels of serum Hcy [3]. A high circulating concentration of homocysteine has been implicated as a risk factor for Alzheimer's Disease and its prodromal stage, mild cognitive impairment. Cognitive and psychosocial impairment has been associated with increased levels of homocysteine [4]. While not a specific marker for schizophrenia, hyperhomocysteinemia occurred in our schizophrenia patients with poor social and relational functioning [5]. Elevations of serum homocysteine levels are a consistent finding in addictions. Hyperhomocysteinemia could enhance the substance consumption increasing the severity of craving in a circular self reinforcing mechanism. [6,7] MTHFR variants and smoking behaviour were associated with homocysteine plasma levels [8] Folate deficiency is associated with depression, attention issues, and other neuropsychiatric disorders, along with irritability and behavioural problems. Cerebral folate deficiency has been linked to self-injurious behaviour. In ASD, "In clinic I have certainly seen some very beneficial effects of using the active forms of folate in ASD" [9] Inflammation induced by by low folate concentrations can significantly be attenuated through treatment with appropriate supplementation and result in cognitive function improvement and decrease of peripheral inflammatory cytokine levels B12 deficiency has been "linked to agitation, irritability, negativism, confusion, disorientation, amnesia, impaired concentration and attention and insomnia; while psychiatric disorders that may be diagnosed in patients having vitamin B12 deficiency include depression, bipolar disorder, panic disorder, psychosis, phobias and dementia". B12 deficiency has presented in younger patients with “irritability, regressive behaviour, apathy, crying and truancy” [1] https://news.osu.edu/hostility-anger-linked-to-chemical-that-may-cause-heart-disease/ [2] https://www.ncbi.nlm.nih.gov/pubmed/14724053. [3] https://www.ncbi.nlm.nih.gov/pubmed/29936555 [4] https://www.ncbi.nlm.nih.gov/pubmed/29306698 [5] https://www.ncbi.nlm.nih.gov/pubmed/26017629 [6] https://www.ncbi.nlm.nih.gov/pubmed/28527647 [7] https://www.ncbi.nlm.nih.gov/pubmed/26885351 [8] https://www.ncbi.nlm.nih.gov/pubmed/23285280 [9] http://www.allnaturaladvantage.com.au/home/wp-content/uploads/2014/11/Cerebral-Folate-Deficiency.pdf Addressing serotonergic aspects The emotional dysregulation was intense. It seemed to be hypothetically a very 5-HT deficient state Both fear/terror and anger/rage are here further assumed to be low-serotonergic. Aggression has also been coupled to serotonergic deficit in many studies, supporting the placement of anger/rage on the low-serotonergic side A first approach would involve the administration of tryptophan and/or BH4. Lack of tryptophan in the diet has been linked to decreases in tissue tryptophan and in brain serotonin - changes in tryptophan availability have a direct impact on the rate of 5-HT synthesis Tryptophan enriched diets in animal models have led to increased prefrontal activation, these results seem to suggest that activation of the PFC could be related to a decrease in anxiety/diminishing amygdalar activity and to decrease in depression-related symptoms L-tryptophan has shown efficacy as an isolated substance in the treatment of depressed patients (it lifted the mood of participants and affected the function of brain regions known to be associated with mood regulation), addition of tryptophan to fluoxetine was associated with a greater improvement within the first week of treatment. It also lessened the fluoxetine-induced decrements in slow wave sleep. There were no cases of serious toxicity of the combination; it was very well tolerated overall [1]. Serotonin syndrome resulting from augmentation of antidepressants with L-tryptophan is ‘rare’ It has found use in OCD as an augmentation strategy [2] L-tryptophan was found to be a well tolerated and useful adjunct and standalone antidepressive agent in treatment-resistant unipolar depressed borderline personality disorder patients, with positive effects on sleep, suicidality and social engagement. [3] [1] https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/11022398/ [2] https://www.ncbi.nlm.nih.gov/pubmed/9393391 [3] https://www.sciencedirect.com/science/article/pii/S221296261500036X Trp as a dietary manipulation "Impulsive, violent and suicidal behaviours have repeatedly been shown to be associated with a reduction in serotonergic activity in the central nervous system. Tryptophan supplementation may be most effective in reducing aggression during times of stress. Tryptophan, an essential amino acid, is the dietary precursor to serotonin, and several lines of evidence have suggested that the amount of tryptophan in the diet relates closely to aggressive behavior. For example, rats given a diet almost lacking in tryptophan develop aggressive behavior In a group of depressed alcoholics, those with a history of aggression, including suicide attempts, also had the lowest tryptophan ratios When hospitalized male schizophrenics were given tryptophan, only those patients with high levels of hostility and a high lifetime frequency of aggressive incidents benefited; these patients showed a lessening of hostility and depression, a reduction in ward incidents and improvement on a standardized psychiatric rating scale." Note: A diet high in Trp, but with a large amount of LNAAs (leucine, isoleucine, tyrosine, phenylalanine, and valine), will not result in higher brain Trp levels, and may even decrease Trp uptake into the brain. An intervention rich in Trp relative to other LNAAs (including is needed in order to boost uptake of Trp, and consequently serotonin production, in the brain. It may be more difficult for the prefrontal cortex to control negative emotional responses that are generated within the amygdala under low serotonin, meaning Trp may help [1] Low tryptophan levels may significantly affect the mood and may contribute to anti-social, aggressive and impulsive behaviours [2] Tryptophan metabolism is disturbed in abstinence Experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50–60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression [3]. It has been claimed by some that simple dietary manipulation is not an effective method to increase brain Trp and 5-HT. The effect of an SSRI on extracellular 5-HT are dependent on the nutritional availability of Trp. Moreover, increased availability of TRP affects behaviour in a manner similar to SSRI administration. While caution is advised, it's being explored as an augmentation strategy [4] "...nutritional factors play an important role in the biosynthesis of 5-HT. Increasing 5-HT levels by increasing the availability of TRP might augment the therapeutic efficacy of SSRIs, whereas malnutrition may render patients refractory to SSRI treatment.” Studies suggest long-term effects of dietary Trp on stress responsiveness Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation in OCD. "Successful selective serotonin reuptake inhibitor treatment of obsessive-compulsive disorder may involve the ability of serotonin to switch habitual responding to goal-directed behaviour." and it has been proposed tryptophan or 5-HTP may augment the effectiveness of antidepressants. Trp supplementation seems to improve control over social behaviour in patients and individuals suffering from disorders or behaviours associated with dysfunctions in serotonergic functioning - in healthy humans supplementation seems to promote social behaviour [5]. Review: Effects of tryptophan loading on human cognition, mood, and sleep [1] https://www.cam.ac.uk/research/news/serotonin-levels-affect-the-brain’s-response-to-anger [2] https://www.salubrainous.com/tryptophan-for-alcoholism/ [3] https://www.sciencedirect.com/science/article/pii/S0165032705000182 [4] https://link.springer.com/article/10.1007/s00213-003-1632-6 [5] https://doi.org/10.1016/j.neubiorev.2016.02.022 Part of the fun with effectively bolstering serotonergic activity is that positive beliefs come on line (or feel positively amendable), what were heavy cognitive self-referential processes taper down there's a socio-emotional dimension that comes on line and cognitive/behavioural flexibility bolsters. Studies show that the relationship between the activation of serotonin and subsequent behaviour is highly dependent on the belief about the circumstances [1] Self-referential processing is a key cognitive process, associated with the serotonergic system and the default mode network (DMN). "Typically, depressed individuals endorse more negative adjectives as self-referential than non-depressed individuals. This bias in self-referential processing is also present in individuals who have remitted depression, suggesting that negative cognitive biases persist even when symptoms are no longer evident." "Analytical self-focused rumination (thinking analytically about self and symptoms) is maladaptive - This cognitive style is associated with overgeneral autobiographical memory, global negative self-judgments, greater negative future thinking, and dysphoria." It appears to reflect DMN connectivity which can be modulated by TRP [3] [1] https://www.eurekalert.org/pub_releases/2018-06/oios-wfi053018.php [2] https://www.sciencedirect.com/science/article/pii/S016801021002835X There are a few 'side effects' to Trp While "involvement of 5-HT in rewarding and aversive processing, hedonic experience, mood and higher cognitive functions such as consciousness or self reflection are undisputed" and there seems to be a good level of "contentedness" and mood/emotional regulation... Manipulations of serotonergic tone affect reward [1] and decision making [2]. Depleted states cause one to be significantly more perseverative over choices and acutely significantly less sensitive to reward (lower reward magnitude) For me, the impulsive reward chasing loops start to seemingly undergo some changes (serotonin has been proposed as a possible encoder of reward and facilitator of reward extinction): you go from impulsive action to greater conscious choice but it doesn't feel as rewarding to do things. It's a little blunting. So those healthy addictions, for me gardening and daily walking, start to feel more effort-driven than impulse driven and require more effort in. If you're not careful, you can become content with inaction. Depletion of 5-HT enhances behavioural and brain responsiveness to aversive signals, while disinhibiting previously rewarded but now aversive behaviours. [3] You start to seemingly have a layer of higher order self-reflection come in. You want better choices. It has been proposed "5-HT encodes beneficialness, and may signal motivation to either maintain or switch current behaviour, for example displayed by 5-HT’s role in facilitating patience for future rewards" [1] https://www.frontiersin.org/articles/10.3389/fnhum.2017.00484/full [2] http://www.jneurosci.org/content/32/17/5833 [3] https://www.ncbi.nlm.nih.gov/pubmed/18069045
  22. Good point @Kindness. Probably quite messed up... Have been seeing what a *little* bit more carbs in the diet does, seems to be one part of the problem, potentially contributing to the shocking sleep quality and waking up 2am every morning... I went quite restrictive on carbs and a lot of people seem to find such messes with their sleep, potentially in part through the influence on 5-HT I've noted how socially modulated it is. The brain state caused by prolonged social isolation seems to involve neuropeptides
  23. I've been struggling with really 'jagged' cognition which makes it super hard to focus which messes up the mood as a consequence. Trying more dietary stuff One is some frequent culinary-medicinal shrooms. I've tried lots of Lion's mane, Reishi, Cordyceps etc but not more widely used culinary mushrooms apart from Oyster (and a little bit of Porchini). Made a big batch of Shiitake (Lentinula edodes) and Oyster (Pleurotus ostreatus) and King oyster mushroom (Pleurotus eryngii) with my homegrown Reishi soup. Seaweed'd it up with the kale which was nice and made it extra shroomy Culinary-medicinal mushrooms may be developed as safe and healthy dietary supplements for brain and cognitive health Mushrooms offer great potential because of the complexity of their chemical contents and different varieties of bioactivities. Available evidence suggests that mushrooms exhibit anti-oxidant, anti-tumor, anti-virus, anti-cancer, anti-inflammatory, immune modulating, anti-microbial, and anti-diabetic activities These mushrooms are known to contain ergothioneine: shiitake, oyster, king oyster or maitake (hen of the woods) can contain up to 13mg in a 3-ounce serving compared to the 5 milligrams in common mushrooms. Ergothioneine may promote neuronal differentiation and alleviate symptoms of depression at plausibly achieved level of daily ingestion [1]. Other findings provide scientific evidence to support the use of Pleurotus ostreatus as a safe and effective mushroom to prevent and treat Alzheimer's disease through the polysaccharides [2]. [1] https://www.ncbi.nlm.nih.gov/pubmed/27134772 [2] https://www.ncbi.nlm.nih.gov/pubmed/27498414 Eating mushrooms may reduce the risk of cognitive decline: https://www.sciencedaily.com/releas…/2019/…/190312103702.htm Trying a few days on some simple rosemary tea over the weekend which I enjoy every now and then. It's one it's easy to dismiss Data suggest potential beneficial properties of acute consumption of rosemary water in humans [1]. Rosemary tea administration exerts anxiolytic and antidepressant effects in mice and inhibits cholinesterase activity [2] "The presence of 1,8-cineole and rosmarinic acid and the absorption of these (and other) compounds may facilitate performance through cholinergic pathways. Serum levels of 1,8-cineole have previously been demonstrated to correlate with task performance following exposure to rosemary aroma." Rosemary polyphenols cause the regulation of several neurotransmitters (dopamine, norepinephrine, serotonin and acetylcholine) and gene expression [3] while the volatiles activate the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production [4] Carnosic acid and carnosol, which are major components of the rosemary extract, were able to promote markedly enhanced synthesis of NGF [5] Also incorporating more 'culinary' sage Sage (Salvia) species effects have been considered and found effective in a range of population groups [6]. A double-blind, placebo-controlled crossover trial involving 30 healthy volunteers found it led to improved ratings in mood post-dose, with the lower dose reducing anxiety (300mg) and the higher dose increasing ‘alertness’, ‘calmness’ and ‘contentedness’ (600mg) Improvements in mood (e.g. alertness, contentedness, and calmness) and cognition were also identified following the single administration of a S. officinalis extract to healthy young adults. The extract was associated with significant enhancement of secondary memory performance at all testing times. The same measure benefited to a lesser extent from other doses. There also were significant improvements to accuracy of attention following the 333-mg dose. In vitro analysis confirmed cholinesterase inhibiting properties for the extract [1] https://www.ncbi.nlm.nih.gov/pubmed/30318972 [2] https://www.ncbi.nlm.nih.gov/pubmed/25910439 [3] https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(12)00657-2 [4] https://www.ncbi.nlm.nih.gov/pubmed/29273038 [5] https://www.ncbi.nlm.nih.gov/pubmed/14600414 [6] https://www.ncbi.nlm.nih.gov/pubmed/27888449 Made Ginkgo pesto from the season's leaves. It's a really nice way to have the stuff Various preclinical and clinical studies have shown a positive effect of Ginkgo biloba to improve cognitive abilities in impaired individuals and reducing anxiety under pathological conditions [1] G. biloba is an effective complementary treatment for ADHD [2] It had a significant difference in ameliorating total and negative symptoms of chronic schizophrenia as an adjuvant therapy to antipsychotics [3]. [1] https://www.ncbi.nlm.nih.gov/pubmed/27908257 [2] https://www.ncbi.nlm.nih.gov/pubmed/25925875 [3] https://www.ncbi.nlm.nih.gov/pubmed/25980333 And keeping the diet diverse I feel you often can't put all your eggs in one basket "___ will effectively fix ___" etc. It's easy to get hyped up about one particular option, float on the wings of expectation, then crash and burn. When you're really mixing it up, I feel the magic starts to come alive. Just like we see in the diet, if you eat the same food all the time, it simply doesn't work and it can easily be detrimental - healthy dietary diversity scores correlate strongly with depression and anxiety in studies. When dealing with healing plants, particularly those used as food, why is it not the same? Often we're tempted to say something will fix something etc and run with it exclusively as a therapeutic. In my experiences, not to discount individual healing potentials, they could be better mixed up in a diverse phytochemical rich diet than using it as a standalone in a more lackluster diet? Today my sprout jar is packed with ready Radish and Broccoli again Yesterday, made Ginkgo pesto with the season's leaves. Along with some Ginkgo, had a Rosemary and Savory tea. Few mixed berries. Have different sprouts with the Ginkgo pesto, which tastes surprisingly nice, also put it on some steamed kale an Roselle leaf with dinner The day before it was a Hibiscus, raspberry, blueberry and citrus peel chia pod. Mistletoe. Green tea The day before a pomegranate session with other healthy additions. Lots of sprouts Unfortunately the "therapeutic merits" of plants and natural products is also propelled by commercial interest so it's easy to buy into that and think one plant is a magic elixir. That's not to say they're not often effective therapeutics but there are strong vested interests Take for example, blueberry research literally funded by Big Blueberry The latest spearmint research for cognition carried out on a propriety blend of a special, patented "high rosmarinic acid" type of Spearmint Ginkgo propelled by trials utilising patented, standardised extracts Saffron research occurring in Iran through government funding, seemingly with the hopes of fortifying the value of their "red gold" etc etc I was one who bought into the promises of Big Blueberry and used them as my almost exclusive fruit... That said, based on the current evidence, a recent review of the available evidence found "blueberries may improve some measures of cognitive performance when consumed for up to six months in duration" [1]. Take for example a variety of fruits are finding therapeutic merit Blueberry, strawberry, pomegranate, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired animal models. Published trials of the benefits of blueberry [2,3], pomegranate [4], grape [5.6,7], flavonoid rich orange [8,9,10] in the treatment of small numbers of cognitively impaired and healthy populations, including on mood, have recently appeared. Some we hear little of - eg raspberries. The health-promoting potential of red raspberries includes modulating metabolic disease risk, especially cardiovascular disease, diabetes mellitus, obesity, and neurodegenerative disorders—all of which share critical metabolic, oxidative, and inflammatory links They contain a unique profile of anthocyanins and ellagitannins (with effects via ellagic acid). Red raspberries contain ~92.1 ± 19.7 mg anthocyanins/100 g of fresh fruit [11] Really it seems they are best used as healthy additions to a balanced, varied diet, not trying to carry so much therapeutic weight on their own? That said, I try to avoid the more carbohydrate dense options a bit [1] https://www.ncbi.nlm.nih.gov/pubmed/30999017 [2] https://www.ncbi.nlm.nih.gov/pubmed/28230732 [3] https://www.ncbi.nlm.nih.gov/pubmed/29882843 [4] https://www.ncbi.nlm.nih.gov/pubmed/23970941 [5] https://www.ncbi.nlm.nih.gov/pubmed/22468945 [6] https://www.ncbi.nlm.nih.gov/pubmed/28429081 [7] https://www.ncbi.nlm.nih.gov/pubmed/26864371 [8] https://www.ncbi.nlm.nih.gov/pubmed/28091350 ' [9] https://www.ncbi.nlm.nih.gov/pubmed/26280945 [10] https://www.ncbi.nlm.nih.gov/pubmed/25733635 [11] https://academic.oup.com/advances/article/7/1/44/4524046
  24. Comprehensive review on the interaction between natural compounds and brain receptors: Benefits and toxicity [sci-hub] In case anyone wanted things to add to their bucket list... or needed a natural product for that receptor... Includes: Natural products interacting with nicotinic nAChR and with mAChR. Natural products interacting with ionotropic and metabotropic glutamate receptors. Natural products interacting with γ-Aminobutyric acid type A receptors (GABAAR). Natural products interacting with cannabinoid (CBR) type 1 (CB1R) and type 2 (CB2R) receptors Natural products interacting with dopamine receptors (DAR). Natural products that act on insulin receptors and insulin-like growth factor receptors (IGFRs). Natural products acting on receptors for advanced glycation end-product receptors (RAGE). Natural products interacting with receptors associated with neurotrophic factors (NTF). Natural products that interact with immune system receptors. Natural products that interact with the scavenger receptors associated with oxidative stress. Natural products that interact with peroxisome proliferator-activated receptors (PPAR) Natural products that interact with ApoE or LDL receptors.
  25. Having a proper read through the tables, a little disappointed. One that stood out to me was 3',4',5',5,6,7-hexamethoxyflavone (Eremophila debilis) Flavonoid Binding activity to M1 mAChRs "The aerial parts of the endemic Australian plant Eremophila debilis (Myoporaceae) contain 3% dry weight of the biologically active 5,6,7,3',4',5'-hexamethoxyflavone" [1] I'd in the past experimented with some different Eremophilas (longifolia etc) thinking it might be phenylpropanoid EOs making it such a respected bush medicine. This adds an interesting aspect - a flavonoid muscarinic.
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