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Alchemica

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Everything posted by Alchemica

  1. Thanks for sharing. I'm not sure how a combination of plants simply targeting specific targets, often with multifaceted phytochemicals, that target many different pathways would go? I'd be personally more inclined to look at what is being used in preclinical models, or clinically with success for different conditions. That said, inosine is a potential disease-modifying therapy for MS, Salvia miltiorrhiza has some promise for cerebrovascular and brain conditions eg stroke recovery. To me, it's a lot of guessing to come up with a formula for neural repair that's going to help people with a diverse range of conditions
  2. Alchemica

    Ashwagandha free seed etc

    If anyone is interested, I have quite a bit of ripe fruit if you want to grow it etc. Harvested quite a few plants yesterday Can throw in a few other seeds: Calendula, Pyrethrum, Feverfew, Chamomile, Romanesco broccoli, have plenty of Milly's morning glory mix too While the fruit can cause GI distress consumed in large quantities, the withanamides, the primary active constituents in W. somnifera fruit extract exhibited neuroprotective effects. They may improve antioxidant status and reduce proinflammatory markers.These compounds may work to prevent Alzheimer's disease at the onset, and it also could prevent its progression [1]. This research was once heralded as a major step forward as there is nothing on the market that slows the progression of Alzheimer's. Can't find anything on how this research has progressed unfortunately. The patent extends to use for mood [2] [1] https://www.sciencedaily.com/releases/2015/03/150311124643.htm [2] https://patents.google.com/patent/CA2538905C Also can help out with leaf for research purposes. While it's less used than the root (and some seem to aim to avoid the withaferin-A), I've found it a nice enough medicinal tea and others use it similarly. The neuroprotective leaf and fruit constituents affect cortical muscarinic acetylcholine (including M1/M2 mAChRs) and neurotrophins, which may partly explain it's cognition-enhancing effect. The leaves possess higher content of active withanolides, Withaferin-A and Withanone, as compared to the roots [1]. Nootropic and CNS therapeutic properties of the leaf have been claimed [2]. Withaferin-A is a potent leptin sensitiser with additional antidiabetic actions and resulted in a 20-25% reduction of body weight in overweight mice [3]. It improves insulin sensitivity [4]. Anti-neuroinflammatory properties have been ascribed to the leaf [5] along with neuroprotective properties [6] Withaferin-A shows anti-neuroinflammatory [7] anti-Aβ properties [8] and dopamine-restoring [9] properties. Improvement of cognitive dysfunction has been ascribed to Withanone [10] including inhibition of AChE, anti-Aβ, protection against oxidative stress and anti-inflammatory effects. Many toxicological studies have demonstrated that Ashwagandha, in its reasonable dose, is a non-toxic, safe and edible herb - despite that, there is sometimes movement away from the cytotoxic constituents towards root extracts which may be less effective [1] https://www.ncbi.nlm.nih.gov/pubmed/27936030 [2] https://www.ncbi.nlm.nih.gov/pubmed/26361721 [3] https://www.ncbi.nlm.nih.gov/pubmed/27479085 [4] https://www.ncbi.nlm.nih.gov/pubmed/30417321 [5] https://www.ncbi.nlm.nih.gov/pubmed/27550017 [6] https://www.ncbi.nlm.nih.gov/pubmed/25789768 [7] https://www.ncbi.nlm.nih.gov/pubmed/26266054 [8] https://www.ncbi.nlm.nih.gov/pubmed/30356847 [9] https://www.ncbi.nlm.nih.gov/pubmed/30544122 [10] https://www.ncbi.nlm.nih.gov/pubmed/29108796
  3. Alchemica

    Passiflora to help a friend

    There was an interesting study done on how different people respond to this medicine In chronic illness, what type of person are you, does it alter how you respond to a herbal medicine? Patients' experiences attributed to the use of Passiflora incarnata: A qualitative, phenomenological study While results of studies point to the effectiveness of the therapeutic use of Passiflora incarnata for nervous restlessness, generalized anxiety disorder, insomnia, attention-deficit hyperactivity disorder, presurgery anxiety and menopausal symptoms, does it matter how you approach the medicine? There seems to be a fundamental aspect in responders: resetting of priorities in life and the new focus on personal growth Do you have a high degree of interest in personal growth and in overcoming your illness (Type 1), or more resigned to your condition (Type 2/3)? Do you try and maintain performance orientation (Type 2) "Type 1 patients reported that their chronic illness and its ailments led them to reset their priorities and to make more room for mindfulness and self care in their lives" Do you reset the priorities in your life (Type 1) or not (Type 2/3) All groups reported that they were frequently "overwhelmed by their daily life", constantly "chewing over everything" and "finding it difficult to distance themselves from overthinking" Interestingly, Type 1 have the best responses to a herbal medicine like Passiflora. Type 3 "did not experience something specific that they related to the use of Passiflora incarnata". Type 2 had some level of calmness. Type 1 patients attained "calmness" while using Passiflora incarnata. Moreover, they reported having a "better foundation" and "being more centered". With Passiflora incarnata,they thought that they were generally better able to "let things go" and felt more "patient" and "calm". "Passiflora, I feel, is providing me with a better foundation for these changes that have come about or that have started. I feel that I am on different ground here, that my new steps on this different ground are somehow more solid. That is, I am not perpetually racking my brain anymore. Therefore, I am not that unstable any more...in everything. That is what I identify with Passiflora." I was able "to take a step back and look at things" now "In the past, I was lived, but now I am living" I suffer "less from anxiety" with Passiflora incarnata. I am surprised that my anxiety "almost does not exist anymore" http://sci-hub.tw/10.1016/j.jep.2018.11.022
  4. Alchemica

    Passiflora to help a friend

    Passiflora incarnata has a really low beta-carboline content and hence the MAOI effect from such, if that's what you're seeking, is likely not relevant at typical doses. There does seem to be a more noted putative GABAergic component through the flavonoids - that's what I'd be more worried about interacting with the alcohol eg. potentiation (possibly also leading to disinhibition and even more drinking). I don't mind it as a mild mental health tool It's a nice enough plant to use but generally mild for someone used to 'intoxication' and probably with a baseline of some mental distress etc. I used to frequently brew up solid (25g) doses but eventually settled on a blend like lemon balm, chamomile and passionflower as more a subtler calm tea at more typical doses. Some people I know who had more typical brains found it sedating at much lower doses. For me, it was mainly a way of displacing drinking/craving onto something healthier but you can bring an emotional/spiritual level to any tea through a more ceremonial aspect and use it as an exercise in mindfulness. I looked for emotion-enhancing plants, that's one aspect I also liked to self-medicate. Thing is, the more you seek something external to enhance/modulate emotions, the worse things can get and the longer they'll likely persist. I ended up super, extra dysregulated through seeking 'emotional improvements' through even mild plants too often. The mere act of some novelty and hope can drive quite a potent - and at times healing - placebo response. If the expectation 'taking something' will help improve the emotional world of this person exists, it's quite likely there will be some of that with any option, just the belief can be powerful. It's worth utilising that belief in oneself and the mildest options available to drive a beneficial response IMO. Lately, I've come to see it's more shifting actions - doing - positively that can drive a better emotional landscape. If you can, get your friend growing some herbal plant allies, relating to them, nurturing them, crafting medicine/cooking with them etc more than taking them. Derive an emotional relationship with the plant more holistically, more so than seeking an emotional outcome of consuming a plant I wouldn't say discount some herbs like Passiflora as options, I would try to limit alcohol with it and start low Even something like Ashwagandha could be useful. It's one that seems quite promising for such things. Can send some seeds if you get interested.
  5. 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
  6. Alchemica

    Ketosis as therapy

    I stuck with a very low carb very keto-like diet, it was good for weight loss but I was so anhedonic... I'd dropped 10kg, my pants were falling off and I felt absolutely no sense of personal reward. Just warning you.
  7. Alchemica

    Milly's Seeds of Love

    Milly was the Morning Glory of My Heart. Today I harvested 'Milly Seeds of Love'. If anyone would like to get close to Milly in spirit and would like some 'Milly seeds', I'll try and send you some. Just to a couple of people to start with, send soonish but need to not rush. No cost. They're a hardy pink Morning Glory, or if you prefer, a Native Convolvulus angustissimus. In loving memory of this beautiful Soul.
  8. Alchemica

    Milly's Seeds of Love

    Milly came to visit a few of us... It was lovely to see some pics of Milly's morning glory flowering for someone else. Coming up to her Birthday, instead of celebrating it with her I'll offer some of this year's morning glory seeds complimentary I have some Milly's lucky mix now and there will be more soon - my vines intertwined so it's a mix, surprise yourself with what comes up! Also a small amount that is Carnevale di Venezia Also have some Grandpa Ott that I grew separately. A few people can put themselves on the waiting list (just has to fully dry) Shoot me a message.
  9. What's the opposite of addiction? Like to hear your views. Addictions are real shape-shifters. You can easily just shift between substance <-> behavioural etc and stay in loops To me, the addictive mindset reflects in things like: Suffering vs Acceptance and Growth Consumption vs Creativity Filling voids vs Creating connecting bonds To me, the most important thing has been trying to re-instate "I'm OK, you're OK". The feeling you're fundamentally OK and worthy, not wounded and different. That the world out there is OK too. You're OK. That interactions can be enjoyable. A feeling of engaging in a reciprocal interaction through simple love, connection and presence In that stance, you can engage with the world healthily, not as a wounded person filling voids. You can embrace yourself in your totality as being "you" as a worthwhile person. The world around you as being worth interacting with. Is it really connection? Some of my most disheartening experiences have been in trying to connect with humans. You can be surrounded by loving people and be miserable trying to connect with them. We promote that people need to connect socially to the point some even say "the opposite of addiction is connection". We even often promote people connect with outer God(s) to heal. Through such an attitude, you induce a state where you're easily not within yourself enough... and when you're struggling with wounds within, at the mercy of social connections. I saw how transient/volatile and impermanent the connections you could seek were. And how there were so many unhealthy things to connect to... and how you could chase more and more connections to fill wounded parts within and how trying to connect from a place of deficiency is really unhealthy. You become heavily dependent on connections. "Being alone feels like a problem that needs to be solved. And so people try to solve it by connecting. But here, connection is more like a symptom than a cure. It expresses, but it doesn't solve, an underlying problem. But more than a symptom, constant connection is changing the way people think of themselves. It's shaping a new way of being. You end up isolated if you don't cultivate the capacity for solitude, the ability to be separate, to gather yourself. Solitude is where you find yourself so that you can reach out to other people and form real attachments. When we don't have the capacity for solitude, we turn to other people in order to feel less anxious or in order to feel alive. When this happens, we're not able to appreciate who they are. It's as though we're using them as spare parts to support our fragile sense of self. We slip into thinking that always being connected is going to make us feel less alone. But we're at risk, because actually it's the opposite that's true. If we're not able to be alone, we're going to be more lonely." - Sherry Turkle "Why the pain?" What if we really need to take a step back from the outer world and sit with something within, "why the pain"? Be enough through our pain? You cant go into the suffering with the victim or deficiency mindsets or that will simply consume you with deeper and deeper suffering. When you feel deficient, you set the stage for a hungry ghost where you fill your inner voids of unhappiness and feelings of unwholeness in a multitude of unhealthy ways. While there's a hole you're filling you'll stay in a loop of more and more. We're taught we aren't enough, that there's something wrong with us. That's amplified by stigma and social exclusion. The more we believe that, the more it becomes a self-fulfilling prophecy. You shrink further and further and fill that place of 'not being enough' with external things, slide into unhealthier and unhealthier ways You stay in deficiency states and poor ability to delay rewards or sit with discomfort - you're permanently on the chase for something to fill a feeling of unworth, poor-self esteem, isolation etc. It's common in every aspect of our society from feeling we 'need a partner' to be complete, to deriving our worth by external things, to 'there's something wrong with you' to every aspect of our life. It's something heavily ingrained in our society that keeps us relentless consumers, often of things that aren't healthy for us, or more than we need. What if you start to think and feel, yeah - I'm hurting and wounded but everything I need to transform that pain is in me. You start to fill the voids from the inside in sustainable and healthy ways? Not saying you don't reach out for help when needed but "you are enough"? If you rely on external things filling those voids, you neglect the impermanence of life. Social settings change, things that provide hope/meaning/purpose can become easily unstable, you're totally on a collision course with going backwards if anything even slightly changes. You live in dependency of being filled from the outside through connections to tackle a fundamental state of inner deficiency What happens when you stop that chase for connections with the outer and instead connect with the wounded parts that feel like they're not enough? You can convince yourself your caring for yourself and you're in self-love but you really need extreme self-compassion. The pain/trauma, shame, the isolation, the anger etc? When we sit with them and transform our inner relationship with them until they're no longer voids of suffering, rather places we feel whole again? That takes acceptance, going into pain and allowing things to transform... I'm not saying you as a stand-alone unit are the complete perfect existence and you don't need to go beyond yourself but "you are enough". "You are enough does not mean that you are a final product, complete and finished, all done growing and changing and learning things" You can get off the constant striving and be OK. You can sit with wholeness of self-care, self-kindness, self-compassion, self-acceptance and self-transformation, self-love etc as a unit of wholeness within yourself. As you take on those traits for yourself, you gain the ability to radiate the same to others.
  10. Alchemica

    Ketosis as therapy

    Thanks for sharing @thegreenriviera One thing about diet changes is you can see how things affect you. Going very minimalistic with food made me see how simple/easily neglected things were driving mood states. One interesting thing is that through a relatively short period of depriving yourself a bit of food, I got a clean slate, not perma-impulsive hunger, to work with. You start to respect how things that you normally dismiss as driving mood changes do play a big role. It's like a nice reset and chance to see how the basics are driving symptoms. I've escaped carbohydrate cravings by eliminating them for awhile and interestingly they haven't returned to crippling levels. A few interesting things I noted: 1. How much those fluctuations in blood sugar do destabilise your mood, change your cognition and how cutting out/reducing/playing with low GI carbs is quite useful just to see how it impacts you 2. Potentially how much changes in electrolytes drive mood changes. I've always supplemented things like calcium/magnesium but overlooked sodium and potassium as driving mood states. 3. How nice a quality planty diet can be for sustained clean sustenance 4. How different fat sources feel and likewise proteins 5. What it's like to experience different states of ketosis Dietary electrolytes are related to mood At the moment, I'm quite interested in what simple electrolytes do for mood and symptoms. For both males and females it is recommended to keep sodium intake below 2,000 mg. Potassium recommendation for males and females are 4,700 mg per day. Magnesium intake for males should be between 330-350 mg per day, and females should intake about 255-265 mg per day. Calcium suggested intake is 800 mg per day for both males and females. Other factors: Dietary patterns seem important in severe mental illness [1] and have in some populations been associated with things like depression, stress and social support satisfaction [2]. Four-Week Supplementation in healthy individuals with a multi-vitamin/mineral preparation treatment was "associated with significantly improved mood, as measured by reduced scores on the "depression-dejection" subscale of the Profile of Mood States" [3] Individual vitamins: Vitamin A: There is a longstanding notion that vitamin A plays a role in psychiatric illness likely based on the profound effects of retinoids on brain development and processes such as long-term potentiation (LTP) and mood regulation. Proposed to be a player and therapeutic in ASD: "supplementation is a reasonable therapy at least for a subset of children with autism" [4]. Vitamin B-group: Thiamine (B1): Exerts antidepressant/anti-stress effects in animal models [5] and improved standard treatment in patients with depression [6] In a small study, thiamine supplementation significantly improved anxiety scores, general well-being and reduced fatigue in patients with Generalised Anxiety Disorder [7] "An improvement in thiamine status was associated with reports of being more clearheaded, composed and energetic. These influences took place in subjects whose thiamine status, according to the traditional criterion, was adequate." [8] Not much has been done on B2 and B3 in psychiatry but they are proposed to play a role. A recent animal study suggests that B2 or B6 vitamins restored the levels of DA and reduced oxidative stress in brain [9] B6: Inadequate amounts of vitamins B6 is linked with a higher incidence of depression and impaired neurotransmitter synthesis. It is proposed to be an effective therapeutic for some women (along with combinations) [10]. Improved attentional performance in males was significantly correlated with increased levels of vitamin B6 B12: Insufficient vitamin B12 status has been linked to poor neurodevelopment and cognitive decline. A significant improvement in depressive symptoms was observed after SSRI and vitamin B12 therapy in one study [11] Folate: see https://www.psychologytoday.com/us/blog/integrative-mental-health-care/201709/folate-depression-schizophrenia-and-dementia Vitamin C: adding vitamin C alone to citalopram did not increase the efficacy of citalopram in MDD patients [12]. That said, in animal models it exerts antidepressant effects dependent on the activation of the opioid system, especially µ-opioid receptors, which might be an indirect consequence of NMDA receptor inhibition elicited by ascorbic acid administration. It may involve an activation of GABAA receptors and a possible inhibition of GABAB receptors, similarly to ketamine. It might be dependent on the activation of PI3K and mTOR, inhibition of GSK-3ß as well as induction of HO-1. These are important mood targets. Vitamin D supplementation, thought to modulate many areas of mental health, is associated with lower depressive and anxiety symptoms in psychotic illness [13] and addition of vitamin D to conventional antidepressive agents can improve antidepressive effect [14]. The core symptoms of ASD fluctuated in severity with changes in serum vitamin D levels in children: high-dose vitamin D3 regimens may ameliorate the core symptoms [15, 16] Vitamin E (α-tocopherol) has been linked to a decrease in the frequency of depressive symptoms. α-tocopherol is a lipid modulator of the cannabinoid system [17] Vitamin E has pain-relieving, antioxidant, antidepressant [18] and anxiolytic-like activities [19]. A low dietary intake of vitamin E is related to altered mood and depression, depression is accompanied by significantly lower serum vitamin E concentrations, vitamin E intake being directly related to the depression score [20].The cognition promoting effects of omega 3 PUFAs may be dietary vitamin E status related [21] and recently, omega-3 and vitamin E co-supplementation was effective in improving parameters of mental health in some individuals with conditions of inflammatory basis [22]. Minerals: Calcium: Ca and Mg may be involved in depression; however there are few data on these mineral nutritional statuses concerning depression and data from human-studies are limited. It thought that Ca intake is related to depression and mental disorders Chromium: Seems to have important effects on insulin signalling and mood. Preclinical and clinical studies reported its potential antidepressant properties [23]. Chromium has shown the most promise for treating subtypes of depression that affect carbohydrate cravings and appetite regulation [24] In some women it "reduced mood symptoms and improved overall health satisfaction" [25] Iodine: Deficiency causes brain structural alterations likely to affect cognition. Low iodine-rich food intake was associated with increased brain volume shrinkage [26] Iron: Human studies link anxiety-driven behaviour and mood changes to poor iron status but excess iron in the brain is detrimental. It is proposed imbalanced iron metabolism plays a role in modulating anxiety and emotional behaviours [27] Magnesium: Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated [28] Magnesium influences the neurotransmission involved in emotional processes, such as the serotonergic, noradrenergic, dopaminergic, GABAergic and glutamatergic systems. Potassium: may be useful in the treatment of mood disturbances - low potassium levels may be linked to symptoms of depression. Selenium: "Intake was associated with a general elevation of mood and in particular, a decrease in anxiety." [29] When taking the selenium the subjects reported a substantial improvement in mood at 100 mcg [30] Persons with low selenium status might experience relatively depressed moods [31] That said, another study found "no evidence that selenium supplementation benefited mood or quality of life in these elderly volunteers" [32]. It is suggested to play an important role in psychological functioning [33]. Zinc: Preclinical and clinical studies have demonstrated that zinc possesses antidepressant properties and that it may augment monoamine-based antidepressants [34] Meta-analyses support zinc for depression [35] It is proposed to cause general improvement in neuronal plasticity as well as reduction of neuronal atrophy and neuronal cell loss, modulation of the serotonergic system including postsynaptic 5-HT1ARs with a possible involvement of dopaminergic neurotransmission [36]. Peripheral Zn concentration may play a role in the physiopathology of some domains of cognitive function, "there was a significant positive correlation between plasma Zn levels and the concentration subcategory" [37] Less/other mentioned: Boron: Boron supplementation altered EEG such that there was a shift toward less activity in the low frequencies and more activity in the high, dominant frequencies of the EEG leading to improved psychomotor skill, and cognitive processes of attention and short term memory [38]. Choline sources: "The extent to which higher intakes of choline have the potential to enhance or influence cognition during childhood, adulthood, and/or age-related cognitive decline needs further investigation" [39]. Carotenoids significantly corresponded to global cognitive abilities including verbal learning, verbal fluency, memory recall, processing speed, and perceptual speed. Serum lutein, zeaxanthin, and β-carotene concentrations were most consistently related to better cognition. Serum zeaxanthin had significant relationships with most measures of cognitive function, with higher concentrations being significantly related to global cognitive performance,and better concept formation/abstraction. Serum concentrations of β-carotene were also significantly correlated to most measures of cognitive function. Serum lutein concentrations were significantly related to measures of global cognition, lower dementia severity, and executive function. Carotenoid levels have also been shown to protect cognitive function in older adults with mild cognitive impairment. Supplements have shown strong cognitive enhancement benefits over longer term studies Review on omega-3: https://www.ncbi.nlm.nih.gov/pubmed/27472373/ [1] https://www.ncbi.nlm.nih.gov/pubmed/30359969 [2] https://www.ncbi.nlm.nih.gov/pubmed/29113038 [3] https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26529011/ [4] https://www.ncbi.nlm.nih.gov/pubmed/29122693 [5] https://www.ncbi.nlm.nih.gov/pubmed/27825907 [6] https://www.ncbi.nlm.nih.gov/pubmed/26984349 [7] https://pdfs.semanticscholar.org/…/53c8c4dbfdccf441a16bcc14… [8] https://www.ncbi.nlm.nih.gov/pubmed/9122365 [9] https://www.ncbi.nlm.nih.gov/pubmed/30413185 [10] https://www.ncbi.nlm.nih.gov/pubmed/28178022 [11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856388/ [12] https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25873303/ [13] https://www.ncbi.nlm.nih.gov/pubmed/30245372 [14] https://www.ncbi.nlm.nih.gov/pubmed/29460820 [15] https://www.ncbi.nlm.nih.gov/pubmed/29629638 [16] https://www.ncbi.nlm.nih.gov/pubmed/27868194 [17] https://www.ncbi.nlm.nih.gov/pubmed/21843633 [18] https://www.ncbi.nlm.nih.gov/pubmed/20144659 [19] https://www.ncbi.nlm.nih.gov/pubmed/30251258 [20] https://www.ncbi.nlm.nih.gov/pubmed/28531460 [21] https://www.ncbi.nlm.nih.gov/pubmed/29656360 [22] https://www.ncbi.nlm.nih.gov/pubmed/29306057 [23] https://www.ncbi.nlm.nih.gov/pubmed/24101396 [24] https://www.verywellmind.com/chromium-for-depression-1066922 [25] https://www.ncbi.nlm.nih.gov/pubmed/24237190 [26] https://www.ncbi.nlm.nih.gov/pubmed/29083437 [27] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253901/ [28] https://www.ncbi.nlm.nih.gov/pubmed/28654669 [29] https://www.ncbi.nlm.nih.gov/pubmed/1873372 [30] https://www.ncbi.nlm.nih.gov/pubmed/2096413 [31] https://www.ncbi.nlm.nih.gov/pubmed/8717610 [32] https://www.ncbi.nlm.nih.gov/pubmed/16181615 [33] https://www.ncbi.nlm.nih.gov/pubmed/12509066 [34] https://www.ncbi.nlm.nih.gov/pubmed/28299207 [35] https://www.ncbi.nlm.nih.gov/pubmed/28988944 [36] https://www.ncbi.nlm.nih.gov/pubmed/28319749 [37] https://www.sciencedirect.com/science/article/pii/S0531556518300639 [38] https://www.ncbi.nlm.nih.gov/pubmed/25063690 [39] https://www.ncbi.nlm.nih.gov/pubmed/29451849
  11. Alchemica

    Ketosis as therapy

    Update on this, be careful with these "trendy" things. I got to quite a deep state of ketosis on this, went from nutritional ketosis to starting to get extremely depriving of food and it started to get to the same level of kind extreme territory I had as a teenager. What are my experiences lately? You can take your consciousness (and suffering) to quite profound, sometimes uplifting and at times very scary places (ie for me going extremely catatonic and in a bad mindset) through these diets that people are broadly normalising and promoting.Yes, you can tap into some spiritual/altered states, maybe lose some weight but also very easily push it to the extreme of depriving yourself to really unhealthy limits, really quickly. It can easily become an eating disorder rather than a health thing, these diets and it's a gradual slide. So while mild nutritional ketosis seems interesting and kind of low GI stuff seems reasonable enough but yeah it easily swings into something less so, particularly for those of us who have struggled with such before... I still feel the most healthy thing to do is change your relationship to food in a healthy way. Get some greater impulse control gradually, cut out unhealthy things and if you want, try something mild like intermittent fasting if depriving yourself takes your fancy.
  12. 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
  13. Alchemica

    Isopropyl extractions

    Please keep it to legal things to do with isopropyl
  14. Hi All. My community plant extracts died when people stopped that from eventuating but in that process, there was a rebirth. I went on a spirited journey to find my Heart and Soul. It's in helping people who are in the hells like I experienced for so long. Not packing small quantities of samples at cost for people. I've also started my own therapeutic community, Adelaide Therapy for Soul Community on facebook for all, including the disadvantaged to get together in the botanic gardens with soulful therapy in mind. Join in if you're in Adelaide. Lately I have developed a deep relationship with Cacao. I have been working on a therapy chocolate, rich in flavonols and alkaloids + minerals which is exceedingly hearty and therapeutic. It has helped me, now I want others to experience this medicine. I've been working on admixtures and noticed how Cacao when enriched with alkaloids is like a gatekeeper to a therapeutic heart-space for those feeling disconnected from themselves and community... the admixtures take it deeper... I think a Heart-strengthening legal therapy chocolate is highly viable. I see this as a potent catalytic therapy ally. In my goal to work with people in real rockbottom states who are totally disconnected from their selves, Hearts and those trying to help them, if we can catalyse a step towards connection, within oneself and mirrored by a supportive community, I see we can jump start new directions in life. These suffering souls, like I was, are severely hardened off, I aim to open them up to love. A mission to bring disadvantaged people to the Heart and into Community. I want to expand my heart space more to offer others the chance for Chocolate Therapy, I'll aim to run at a donation going towards costs. I'm going to invest a bit getting this happening and run at a loss. It sounds insane but after seeing how potently therapeutic a change I can make in my life through plant allies, I want to do the same for others and inspire a shift towards such healing, legally. Seeing I'm mainly wanting to cater to people where money is already an issue, I can't ask for money. I just ask that people use this medicine to inspire real life heart changes. That said, I will open myself to external donations from others if they want to support such a mission. I'm going to use a GoFundMe page to inspire grassroots cacao therapy for the disadvantaged. GoFundMe's fee is 5% from each donation you receive. The payment processor fee is 2.25% + $0.30 per donation. If you want to be more direct and know me, do it that way. PM me for paypal details! All donations are strictly for expanding my medicine circle. All funds will support local suppliers and ethical cacao products Not expecting I'll recover costs but this is a mission from the Heart, not the pocket so that's cool. Much love and gratitude for any support you can offer! ~~~ Cacao therapy is so synergistic as a whole medicine for the Soul. Extracting just the alkaloids takes part of the magic out but it looks like spicing up the magic of the raw cacao flavonols with solid levels of spirited methylxanthines is really therapeutic... A substantial interaction between cocoa flavanols and methylxanthines exists at the level of absorption, in which the methylxanthines mediate an increased plasma concentration of (-)-epicatechin metabolites that coincides with enhanced CNS/vascular effects commonly ascribed to cocoa flavanol intake. MTXs act through a variety of different molecular mechanisms: mobilization of intracellular calcium, inhibition of phosphodiesterases (PDEs), modulation of gamma-amino butyric acid (GABAA) receptors, inhibition of high affinity ATP-dependent cyclic nucleotide transporters and antagonism of adenosine receptors. The plasma levels that could be reached under dietary regimes and the fact that MTXs readily cross the blood-brain barrier indicate that these drugs inhibit adenosine receptors in the CNS; higher doses may be required to mobilize intracellular calcium, inhibit PDEs or modulate GABAA receptors, or to unselectively inhibit ABCC5 and ABCC4 transporters. Moreover, despite the physiological relevance, also under scrutiny is how caffeine, theobromine and theophylline are able to interact with native double helical DNA Cocoa and chocolate are not just treats -- they are good for your cognition: https://www.sciencedaily.com/releases/2017/06/170629101648.htm Health benefits of methylxanthines in neurodegenerative diseases: https://www.ncbi.nlm.nih.gov/pubmed/28074613 PM me if you can support this mission. Love and best wishes! https://www.gofundme.com/cacao-therapy-for-the-ill
  15. I call this one "The Journey of an Upside Down Heart to Love and Spirit" It's been through the plants, Milly, family and support of my friends, I've gone from abysmal darkness to find a place of growth and upward evolution. I really struggled from an early age. It's been slow, bit of up and down but as you grow and regain conscious choice from long-term illness, you find a good place. I'm really new to any sort of creativity, I'm not an artist but this is like the way it feels to, through nature and lovely souls, grow into healthier place. This not a tea, just a mindful moment of reflection on Life. I've found deep healing in a mild plant spirit medicine approach. I've modified this from here: How to Connect with Plant Allies Our Plant Allies captivate us through our senses first, and then when we slow down enough to look deeper, we become engaged on a soul level. This is the heart of plant spirit medicine. Immersed in the energy of a Plant ally, we begin to get a glimpse of the world through it's eyes. We begin to understand an aspect of being-ness in a new way that we hadn’t seen before. We can apply this to our lives, the cycles we go through, our relationship patterns and habits of thought. When we are in creative mode, we are able to simultaneously give and receive. We give the Plant our awareness and attention, and we receive its healing vibrations and messages. As we create, we clear space within ourselves to listen. Find a way to work with you plant allies as to engage creatively. You are observing the plant in fine detail, etching it into your memory, and creating pathways between its image, your heart, and hands. You will be connected again to your experience with the plant, remember, and practice bringing it's vibration into your everyday thoughts, perceptions, and decisions. Trust your intuition and your unique creative process, as we interact more and more with our plant friends, we receive more and more ideas of how to interact creatively. As your energy and your plant friends energy merges, you begin to co create and manifest your most exquisite visions of harmony. It is helpful at this time to observe the thoughts, feelings, perceptions and sensations that arise in the body in response to the Plant. This information holds seeds of consciousness about how we can grow spiritually/emotionally in the area that comes to mind. The intuitive connection that is made between observation of the Plant and observation of oneself is a catalyst for a new cycle of awareness and understanding. Study a plant in its natural environment. Plants give us clues to help us identify how they might help us. By observing a Plants colour, shape, growth pattern and environment, we gather information and begin to make a connection with something we already know. ~~~ Today a mindful tea before I ventured into the World, fresh from the garden, for finding my Wings, a spiritual soul ascension tea. It's not just a procognitive nootropic tea, it's a spiritual tea. I really enjoy getting creative in the garden and making just simple sustainable medicinally healing teas. This one establishes connection between Earth, Self and the Heavens. Morning glory represents love, affection and longing but in a spiritual way, this represents my spiritual connection to Milly. Ginkgo also associated with duality, a concept that recognises the female and male aspects of all living entities and that is often expressed as yin and yang. Ginkgo celebrates duality that could be reunited in a single entity. For centuries, the ginkgo tree has been considered a symbol of hope and peace Brahmi is a Sanskrit word derived from “Lord Brahma” or “Brahman”. Lord Brahma is the divinity responsible for all of the creative forces in the world Basil Is a symbol of love and good wishes· Symbolises Love and good wishes, herbs of kings - love, holiness, purity, and sanctity Sage has a protective effect, "to save" Gardenia is one of the most frequently used herbs in Chinese medicine.
  16. I still have moments I tune into these things, lately endogenously I found myself spontaneously creating a chakra Full Moon Mandala Did some reading, surely I'm not the only one who does these things? "The season of Spring presents a time for us to align with our inner truth, the seeds inside of us waiting to blossom with the droplets of rain and sun. One of my most loved rituals is the practice of creating an Earth Mandala, a Healing Circle, a Flower of Life, a cosmic diagram connecting us to the Universal oneness. It is an offering of prayer and love to Mother Earth and the Spirit of the land where you live. This ritual was inspired by the sacred Andean Despacho ceremony of the Inka tradition. Since ancestral times, people of the Andes have used this ceremony to connect themselves with the harmony of nature and to live in Ayni, in reciprocity and right relationship. To practice Anyi is to acknowledge the interconnection between human beings and the natural world that sustains us. In Peru, a Despacho ceremony is performed by the Q’ero shaman to honor Pachamama, Mother Earth or the Apus, the Mountain Spirits. Using various natural elements as offerings to represent the stars, rivers, clouds… the shaman creates a three dimensional Mandala composition as a symbolic act of respect for all of life." https://puakaihealing.com/earth-mandala/ I've been experiencing a strong connection to the natural world lately, plants, birds etc. "When a feather arrives for you, Spirit is reminding you of your spiritual origins and deep connection to your home beyond earthly realms." "Feathers come to us as gifts. They come from the sky, from the sea, from trees and deep grasses, even appearing within enclosed spaces never inhabited by winged creatures. They come to us unexpectedly, but not without purpose. Their messages may be startling, soothing or sudden, but they are always an opportunity for seeing – for finding answers to questions we may not even have known we were asking. What, then, is a feather? It is a part of a bird’s body, and it is a part of us. It exists for itself, to serve its primary purpose in the cosmos, and it exists in alliance with every other aspect of the cosmos. Just as we bring life-inspiring messages for others while simply fulfilling our own lives, so do feathers bring their messages to us. They remind us that we walk in a world overflowing with meaning." https://www.shamanicquest.co.uk/blog/2017/05/15/Shamanic-Practice-And-Feathers.aspx
  17. Alchemica

    Visitation by birds

    I too like to see birds symbolically and as spiritual messengers. I've also been feeling attunement to all animals/insects on a deeper level. I feel it's more a personal relationship that you find in their presence than any general one but just observing the bird can form some relevant "lesson" or insight. For example, some have taught me that I need to be more friendly with their general friendly nature. Others reaching for higher transcendence of self through their flight A more detatched view on the earthly pleasures and greater spirit etc There's plenty on spiritual views on the net but see what inner work it brings to your awareness?
  18. This one - the dragonfly - came to me in a time where I was embracing change - new place, new attitudes, new behaviour, new light "...change what needs to be changed, survive, become better, and flourish!"
  19. You can eat the kale, do the meditations, sip on the plant medicine but how healing is that really? I got disenchanted with 'plant medicine' as it was often turning into a bunch of band-aid experiences and pits of continuous self-medication. I saw lots of people embarking on the same loop, it seemed to be a pathway of less healing than expected. Anyone else found that? I think we've often lost some aspect of simply nurturing something that doesn't give back to us with food or medicine etc. A deeper connection to the Web of Life. I started growing some non-medicinals, things that weren't providing me with anything, and noticed something... From the butterfly attracting Milkweed to Milly's forget-me-nots to Acacias I'd never had any interest in... In the past, a plant's worth was dictated to me by what it could do for food or medicine, a very ego-centric view on the plant. There was nothing spiritual or worthwhile about a plant being simply a living entity, the essence of respect was often not there/not as deep - what did it do for us other than provide a bit of oxygen?!? It's "just a plant"... I was centred around always taking something from a plant, be it food, medicine, boosts in self etc. If we treat humans in such a way, constantly dictating their worth by what they can do "for me/us" and with limited respect for their unique worthwhile existence, that's a very unhealthy view that's all too prevalent in society - I believe our human relationships are often mirrored in the way we treat the Earth. If we flip that "for me/us" around into what we can do "for them" without expectation of something in return, that's the start of some healing. In that flip, you also seemingly make room for healthy natural reciprocity Today I see the worth of a plant beyond that narrow view. I'm starting to nurture something that I don't expect anything in return from. The essence of each plant has it's own gift, beyond a phytopharmacological or nutritional cocktail, and deserves respect - a more eco-centric and spirited view Looking forward to Trees for Life
  20. Well said @Inyan Coming from only ever being interested in plants for medicinal aspects, to then finding the enjoyment of creating that nourishing connection to food, I always dismissed anything else as aesthetic gardening and pointless. Not saying food/medicine isn't important, I'm just surprised to find how the act of relationship with something that won't deliver a therapeutic brew or even food really breaks the addictive consumption mindset - something I was always struggling with
  21. Well modulating 5-HT did something helpful, temporarily... In a moment of impulsivity went back to what was my first point of call after abstinence. Cheap old thiamine, was my body really getting enough or could that help explain the scary deteriorating struggle town I was in each day? Not going to neglect the other vitamins see table in this article The B vitamins: nomenclature, dietary sources, coenzyme forms (roles), symptoms of deficiency, and risk factors (over and above low consumption). Of all the evidence based things I've tried to stay on top of, thiamine was one major legitimate concern. Thought I was including enough to try and cover that concern... but I upped the thiamine quite a bit.... and felt slightly better. A few days, even better. These days of supplements being so dodgy in quality, I'll only use simple cheap pharmaceutical grade thiamine I trust from the chemist not some novel derivative. B1 Thiamine - brain deficiency particularly seen in alcohol abuse, obesity Mild deficiency: irritability, emotional disturbances, confusion, disturbed sleep, memory loss Deficiency: Wernicke-Korsakoff syndrome (neurodegeneration, within the medial thalamus and cerebellum). Ataxia, abnormal motor function and eye movement, amnesia, apathy, confabulation - Thiamine deficient rats developed learning and memory deficits as well as aggressive behaviour - There was significant cognitive deteriorations in the psychoneurotic scales in thiamine deprived participants . - There was significant association between improved thiamine status and enhanced performance across a range of cognitive-function test [ref] Thought I was on enough but if you start getting weird neurological symptoms and cognitive decline, it seems to be a really good thing to knock out as a potential causative factor ASAP rather than fluffing around, particularly if you've been on anything thiamine depleting. Not just take a bit but saturate your system with it for awhile... Particularly when if you're getting changes in mental state and cognitive deterioration - disoriented, inattentive, agitated etc Any thiamine experts? How much thiamine is actually needed for abstinence recovery? How long do you need to maintain high-dose supplementation for? I used 100mg/day for a bit then I was using about 50mg/day. Maybe that simply wasn't enough Alterations of serotonergic parameters have been demonstrated in experimental thiamine deficiency. "...data suggest that 5-HT neurons, although structurally intact, are functionally affected early during the progression of thiamine deficiency. These alterations, which are likely a part of adaptive neuronal change consequent to thiamine dysfunction, may be important in the physiological manifestations and the learning deficits commonly encountered in experimental thiamine deficiency. " Stuck with it a few days, got out in the garden more. Feel just clearheaded, been more able to persist with goal-directed tasks, not irritable. Calm and collected in the most grounded way I've felt for awhile. Stability of mood. I've actually slept in past my usual 3.30am wake up time, too. With 50mg in healthy subjects: An improvement in thiamine status was associated with reports of being more clearheaded, composed and energetic. These influences took place in subjects whose thiamine status, according to the traditional criterion, was adequate. Once again, this seems to have antidepressant augmenting effects in human studies [1]. In a small study, thiamine supplementation significantly improved anxiety scores, general well-being and reduced fatigue in patients with Generalised Anxiety Disorder. "Interestingly these patients were able to discontinue taking anxiolytic and β-blocker medications." [2]. It has also been found thiamine supplementation shows a beneficial clinical effect on children with autism [3]. [1] https://www.ncbi.nlm.nih.gov/pubmed/26984349 [2] https://pdfs.semanticscholar.org/7c1b/53c8c4dbfdccf441a16bcc1464b2b26c9c55.pdf [3] http://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20130102.11.pdf "Thiamine is being used to improve brain function and it is also shown to help treat neurodegenerative disease such as Alzheimers and Parkinsons" It's established "thiamine supplemented abstinent rats made a faster recovery of hepatic and neuronal damage than in the abstinence group. Changes in neurotransmitter levels in brain were also reversed by thiamine supplementation. DNA damage was decreased and DNA content increased in thiamine supplemented group compared to abstinence group showing a faster regeneration" [1] It is claimed Steve Jobs took massive doses of thiamine when he was experimenting with other stuff and said both were about equally effective as idea stimulators, but B1 did not have the psychoactive effect. Thiamine compounds may act by boosting anti-oxidant cellular defenses and prevent stress-induced inhibition of hippocampal neurogenesis [2] Thiamine has antidepressant/anti-stress effects that are associated with reduced GSK-3β expression and conditioning of adverse memories [3] High doses have some utility in dementia potentially due to a cholinomimetic effect of thiamine in the central nervous system [4] Thiamine is required to synthesise acetylcholine (ACh). Thiamine is involved in the presynaptic release of ACh; thiamine binds to nicotinic receptors and exhibits anticholinesterase activity The treatment with thiamine led to a significant improvement of Parkinson's symptoms. Experimental findings showed an increased dopamine release in rat striatum after the intrastriatal thiamine administration and "high doses of thiamine, could lead to an increase of synthesis and release of the endogenous dopamine, to an increase of activity of the thiamine-dependent enzymes" [5] A thiamine derivative promotes voluntary activity through dopaminergic activation [6] The same derivative has been found to make mice engage in more passive cuddling-type behaviours. Likewise acute sulbutiamine induced a modulatory effect on glutamatergic and dopaminergic cortical transmissions in the rat brain It has anticonvulsant effects [7] One report of a healthy subject taking mega-doses: "I have been using megadoses of Thiamine (Vit. B1) on and off for over a year and am greatly impressed. I always take a 250 mg or 300 mg B1 pill with a Vitamin B Complex (100 mgs/mcgs of the various B Vitamins) usually twice per day (once with breakfast and once with lunch). Good things about Thiamine megadoses: - Greatly improves my attention to detail on reading tasks. Without it I often struggle reading through pubmed articles for example, with it I read every single word quickly and understand what the article is about without giving up (I often 'give up' without this given that I have inattentive type ADD). - Greatly improves ability to do 'boring' mundane tasks. For example, when doing boring checking tasts at work, this helps me rip through them better than anything else. Also lets me rip through chores easily. - Improves my motivation. It allows me to follow a more disciplined lifestyle (eating healthier, sticking to routines, doing boring chores without too much hassle, etc.) - Gives me more mental energy and I feel more awake generally in the daytime." [8] [1] https://www.ijpp.com/IJPP archives/2013_57_4_Oct - Dec/406-417.pdf [2] https://www.ncbi.nlm.nih.gov/pubmed/28506637 [3] https://www.ncbi.nlm.nih.gov/pubmed/27825907 [4] http://www.ncbi.nlm.nih.gov/pubmed/8251051 [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828997/ [6] https://www.nature.com/articles/s41598-018-28462-2 [7] https://www.ncbi.nlm.nih.gov/pubmed/28766407 [8] https://www.longecity.org/forum/topic/65238-megadosing-thiamine-for-motivation-and-sexual-arousal/ I've learned with a potential deficiency ie thiamine, don't skimp on doses of the safe ones. Doses of high magnitude for longer periods are required to replenish many B vitamin levels and correct enzymatic activity, particularly with those who have restriction in their ability to absorb them. There is a linear dose response following single oral doses of thiamine in terms of whole blood and plasma levels up to the maximum administered dose of 1500 mg (corresponding to more than 1000 times the RDA). Higher doses have also been used such as 3g. It's seemingly better to get those levels up. "Epidemiological evidence suggests that the benefits of B vitamins extend well beyond the accepted biochemical cut-offs for deficiency or marginal deficiency" Other B deficiencies from [ref]: B2 Riboflavin Fatigue, personality change, brain dysfunction B3 Niacin - Particularly seen in alcohol abuse Depression, anxiety, progressing to vertigo, memory loss, paranoia, psychotic symptoms, aggression (Pellagrous insanity) B5 Pantothenic acid Encephalopathy, behaviour change, demyelination B6 Vitamin B6 (referring to: pyridoxal, pyridoxamine, pyridoxine) Particularly seen in Alcohol abuse, age-related malabsorption, contraceptive medications Irritability, impaired alertness, depression, cognitive decline, dementia, autonomic dysfunction, convulsions B7 Biotin - particularly seen in Type II diabetes, poor gluco-regulation Depression, lethargy, hallucinations, seizures B9 Folic acid/folate - particularly seen in Common genetic polymorphisms (inc. MTHFR C667T) Low Riboflavin and B12 B12 Vitamin B12 - particularly seen in age-related malabsorption, vegetarians, vegans, genetic polymorphisms Both cause affective disorders, behaviour changes, psychosis, cognitive impairment/decline, dementia (inc Alzheimer’s disease and vascular dementia) Observational and controlled trial research being focused disproportionately on just three of the vitamins—folate and vitamins B6 and B12. "Unfortunately, there is a general dearth of controlled trial research into the effects of the remaining B vitamins on brain function"
  22. Keep us in the loop on any improvements or anything you note @Xperiment. I doubt you got up to as much thiamine depleting shenanigans as I did but if you did, be liberal with doses... Longer term, I've noted it's not the panacea for me - don't expect it to be - if I get stressed I get symptom flares but they actually resolve over a bit of time whereas before nothing would shift a continuous spiral down.
  23. This continues to deliver day by day. So much so I think the quest for some stability might be over I find the effects are very dose dependent in line with the dose-response noted above - using 500mg+ (I haven't noted side effects up to 1.5g) and keeping those levels elevated throughout the day has given me some good stability, I might be able to reduce doses soon. Why did my brain feel daily like it was being eaten alive, was pure negative affect constantly over-riding my emotional world, was I in pure dysphoria with constant fluctuations in mental state and deteriorating cognition? This seems to be the closest I've found to a solution and an affordable one at that The encouraging thing is that on returning to what was my first point of call but really upping the thiamine dose with just healthy dietary diversity and maintenance, it feels like there's nothing too much needing continuous time investment in attempting 'fixing' which has been a super challenging loop for me to break free from when minute to minute your mental state, memory and cognition is doing weird things. Hopeful I can maintain that. I'm currently having manageable stable-ish days without extreme and constant mood, emotional and other weird neuropsychiatric stuff happening. That said, it's been a long time of symptoms so there's likely been damaging effects from that. I'm not saying it's at all perfect but it's workable and stable 'good enough'. I can actually do some things I want to do for a few hours, particularly manage some family time, without it being absolute torture for my fluctuating brain state. Get on with living life.
  24. Switching this around, how do we use the social to modulate monoamines? Is 5-HT something that is successfully modulated by the social? That's the other thing that causes a drastic reduction in symptoms for me - nourishing social interaction. The serotonergic system itself is highly responsive to social influences and social isolation has been shown to affect endogenous 5-HT release and 5-HT turnover and leads to a reduction in the excitability of DRN 5-HT neurons. Sure, initially the elevated serotonergic states where nice but eventually things seem to return to a homeostasis, likely as seen in clinical studies with Trp augmentation "During the first week of treatment, there was a significantly greater decrease in depression scores. No significant differences were noted at later time points." and if you're adding additional Trp, are you potentially providing extra fuel for an activated kynurenine pathway? Upping the monoamines helped but... I mean really, is fancy supplementation really alleviating issues at the source and improving life, or just a band-aid for real problems, like persistent social isolation? Part of me says, fix the aberrant underlying deficits and you'll start having better social approach and try more socialising whereas in reality, each "band-aid" is directing life force away from actively tackling the root causes. The bidirectional effects of the social on the biological could be more effective and stable than trying to up monoamines with anything. I've tried that approach before, a few times, but it's worth a retry. Riding through the nastiness of 'augmentation cost cutting', feeling quite extra crap, and more attempted action even though I feel crap. Often the only way that works... I'm at the point Trp isn't doing much more, other than inducing side-effects and becoming very blunting. More so than just switching favour between hedonic short-term rewards in favour of longer-term ones, actually feeling extremely anhedonic. It switched the impulsivity down, tackled negative emotional dysregulation well, for a bit. PRN stuff it feels. Do social factors induce cascading serotonergic abnormalities? It seems very difficult to climb back to any level of health if you condition social defeat and isolation. We too easily isolate and subordinate people with lower mental health, as they do to themselves, how much does that cascade into crippling mental illness? How much of a role does the serotonergic system play in that? Serotonin is probably most central in its relation to social status functioning [1] Changes in serotonergic function seems to directly affect perceived social status. "Social subordination leaves one fidgety, easily perturbed, and their behaviour seems to be largely controlled by external stimuli rather than being self-directed. [they are] prone to impulsive behavior including impulsive aggression." 5-HT appears - important in developing nourishing social contacts - contributes to the appraisal of the social emotional cues - increases the perception/interpretation of social stimuli - It stimulates pro-social behaviour, which leads to high levels of cooperation and improved perception of social cues In a simplistic framework: "Serotonin levels are not innate and inflexible. They are themselves the product of social status. The higher your self-esteem and social rank relative to those around you, the higher your serotonin level is. Experiments with monkeys reveals that it is the social behavior that comes first. Serotonin is richly present in dominant monkeys and much more dilute in the brains of subordinates. Cause or effect? Almost everybody assumed that the chemical was at least partly the cause: it just stands to reason that the dominant behavior results from the chemical, not vice versa. It turns out to be the reverse: serotonin levels respond to the monkey’s perception of its own position in the hierarchy, not vice versa." “Contrary to what most people think, high rank means lower aggressiveness, even in vervet monkeys. The high-ranking individuals are not especially large, fierce or violent. They are good at things like reconciliation and recruiting allies. They are notable for their calm demeanor. There is little doubt that the monkeys mood is set by its high serotonin levels. If you artificially reverse the pecking order so the monkey is now a subordinate, not only does its serotonin drop, but its behavior changes, too. Moreover, much the same seems to happen in human beings." - Genome The activity of 5-HT neurons is highly vulnerable to stress. Stress → social withdrawal/low mood → social isolation and continuous social subordination. Each of those declines is another hit to the functionality of the serotonergic system. It forms a negatively re-enforcing cascade. [1] https://www.ulm.edu/~palmer/TheBiochemistryofStatusandtheFunctionofMoodStates.htm "Serotonin dysregulation found in depression and other psychiatric disorders may go hand-in-hand with deficits in initiating social interaction, impaired learning from social interaction experience and making adverse decisions in social situations."
  25. Thanks @tarenna and @LikeAshesWeFade for the kind words Still going with the Trp. Finding it really quite useful. It's not so much a mood boost as what I need Modulating 5-HT more given me a view on 5-HT beyond it being a way of increasing personal "happiness". I'm not more "happy" - it's deeper than that. It's also deeper than 5-HT making octopi cuddly with empathogens, too. I like the model where "Serotonin influences social behaviour by shifting social preferences in the positive direction, enhancing the value people place on others’ outcomes." Trp augmentation may "influence the way they feel and think about themselves in a social context" and "serotonin function is related to positive social preferences, that is, the positive valuation of others’ outcomes" Serotonin's effects appear to depend on the social context: "serotonin amplifies neural representations of positive social preferences, whereas serotonin depletion shifts neural value computations toward selfish or even negative social preferences" "Serotonin is concentrated in discrete brain regions known to regulate social cognition and decision-making that have been collectively called “the social brain”. Depleting serotonin in normal individuals shifts their behaviour toward lack of impulse control and short-term gratification at the expense of long-term benefits. Enhancing brain levels of serotonin causes people to become more averse to harming others" Depleting brain serotonin levels in normal individuals results in a shift away from cooperative behavior in favor of short-term gain and results in antisocial behaviour, increased uncontrolled aggressive behavior, feelings of anger, quarrelsome behavior, and self-injury Low functioning "compromises the decision-making process by altering the ability to distinguish the magnitude of differences between immediate versus long-term rewards" and increases the tendency to choose the less probable outcome Low Trp manipulations result in the use of more self-references, more negative words, and fewer positive words Reduced serotonin function indeed impairs ones empathic abilities. Serotonin is important for promoting behavioural suppression or withdrawal in the face of aversive predictions Serotonin modulates human concerns for harm and fairness Serotonergic activities might strongly influence the sharing effect of emotions. It plays important roles in the regulation of individual behaviours that organize social group dynamics. Read How serotonin shapes moral judgment and behavior Vitamin D and 5-HT I'm a month into the L-methylfolate with the later added amino acids. It's reduced some symptoms quite nicely but it's pricey when I have house expenses. Trp will definitely remain as a useful amino acid for me but I'm keen for more affordable monoamine modulating vitamin options - maybe massive doses of L-methylfolate aren't needed and I can just use a mg/day or something. I also note how much the sun does for me... when I get out there properly "Vitamin D acts not only to induce serotonin synthesis, but also functions at an indirect, molecular-genomic stage to mimic SSRIs and MAO inhibitors" [1] "Fine-tuning serotonin concentrations in the synaptic cleft, vitamin D may be able to steer neurological control of such processes as social behaviour and depression." It is "hypothesized that an association between vitamin D insufficiency and low central serotonin concentrations represents a common denominator in a myriad of neuropsychiatric disorders." How does this apply to health? The core symptoms of ASD fluctuated in severity with changes in serum vitamin D levels in children: high-dose vitamin D3 regimens may ameliorate the core symptoms [2, 3] "...core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL." Vitamin D supplementation is associated with lower depressive and anxiety symptoms in psychotic illness [4] and addition of vitamin D to conventional antidepressive agents can improve antidepressive effect [5] I was always on the lower end dose when supplementing. A daily vitamin D intake of 1000–4000 IU (25–100 micrograms) should be enough to ensure optimal blood levels for most people [6] Anyone attest to benefits dosing higher? [1] https://www.ncbi.nlm.nih.gov/pubmed/30008960 [2] https://www.ncbi.nlm.nih.gov/pubmed/29629638 [3] https://www.ncbi.nlm.nih.gov/pubmed/27868194 [4] https://www.ncbi.nlm.nih.gov/pubmed/30245372 [5] https://www.ncbi.nlm.nih.gov/pubmed/29460820 [6] https://www.healthline.com/nutrition/how-much-vitamin-d-is-too-much
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