Alchemica

Some experiments trying to get better sleep, rough notes I kept while I was quite struggling so excuse the poor referencing, I'm still struggling getting sleep at times. I get some effects from Jujube/Zizyphus seed. It's worth a shot for people. Finally got around to trying some Jujube seed extract. Didn't get much from the fruits. I like it, initially I blended it with a bit of Ashwagandha. I don't get worthwhile kava effects anymore but this is quite nice at a decent dose. I'll likely use it for sleep (wasn't expecting it to be strong enough to consider using for sleep) It has been also traditionally used for psychiatric disorders in Chinese and Korean medicine. Traditionally, one of the main functions of jujube, as described in herbal medicine, is to benefit our brain by calming down the mind and improving quality of sleep. Jujube possesses neuroprotective activities, including protecting neuronal cells against neurotoxin stress, stimulating neuronal differentiation, increasing expression of neurotrophic factors, and promoting memory and learning. The plants secondary metabolites modulate GABAergic activity and the serotonergic system, interestingly the postsynaptic 5-HT1A receptors. Intriguingly, it exhibited significant effects on both the expression and activation of GABAA receptors. It improves memory impairment through BDNF/TrkB signaling and is suggested to have a protective effect against chronic depressive disorders The Zizyphus seed/hops/chamomile is nice, more chill than sleep for me but last night I added valerian and lemon balm. Once again, for someone who has severe GABAergic dysregulation/tolerance and sleep issues, it's quite anxiolytic but not so pronounced in it's sedative action for me. I'll get there eventually. "This clinical investigation on safety and effectiveness of a herbal compound made of valerian, hop, and jujube opens interesting perspectives on usage of herbal compound to manage primary insomnia." https://www.ncbi.nlm.nih.gov/pubmed/28603433 Explored some valerian by itself as a sleep aid for a bit. Once again, anxiolytic, not exactly sleep promoting for me. Added things like lemon balm etc. They're something you can tune to. Interestingly, the use of combined valerian and lemon balm phytomedicine extract provides a viable treatment option for hyperactivity, attention deficits, and impulsiveness, in addition to nutritional and lifestyle modifications Valeriana officinalis extract is a popular herbal medicine used for the treatment of anxiety and sleep disorders. The anxiolytic and sedative effects are mainly attributed to the modulation of GABAergic transmission but the selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant. Binding affinities could also be demonstrated at some of the screened melatonin (ML1 and ML2) and serotonin (5-HT4e, 5-HT6 and 5-HT7) receptor subtypes. A single oral dose of valerian modulates intracortical facilitatory circuits. While none of the valerian extracts displayed sedative effects, they did produce pronounced anxiolytic and antidepressant effects in one study. Valerian root extract may reduce emotional, physical, and behavioral symptoms of premenstrual syndrome. Its pharmacological activity may result from interactions among multiple constituents rather than any one compound or class of compounds. The primary active constituents include valerian’s essential oil and its corresponding sesquiterpenes (valerenic acid), the iridoid esters (valepotriates) Throughout history, lemon balm has been used medicinally to heal wounds, prevent and treat cold sores, soothe nerves, improve sleep, and strengthen the memory and the mind. The ancients are known to steep lemon balm in wine, a traditional medicinal dosage form, for fevers and to uplift the spirits. Lemon balm contains more than 100 chemicals including the flavonoids (quercitrin and rhamnocitrin), which have an antioxidant effect; phenolic acids and tannins, primarily rosmarinic acid; the 7-glucosides (apigenin, kaempferol, quercetin, and luteolin); caffeic and chlorogenic acids; triterpenes; and volatile oils citral a, citral b, (10%-30%), and citronellal (30%-40%) that render its lemony flavor and aroma. Some evidence indicates that valerian preparations may have a mechanism of action and clinical characteristics that differ from the benzodiazepine-related sedative/hypnotics, making them more suitable for long-term use. A one-time valerian 1600mg dose, often used to treat insomnia, does not appear to impair driving simulator performance after acute ingestion. How a few things impact at the EEG level: "Under diazepam the power in the theta frequency band decreased while it increased in the beta band. In contrast, some plant extracts showed an increase of power in the theta frequency band, but no increase in the beta frequency range. Valerian extract, which was administered in both studies, displayed an increase of power in the delta and theta band and a decrease in the beta band. Kava-kava preparation caused a decrease of relative alpha power in the vigilance controlled EEG. This effect was more pronounced 6 h than 2 h after drug administration. In a polygraphic sleep study two dosages of a Kava-kava preparation, given for one night, did not alter the sleep stage distribution significantly, while the sleep spindle density was increased.The most consistent single effect was a power increase in the theta band. Fronto-centrally a decrease in power in the high frequency beta band was also observed 180 minutes post administration Valerian Absolute power in the theta frequency band increased 120 minutes post administration Power increases were also observed in the neighbouring delta and alpha bands Total power remained unchanged under Lavandula extract 120 minutes post administration, and there were only very few changes in the different frequency bands. 180 minutes post administration total power decreased in the fronto-centrallead under RT and RS conditions. This power decrease could also be seen for absolute power in all frequency bands Total power increased 120 minutes post intake of Passiflora extract in the occipito-temporal lead. Other changes were essentially restricted to an increase in theta power 120 minutes post Lemon Balm administration total power increased fronto-centrally under resting conditions (RS). At this time point power increases were observed with a maximum in the delta, theta and slow alpha band occipitotemporally. For the fronto-central lead these power increases extended from the theta to the beta frequency band. Californian poppy: 120 minutes post administration absolute and relative power increased mainly in the theta and alpha frequency bands'"

I've been revisiting this trying to improve sleep by changing macronutrient profiles a bit. I was finding restricting carbs with higher protein intake was seemingly messing with sleep even more. Dietary intake habits (affecting the state of nutrition) are perceived to be one of the factors predisposing, causing and consolidating sleeping disorders When it came to one study [1], two thirds of the subjects with sleep difficulties were characterised by an inappropriate state of nutrition. Sleep disorders could have been influenced by the low energy value of the subjects’ diets, as it has been shown that lowering the energy intake significantly decreases melatonin, a low intake of assimilative carbohydrates could have an influence on pinealocytes and the sleep-wake cycle. Similar results were seen in [2] where beans/carbohydrates and dairy were associated with improved sleep quality. "It was ascertained that, despite the insufficient energy value of the subjects’ diets, too much energy came from proteins [they] showed insufficient energy value, insufficient intake of assimilative carbohydrates, fibre, K, Ca, vitamin D3 and water with simultaneous excessive intake of Na, P, Fe, Zn, Cu and vitamins: A, B2 , B6, B12, PP, and C" Inbalanced intake of energy and nutritive value could have affected the proper synthesis of neurotransmitters regulating sleep-wake cycle and melatonin hormone. https://www.ncbi.nlm.nih.gov/pubmed/29265779 https://www.cureus.com/articles/16904-influence-of-dietary-intake-on-sleeping-patterns-of-medical-students

Sounds good, hope the terpenes help - keep us updated! Sorry to hear you're being troubled with more struggles, that's no fair

Saw this and thought of your post @FancyPants Protein Kinase C: Targets to Regenerate Brain Injuries? "Recent reports describe several non-tumorigenic diterpenes isolated from plants of the Euphorbia genus, which specifically modulate the activity of PKC isozymes promoting neurogenesis." There's lots of attempts to use pro-neurogenic plant compounds for example Ar-turmerone from turmeric essential oil Other molecules include: Eg TrkB (BDNF) 7,8-Dihydroxyflavone (Present in several plants such as Tridax procumbens L., Godmania aesculifolia (Kunth) Standl. and Primula sp. Huperzine A (Huperzia serrata (Thunb.) Deoxygedunin (Azadirachta indica A. Juss) Hyperforin (Hypericum perforatum L) and other polyphenols etc See more botanicals here Eg TrkA (NGF) β-caryophyllene Lion's mane etc GDNF Ibogaine β-Asarone (promotes expression of GDNF, BDNF, and CNTF genes)

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

Good point @Kindness. Probably quite messed up... Have been seeing what a *little* bit more carbs in the diet does, seems to be one part of the problem, potentially contributing to the shocking sleep quality and waking up 2am every morning... I went quite restrictive on carbs and a lot of people seem to find such messes with their sleep, potentially in part through the influence on 5-HT I've noted how socially modulated it is. The brain state caused by prolonged social isolation seems to involve neuropeptides

I've been struggling with really 'jagged' cognition which makes it super hard to focus which messes up the mood as a consequence. Trying more dietary stuff One is some frequent culinary-medicinal shrooms. I've tried lots of Lion's mane, Reishi, Cordyceps etc but not more widely used culinary mushrooms apart from Oyster (and a little bit of Porchini). Made a big batch of Shiitake (Lentinula edodes) and Oyster (Pleurotus ostreatus) and King oyster mushroom (Pleurotus eryngii) with my homegrown Reishi soup. Seaweed'd it up with the kale which was nice and made it extra shroomy Culinary-medicinal mushrooms may be developed as safe and healthy dietary supplements for brain and cognitive health Mushrooms offer great potential because of the complexity of their chemical contents and different varieties of bioactivities. Available evidence suggests that mushrooms exhibit anti-oxidant, anti-tumor, anti-virus, anti-cancer, anti-inflammatory, immune modulating, anti-microbial, and anti-diabetic activities These mushrooms are known to contain ergothioneine: shiitake, oyster, king oyster or maitake (hen of the woods) can contain up to 13mg in a 3-ounce serving compared to the 5 milligrams in common mushrooms. Ergothioneine may promote neuronal differentiation and alleviate symptoms of depression at plausibly achieved level of daily ingestion [1]. Other findings provide scientific evidence to support the use of Pleurotus ostreatus as a safe and effective mushroom to prevent and treat Alzheimer's disease through the polysaccharides [2]. [1] https://www.ncbi.nlm.nih.gov/pubmed/27134772 [2] https://www.ncbi.nlm.nih.gov/pubmed/27498414 Eating mushrooms may reduce the risk of cognitive decline: https://www.sciencedaily.com/releas…/2019/…/190312103702.htm Trying a few days on some simple rosemary tea over the weekend which I enjoy every now and then. It's one it's easy to dismiss Data suggest potential beneficial properties of acute consumption of rosemary water in humans [1]. Rosemary tea administration exerts anxiolytic and antidepressant effects in mice and inhibits cholinesterase activity [2] "The presence of 1,8-cineole and rosmarinic acid and the absorption of these (and other) compounds may facilitate performance through cholinergic pathways. Serum levels of 1,8-cineole have previously been demonstrated to correlate with task performance following exposure to rosemary aroma." Rosemary polyphenols cause the regulation of several neurotransmitters (dopamine, norepinephrine, serotonin and acetylcholine) and gene expression [3] while the volatiles activate the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production [4] Carnosic acid and carnosol, which are major components of the rosemary extract, were able to promote markedly enhanced synthesis of NGF [5] Also incorporating more 'culinary' sage Sage (Salvia) species effects have been considered and found effective in a range of population groups [6]. A double-blind, placebo-controlled crossover trial involving 30 healthy volunteers found it led to improved ratings in mood post-dose, with the lower dose reducing anxiety (300mg) and the higher dose increasing ‘alertness’, ‘calmness’ and ‘contentedness’ (600mg) Improvements in mood (e.g. alertness, contentedness, and calmness) and cognition were also identified following the single administration of a S. officinalis extract to healthy young adults. The extract was associated with significant enhancement of secondary memory performance at all testing times. The same measure benefited to a lesser extent from other doses. There also were significant improvements to accuracy of attention following the 333-mg dose. In vitro analysis confirmed cholinesterase inhibiting properties for the extract [1] https://www.ncbi.nlm.nih.gov/pubmed/30318972 [2] https://www.ncbi.nlm.nih.gov/pubmed/25910439 [3] https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(12)00657-2 [4] https://www.ncbi.nlm.nih.gov/pubmed/29273038 [5] https://www.ncbi.nlm.nih.gov/pubmed/14600414 [6] https://www.ncbi.nlm.nih.gov/pubmed/27888449 Made Ginkgo pesto from the season's leaves. It's a really nice way to have the stuff Various preclinical and clinical studies have shown a positive effect of Ginkgo biloba to improve cognitive abilities in impaired individuals and reducing anxiety under pathological conditions [1] G. biloba is an effective complementary treatment for ADHD [2] It had a significant difference in ameliorating total and negative symptoms of chronic schizophrenia as an adjuvant therapy to antipsychotics [3]. [1] https://www.ncbi.nlm.nih.gov/pubmed/27908257 [2] https://www.ncbi.nlm.nih.gov/pubmed/25925875 [3] https://www.ncbi.nlm.nih.gov/pubmed/25980333 And keeping the diet diverse I feel you often can't put all your eggs in one basket "___ will effectively fix ___" etc. It's easy to get hyped up about one particular option, float on the wings of expectation, then crash and burn. When you're really mixing it up, I feel the magic starts to come alive. Just like we see in the diet, if you eat the same food all the time, it simply doesn't work and it can easily be detrimental - healthy dietary diversity scores correlate strongly with depression and anxiety in studies. When dealing with healing plants, particularly those used as food, why is it not the same? Often we're tempted to say something will fix something etc and run with it exclusively as a therapeutic. In my experiences, not to discount individual healing potentials, they could be better mixed up in a diverse phytochemical rich diet than using it as a standalone in a more lackluster diet? Today my sprout jar is packed with ready Radish and Broccoli again Yesterday, made Ginkgo pesto with the season's leaves. Along with some Ginkgo, had a Rosemary and Savory tea. Few mixed berries. Have different sprouts with the Ginkgo pesto, which tastes surprisingly nice, also put it on some steamed kale an Roselle leaf with dinner The day before it was a Hibiscus, raspberry, blueberry and citrus peel chia pod. Mistletoe. Green tea The day before a pomegranate session with other healthy additions. Lots of sprouts Unfortunately the "therapeutic merits" of plants and natural products is also propelled by commercial interest so it's easy to buy into that and think one plant is a magic elixir. That's not to say they're not often effective therapeutics but there are strong vested interests Take for example, blueberry research literally funded by Big Blueberry The latest spearmint research for cognition carried out on a propriety blend of a special, patented "high rosmarinic acid" type of Spearmint Ginkgo propelled by trials utilising patented, standardised extracts Saffron research occurring in Iran through government funding, seemingly with the hopes of fortifying the value of their "red gold" etc etc I was one who bought into the promises of Big Blueberry and used them as my almost exclusive fruit... That said, based on the current evidence, a recent review of the available evidence found "blueberries may improve some measures of cognitive performance when consumed for up to six months in duration" [1]. Take for example a variety of fruits are finding therapeutic merit Blueberry, strawberry, pomegranate, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired animal models. Published trials of the benefits of blueberry [2,3], pomegranate [4], grape [5.6,7], flavonoid rich orange [8,9,10] in the treatment of small numbers of cognitively impaired and healthy populations, including on mood, have recently appeared. Some we hear little of - eg raspberries. The health-promoting potential of red raspberries includes modulating metabolic disease risk, especially cardiovascular disease, diabetes mellitus, obesity, and neurodegenerative disorders—all of which share critical metabolic, oxidative, and inflammatory links They contain a unique profile of anthocyanins and ellagitannins (with effects via ellagic acid). Red raspberries contain ~92.1 ± 19.7 mg anthocyanins/100 g of fresh fruit [11] Really it seems they are best used as healthy additions to a balanced, varied diet, not trying to carry so much therapeutic weight on their own? That said, I try to avoid the more carbohydrate dense options a bit [1] https://www.ncbi.nlm.nih.gov/pubmed/30999017 [2] https://www.ncbi.nlm.nih.gov/pubmed/28230732 [3] https://www.ncbi.nlm.nih.gov/pubmed/29882843 [4] https://www.ncbi.nlm.nih.gov/pubmed/23970941 [5] https://www.ncbi.nlm.nih.gov/pubmed/22468945 [6] https://www.ncbi.nlm.nih.gov/pubmed/28429081 [7] https://www.ncbi.nlm.nih.gov/pubmed/26864371 [8] https://www.ncbi.nlm.nih.gov/pubmed/28091350 ' [9] https://www.ncbi.nlm.nih.gov/pubmed/26280945 [10] https://www.ncbi.nlm.nih.gov/pubmed/25733635 [11] https://academic.oup.com/advances/article/7/1/44/4524046

Comprehensive review on the interaction between natural compounds and brain receptors: Benefits and toxicity [sci-hub] In case anyone wanted things to add to their bucket list... or needed a natural product for that receptor... Includes: Natural products interacting with nicotinic nAChR and with mAChR. Natural products interacting with ionotropic and metabotropic glutamate receptors. Natural products interacting with γ-Aminobutyric acid type A receptors (GABAAR). Natural products interacting with cannabinoid (CBR) type 1 (CB1R) and type 2 (CB2R) receptors Natural products interacting with dopamine receptors (DAR). Natural products that act on insulin receptors and insulin-like growth factor receptors (IGFRs). Natural products acting on receptors for advanced glycation end-product receptors (RAGE). Natural products interacting with receptors associated with neurotrophic factors (NTF). Natural products that interact with immune system receptors. Natural products that interact with the scavenger receptors associated with oxidative stress. Natural products that interact with peroxisome proliferator-activated receptors (PPAR) Natural products that interact with ApoE or LDL receptors.

Having a proper read through the tables, a little disappointed. One that stood out to me was 3',4',5',5,6,7-hexamethoxyflavone (Eremophila debilis) Flavonoid Binding activity to M1 mAChRs "The aerial parts of the endemic Australian plant Eremophila debilis (Myoporaceae) contain 3% dry weight of the biologically active 5,6,7,3',4',5'-hexamethoxyflavone" [1] I'd in the past experimented with some different Eremophilas (longifolia etc) thinking it might be phenylpropanoid EOs making it such a respected bush medicine. This adds an interesting aspect - a flavonoid muscarinic.

Said three people but I'll likely have enough to send with the next lot of Roselle @superdan Thanks all for the interest.

Still going with this. I particularly enjoy a Radish and Broccoli mix. I buy a wheatgrass/barley grass, spirulina and chlorella affordable mix (from Aldi of all places) that is much easier than doing the wheatgrass though Sorting out the Value of Cruciferous Sprouts as Sources of Bioactive Compounds for Nutrition and Health Edible sprouts are a valuable vehicle and opportunity to impact health, delivering beneficial bioactive compounds once incorporated in the diet on a regular basis. Sprouts of Brassicaceae, like broccoli, radish, kale, mustards, radishes etc are noticed because of their high content of micronutrients, nitrogen–sulfur compounds (glucosinolates (GLSs) and their derivatives, isothiocyanates (ITCs), and indoles) and phenolic compounds (mainly phenolic acids, flavonols, and anthocyanins) Apart from broccoli, red radish sprouts contain high concentrations of glucoraphasatin (4-methyl thio-3-butenyl) and glucoraphenin, which are its major GLSs. Glucoraphenin is hydrolyzed to the ITC sulphoraphene (SFE) It is possible to get "reduction of fasting blood glucose and insulin concentration and resistance to almost [normal] physiological levels. There is notable normalisation of blood glucose levels and the lipid profile

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 " [it] may have considerable potential for use in the control of aggression " [ref] - 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"

Finally got around to exploring this but in a different way. Want to see how it goes for exhaustion at very low doses, not in the stacks that I used to be into... The science of liquorice: whether you love the dark root – or hate it Glycyrrhizic acid itself seems to have neuroprotective effects and other constituents antidepressant and beneficial effects Making my own liquorice Licorice root with Star anise, a little or a lot, to taste has been used to flavour such things [1] It is suggested to consume only low doses at a time of the root I used root (I'm using Glycyrrhiza uralensis) and home grown Aniseed Myrtle, Star Anise etc Aqueous extraction of a decent qty of herbs afforded this solution that I didn't even end up colouring. Smelled delightful. No need for sweetener. Which was then set into little squares with only small doses of root in each. I also made sugar free homegrown Hibiscus, Monk Fruit, Cinnamon and Clove 'jam' that turned out really nice for Hibiscus' medicine in a sugar free way and family enjoyed that

Trying different proteins for serotonergic effects (along with Mg/Zn etc) these days Protein source tryptophan from seeds with a high tryptophan-to-total protein ratio can be comparable to pharmaceutical grade tryptophan in some studies [1, 2] They are nutrient-dense and mostly anti-nutrient-free. The seeds of Cucurbita sp.have been traditionally used as medicine. Among the Cucurbitaceae members, pumpkin seeds are big, abundant, and edible. Yet, these seeds are mostly discarded as agro-industrial wastes [3]. They are rich in protein, polyunsaturated fatty acids (PUFA), minerals (magnesium, phosphorous, copper and potassium, iron, zinc, manganese), carotenoids, beta-carotene, and Vitamin E "...a remarkable assortment of health-enhancing nutrients, from magnesium, protein, niacin, and zinc, to its high concentration of tryptophan and essential fatty acids, pumpkin seeds provide a powerful health punch" - anti-inflammatory and anti-oxidative properties - protective activity against cardiovascular diseases - hypoglycaemic properties: Acute consumption of 65 g of pumpkin seed markedly reduced postprandial glycemia. Pumpkin seed has potential as a hypoglycemic food [4] - because of the high tryptophan content, pumpkin seeds might ease depression, anxiety, nervous irritability and insomnia - shown to improve the iron status I like other 'waste' products that are healing, too. [1] https://www.ncbi.nlm.nih.gov/pubmed/18066139 [2] https://www.ncbi.nlm.nih.gov/pubmed/16053244 [3] https://www.ncbi.nlm.nih.gov/pubmed/28463796 [4] https://www.ncbi.nlm.nih.gov/pubmed/30055778 Sure I try to put love into some meals but other times, just need sustenance. I chew through quite a bit of protein powder to keep at 0.8g/kg. Was doing well dropping weight by using that. I've tried so many proteins from hemp to soy but just settle on whey most of the time. Epidemiological and clinical studies have shown that dairy products have beneficial effects on cognitive decline and dementia, which may in part occur through whey peptides [1] As I've sort of subjectively noticed, chronic ingestion of diets differing in protein source elicits marked differences in the brain tryptophan concentrations and serotonin synthesis [2]. and tryptophan concentrations and serotonin synthesis in brain neurons are remarkably sensitive to which protein is present in a meal [3]. Whey protein has been proposed as a potential functional nutritional food supplement that prevents the progression of neurodegenerative disorders [4] and and useful for metabolic disorders [5,6] A hydrolyzed protein source may be more adequate to increase brain tryptophan and 5-HT function compared with intact alpha-lactalbumin protein or pure tryptophan [7]. While there have been "no significant changes in clinical outcomes" in some neurodegenerative disorders like Parkinson's in human studies, it improves some biomarkers [8] Whey consists of a heterogeneous group of proteins, including beta-lactoglobulin (35%), alpha-lactalbumin (12%), proteose peptone (12%), immunoglobulins (8%), and bovine serum albumin (5%) Due to greater solubility, more rapid digestion, and resultant higher plasma concentrations of amino acids, whey appears to be a favourable protein to provide nutritional and functional benefits. alpha-lactalbumin: - Lactalbumin increased plasma tryptophan (3-fold) and the tryptophan ratio (50%) [9] - may enhance sustained alertness early in the morning after an overnight sleep, most likely because of improved sleep [10]. - Dietary protein rich in alpha-lactalbumin improves cognitive performance in stress-vulnerable subjects via increased brain tryptophan and serotonin activities. - Supplements of lactalbumin may be useful for nutrition research in relation to age- or disease-related memory decline [11] [1] https://www.ncbi.nlm.nih.gov/pubmed/30011836 [2] https://www.ncbi.nlm.nih.gov/pubmed/23395255 [3] https://www.ncbi.nlm.nih.gov/pubmed/19454292 [4] https://www.ncbi.nlm.nih.gov/pubmed/29199432 [5] https://www.ncbi.nlm.nih.gov/pubmed/26516411 [6] https://www.ncbi.nlm.nih.gov/pubmed/25888881 [7] https://www.ncbi.nlm.nih.gov/pubmed/18648776 [8] https://www.ncbi.nlm.nih.gov/pubmed/27423583 [9] https://www.ncbi.nlm.nih.gov/pubmed/23395255 [10] https://www.ncbi.nlm.nih.gov/pubmed/15883425 [11] https://www.ncbi.nlm.nih.gov/pubmed/16174675

Yeah that's the one, I assume it could have been a niacin flush but have never had niacin as nicotinic acid, always nicotinamide and never had issues so not sure.

Happy Bicycle Day all. One plant I was really impressed with over the heat was Hibiscus sabdariffa. I didn't know if it would do very well down here but it's pretty much everything I'm looking for in a plant over the warmer time of the year, it thrived in the crazy heat without being a pain to water. Easy to grow, super tough, high yielding as a medicinal and for food. First you get a barrage of beautiful aesthetic flowers then a continuous supply of calyx (albeit mine a little smaller than what I often see commercially) and leaf. The leaf is nice as a cooked/salad green (if you like lemon flavours) and if you want a hit of tasty sourish goodness, the calyx are nice even raw. Plants like this really do make your food your medicine. I have quite a bit of Roselle this year if anyone has interest in free seed soon (No WA/Tas), feel free to express interest. Actually after tips on the best way to collect the seeds, just let them ripen fully on the plant? if anyone has knowledge? I'm a bit conflicted, one source says "usually harvested ten days after the flower blooms. The large flowers fade and fall off, leaving behind their bright red, fleshy lotus shaped calyces. The Roselle flower seeds are then dried to be planted later and the fleshy red calyces are dried or eaten fresh." I've got lots of pods from when I was harvesting calyx - these viable or do the pods need more specific ripening time on the plant? These look viable and currently available: Some permaculture people "definitely recommend planting Rosellas in the garden if you are in a warmer climate." [Good review on this plant] [2] Review on the pharmacology The plant showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others. [3] Using the leaf as a cooked green: Hibiscus sabdariffa is "high in essential nutrients required for optimal performance of health and the maintenance of good health together with the reduction of aging". 10 polyphenols including chlorogenic acids, quercetin, kaempferol etc were identified in the leaves along with good levels of carotenoids showing good antioxidant and anti-inflammatory activity Hibiscus derived polyphenols are known to ameliorate various inflammation-related conditions, including obesity. The mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications [4] It can be considered as a food rich in lutein, chlorogenic acids and anthocyanins [5]. The organic acids such as hibiscus, dimethyl hibiscus, and hydroxycitric acid were strongly associated with some beneficial health effects [6]. A preliminary study on the use of this as an alternative source of iron for the treatment of anaemia and some other mineral deficiency diseases was promising Different works have demonstrated that Hibiscus sabdariffa extracts reduce blood pressure in humans - this effect is due to angiotensin converting enzyme (ACE) inhibitor activity [7]. The polyphenol content in H. sabdariffa works as an anti-inflammatory by improving antioxidant conditions and regulating the expression of cyclooxygenase-2 [8]. Other Hibiscus anthocyanins have anti-depressant properties through dopaminergic, adrenergic and serotonergic mechanisms [9] . Possibly Effective for: Hibiscus flower normalises blood pressure and exerts a protective effect on the heart. New research is underscoring the possibility of using hibiscus to normalise blood sugar. Reports have shown that H. sabdariffa derived bioactive compounds are potent in the treatment of obesity with an evident reduction in body weight, inhibition of lipid accumulation and suppression of adipogenesis through the PPARγ pathway and other transcriptional factors [10] Low doses of Roselle tea or supplements appear to be effective in reducing blood pressure, and may be anti-diabetic. High blood pressure. Some early research shows that drinking hibiscus tea for 2-6 weeks decreases blood pressure in people with mildly high blood pressure. Other early research shows that taking a hibiscus extract by mouth for 4 weeks may be as effective as the prescription drug captopril for reducing blood pressure in people with mild to moderate high blood pressure. However, an analysis of results from various clinical studies suggests that there is not enough evidence to draw strong conclusions about the effects of hibiscus in reducing high blood pressure [11]. Also heaps of Ashwagandha seed still left.

On that, I did use a bit of Nutritional Yeast for a bit thinking it would be good to be all dietary and stuff, bit of protein too. Cheesy and stuff. Good in theory. It's got a fair bit of niacin, don't know if that's why I'd break out in a strange peripheral reaction but really just doesn't compare to supplements many a time IMO. RDIs are not always applicable IMO

Did you not anything @Xperiment Hope you're going OK! Trying to work out what I need without wasting money has been interesting. I've been on and off these. Simply supplementing only B1 leaves you open to not getting enough of the others but I wanted to see if those "Executive B Stress Formulas" etc do anything other than give you fluoro pee? That was what I wanted to see, how I'd go without them. What's your opinion? Do you use them? It is proposed that "supplementation, particularly with those higher in B vitamins, may improve cognition and mood, which might be facilitated by improving brain health" and that dietary intake above the RDI is often useful, particularly for brain health and even when vitamin status, according to the traditional criterion, is adequate there may be significant mental improvements [1]. I stopped my B-group supplementation for quite some time thinking I'd save some slight cash but despite attempts to eat well, I'm not sure it is providing adequacy for B-groups in particular, I started to show some potential deficiency signs physically. I was one of those that tried everything from L-methylfolate to thiamine etc at very high doses but there seems to be personally better effects with the spectrum. I use one with all B-groups at high doses (and methyl-B12), which is realistically affordable as a daily addition A meta‐analysis found that adjunctive treatment with high‐dose B‐vitamins significantly reduced total psychiatric symptoms among 297 long‐term patients in 7 different studies [2] I found thiamine quite a useful addition, but tended to feel it's better to go for the full spectrum at a higher dose. The B-group is proposed to be a useful "complementary therapy in several neuropsychiatric disorders" and "may have specific neuroprotective properties in attention/vigilance" in psychotic disorders [3] and "B vitamins can be useful as complementary strategies" [4] but currently the evidence is "inconsistent". It has been claimed that "administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health" [5]. "Even in healthy humans, multivitamin supplementation has been shown to improve cognitive performance and reduce negative mood states, including depression, anxiety, and stress" and several studies point "toward the efficacy of vitamin and mineral supplementation, particularly B vitamins, in preventing and alleviating disease and disability" High-dose B-group supplementation [6]: - acutely may improve contentment and cognitive task performance in adults - shown to reduce negative mood states of personal strain, confusion, and depression when administered chronically in healthy individuals - reduced fatigue and improved performance during a cognitive tasks - shown to reduce blood markers for oxidative stress, inflammation and increase brain markers for oxidative metabolism and myelination [1] https://www.ncbi.nlm.nih.gov/pubmed/9122365 [2] https://www.ncbi.nlm.nih.gov/pubmed/28202095 [3] https://www.ncbi.nlm.nih.gov/pubmed/30771856 [4] https://www.ncbi.nlm.nih.gov/pubmed/29171643 [5] https://doi.org/10.3390/nu8020068 [6] https://www.ncbi.nlm.nih.gov/pubmed/30513795

Hope all are well. I'm still trying to manage this with diet and exercise before it becomes more problematic for me. I'm still dropping kg but have had lots of use of SGAs which cause severe lasting metabolic adverse effects, such as elevated blood glucose and insulin resistance (IR) Still like cinnamon and anthocyanins and a planty diet but have problems still. Trying to find as close to food options as possible. While plain tea can offer some slight dietary support, I'd like more glucoregulatory function Several herbs have also demonstrated benefit in glycemic control in clinical trials. These herbs and herbal extracts include berberine, ginseng, gymnema, banaba, cinnamon, fenugreek, and kudzu. While many of these herbs appear to be promising when used in isolation, the practice of herbal medicine most often utilizes polyherbal combinations for purported synergistic effects [review] While berberine is promising both for it's metabolic effects and on the brain, it's one I do have concerns with regard to interactions with that are clinically relevant "interactions should be considered when berberine is administered" for CYP2D6, 2C9, and CYP3A4. I like fenugreek but it does seem to have some effects on the GI tract that can be less wonderful. Cinnamon seems a useful adjunct as the "polyphenolic polymers, found in cinnamon, appear to potentiate insulin action by increasing phosphorylation of the insulin receptor, thereby increasing insulin sensitivity, which may lead to improvements in blood glucose control and lipid levels". [1] but often with "modest effects" [2] As an isoflavone option that is food based, I like the idea of Kudzu Pueraria lobata could interfere with SGA-associated IR and revert overexpressed IR-related proteins [3]. This is intriguing as it's also a promising rapid-acting antidepressant compound through AMPAR-mTOR signaling pathway activation and increased BDNF [4] exerts anxiolytic-like effects, which may be "associated with normalization of 5-HT levels and biosynthesis of allopregnanolone in brain" [5] and alleviated the behavioural deficits induced by chronic stress [6] and may be a "potentially valuable preventative therapeutics for memory-related nervous disorders" [7]. Have a big bag of standardised kudzu. While chromium supplementation has been promising results are mixed. Saffron is also promising. Review: https://www.ncbi.nlm.nih.gov/pubmed/30616613 [1] https://www.ncbi.nlm.nih.gov/pubmed/30144878 [2] https://www.ncbi.nlm.nih.gov/pubmed/27618575 [3] https://www.ncbi.nlm.nih.gov/pubmed/30946280 [4] https://www.ncbi.nlm.nih.gov/pubmed/30284466 [5] https://www.ncbi.nlm.nih.gov/pubmed/29101599 [6] https://www.ncbi.nlm.nih.gov/pubmed/28740098 [7] https://www.ncbi.nlm.nih.gov/pubmed/28734961

Really good review, some people here will likely be interested. One I'm surprised didn't get mentioned is β-caryophyllene for it's notable CB2 affinity. I've never been interested in potent CB1 agonists but these other plants interest me. New to me is seeing anthocyanins as cannabinoid modulators Cannabimimetic plants: are they new cannabinoidergic modulators? https://dx.doi.org/10.1007/s00425-019-03138-x [sci-hub] In nature, surprisingly many molecules act on the endocannabinoid system through cannabinoid receptors, degradation or synthesis enzymes. Phytochemicals and secondary metabolites able to interact with the endocannabinoid system have been recently described in a broad range of plants and fruits. It's interesting how changes to diet have likely altered our endocannabinoid system: "...the transition from high-protein hunting and gathering society, to one based on agriculture, and hyper-glucidic and -lipidic, has favored the over-activation of CB1R" Some plants Cannabigerol-like phytocannabinoids called amorfrutins have been identified in the genus Helichrysum Several amorfrutins have been isolated from liverwort belonging to the genus Radula and from two species of the Fabaceae family, Amorpha fruticosa and Glycyrrhiza acanthocarpa Molecules structurally similar to CBD are ferruginene compounds and methylpenanol analogs of CBD extracted from Rhododendron ferrugineum, species belonging to the Ericaceae family. Rhododendron dauricum, a flowering plant belonging to the family Ericaceae native to the North Asian forests, produces daurichromenic acid (DCA) Guineensine belongs to a class of N-alkylamide alkaloids, first isolated from West African pepper (Piper guineense). They are also abundant in numerous other species of Piper genus, such as in P. longum and P. nigrum (the dietary pepper species) guineensine has ability to inhibit the central reuptake of the major endocannabinoids Chelerythrine, present in the plants Chelidonium majus, Zanthoxylum clavaherculis, and Zanthoxylum rhoifolium, and sanguinarine, extracted from Sanguinaria canadensis, Argemone mexicana, Chelidonium majus, and Macleaya cordata, are two benzophen-anthridine alkaloid with potential cannabimimetic action Out of six kavalactones, yangonin has shown good selectivity for CB1R compared to CB2R γ-Sanshool is another alkaloid, extracted from plant genus Zanthoxylums uch as Z. clava-herculis, Z. armatum, Z. bungeanum, Z. piperitum. γ-Sanshool displayed an antagonist profile for CB1R and simultaneously an agonist activity for CB2R From Voacanga africana, three alkaloids with CB1R antagonism, voacamine, 3,6-oxidovoacangine, and 5-hydroxy-3,6-oxidovoacangine, have been isolated. The crude extract of Voacanga africana has been used for the treatment of diseases connected to endocannabinoid systems such as chronic inflammation, mental disorders, and convulsions in children. Indeed, based on binding studies, it was established that these three alkaloids could be considered modulators of CB1R. α-Amyrin and β-amyrin are pentacyclic triterpenes, ubiquitously distributed in the plant kingdom, known to have a number of biological effects produced via indi-rect cannabimimetic mechanisms. α-amyrin is isolated from the resins of Bursera and Protium species of the Burseraceae family. The key sources for β-amyrin include Amphipterygium adstringens, Eucalyptus globulus, Ficus carica, Ficus cordata, Nelumbo nucifera and Byrsonima crassa Even betulinic acid, a pentacyclic triterpenoid, can bind to both CB1R and CB2R Falcarinol, found in many plants of the Apiaceae family (Daucus carota specifically), exhibits binding affinity to both CB1R and CB2R but selec-tively acts as a covalent inverse agonist in CB1R Polyphenols: Biochanin A has cannabimimetic activity seems linked to inhibition of fatty acid amide hydrolase, an enzyme for anandamide degradation A growing body of evidence suggests that anthocyanins incl. cyanidin may have analgesic, neuroprotective and anti-inflammatory properties, and these biological effects are tied to its potential action on cannabinoid receptors. Cyanidin is a ligand with moderate affinity to human CB1R and CB2R There is moderate affinity of catechins to CB1R. Curcumin is an antagonist/inverse agonist towards CB1R but contradictory results have been also produced Magnolol showed a profile of partial agonist with selectivity for the CB2R, while honokiol possesses a signifi-cantly lower affinity for the CB1R The cannabimimetic action of kaempferol may be due to its inhibitory capacity towards the FAAH degradation enzyme. Quercetin, a flavonol associated with rutinose to form the glycoside rutin, showed an upregulation of CB1R Maca - Lepidium meyenii - has action on the endocannabinoid system N-alkylamide lipids show structural similarity with anandamide and bind to CB2R more potently than endogenous cannabinoids. N-alkylamides have been isolated from Echinacea purpureaand Echinacea angustifolia. Moreover, other extracts of Echinacea spp. have demonstrated anti-inflammatory property by PPAR activity. Even Otanthus maritimus (family: Asteraceae) possesses N-alkylamides with a good CB2R affinity

If it is present to an appreciable degree, it is theoretically degraded so quickly by FAAH after oral administration that it's likely not that relevant but some propose there are N-acylethanolamines that slow degradation also in the chocolate. That said some of the fatty acid amides I've found orally sometimes do something at high enough doses. It may be that the abundant catechin flavonols, which seem to have moderate affinity to cannabinoid receptors (and other receptors) are more active. You've got a good lot of fatty acids, some with affinity to CNS receptors, that could also alter endocannabinoid tone. The pharmacology of the tetrahydro-beta-carbolines and isoquinolines in chocolate isn't well established from my understanding One fairly recent review links most of the psychoactivity to these main constituents: "...we would like to propose the “mood pyramid” as a model, summarizing the more general up to the more specific psychopharmacological actions of cocoa and chocolate. There is a large amount of scientific evidence that the flavonoids, more in particular CF, are involved in the cognition-enhancing effects, although this may not be very specific for cocoa or chocolate, since these constituents are widely distributed in nature and in food. At the second level, the methylxanthines caffeine and theobromine have additive and maybe synergistic effects on cognition and alertness, although the role of theobromine remains unclear. Methylxanthines are less common in nature than flavanols, but still not restricted to T. cacao. At the third and gradually more specific level, the tetrahydro-isoquinoline alkaloids, more in particular salsolinol, may exert additive or synergistic activities" [1].

Anyone else gone and planted a few common Camellias for tea purposes? It's quite debated whether non-sinensis teas are caffeine/theanine containing but those who have made tea from it often say it seems more potent. I like to have a mutual living relationship with the medicine I'm using - not simply a commercial consumptive one - so will plant a few common (related) C. japonica which can be used to make tea It, according to some, contains caffeine and catechins of the same kind as C. sinensis but "Japonica seems much more potent, even when processed as green tea." with >5% per weight caffeine in dry leaves but "..not all cultivars will be equally potent" [1] (another study on the contrary found no caffeine [2] and some say the "entire series of reactions required for the synthesis of purine alkaloids was deficient in both C. japonica and C.sasanqua". ) and triterpenes, flavonoids, tannins and fatty acids. It has 42% of C. sinensis' theanine compared to Camellia sasanqua which is slightly higher [3] [1] http://www.koreascience.or.kr/article/JAKO200403042358213.page [2] http://dx.doi.org/10.1270/jsbbs1951.34.459 [3] https://www.tandfonline.com/doi/abs/10.1080/00021369.1984.10866604 Explorations into the effects of tea on behaviour and mental health come at a time of growing scientific interest in the role of nutrition in mental health and preventive medicine. Physicians need more ways of tackling anxiety, depression and age-related cognitive decline — these conditions place a huge burden on health systems, and treatment options are limited - due to the lack of available therapies — around one-third of all people with anxiety and depression never find an effective therapy [1] Tea is on the rise, because so is stress. It embodies mindfulness and the serenity that a lot of stressed people need in their lives, along with being connected to emotions, and promotes a calming sensation for many drinkers [2] [1] https://www.nature.com/articles/d41586-019-00398-1 [2] https://www.sbs.com.au/food/article/2019/03/20/tea-drinkers-are-better-people-and-probably-less-stressed-too

That was beautifully written @mysubtleascention I like the mention so often of harmony - that's a wonderful way to put it. Thanks for sharing.

Yeah I get you on that, it's sad that's the way things are for so many - I too sought the void all too often as life felt totally futile and full of pressures I couldn't handle. I've had to essentially disconnect from the majority of the ways our society runs, which isn't doable for everyone, as it is simply really bad for my health and not feel too guilty about it, the other way was literally killing me way too quickly Thing is, I got a 'safer alcohol substitute' like pregabalin (don't mention the way phenibut went) and tried to use that instead of drinking and got blatantly addicted to it. Dose escalations. Tolerance and withdrawals. These things, if they offer any sort of nice effect, they will have abuse potential and really serious potential for harm away from being not that damaging in themselves - eg people operating heavy machinery is just one I feel if many people got a clean break from drinking even to socially normal levels, ie a good period of total abstinence going, they'd find themselves in a better place where they didn't have to get persistently blasted by anything. So many., even those doing socially acceptable drinking, are in the cycle of use-withdrawal that they don't know what they feel like without it in their lives, which is scary. It really is such a nasty substance for mental health, for spiritual growth for everyone and society. They could too become teetotallers getting bent on a wholesome cup of tea etc I'd rather some decent kava be allowed in, or something planty that could build up a responsible culture of use around it. But while people are used to getting inebriated as culturally accepted there will be issues

Yeah originally they were looking at pagoclone but it could be any α-subtype GABAA targeting drugs/PAM But really, this is another cultural symptom... sure it may be safer than ethanol but seeking such a quick fix is a consequence of a problem, not a solution This was once my Holy Grail quest - to have a safe alcohol substitute/pro-social aid through through things like this Then I noticed how empty mere anxiolysis was. Spiritually devoid. It had no ability to grow you into your Divine Self, it just let you run away Sure, there's severe pathological anxiety which I know is all too crippling but we need more wholesome tools that allow one to be themselves. I still feel plants offer a better tool to return to wholeness. Sure, they may not offer blatant inebriated anxiolysis but that's part of the challenge I feel, to be comfortable with things like anxiety until they no longer over-power you. We need to consider why people are seeking such anxiolysis and feed their spirit to a place where they can have calm loving self-acceptance and compassion, not allow them to run away with another vice. For me, this weekend I could go out... but in all honesty I'd rather not. eg in our society, you have to be absolutely off your head to find the majority of people interesting enough to even be interested in having a convo with them thanks to their cultural conditioning...