Alchemica

Had a good plant medicine session which made me decide to take up daily running with mindful time in nature. EE as a tool can't be discounted. While I'm used to doing brisk walks each day, a run is so much better. They're not the longest at the moment, do a sprint then walk then sprint for as long as I can to go around the block a bit. Seems even acutely, just a couple of days of it superior to brisk walks for a long time etc. Why discounting exercise as a mental health aid is short-sighted I think it hits self esteem really hard when you suffer from depression, anxiety or just the occasional low’ ‘Exercise can be really intimidating because you’re forced to put yourself in front of other people doing something you may not necessarily be good at – which can obviously be really scary. ‘So it’s easier to sh*t on something than try doing it. Novel approaches to alcohol rehabilitation: Modification of stress-responsive brain regions through environmental enrichment Relapse remains the most prominent hurdle to successful rehabilitation from alcoholism. The neural mechanisms underlying relapse are complex, but our understanding of the brain regions involved, the anatomical circuitry and the modulation of specific nuclei in the context of stress and cue-induced relapse have improved significantly in recent years. In particular, stress is now recognised as a significant trigger for relapse, adding to the well-established impact of chronic stress to escalate alcohol consumption. It is therefore unsurprising that the stress-responsive regions of the brain have also been implicated in alcohol relapse, such as the nucleus accumbens, amygdala and the hypothalamus. Environmental enrichment is a robust experimental paradigm which provides a non-pharmacological tool to alter stress response and, separately, alcohol-seeking behaviour and symptoms of withdrawal. In this review, we examine and consolidate the preclinical evidence that alcohol seeking behaviour and stress-induced relapse are modulated by environmental enrichment, and these are primarily mediated by modification of neural activity within the key nodes of the addiction circuitry. Finally, we discuss the limited clinical evidence that stress-reducing approaches such as mindfulness could potentially serve as adjunctive therapy in the treatment of alcoholism. Besides modulating stress hormone production in the periphery, environmental enrichment also regulates stress response by affecting central brain regions. Perceiving repeated aversive events can cause one to become chronically stressed. Chronic activation of the hypothalamic–pituitary–adrenal (HPA) axis can have deleterious consequences on physiological parameters and behaviour (e.g. emotional reactivity, stereotypies, cognition). Environmental enrichment is a robust paradigm which provides a non-pharmacological tool to alter stress response and seems to alter mood and things like risk of relapse. Neurogenesis is stimulated by enriched environments, exercise, and learning and is inhibited by stress and aging. Even the stages of neurogenesis are influenced by these environmental factors. Enrichment and exercise stimulate the proliferation of neural stem cells 1 week of EE is reportedly sufficient to elicit increased cell proliferation and differentiation in the amygdala of adult non-drinking mice, resulting in greater numbers of oligodendrocytes and astrocytes and likely impact higher order brain regions. Physical activity is often investigated as an easily dissociable component of environmental enrichment and elevating the level of physical activity has consistently been reported to modify behaviour, including alcohol seeking etc. "The benefits of EE are well-accepted to be driven primarily through increased neuronal plasticity. This broadly involves alterations to the physiological properties of neurons, enhanced LTP, firing rates and network rhythms, most of which are wellcharacterised by studies of the hippocampus and cortical regions The impact of EE on neuronal networks and region-to-region signalling could account for enrichment-mediated modifications of drugseeking behaviour, e.g. the prevention of drug-induced reinstatement attributed to the modulation of infralimbic cortex activity and reduced cue-induced reinstatement associated with increased perineuronal net intensity within the medial prefrontal cortex"

5HT1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits. They may be important for the normalisation of empathy deficits and increased negative reaction to social exclusion in depressed patients. Recent findings show it is possible to reduce the neural response to negative emotional stimuli and ameliorate social pain in key brain regions responsible for emotion processing and social interactions. There seems to be a strong effect of 5-HT2ARs in mediating things like happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy and impairing the recognition of sad and fearful faces. The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced by 5-HT2A/1A agonist administration compared to placebo. Furthermore, emotional empathy was enhanced 5-HT2 receptors seem to mediate robustly improved behavioural flexibility, elements of prosociality and emotionality, some aspects of mood improvement and reduction of obsessive compulsive aspects. They also are suggested to cause a shift towards 'active coping' while 5-HT1ARs might mediate 'passive coping'. What happens when you choose or bias a plant medicine's actions towards 5-HT1AR but include other serotonergic elements? What element does 5-HT1A bring to their therapeutic potential? I've been biasing my medicines towards 5-HT1ARs lately and amplifying them in that direction. Utilising a 5-HT1A biased medicine approach seems to personally encourage a more friendly emotional aspect towards self and other IMO. Less fear of ego dissolution etc. The stronger 5-HT1A background seems to promote some prosocial aspects and axiolysis while you're working with a medicine. Brings a stronger empathetic heart dimension. Examples of medicines with strong 5-HT1A mediated effects include stronger heart medicines and things like this include DPT and 5-MeO-DiPT: DPT found quite a bit of use awhile back as a shorter acting option. According to therapists' ratings, there was a significant enhancement in recall of memories and experiences, greater emotional expressiveness, deeper levels of self-exploration, and greater psychodynamic resolution. 5-MeO-DIPT is generally known to generate more empathogenic qualities. To me, 5-HT2A agonism has a key role on emotionality (including empathy), spirituality and boundaries between self and other. It also has a strong beneficial effect on behavioural flexibility at seeming even sub-blatantly psychoactive levels. To me, 5-HT1A receptors are, as literature suggests, involved in mediating the emotional state I consider more selective 5-HT2A agonists can be quite counter-productively mind-trippy, they can induce pure loops of mind crap at times. I've always gravitated to ones with naturally more 5-HT1A affinity as being better medicines. 5-HT1A receptor agonism may act to buffer 5-HT2A-mediated effects. 5-HT1ARs are implicated in the prosocial effects of empathogens but that action may be codependent on 5-HT2ARs. 5-HT2A receptors may strongly influence the emotional state, they seem to be 'valves to experiencing self and other' Antagonism of 5-HT2A prevents the prosocial behaviours. 5-HT1A receptors are believed to be crucial in physiological processes linked to emotional balance While it's not always the case that co-agonism of 5-HT1A reduces the intensity of an experience of a classical 5-HT2A (partial) agonist, consider 5-MeO-DMT which is a potent 5-HT1A agonist with lesser 5-HT2A affinity (5-MeO-DMT alters cortical activity via both 5-HT1A and 5-HT2A receptors) - What intrigues me is the therapeutic potential of serotonergics with stronger 5-HT1A effects. Targeting this receptor over a light background of 5-HT2A mediated effect. The action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory and associative (PFC) cortical areas, supporting a role of 5-HT1AR stimulation in sensory and PFC regions, in addition to the well-known action on 5-HT2ARs.

Only few days of having an evening session with Lotus embryo each evening instead of high dose chamomile which was helping get to sleep but not improving sleep quality. While I was mainly using this as a mood tonic, this is used in TCM for insomnia but I find I need high doses initially. While being on a nicotine patch has possibly made sleep easier, I'm finding I'm finally getting to sleep with ease and getting a more solid sleep (instead of being broken I get sleep and don't wake up multiple times a night), with results better than I got with high dose Zizyphus (when stronger meds like low dose quetiapine doesn't work for me anymore -it's pure side effects), I also enjoy the Lotus state. It's a reasonably short lasting state but there seems to be more lasting effects. Literature suggests there is an up-regulatory effect on monoaminergic and GABAergic systems Intriguingly, neferine is not just serotonergic and active at 5-HT1ARs. These Lotus alkaloids display a weak cannabimimetic- type behavioural effect In vivo studies demonstrated sedative, and analgesic effect of N. nucifera embryo extract, and sedative and antidepressant effect of neferine Neferine displayed affinities for δ-and µ- opioid receptors with Ki values of 0.7 ± 0.1 and 1.8 ± 0.2 μM, respectively, and was determined to be a weak δ agonist Decided to explore the dose-response curve for Lotus embryo. Is more a better experience? You have to account for the 'plant spirit synergy'. It's more than neferine. You've got a high flavonoid/polyphenol content and spectrum of alkaloids, all of which seemingly have activity. These alkaloids seemingly require a bit of citric acid etc to liberate a good dose. That helps with the extreme bitterness, too. To me, pushing the dose even higher seemed to induce more hazy uninteresting sedation over an enhanced emotional and spiritual state. There's a middle ground moderate dose pleasant space where you're simply at ease with yourself and able to work through life better, a bit of spiritual attunement etc. While a more moderate dose is anxiolytic, pushing it became seemingly more traditionally sedative. It became duller, benzo-esque - I just had a bit of an uninteresting unenlightening sleep - over catalysing a peaceful state of mind. While TCM dose are quite low, a suggested dose on the pack is 10g. That's where I'd start for explorations. I can't particularly notice that dose. I'm not keen on going extremely high dose, Neferine displays hypotensive effects and inhibits platelet aggregation. It has actions on the heart - neferine displays anti-arrhythmic action due to its inhibitory effect on K+, Na+ and Ca2+ currents of the myocardium and inhibitory actions on hERG channels so you need to use caution. That said, it seems to be relatively safe for long-term treatment While neferine did not affect muscle coordination, it dose-dependently inhibited locomotor activity in mice. It induced hypothermia in mice and apparently potentiated thiopental-induced sleeping time. With the seeds, which contain neferine but at lower levels, in an animal model night-time activity reduced by 53%, but total sleep time was increased by 60%. The sleep-promoting effect was associated with up-regulation of GABAA/GABAB and serotonin receptors. There are suggestions that the Lotus alkaloids exert sedative–hypnotic and anxiolytic effects via binding to the GABAA receptor and activating the monoaminergic system but research on neferine itself seems to be less suggestive on a GABAergic MoA. Other uses of the embryo covered here Contraindications: This is not well studied. It use as a food and lack of serious indications is a good start but caution is required. While the embryo alkaloids have not been specifically studied, lotus leaf alkaloids has a strong inhibitory effect on CYP2D6 isoenzyme activity in vitro. This seems to be due to the more classic aporphine alkaloids over the bisbenzylisoquinolines. That said, neferine is predominantly metabolised in the liver and undergoes initial bioconversion by CYP2D6 into liensinine, isoliensinine, dimethylliensinine, and dimethyl- isoliensinine. There is also known involvement of CYP3A in neferine metabolism Lotus might lower blood sugar levels in some people. Watch for signs of low blood sugar (hypoglycemia) and monitor your blood sugar carefully if you have diabetes and use lotus as a medicine.

Gardenia vs Saffron As for the Gardenia, today is the last session I'll have with that for a bit, likely pursue it more later down the track when I get more, only bought a small quantity. As seen in clinical studies, I'm maybe noting a mood improvement. It's hard to attribute a sole effect to it as I've been using Gardenia in the morning and then unwinding in the evening with Lotus but my initial impressions of it as a medicine from the days I've had with it: Fairly acutely, It seemingly has some energetic balancing qualities but I think saffron is potentially more uplifting - there's a slight beneficial quality I attribute to the dopaminergic activity of saffron, I didn't get that with Gardenia at the TCM-style doses and I don't want to dose too high on it. Despite both being crocin sources and the gardenia containing beneficial iridoids, I find the saffron has potentially more mood effects than the Gardenia at the doses I used but I've used more saffron than Gardenia so have a greater attunement to it's qualities. I'd say the Gardenia at higher TCM doses builds a foundation of greater balance, a somewhat harmonising energy, the traditional medicinal actions attributed to gardenia include calming irritability; cooling and clearing away heat (a yin/yang imbalance often characterized by deficient yin). The saffron on the other hand is what I'd call dose dependently a spiritual energiser when used correctly. They're both useful but I'm going to stick with saffron in the morning for a bit and re-visit Gardenia a bit later. "Saffron is a spiritual and energetic food ... it can affect so much change and offer incredible healing to the body/mind/spirit complex. Through balancing, the energetic body is also brought into cooperation wherein the associating masculine and feminine energies are able to more fully work together." In Ayurvedic Medicine, it helps to enhance qualities of love and spirituality. Saffron currently has a larger clinical body of evidence for neuroprotective, procognitve, anxiolytic and antidepressant effects with preclinical anti-psychotic effects. While Gardenia has preclinical cognitive improvement in studies, there seems to be a decent clinical improvement in cognitive functions with saffron. It was found to be as effective as donepezil for treatment of mild-to-moderate AD. The beneficial effects of saffron on memory have also been suggested to be mediated by the cholinergic system An interaction with glutamatergic system for saffron and its components might be postulated involving NMDAR modulation, there is functional interaction between crocins and the DAergic system. C. sativus and its constituents increased dopamine levels in the brain in a dose-dependent manner. It also interacts with the opioid system

Apart from 5-HT2A agonists, Aya and scopolamine what else is there? Bought some seeds to grow of this one... Gardenia jasminoides possess multiple biological activities, such as antioxidant properties, hypoglycemic effect, inhibition of inflammation, antidepressive activity, and improved sleeping quality. A number of chemical components of G. jasminoides have been isolated and characterized, including iridoids, iridoid glucosides, triterpenoids, organic acids, and volatile compounds. Geniposide, genipin, gardenoside, crocin, and iridiod are the major bioactive compounds found in G. jasminoides. For instance, the yield of geniposide reached 10.9% under certain extraction conditions [1] Gardenia jasminoides showed a significant rapid acting antidepressant effect [2]. The antidepressant response started at 2 hours after administration - similar to ketamine, it may have a great clinical potential for treating patients with depression [3]. It's used in Yueju pill, a traditional Chinese medicine formulated to treat syndromes of mood disorders. Yueju has been shown to promote a fast-onset antidepressant effect clinically and in preclinical studies. An extract had the functions of learning and memory improvement and the neuroprotection [4] Alongside this neuroprotective effect, geniposide enhanced cholinergic neurotransmission, which likely contributes to its memory enhancing effect [5]. Gardenia yellow pigment (GYP) is a collection of compounds with shared structure of crocin, which confers antidepressant activity. These compounds are remarkably enriched in Gardenia jasminoides, implicated in rapid antidepressant effects that are exerted through enhanced neuroplasticity. Antidepressant response was detected at 30 min, and lasted for at least 3 days post a single administration of GYP [6] There's an affordable 10:1 polygala root extract in Aus now. I tried the plain root but found it too mild, an extract might be interesting. "Root of Polygala tenuifolia (Radix polygalae) is a traditional herb used for its tranquillizing and anti-amnesic effects in East Asian countries. Recent research disclosed wide range of biological activities of Radix polygalae and it active compounds, such as dopaminergic D2 and serotonergic 5-HT2 receptor binding, NMDA toxicity protection, prevent depression symptoms in chronic mild stress model animals, and induction of brain-induced neurotrophic factor (BDNF) in the hippocampus. Behavioral tests such as female urine sniffing test, novelty suppressed feeding, learned helplessness paradigm and anhedonia in chronic mild stress exposed animals require repeated dose of monoaminergic antidepressant reagents to exert antidepressant-like effects. But single or two doses of Radix polygalae extract improved depression related behaviors in these tests. Like ketamine, pretreatment of an AMPA receptor antagonist abolished the antidepressant-like effect of Radix polygalae. Also the phosphorylation of hippocampal AMPA receptor GluR1 subunit was changed. Radix polygalae is a commonly prescribed reagent by practitioners of traditional medicine. According to these recent findings, Radix Polygalae extract may have rapid-onset antidepressant effect which can be a safer alternative to ketamine and lead to the development of life-saving medications by reducing the risk of suicide in emergency situations" [7] There's also saffron The crocins are hydrophilic carotenoids that can act as antioxidants, improve learning and memory, be used for treatment of brain injury, mood disorders, OCD, joint pain and muscle dysfunction in osteoarthritis, metabolic syndrome and related mood disorders and neurodegenerative damage, and have a protective effect against brain damage Aside from the NMDA affinity and sigma-1 binding, there is evidence that crocins act as reuptake inhibitors of dopamine and norepinephrine, while aside from it's GABAA affinity, safranal acts primarily on serotonin reuptake. "The antioxidant properties of saffron derivatives may also be relevant. Mood disorders are associated with elevated oxidative stress and a deficit of exogenous antioxidants, affecting immune and inflammatory responses in a way, which may promote neurodegeneration (Leonard and Maes, 2012). There is good evidence that the antioxidants in saffron extracts protect against oxidative stress in the central nervous system (Mehri et al. 2015; Oruc et al. 2016), constituting a second potential mechanism of therapeutic action. The most important indicator of the quality and commercial value of the saffron is its contents of crocin I and II, which are specified in trade standards. The Chinese Pharmacopoeia stipulates that the total content of crocin I and II should not be less than 10.0 %." In an analysis of 63 saffrons, the crocin I content range was 6.6–23.7 %. There is a TGA listed coated tablet containing either 11 mg or 14 mg of standardised saffron extract (affron), derived from the stigmas of Crocus sativus L. and standardised to contain >3.5% Lepticrosalides® (a measure of bioactive compounds present in saffron, including safranal and crocin. Two tablets daily constitutes a dose. Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. It reputedly has acute effects. Safranal is an effective anticonvulsant in animal models, shown to act as an agonist at GABAA receptors. Saffron extracts and crocetin had a clear binding capacity at the PCP binding side of the NMDA receptor and at the sigma-1 receptor while crocins attenuated schizophrenia-like behavioural deficits. Crocin has been shown to be an antioxidant and neural protective agent Saffron is a potential efficacious and tolerable treatment for major depressive disorder with anxious distress. [1] It increased mood, reduced anxiety and managed stress without side effects, offering a natural alternative to standard treatments [2] Saffron is as effective as fluvoxamine in the treatment of patients with mild to moderate OCD [3] More on saffron here:

Rethinking medicinal plants and plant medicines We need to “engage conversation between different ways of making medicine ‘work’ in-the-world” When medicinal plants become mobile and are studied in laboratories or in different cultures they are conceivably dislocated from the knowledge and rituals of the healers. Hence, medicinal knowledge is seen as not necessarily located within entities such as plants, but rather in the therapeutic transformation/s that emerge from healing “encounters and their traces”. How much therapeutic efficacy are we losing by doing that? What happens if I interact with medicines with the plant as an entity over being a mere source of bioactives? What happens when you include Ritual, Ceremony and the Sacred Element of Art [1] Currently, medicinal plants are increasingly being integrated into economic enterprises and scientific investigations. Medicinal plants are acted on: removed, pressed, catalogued, chopped up, transplanted and exploited. In their biocultural diversity, plants ... act on and within people. Enmeshed with humans, these plants, arguably, encourage their own cultivation. In much anthropological literature, it is argued that the ability of medicinal plants is activated by the knowledge of healers, their rituals, preparation methods and interaction with the spirits. A number of scholars describe the social-cultural power of plants and plant intelligence, as well as their volitionality, vibrancy and communication. In many cultures, medicinal plants have potency and are viewed as “masters,” “teachers” or “doctors,” able to impart strength and wisdom and to aid in learning. "They [healing plants] know [ǂang] how to change/repair what is wrong [the sickness]. Medicinal plants have a good/strong spirit, they are of nature [tci kxao]. I ask the plant for its strength/power to heal, but I must always give something back to the plant." Certain medicinal plants have the power to bring about change and healing. This ability and knowledge comes from nature, the spirit, soul or breath-essence of the plant, apart from the skill of the healer and his respectful relationship with the plant. The chemical potentiality of psychoactive plants arguably becomes enmeshed with healers’ and users’ collective and individual histories, their physiological and psychosocial dispositions, as well as their beliefs, meanings and intentions to relationally become-with in healing and bringing about spiritual, mental and therapeutic effects. Could we, in fact, make sense of plants as actants, entities that can have an effect on their environments and relationships within it? If we see “elements in the environment as persons,” that is they are gifted with “cognitive, moral and social qualities analogous to those of humans.” These approaches assimilate plants and spirits in the category of persons. Plants play a key role in human existence, but are also viewed as “entities that act as humans and thus as social agents — not just in … healing and magic, but also in everyday life.” Many medicinal plants are administered internally and have “mutually inclusive physical, psychological and spiritual therapeutic effects”. These are activated through the interaction between ritual dynamics, the phytochemical synergy of the plants’ therapeutic capacity, the mixtures utilised and the psyche of the user The plant “made/turned it [sickness/sick person] into something else [kuru ka ko tci dore]”: by bringing about transformation, it could heal [dù !kóbó]. "The ability to heal comes from the n/umkxao’s openness to and management of the relationship with the kgwe (power), the breath/essence/good spirit [ma’a cua] of the plant itself, the environment, the air [n|a’àn], the wind [màq], the spirits [//gauwasi]" etc [1] http://creativeawakeningnow.podbean.com/e/ep-5-ritual-cere…/ Full text: http://sci-hub.tw/…/…/doi/full/10.1080/23323256.2017.1415154

As we shift with the seasons, how is your medicine shifting? What's coming up for use in your plant medicine apothecary? I'm trying to get used to shifting my medicine with the seasons. I already strongly feel the energetics shift, trying to use Nature's abundant gifts seasonally to stay healthy is an interesting challenge. Seasonal Plant Medicine "It is the natural ebb and flow of relationship, the giving and the taking, and all the emergent properties that develop in response to dynamic interaction. Wild medicine, medicine infused with relationship and interconnection, is the strongest medicine because of its gentle harmony." The decrease in sunlight will signal diametrical changes in the body. The flush of flavonoid rich plants became useful as one enters an elevated inflammatory state during the darkest and coldest part of the year. There is a rhythm and a balancing implicit to our dance with the plant world across the seasons. "It is a relationship that has evolved over impossible expanses of time. It is the opposite of a new, synthetic wonderdrug hastily derived in an isolated lab and quickly delivered to market. It is slow medicine, derived over millennia in concert with all creation, as each season of sun and wind and rain unfolded to inspire a new genetic expression. The therapeutically “active” chemical compounds found in medicinal plants are actually secondary metabolites that are expressed explicitly in plants when they are in relationship with other energetic and physical phenomena. The “stressors” of exposure to sun, heat, cold, herbivores, and microorganisms inspire a new set of chemical expressions by the plant, and these medicinal compounds are considered its immunological defense. Which is another way of saying, the medicine song of a plant is the same tune that resonates and inspires healing within us. We join in sacred relationship with the plant world when we warm up with a cup of tea blended with the right herbs to send blood flowing to our periphery in winter." Of late, that's been upping my olive leaf polyphenols, whereas diversity was really healing, this will be a bit of a background to have going as seasons shift. I use a supplement as well as the leaf as raw medicine. Olive leaf polphenols act as modulators of the human immune response. These have strong neuroprotective, antioxidant, anti-inflammatory and immunomodulatory properties. They seem strongly protective in animal models of neurodegenerative disorders, from Alzheimer's to MS. They increased the levels of NGF and BDNF in the serum, maintain healthy redox status and boost neurotrophins which play key roles in learning and memory processes and in the proliferation and migration of endogenous progenitor cells.

While I've had a few people explore the leaf and nuciferine rich extracts, I personally find the embryo the most healing component. Soma as Nelumbo? Keen to know anyone who's played with high dose Nelumbo? Particularly embryo. I've seen a few reports on here with stamen are interesting, I found embryo a nicer medicine. I'm keen to have it in my diet more often. A Botanical Perspective on the Identity of Soma (Nelumbo Nucifera Gaertn.) Based on Scriptural and Iconographic Records "If and when Nelumbo proves to possess psychoactive constituents that live up to the reputation of Soma, our current perspectives on the origin and development of eastern religions will require a thorough re-examination." I've explored nearly all parts of the lotus, bar the petals (but have used stamen). They embryo is my preferred part. The root is nice as a grounded healing polyphenol source, the seed mild, the leaf and nuciferine leaf extracts personally not desirable, while the embryo possesses nice qualities. In high doses, I find it possesses an almost dream like hypnotic state of anxiolytic softness, uplift, vividness and peaceful spirited attunement. In the right set and setting and a cultural background involving spiritual awareness, it could be a candidate for something along the lines of Soma. As a plant which can be used as both food and medicine, lotus plumule has high nutritional values and pharmacological effects, such as treating cardiovascular diseases, nervous disorders, insomnia and high fevers, etc Various chemical constituents including alkaloids, flavonoids and volatile oil have been isolated from lotus plumule Among these compounds, alkaloids are the main composition in lotus plumule. Liensinine, dauricine isoliensinine, neferine and nuciferine show good bioactivity and healthcare function [1] A few times now I've used embryo at higher doses to de-stress, get some mood improvement, find some spiritual attunement and get a nice sleep. Contrary to many extracts, often from leaf, that are nuciferine rich and not overly spiritual (they possess atypical antipsychotic-like profiles), I can see a spiritual aspect to these parts richer in bisbenzylisoquinolines like neferine with 5-HT1A serotonergic dimensions. Neferine is a direct 5-HT1A receptor agonist and may inhibit 5-HT reuptake or activation of 5-HT metabolism. It alters 5-HT1A receptor binding in stress induced depressive conditions so it may be possible that habitual ritual intake induces changes, too that may heighten day-to-day spirituality? Neferine is not just serotonergic and active at 5-HT1ARs. These Lotus alkaloids display a weak cannabimimetic- type behavioural effect. In vivo studies demonstrated sedative, and analgesic effect of N. nucifera embryo extract, and sedative and antidepressant effect of neferine Neferine displayed affinities for δ-and µ- opioid receptors with Ki values of 0.7 ± 0.1 and 1.8 ± 0.2 μM, respectively, and was determined to be a weak δ agonist While there have been mixed findings and difficulty in replication, 5-HT1A receptor binding has been implicated in spirituality/self-transcendence (incl. the degree to which an individual feels part of nature and the universe at large, and to extraordinary experiences such as extra sensory perception and sense of a transcendent being or presence). Prosocial behaviour and oxytocin release can be stimulated through 5-HT1A receptors, oxytocin bolsters feelings of spiritual connectedness. It is proposed postsynaptic 5-HT1AR signalling is involved in stress moderation. The other alkaloids liensinine and isoliensinine from Nelumbo nucifera have antidepressant-like effects, closely related to serotonergic mechanisms, also involving 5-HT1ARs. Coupled with alkaloids, the high levels of interesting polyphenols makes it nice.. I've had much more notable responses to Lotus embryo (that's $2 for a bag from the Asian supermarket) than I've ever had from Nymphaea. The most noticeable subjective effects are that Nelumbo embryo exerts antidepressant, anxiolytic and sedative effects, quietens a chattering mind, increases the vividness of experience, while deepening sleep at the same time. Lian Zi Xin. (Lotus). (plumule). Embryo of lotus seeds are used in traditional Chinese drug called ‘Lian Zi Xin’, which primarily helps to overcome nervous disorders, insomnia, high fevers (with restlessness) and cardiovascular diseases (e.g. hypertension, arrhythmia). It is a herbal medicine frequently used in treatment of depression in many Asian countries. The green embryo of Nelumbo nucifera seeds mainly contain three structure-related bisbenzylisoquinoline alkaloids including liensinine, neferine, and isoliensinine. These three bisbenzylisoquinoline alkaloids are reported to possess a wide range of biological activities including anticarcinogenesis, anti-arrhythmia, anti-hypertension, anxiolytic/sedation, and anti-depression. Studies have documented that liensinine, neferine, and isoliensinine can cross the blood–brain barrier and have recently received much attention for their neuroprotective effects. Liensinine, neferine and isoliensinine have anti-neuroinammatory effect and open a new avenue to understand the potential of this health food in the treatment of neurodegenerative diseases Experimental evidence suggests Lotus embryo provides drastically greater anti-depressant effects than Hypericum perforatum (commonly referred to as St. John's Wort, perhaps the most widely used natural anti-depressant today). The antidepressant effect was comparable with that of maprotiline and imipramine. Neferine itself attenuated learning deficits induced by scopolamine "Neferine itself at 10-100mg/kg was able to acutely (within 30 minutes) reduce immobility time in a forced swim test indicative of anti-depressive effects; when compared to Imipramine HCl as active control, it slightly (but nonsignificantly) outperformed at equimolar doses." Neferine, Liensinine, isoliensinine, lotusine, methyl-corypalline, demethyl-coclaurine have been detected in the embryo. Neferine shows antidepressant-like effects in mice similar to typical antidepressants and that these effects are mediated by the 5-HT1A receptor. It reverses a decrease in 5-HT1A receptor binding in rats with depression-like symptoms induced by chronic mild stress. Neferine shows anxiolytic activity similar to diazepam "The therapeutic properties of neferine is widely diverse, while it shows toxicity to cancer it also shows cyto-protective effects against cardio-vascular diseases, pulmonary disease, and is also effective against Alzheimer's disease and elicits anti-oxidative effect in many cellular systems." [2] While TCM dose are quite low, a suggested dose on the pack is 10g. That's where I'd start for explorations. I can't particularly notice that dose. I'm not keen on going extremely high dose, Neferine displays hypotensive effects and inhibits platelet aggregation. It has actions on the heart - neferine displays anti-arrhythmic action due to its inhibitory effect on K+, Na+ and Ca2+ currents of the myocardium and inhibitory actions on hERG channels so you need to use caution. That said, it seems to be relatively safe for long-term treatment While neferine did not affect muscle coordination, it dose-dependently inhibited locomotor activity in mice. It induced hypothermia in mice and apparently potentiated thiopental-induced sleeping time. With the seeds, which contain neferine but at lower doses, in an animal model night-time activity reduced by 53%, but total sleep time was increased by 60%. The sleep-promoting effect was associated with up-regulation of GABAA/GABAB and serotonin receptors. There are suggestions that the Lotus alkaloids exert sedative–hypnotic and anxiolytic effects via binding to the GABAA receptor and activating the monoaminergic system but research on neferine itself seems to be less suggestive on a GABAergic MoA. Other uses of the embryo: Neferine decrease fasting blood glucose, insulin levels, triglycerides and tumor necrosis factor-α and also possess anti-obesity effects. Neferine also enhances the insulin sensitivity in insulin resistance. Thus, neferine is a potent anti-diabetic agent that is equivalent in its potency to rosiglitazone, an insulin sensitizer used in treatment of diabetes mellitus type 2 Lotus embryo also contains polysaccharides with strong TLR antagonistic anti-inflammatory effects for inflammatory diseases. Significant anti-cancerous properties of neferine have been reported in a number of studies on different in vitro and in vivo models of cancer There is a direct antitumor effect of neferine, suggesting that consumption of neferine may have cancer-preventive and cancer-therapeutic benefit. Neferine is an apoptosis inducer in lung cancer cells. Neferine has shown anti-amnesic effect with significant improvement in cognitively impaired animal models which had been induced with scopolamine. As I've mentioned, there is strong anti-Alzheimer and neuroprotective effects of Liensinine and neferine, including potent inhibitory activiton β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), Acetylcholine esterase (AChE) and Butyrylcholinesterase (BChE). The anti-amnesic activity of neferine may be occurring through anti-oxidant and anti- inflammatory activities and also due to inhibition of BACE1 and ChEs. Efficacy of neferine is also reported against neuro-degenerative disorders. have been demonstrated to have anti-AD activities by inhibiting acetylcholinesterase (AChE), Contraindications: This is not well studied. It use as a food and lack of serious indications is a good start but caution is required. While the embryo alkaloids have not been specifically studied, lotus leaf alkaloids has a strong inhibitory effect on CYP2D6 isoenzyme activity in vitro. This seems to be due to the more classic aporphine alkaloids over the bisbenzylisoquinolines. That said, neferine is predominantly metabolised in the liver and undergoes initial bioconversion by CYP2D6 into liensinine, isoliensinine, dimethylliensinine, and dimethyl- isoliensinine. There is also known involvement of CYP3A in neferine metabolism Lotus might lower blood sugar levels in some people. Watch for signs of low blood sugar (hypoglycemia) and monitor your blood sugar carefully if you have diabetes and use lotus as a medicine. "A close examination of the mythic and artistic records of India and Southeast Asia indicates that the famous inebriant of the ancient Aryans was the eastern lotus, Nelumbo nucifera. Vedic epithets, metaphors, and myths that describe the physical and behavioral characteristics of soma-as a sun, serpent, golden eagle, arrow, lightning bolt, cloud, phallic pillar, womb, chariot, and immortal navel-relate individually or as a whole to the eastern lotus. Since most Hindu and Buddhist gods and goddesses trace their origins from the Vedas (or at least share a pedigree of Vedic origin), and have always shared close symbolic associations with Nelumbo, there is reason to believe the divine status of this symbolic plant derives from India's prehistoric past. Various plants that are known to produce psychoactive properties, such as marijuana (Cannabis sativa L.), Ephedra, opium poppy (Papaver somniferum L.), Syrian rue (Peganum harmala L.), ginseng (Panax), and the fly-agaric fungus, Amanita muscaria (Fr.) S.P. Gray (Doniger 1968; Falk 1989; Flattery and Schwartz 1989; Mahdihassan 1981; Nyberg 1995; Spess 2000), continue to provoke heated debates and discussions among linguists and students of the ancient Orient. Many plant species that have been proposed thus far as possible soma candidates have proven unable to elicit psychoactive responses in human beings, such as rhubarb (Rheum), grapes (Vitis), pomegranates (Punica), moonseeds (Cocculus), ironweeds (Vernonia), hops (Humulus), ginseng, and various milkweeds (Doniger 1968; Flattery and Schwartz 1989; Nyberg 1995)." The use of 5-HT1A modulators interests me. I find them more social and emotional allies. There is a substantial role of serotonin activity in the expression of social behaviour including affiliative behaviours and 5-HT1ARs seem to be strong modulators of this. There are distinct roles for autoreceptors and postsynaptic receptors in mediating emotion-related behaviour. 5-HT1A receptors modulate the fear memory associated with the social defeat experience. There are decreased levels of 5-HT1A following social defeat in the PFC Mice lacking the 5-HT1A receptor display decreased exploratory activity and increased fear of aversive environments suggesting reductions in density of the receptor might result in heightened anxiety. Some 5-HT1A agonists increase social behaviour and have potent effects on aggressive behaviours, being 'serenic'. Acute and chronic administration of 5-HT1A receptor agonists seems to have antidepressive/anxiolytic effects. There is robust anti-aggressive effects of 5-HT1A receptor agonists in dose ranges that concomitantly inhibit 5-HT neurotransmission. There is a critical role of raphe somatodendritic 5-HT1A autoreceptors, and hence phasic 5-HT neuron activity, in the initiation/execution of aggressive actions. Agonists of 5-HT1A subtype receptors are among the most potent drugs to suppress the initiation and execution of offensive aggressive behavioural displays 5-HT1A receptor is the most abundant serotonin subtypes expressed in the brain. It is widely distributed in regions such as prefrontal cortex, limbic system, and hypothalamus that receive serotonergic input from the raphe nuclei. Presynaptically, the 5-HT1A receptor is the major somatodendritic autoreceptor on the soma and dendrites of serotonergic neurons, where it acts as a “brake” to inhibit the activity of the entire 5-HT system while postsynaptic 5-HT1A heteroreceptors are expressed in target areas receiving serotonergic innervation. Activation of 5-HT1A heteroreceptors on these distinct neurons mediates hyperpolarising response to released serotonin and usually reduces neuronal excitability and firing Activation of 5-HT1A heteroreceptors plays a prominent role in the antidepressant and neurogenic actions of SSRIs and 5-HT1ARs are implicated in the prosocial effects of empathogens. Stimulation of 5-HT1A receptors in prefrontal cortex enhances forebrain catecholamine release, an effect possibly involved in the antidepressant action of the receptor agonists. 5-HT1A agonists consistently increase dopamine release in the prefrontal cortex, which is an effect that might be predicted to improve negative symptoms. 5-HT1A receptor agonists may reduce the activity of serotonergic projections that inhibit dopaminergic nigrostriatal neurones, therefore increasing dorsal striatal dopamine levels. 5-HT1A autoreceptors act to modulate dopamine levels in the nucleus accumbens. Postsynaptic 5-HT1A receptors interact with NMDA-receptor subunits important for cognition and depression

A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development. Full text: http://sci-hub.bz/10.1002/ptr.5732 Nelumbo nucifera, also known as sacred lotus, has primarily been used as food throughout the Asian continent, and its medicinal values have been described in Ayurvedic and Traditional Chinese Medicine. The purpose of this study is to systematically characterize the chemical profiling and pharmacological activities of N. nucifera. Herein, we critically reviewed and analysed the phytochemical and pharmacological reports of N. nucifera. Our search for the keyword 'Nelumbo nucifera pharmacology' in all databases reported in Web of Science yielded 373 results excluding reviews and abstracts in document types. Two hundred and forty-three spectrum natural compounds from different parts of N. nucifera belonging to diverse chemical groups, including alkaloids, flavonoids, glycosides, terpenoids, steroids, fatty acids, proteins, minerals, and vitamins have been reported. In addition, distinct pharmacological activities, mainly against cancer, microbial infection, diabetes, inflammation, atherosclerosis, and obesity, have been associated with crude extracts, fractions, and isolated compounds. This review highlights potential use of neferine, liensinine, isoliensinine, and nuciferine in clinical trials. In depth, mechanism of the potential chemical entities from N. nucifera via structure activity relationship needs to be explored to guarantee the stability and safety for the clinical use.

Agreed @MeanGreen, I've had good experiences with sceletium, I'd rank it much better than most conventional antidepressants for it's dual serotonergic/PDE4 mechanism but also times when it's seemingly 'pooped out' or just given me a kind of sleepless elevation. There's seemingly so much difference between different extracts, too. That's why I've kind of been exploring other things with different mechanisms of action.

Finally meet Gardenia fruit. The fruit is the main medicinal part of the plant. Gardenia tea can be used for yin deficiency disorders, which include irritability, restlessness, sensations of tightness in the chest and insomnia. Gardenia is also used in formulas to treat anxiety. In TCM, Zhi Zi recommended dosage is 3 to 12 g daily. 10g Gardenia jasminoides fruit in tea - Not the nicest tasting tea but I'll see what I think of it. You can see the saffron-like apocarotenoids constituents in solution Baseline mood is a background of 'yin deficiency', just too much heavy negative cognition, too much rigid analysis etc and I'm quite anhedonic. I've been struggling, forcing myself to do things and playing with diet just to manage life a bit, I could seriously do with a bit of stronger plant medicine. I'm just struggling with totally dyregulated stress responses, sleep problems and affective issues that aren't getting better by themselves. The medical need for rapid antidepressant actions without the limitations of ketamine has lead to a research interest in Gardenia/Yueju which has been characterised using a number of acute, subacute and chronic behavioral paradigms and clinically [1]. As preclinical findings indicated this plant showed ketamine-like rapid antidepressant effects, and as a polyherbal formal (Yueju) which had antidepressant potency in a relatively rapid manner clinically [2]. Results from an experimental investigation uncovered ketamine-like rapid antidepressant effects - increased BDNF expression, in parallel with its rapid antidepressant efficacy in behavior paradigms and Involvement of normalised NMDA receptor and mTOR-related signaling [3] in rapid antidepressant effects, along with epigenetic DNMT1 activity [4]: acute administration of Yueju rapidly attenuated depression-like symptoms in learned helplessness paradigm and novelty-suppressed feeding test, tasks which normally require chronic treatment of SSRI to exhibit antidepressant efficacy. In a chronic mild stress model that mimics clinical depression, a single administration of Yueju also showed rapid and lasting antidepressant effects similar to ketamine. These findings suggest that Gardenia/Yueju may be potentially used as a rapid antidepressant in the clinical setting. The primary active components of gardenia are iridoid glycosides (mainly geniposide and gardenoside), chlorogenic acid, and ursolic acid. In a water-ethanol commercial extract of the fruits, gardenoside and other iridoids made up 70% of the extract, chlorogenic acid 20%, and ursolic acid 10%. In addition, a complex iridoid glycoside, crocin, is the yellow pigment seen in the fruit. The yellow pigment causes immediate antidepressant responses, dependent on synthesis of proteins, including synaptic proteins. This was followed by enhanced expression of CREB and BDNF, which likely mediated the persistent antidepressant responses in solution, these have very rapid antidepressant effects in animal models [5] [1] https://www.sciencedirect.com/…/artic…/pii/S0378874116318086 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654702/ [3] https://www.nature.com/articles/srep13573 [4] https://www.ncbi.nlm.nih.gov/pubmed/29522357 [5] https://www.ncbi.nlm.nih.gov/pubmed/27203575 Update: Seems to have a cumulative effect when used in combination pills, effects becoming quite evident by day 3: Post hoc tests indicated a significant improvement for experimental group over control group from the 3rd day to the 7th day of treatment https://www.ncbi.nlm.nih.gov/.../figure/f2-ndt-11-2013/ The Gardenia fruit seems pleasant so far (3 hrs), maybe a balancing energy over an uplift so far. Had the water soluble portion first and enjoyed that, then thought I'd ingest the pulp for maximum benefits which caused a bit of GI disturbance. Went to connect with and nurture the Gardenia plants I had growing after having the tea and that was nice then went for a nice river walk. Gardenia jasminoides is said to have the energetic properties, in more Western though, of: Releasing stress and worry, encouraging you to have fun, bringing joy and playfulness. It's said to target the root, heart and crown chakras. Modern studies have indicated G. jasminoides showed positive effect in treating type 2 diabetes mellitus (T2DM). Numerous studies have confirmed that crocins and iridoid glycosides had effects of antioxidation, anti-inflammatory, anti-atherosclerosis, neuroprotective/anti-ischemic brain injuries, anti-platelet aggregation, anti-hyperglycemia, anti-hyperlipidemia, anti-hypertension, and so on. It had functions of learning and memory improvement. There is concern about hepatotoxicity at high doses. "If we all did value Yin energy a bit more, we would be receptive to new ideas, to new people, to the actual attainment of prosperity and the experience of love." "Lifestyle patterns and the environment begin to consume Yin over the years. Stress and other emotional strains can lead to Yin depletion When one’s yin is replaced, the body’s ability to heal itself is enhanced dramatically. Herbs and foods nourish yin energy, but nourishing yin is not as simple and easy as popping a pill. Optimal productivity/Yang must have equal and opposite quieter times of rest, rejuvenation and planning. Nourishing yin requires mindfulness — mindfulness in how you spend your energy, mindfulness in what you eat and mindfulness in feeding your spirit." The nature of any entity, living or not, is determined by the intrinsic balance between opposing states, Yin and Yang. Disturbances in balance result in changes in nature, often expressed in living systems in the form of symptoms or signs of disease. TCM treatments are intended to restore balance. Balance is accomplished by influencing the vital energy, the Qi. In the TCM paradigm, Qi flows through channels in the body and in the spaces between muscles and the skin. Qi has many functions including warming, moistening, and nourishing; promoting normal function of the organs; providing energy for different processes; regulating the body; protecting the body; and ensuring that organs remain in their proper positions. A very important role of Qi is in maintaining balance. In this sense, it is a homeostatic mechanism by which the body can heal itself and establish a state of wellness. If Qi encounters a Yin–Yang imbalance, Qi corrects the situation by transforming one to the other, thus restoring balance and harmony. If, however, a blockage exists that impedes the flow of Qi, a factor is present that is interfering with the Qi, or if there is a Deficiency of Qi, this healing transformation does not take place. There are TCM techniques for opening blocked channels; for expelling pathogenic factors that are interfering with normal processes; and for boosting Qi in cases of Deficiency https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870484/ Got a good gauge of the Gardenia. I think you could easily come up with an effective herbal antidepressant/anxiolytic centred on Gardenia, perhaps with Lotus embryo and Radix Polygalae which may have rapid-onset antidepressant effect which can be a safer alternative to ketamine and lead to the development of life-saving medications. Day 2: There hasn't been super acute robust elevation notable yet with the intake of Gardenia at higher TCM-style doses but some element of simple contentedness is slowly creeping in.

While slow drying seems useful for some cyanogenic glycoside containing plants, with the Passifloras that are more untested, I follow by oven drying at ~120 deg C. I've found simply boiled for at least half an hour to remove cyanogenic glycosides seems feasible, I think preferably in an acidic environment (I use citric acid). You get some noticeable liberation of odour with capsularis, I don't recommend that one for experimentation particularly Processing operations such as fermentation, boiling/cooking, and drying, applied to process food‐containing cyanogenic glycosides have been reported to reduce cyanide content to acceptably safe levels. [1] Food‐processing methods generally disintegrate cyanogens contents of plants, and this leads to the production of cyanide. Since cyanide is volatile, further processing techniques, such as roasting and drying, will volatilize the remaining cyanide to low level. Cyanogenic glycosides are generally water soluble. During cooking, significant amount of cyanogens are leached into cooking water. Several studies have reported increased reduction of cyanide in cooked products. Steaming of a cassava product (akyeke) was reported to result in a 74–80% reduction in total cyanide levels. “Garification”, a process whereby fermented and dried cassava mash is simultaneously cooked and dried in a shallow wok, resulted in a 90–93% reduction in total cyanide content. Optimal cooking conditions for the reduction of cyanide levels in bamboo shoots (98–102°C for 148–180 min) resulted in a 97% reduction in cyanide [31]. Generally, traditional African processes typically decrease the cyanide content of cassava by 97–>99%. Also when the cooking method chosen is heating under dry, heat or at low moisture contents, the intake of the cyanogen is limited to only small amounts. ~~~ How would I describe the high dose Passiflora edulis flavicarpa? Once again I went ad libitum. Sipped away on a high dose brew (got through quite a bit of the 40g I brewed up) to titrate a nice state. I'll more accurately measure another time. It's not super sedative for me, my tolerance to anxiolytics/sedatives is crazy, but it's nice. It's similar to other Passifloras but this feels more grounded than when I was exploring the high dose incarnata. It's just easy merging with the moment and your being and some spirit "Coming home to yourself with slight self-transcendent ease" is how I'd put it. It's a simple stillness of presence, connection to yourself and with the melting away of a background of stress and anxiety, some uplifting transcendent qualities but in a subtle way. When you're stressed, anxious etc, you're far from home. This just guides you back to yourself. The plant feels to be a good anxiolytic and 'vitalistic spiritual awakener'. Sitting with a strong dose, you are not "fighting yourself", pushing away from your Self, or your internal processes. There's a simple ease of being. Emotions flow freely, you feel things without blocks. Enough anxiolysis to not build walls to feeling and accepting your being, in it's full expression. It seems like a good therapy tool, attunement to deeper presence of being, with acceptance, liberation from a chattering busy monkey mind, into stillness and peace. Passiflora, a "Christ-consciousness plant" embodies a feeling of deeper still presence and connection. It is noted as a GABAergic plant but I feel it's deeper than that. It doesn't knock you into a devolved consciousness. Research has expanded the understanding that flavonoids act as cognition-enhancing and neuroprotective agents, some combinations are proving to be highly effective in the modulation/extinction of fear memory. I'd say, as it is used as a social brew (incarnata anyway) Passiflora could be a viable social therapy aid. Might brew some for a social gathering another time.

Wanted to revisit Passiflora. Anyone have experiences with more commonly grown Passifloras as medicines? I've brewed up quite a bit of different Passifloras from P. incarnata to capsularis (the latter I noted did seem to be quite cyanogenic). P. edulis flavicarpa is more potent than the variety ‘edulis' as an anxiolytic in studies but maybe a less potent sedative. I haven't played with the common edulis. Both varieties of P. edulis could be used as a remedy for anxiety and depression. Last night I had what I thought was a lowish dose of Passiflora edulis flavicarpa, it seemed quite potently active, more active than I noted with incarnata gram for gram and not notably cyanogenic compared to the capsularis. Don't know if it was just a break from Passifloras but I had a solid sleep last night, even slept in past my normal 3am wake up, it lived up to feeling really decent. The six major flavonoid compounds isolated from the leaves of Passiflora edulis ‘flavicarpa’, lucenin-2, vicenin-2, isoorientin, isovitexin, luteolin-6-C-chinovoside, and luteolin-6-C-fucoside, had not been detected in Passiflora edulis ‘edulis’. It produces a strong anxiolytic-like effect, albeit requiring reasonable doses in studies. Having a bit more tonight, see what I think of tonight's dose. It's a weed at the community garden at the moment and I'm growing at home, seems decent enough medicine.

I've been addicted to nicotine for far too long... I've been free from tobacco for over a year but I'm now addicted to the 'step 1' (21mg) patch (cut in half) plus 40mg/day as gum It's time for me to quit this addiction. I haven't managed to step down successfully myself and think I might need some assistance. Is it worth going cold turkey? I've tried buproprion in the past but it wasn't that effective at the time. Here's an inspiring article I'm considering but I'm happy to hear from anyone who may have gotten in a similar situation. The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study. Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]). Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.

I agree, fighting an addiction if you're not on board doesn't work. I'm sitting with just a lower dose patch today - that's maintaining sanity and minimising symptoms, much less nicotine than usual but seems to address symptoms. At least I can't escalate patch doses easily while with gum, it's easy to do that. See what a little while on patches is like, might be able to drop from there to minimal effective doses/none but for the moment, just stabilisation is needed. I like this view. How do we change from 'using and being used' by a substance in a detrimental way, to being in Plant Spirit symbiosis? https://www.elephantjournal.com/2018/03/are-we-really-addicted-to-the-substances-or-to-the-feeling/ Do we want to fill a void or do we want to gain insights? Do we want to escape our pain or do we want to dive into it? Do we want to hide from ourselves or meet ourselves? This is the essential difference and the deciding factor to either create an addiction or experience the benefits of a symbiosis. ...we need to address the pain. We need to fill the inner void in other ways, or we can ask the plant to teach us how to properly fill it. It is never a question of controlling but it is about meeting an unmet need for ourselves that oftentimes hides so well that we are not even aware of it. It’s about changing the environment, it’s about feeling seen and received in relationships, it’s about creating a connection. If our intention is to fully meet ourselves, we can enjoy the offerings without risking to fall into addiction. We can learn from them and enjoy their teachings, dive into our pain and have fun times, relax or feel blissful, and take new insights about ourselves and put the universe back into our reality. Some stronger plants take us right into our pain. There is no more escape. The plants guide us to deal with the pain and show us how to fill the inner void. The tobacco plant is a sacred plant, used in the Amazon by indigenous people for its protective spirit. It is a masculine energy that helps to ground us, eases anxiety and unrest. It calms us, helps us when we forget because we are anxious inside. Is it possible that people are actually searching for that inner peacefulness? Our fast-paced society that values productivity over emotional wellbeing causes many of us to feel uneasy and restless, and often, we are so used to these sensations that we are not even aware of them. The tobacco plant provides a feeling of inner safety and stillness.

What are people's favourite protein sources for plant based diets? I'm not happy with the spectrum of amino acids that are going into my diet yet, I was becoming a little anti-social and mood heading down a bit. Impact of nutrition on social decision making Food intake is essential for survival in all species for meeting energetic demands. However, food intake also modulates various biochemical processes underlying cognition. Across two studies, we showed that different macronutrient compositions in standard European meals affect plasma neurotransmitter precursor levels, and these in turn influence social decision making. Our results provide evidence that variations in the macronutrient content of a normal European meal exert a significant impact on high-level human cognition. This study opens perspectives on nutrition-driven cognition modulation. The results have implications for education, economics, and public policy by emphasizing the importance of a balanced diet on fundamental expressions of cognition. I have to admit, going more plant-based can limit protein intake and if macronutrient profiles not addressed, pathologically alter the profile of what amino acids are going in and lead to less desirable health outcomes. I've been looking for complete good protein sources, have to get back to keeping on top of that maybe. While I've been staying on top of vitamins/minerals and phytochemicals, I was thinking it was OK to run a quite low protein, albeit good quality protein sources, intake, I was feeling OK that way for awhile. This morning, seeing what, along with a planty polyphenol rich, good fatty acid and carotenoid breakfast, seeing what providing a solid dose of the spectrum of essential amino acids does. Going to dose up on my lysine powder during the day which I tried some years ago. Aside from monoaminergic modulation through the phenylalanine/tyrosine/tryptophan etc, many amino acids modulate mTOR, mammalian (or mechanistic) target of rapamycin, the master regulator of cell growth and proliferation. While acute BCAA administration, I elevated BCAAs quite a bit this morning (along with some monoamine precursor amino acids), seems to increase the pro-BDNF/total-BDNF ratio (decreasing NGF through oxidative stress long term and acutely, prevented by suitable antioxidant treatment) and can promote mammalian target of rapamycin (mTOR) signaling in oligodendrocyte differentiation and myelination, longer term BCAA administration, while increasing hippocampal and cortical BDNF, increases oxidative stress and causes memory impairments which can be prevented by antioxidant treatment Changing the amino acid composition may alter social behaviours - dietary interventions that reduce mTOR activity rescue autistic-like behavioural deficits In one study, the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling (other studies note leucine influences critical cellular processes through mTOR activation) Preliminary clinical evidence suggests that consuming wheat that has been fortified with lysine 4.2 grams/kg reduces stress in females and reduces anxiety in males in economically weak populations that typically consume cereal-based diets Dietary L-lysine deficiency increases stress-induced anxiety through serotonergic mechanisms in the amygdala and interfered with the normal circadian rhythm. This amino acid, particularly with arginine, may induce anxiolytic effects, modify hormonal responses during psychosocial stress in humans. Clinical research suggests that taking L-lysine 2 grams three times daily for 8 weeks improves symptoms by approximately 34% compared to placebo in schizophrenia patients who are not stabilized on risperidone (up to 6 mg/day). Negative and psychopathology symptoms appear to improve the most. In schizophrenic patients stabilized on antipsychotic medications, preliminary clinical research suggests that taking L-lysine 6 grams daily for 4 weeks in a single drink improves positive symptoms of schizophrenia, particularly delusions and suspiciousness/persecution, compared to baseline.

Keen to hear a few words from people who have adopted a new diet and found benefit, particularly for managing mental health. What was the change and how was it beneficial? Dietary patterns, body mass index and inflammation: Pathways to depression and mental health problems in adolescents. Habitual intake of a Western dietary pattern may exacerbate low-grade systemic inflammation, not solely attributable to BMI A 'Western' dietary pattern (characterised most strongly by processed foods, red and processed meats, dairy, potatoes, refined grains, soft drink, sauces and dressings and take away) associates with an increased risk of mental health problems including depressive symptoms in adolescents, through biologically plausible pathways inflammation and adiposity, whereas a 'Healthy' dietary pattern (he ‘Healthy’ pattern was characterised by higher loadings on whole grains, fruit, vegetables, legumes and fish) appears protective in these pathways. Longitudinal modelling into adulthood is indicated to confirm the complex associations of dietary patterns, adiposity, inflammation and mental health problems, including depressive symptoms [1] http://sci-hub.tw/10.1016/j.bbi.2018.01.002 Other research has found a study a strong relationship between higher scores for a ‘Western’ dietary pattern and increased BMI, cardiometabolic risk, attention deficit hyperactivity disorder and higher withdrawal, depression, delinquency and aggressive behaviours. A significant proportion of depressed persons show up-regulation of inflammatory markers. It has been suggested that chronic inflammation may underlie the association between diet and depression, since negative health behaviors, such as a poor diet, may lead to both inflammation and depression in susceptible individuals Nutrients such as magnesium, fibre, ω-3 polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids, flavonoids, and carotenoids from food associate with a Healthy diet and decreased levels of inflammatory markers Dietary influences on cognition. Full text: http://sci-hub.tw/10.1016/j.physbeh.2018.02.052 The fact "dietary changes can also affect the biological functioning of the brain and seriously impact cognitive function has yet to fully penetrate our social consciousness, with possibly disastrous consequences as the obesity pandemic threatens to overwhelm healthcare services." Epidemiological studies suggest that introduction of a more healthy diet positively impacts cognitive domains, strongly. "From a neurobiological perspective, both addictive drugs and highly palatable foods increase dopamine release in the reward centers of the brain, and maladaptive changes in dopamine signaling have long been implicated in the etiology of addiction. In particular, a reduction in striatal D2/3 receptor density ... has also been documented in overweight subjects, coupled with impulsivity. Recent data from the Winstanley lab using one such behavioral assay of impulsivity, the five-choice serial reaction time task (5CSRT), suggest that macronutrients themselves may be able to alter this form of cognition, the ability of certain hypercaloric macronutrients to increase impulsivity is noted. Consumption of diets high in saturated fats and refined carbohydrates are associated with neurocognitive dysfunction, including increased risk for mild cognitive impairment and dementia. they are associated with impairments in decision-making, planning and problem solving (all of which are features of executive function) with less evidence for associations with other cognitive domains, such as verbal fluency and learning and memory, along with with alterations in appetitive functions, such as, reinforcement learning and effort, reward cue reactivity and incentive motivation, all of which are regulated by neural systems that support executive functions. From a mechanistic perspective, these cognitive deficits may result from decreases in neurotrophic factor expression, increases in oxidative stress and neuroinflammation, as well as structural and functional deficits in brain regions like the hippocampus and prefrontal cortex" It's been shown three weeks on a super healthy diet starts to crank up regions of the brain like the dorsolateral prefrontal cortex (DLPFC) and causes modulation of regions like the nucleus accumbens, orbitofrontal cortex and amygdala. This area appears to be critical for working memory, planning, selective attention, temporal integration and volition. Damage in the dorsolateral prefrontal cortex in humans leads to a lack of spontaneous activity, distractibility by environmental cues, and the repetitive, stereotypic use of inappropriate behavioral responses (perseveration). I've mentioned the polyphenols lots, in short they seem very helpful Reduced mortality risk by a polyphenol-rich diet: An analysis from the Moli-sani study. High polyphenol and healing phytochemical intake is for me not just the best way to manage my mental health. The polyphenol content of the diet was, in a recent analysis, associated with reduced mortality risk: "Participants included in the highest quintile of intake of various polyphenol classes and subclasses presented a significant lower all-cause mortality risk compared with those in the lowest group of consumption ...the present results together with the recent literature, extend the role of dietary polyphenols from natural compounds potentially active on disease prevention to important nutrients for the reduction of mortality risk in a general population." In depression, there is an inverse relationship between consumption of fruits and/or vegetables and depressive symptoms. Less than 5% of depressed subjects reported consuming the amount of fruits and vegetables recommended by the WHO. I'm finding mixing up the diet to be more important - just a one-unit increase in the dietary diversity scale was associated with a 39% reduction in the risk of severe depression. Adherence to a high-quality diet, regardless of type (i.e., healthy/prudent or Mediterranean), was associated with a lower risk of depressive symptoms over time (odds ratios ranged 0.64-0.78 in a linear dose-response fashion [P < 0.01]). A relatively low dietary inflammatory index was also associated with a somewhat lower incidence of depressive symptom (odds ratio = 0.81), although not in a dose-response fashion. Similar associations were found for the consumption of fish and vegetables (odds ratios 0.86 and 0.82 respectively) but not for other high quality food groups (e.g., fruit). I've touched on this here

Thanks for the input I'm going to justify this addiction: Honestly, it's better to be on the nicotine that precipitating severe pathology. It's not so much about hardening up when nicotine is addressing symptoms that can be lethally scary. I'm not using other more typical Western medicines to manage things, when before I was on ECT/ supratherapeutic doses of antidepressant, maximal doses of other potent psychotropics. I haven't found superior ways to manage these sort aspects of my health, the other meds weren't doing it well. Like I've said, I don't particularly want to give up because it is an effective medication and it keeps me from turning to worse things. I'd rather be in control more of my use. Sometimes I just need a break for a 'reset' I feel. Pressure from the external world to give up when I think more more people should appreciate it as viable medicine. I've always found that I need to just minimise the risk using it. The pros are it works well, it is virtually devoid of side effects. Better tailorable PRN symptom reduction for affective issues than anything I've found that's readily available. Cons cost and tolerance. I do several walks a day but nothing too high intensity, could step that up. If you've been exposed to nicotine and seem to be able to manage your intake, it seems viable but I wouldn't risk a severe addiction by starting that as a medication in someone not exposed to nicotine, except as a more serious consideration. @MapachoHave you considered proanthocyanidins like Pine Bark ? I'd also consider something like galantamine if you can find it, or trying Spanish Sage EO, just to see if they help over nicotine.

Caved in on attempting this after 3 and a bit days. The affective dysregulation of not using nicotine was too severe. Just got the tolerance down to a more manageable level. Might switch to patches or something... again

Revisiting this. Still struggling with this one.... Rather than more exotic things, trying some food based cholinergics and anti-craving NAC. Thing is I don't know if I want to quit, I find it a useful substance at times, until effects are negated by tolerance but use went up after Milly's passing. Decided it wasn't worth trying N. glauca for the moment, too risky. Sometimes I wonder if my nicotine use goes up not just through stress but particularly when cholinergic activity isn't being addressed through diet. I got a bit slack with supplementing needed dietary choline intake recently, while I never thought highly of choline sources in noticing strong different effects really, I see them as potentially useful buffering pathology and in low intakes boosting issues, sometimes I wonder how detrimental that can be if, when particularly vulnerable, you don't get those choline sources into you? Anyone noted anything like that? Going to get a little bit of a break/tolerance reset from nicotine, even though it's really unpleasant - I use it to help address cognitive concerns and mood issues but tolerance etc is problematic. Lately with Milly and trying to do more, the stress got to me, intake goes up, you end up using it to try and manage more than you should. Decided to steer clear of all nicotinic alkaloids of other plants for the day, even though I earlier thought I'd try and taper with nicotine to keep some sanity, instead I'm trying to boost endogenous cholinergic activity and using anti-craving NAC to see how that goes Drop of Spanish sage EO twice daily (strong AChE activity/neuroprotective etc: solid mood and cognitive improvements in studies in healthy individuals), couple of good doses of soy lecithin*, a dose of N-acetylcysteine (1.2g bd. which might offer a valid therapeutic approach for maintaining abstinence due to craving suppression, the safety profile of NAC and its favorable tolerability alongside superiority to placebo for craving reduction makes it useful) *A positive influence of soy lecithin on memory, mood, and cognition was demonstrated among elderly test subjects. Short-term supplementation in patients with AD showed a stabilising effect on daily functioning, emotional state and self-reported general condition. Supplementation is encouraged in AD patients, the elderly or those with memory or cognition problems. Supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD. Supplementation may be beneficial for buffering stress responses. ~~~ Day three no (alright, one small dose to manage some worsening, quite severe pathology) nicotine. Firstly, it's worth considering why someone might use nicotine. In serious mental illness, there is an established therapeutic role that needs to be understood. "Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of major mental illness and nicotine use may represent a strategy to remediate these symptoms." Importantly, nicotine can enhance cognitive function and regulate mood and affect in serious mental illness. It also plays a putative neuroprotective role, nicotine has long been considered a potent therapeutic agent for neuroprotection. The metabolite cotinine also has emerging evidence for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) and PTSD. Chronic nicotine significantly improved chronic stress-induced impairments of cognition, attenuation of neuroinflammation and the hippocampal synaptic plasticity relating to depressive and other CNS disorders. In trying to reduce, I tried cold-turkey, what arises are some of the worst withdrawals, even from gum. In uncomplicated cases, it's straightforwardish, you can kindle will-power but still super challenging for a relatively healthy person. With psychiatric comorbidity, where there is some established therapeutic role for nAChR modulation in reducing symptoms and consequently the person uses it as self-medication, it's really hard. Pharma options are often not desirable, things like some of the options there can worsen suicidality and cause strange violent behaviours, some are very mildly effective, but not standouts. I've been going the Spanish sage EO, soy lecithin and N-acetylcysteine. The Spanish sage is mildly useful, it gives some stabilisation of the absolute rollercoaster of mood-destabilisation and affective issues that can be uncovered through dropping nicotine intake. Some mood lift, with some therapeutic saffron, you can get a little bit of coverage from strong serious mood declines. Some people I think almost need to stay on nicotine for safety's sake at times. You can't do these withdrawals lightly, from severe affective issues, to suicidal ideation to precipitation of major depressive/anhedonic crises... much of today was in a strange light headed impulsive flat out dysphoria, staring into space unable to do anything at all, mood flipping all over the place at the slightest provocation. The N-acetylcysteine seems to mildly reduce impulsivity and craving at 1.2g bd. stop you from turning to trying to find anything, no matter how abhorrent containing nicotine, to take... it's not super effective but a slight help. See how I go tomorrow.

How can we use a safe plant medicine to therapeutically help one of the most marginalised groups out there? How can we help them is what we should be asking, not how should we make things worse, stigmatise, narrow opportunity etc. Things like this can give people a break free from personal hells which are often induced by a sick society ie the one we live in, contracted through hardship and vulnerability. This approach interests me. There is often high comorbidity between addictions and psychiatric disorders and the two feed each-other. The Effect of Saffron on Depression among Recovered Consumers of Methamphetamine Living with HIV/AIDS. Saffron has a positive effect on reducing depression among a strongly marginalised population. This intervention can reduce depression among this particular group by high effect size (81%). Mental disorders including depression are among factors that increase the tendency to use methamphetamines. In fact, methamphetamines and other drugs are used as self-medication for mental disorders One of the major triggers for relapse among methamphetamine abusers is depression and the symptoms continue after treatment, can saffron help? http://sci-hub.tw/10.1080/10826084.2018.1447583 There's also recent summary for neurodegenerative disorders

While I'm a polyphenol fiend, I also cherish the healing phytochemical rainbow. Today for my carotenoids, I'm having a tiny bit of saffron, some T. erecta flowers and kale. Have a glass of tomato juice, too. Still got some chlorella left, so I'll have a dose. While saffron crocins are really healing, so are β-Carotene, lutein, zeaxanthin and things like lycopene, which keep the brain working well β-Carotene β-Carotene improves memory, recognition and verbal skills Really became a fan of spirulina for awhile but cost made it a bit of an issue. Keen to know if anyone here with mental illness or autism has tried it themselves? Started to start add chlorella - chlorella tended to reduce oxidative stress and significantly prevented the decline of cognitive ability, it also buffered stress responses, diminishing the impact of stressors by reducing the HPA response. Noticed the spirulina not only helps with mood and cognition but when I was using that, helped the ASD stuff (my premorbid issue). It's also good for the body on the whole, nicely restorative. One component, β-carotene is a strong antioxidant but interestingly may do more for autistic traits. While phycocyanin and related constituents are one interesting component, potently neurorestorative, improving oxidative status, improving neuroinflammation, protecting from demyelination and axonal loss, modulating the expression of genes related to remyelination, gliogenesis and axon-glia processes etc, spirulina is rich in β-Carotene β-Carotene oral supplementation to animal model of ASD significantly reduced restricted and stereotyped behaviours and interests, increased social interactions and communication, CD38, and oxytocin, probably by enhancing brain neuroplasticity without toxicity [ref]. All-trans retinoic acid is a potent inducer of CD38 and can be used as a novel therapeutic strategy in autism. It's been put forward the prospect that retinoids are potential therapeutic agents in autism and possibly other disorders that are characterized by dysfunctional social cognition/relationships especially where oxytocin has been suggested to play a role. "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 Intriguingly, the cortex of retinoic acid deprived rats is characterized by beta-amyloid accumulation and other changes that parallel those in Alzheimer’ disease. Additionally, normal memory loss in aging rats can be alleviated by vitamin A therapy. In the adult hippocampus, retinoids are essential for the maintenance of synaptic plasticity including LTP and neurogenesis. The hippocampus is a brain region dependent upon neural plasticity for its function in learning and memory. CD38 transcription is correlated with cognitive function in ASD and secondly, that retinoids are potential therapeutic agents in autism." Crocins The crocins are hydrophilic carotenoids that can act as antioxidants, improve learning and memory, be used for treatment of brain injury, mood disorders, OCD, joint pain and muscle dysfunction in osteoarthritis, metabolic syndrome and related mood disorders and neurodegenerative damage, and have a protective effect against brain damage Aside from the NMDA affinity and sigma-1 binding, there is evidence that crocins act as reuptake inhibitors of dopamine and norepinephrine. "The antioxidant properties of saffron derivatives may also be relevant. Mood disorders are associated with elevated oxidative stress and a deficit of exogenous antioxidants, affecting immune and inflammatory responses in a way, which may promote neurodegeneration (Leonard and Maes, 2012). There is good evidence that the antioxidants in saffron extracts protect against oxidative stress in the central nervous system (Mehri et al. 2015; Oruc et al. 2016), constituting a second potential mechanism of therapeutic action. The most important indicator of the quality and commercial value of the saffron is its contents of crocin I and II, which are specified in trade standards. The Chinese Pharmacopoeia stipulates that the total content of crocin I and II should not be less than 10.0 %." In an analysis of 63 saffrons, the crocin I content range was 6.6–23.7 %. Considering a therapeutic dose is sometimes considered to be 30mg crocins that works out to be about 127-455mg saffron going on crocin I. I stuck with 300mg/day for my saffron dose for bad days - cost is ~ $4/gram from my Indian shop for decent stuff. There is a TGA listed coated tablet containing either 11 mg or 14 mg of standardised saffron extract (affron), derived from the stigmas of Crocus sativus L. and standardised to contain >3.5% Lepticrosalides® (a measure of bioactive compounds present in saffron, including safranal and crocin. Two tablets daily constitutes a dose. As I mentioned before: Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. It reputedly has acute effects. Quite quickly, it increases mood, reduces anxiety and manages stress without side effects in studies. It has been traditionally used for the treatment of insomnia and other diseases of the nervous systems, it has sleep quality improving effects. Crocins attenuated schizophrenia-like behavioural deficits. It has a satiating effect and decreases the frequency of snacking events. It's been used in emotional disorders and it was found that using saffron (30 mg/day) was effective in relieving symptoms in some cases. Crocin can regulate HPA axis activity and has therapeutic effects in stress disorders, potentially PTSD where it is effectve in an animal model. It may serve an appropriate treatment for subjects who experience a extremely stressful or traumatic event. Saffron and its metabolites have proven to be effective in different models of psychiatric disorders, including depression and anxiety. It is as least effective as first-line medications for MDD in quality studies with less side effects. It's got a good safety margin, while 30mg may prove effective “to a daily maximum dose of 1.5 grams there has not been any risk documented. Lethal dose is 20 g and the abortive dose, 10 g, because as such it was employed in the past due to its stimulating action on the smooth muscle of the uterus. 5 g daily dose can already cause intoxication accompanied by vomiting, bloody diarrhea, hematuria, skin hemorrhages in nose, lips and eyelids, vertigo and dulling. The skin and mucous membranes take a yellowish colour similar to jaundice”. Crocin is an isolated chemical compound that belongs to a group of commercial carotenoid derived from the stigma branches of dried saffron. The spice’s high antioxidant capacity explains most of its preventive or healing properties in relation to chronic and degenerative diseases Crocin and crocetin may have a neuroprotective effect because of their anti-inflammatory action in microglial cells, as tested in rat brains, accompanied by a reduction in neurotoxic molecules (TNF-α, interleukin-1β and intracellular ROS. The restoration of a redox balance in brain tissues can be a good therapeutic strategy to limit neuro-inflammation and consequently tissue oxidative damage). Many of the anti-inflammatory effects of crocin demonstrated in animal models of neuronal degeneration could be mediated by its direct effects on microglia homeostasis. It also has anti-adiposity effects Crocin can be considered as healthcare product to prevent age-related brain diseases, it is able to enhance memory function in an aging model through anti-glycative and anti-oxidative properties which finally can suppress brain inflammatory mediators and increase protective pathways Crocin can improve learning and memory and may prevent neurodegenerative disorders including Alzheimer's disease. Saffron is a source of novel acetylcholinesterase inhibitors. It is not mutagenic and prevents alcohol-induced disorders of memory and learning. Its mechanism is thought to be prevention of the inhibitory effect of ethanol on N-methyl-D-aspartate (NMDA) glutamate receptors in the hippocampus. It has clear binding capacity at the PCP binding side of the NMDA receptor and at the sigma(1) receptor There is an anti-fatigue effect of crocetin - its intake improved performance when taken 4 h before a physical fatigue-inducing task Treatment with saffron extract for seven consecutive days in a study conducted in rats in an experimental model of MS improved learning and memory impairment and alterations in the parameters of oxidative stress in the hippocampus. Clinically saffron was able to reduce MS symptoms - crocetin might prevent demyelination and neurodegeneration. Such findings show that saffron may potentially prove useful in the treatment of MS through the inhibition of oxidative stress and the infiltration of leukocytes to the CNS. Saffron protects many cells of the dopaminergic system with relevance to Parkinson's disease. Studies on the bioactive substances of saffron in depression indicate that the crocin acts by inhibiting the reuptake of dopamine and norepinephrine neurotransmitters, while safranal inhibits the reuptake of serotonin. There are in vivo studies suggesting inhibitory effects on the monoamine oxidases, MAO-A and MAO-B, enzymes responsible for the degradation of the neurotransmitters, as mentioned above, leading to an increase in their levels in the synaptic space and reducing depressive symptoms. Saffron extracts and crocetin had a clear binding capacity at the PCP binding side of the NMDA receptor and at the sigma-1 receptor while crocins attenuated schizophrenia-like behavioural deficits. Crocin has been shown to be an antioxidant and neural protective agent Saffron is a potential efficacious and tolerable treatment for major depressive disorder with anxious distress. [1] It increased mood, reduced anxiety and managed stress without side effects, offering a natural alternative to standard treatments [2] Saffron is as effective as fluvoxamine in the treatment of patients with mild to moderate OCD [3] A recent review found: "Saffron, derived from the stigma of Crocus sativus flower, is commonly used as a spice and as medicine in the Middle East and in South Asia. In patients with mild to moderate anxiety, extracts of saffron were reported to be effective in relieving symptoms in several RCTs (Akhondzadeh et al., 2005; Mazidi et al., 2016; Talaei, Hassanpour Moghadam, Sajadi Tabassi, & Mohajeri, 2015). Studies also show that the effects are comparable to standard antidepressant drugs such as fluoxetine (Moosavi, Ahmadi, Amini, & Vazirzadeh, 2014; Noorbala, Akhondzadeh, Tahmacebi‐Pour, & Jamshidi, 2005; Shahmansouri et al., 2014) and imipramine (Akhondzadeh, Fallah‐Pour, Afkham, Jamshidi, & Khalighi‐Cigaroudi, 2004).Saffron reduced anxiety and depression scores in women with premenstrual syndrome as well (Agha‐Hosseini et al., 2008)." [1] https://www.ncbi.nlm.nih.gov/pubmed/27701683 [2] https://www.ncbi.nlm.nih.gov/pubmed/28735826 [3] https://www.ncbi.nlm.nih.gov/pubmed/29062366 Lutein & Zeaxanthin Good sources of lutein and zeaxanthin include kale, spinach, turnip greens, summer squash, pumpkin, paprika, yellow-fleshed fruits and avocado Supplementation with the these carotenoids significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Low blood serum or plasma concentrations of the xanthophyll carotenoids lutein and zeaxanthin have been implicated in poorer cognitive health in older adults. They may assist with cognitive control. They have anti‑inflammatory and antioxidative effects and putative neurotrophic effects. The dietary intake of carotenoids should be promoted as this may have a substantial positive effect on cognition, memory and things like stroke prevention and stroke mortality reduction. Supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. Higher intakes may result in the ability to respond to cognitive tasks more efficiently, maintaining high performance while displaying neural indices indicative of lower cognitive load. Lycopene Lycopene is the major carotenoid in tomatoes. Tomatoes contain a matrix of many bioactive components, including vitamin C, vitamin E, other carotenoids (a-, beta-, gamma- carotene, lutein), and flavonoids. The processing that heated tomato products is said to increase the bioavailability of key phytonutrients and antioxidants, such as lycopene, lutein and other carotenoids The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. Lycopene helps to protect against induced cognitive dysfunction. Lycopene inhibits glutamate release in cortical synaptosomes Lycopene food sources may be useful in neurodegenerative conditions, including AD ad PD. Lycopene significantly improved cognitive deficits and were accompanied by the attenuation of inflammatory injury via blocking the activation of NF-κB p65 and TLR4 expressions and production of cytokines. It could ameliorate oxidative stress induced neuroinflammation and cognitive impairment possibly via mediating Nrf2/NF-κB transcriptional pathway. In degenerative conditions, it causes modifications in the activity of cholinesterase and antioxidant pathways. Lycopene reverses neurochemical deficts, oxidative stress, apoptosis and physiological abnormalities in PD mice Oral lycopene administration attenuates insulin signaling deficits, oxidative stress, neuroinflammation, and cognitive impairment In models of epilepsy, when used alongside conventional anti-convulsants, lycopene significantly restored the seizure score, latency, thiobarbituric acid reactive substance, reduced glutathione, catalase, superoxide dismutase, and gamma-aminobutyric acid levels near to normal Carotenoids may modulate inflammation and enhance antioxidant defenses within both the central nervous system (CNS) and systemic circulation. Increased levels of lycopene also appear to moderate decline in the essential pyridine nucleotide [NAD(H)] in both the plasma and the CSF.

Anyone have experiences with this plant? N. glauca, through anabasine, is actually potentially anti-addictive for multiple substances, see below for more. While I've used it in the past, I was using it *with* nicotine, chasing a buzz and the effects may (?) addictively synergise. What happens with just one? I'm heavily nicotine dependent. Stopping nicotine for a day is hellish. I use gum as a mood manager etc. This is an area of research I can't suggest, albeit an interesting research direction. I recommend extreme caution with all nicotinic alkaloids. I put a day on glauca to the test a bit. I did an experiment to see how long I can stay free from nicotine intake with N. glauca. Got through quite a bit, a day and a bit, on a small dose of intranasal N. glauca with no nicotine gum. Just one dose of glauca vs a day of cycling up and down through many gums. It didn't totally negate the withdrawal, I started feeling flat, very hard for me to cut out nicotine. Out of all the things I've tried, this maybe the most effective I've found, at least it's long half-life and definitely feels less addictive. Normally stopping nicotine is absolute hell for me, this is still quite hard but better than the other things I've tried, from pharma to Lobelia to Cytisus (which is interesting but I don't find the plant material overly potent, there's potential exploring that more) The toxicity of the anabasine is a bit of a concern, as to the variability of alkaloid levels in the plant which makes accurate dosing a challenge. I'm not sure how much cross tolerance there is between nicotine and anabasine but I decided I need to taper down the nicotine, not put myself through hardcore withdrawals and using anabasine. It's really promising as an anti-addictive agent, I just don't want to be the big research experiment at the moment. The science Quantitatively, anabasine forms 99% of the alkaloid content of N. glauca. While considered potentially more toxic than nicotine, Half-lives are 16 h for anabasine vs. nicotine ca. 120 minutes The behavioral effects of anabasine are similar to those of nicotine, although anabasine, unlike nicotine, does not have addictive effects (Caine et al., 2014). Other studies have found minor tobacco alkaloids can either fully (nornicotine, anabasine) or partially (myosmine) mimic nicotine’s addiction-related effects albeit at reduced potency. Some of these nicotinic alkaloids, which are structurally similar to nicotine, may play a role in addiction to nicotine or other drugs In vitro studies have shown that anabasine, acting as a putative α4β2 partial agonist, increases midbrain levels of dopamine which plays an important role in addiction. Anabasine has also been shown to fully substitute for nicotine and partially substitute for d-methamphetamine in drug discrimination paradigms. Anabasine shows anti-addiction properties in some studies, "anabasine at 2 mg/kg significantly reduced alcohol intake during the 0–2 h and decreased alcohol preference during 2–4 h and 6–24 h periods but increased water intake during the 2–4 h period." Anabasine is a partial agonist at α4β2 nAChRs with lower affinity than nicotine, but it has a greater affinity than nicotine for the α7 subtype of nAChRs, at which it is a full agonist and hypothesised to exert most of its effects in vivo. Both α4β2 and α7 subtypes of nAChRs have been shown to play an important role in regulating alcohol and drug intake "One can speculate that anabasine, as a nicotinic partial agonist, by desensitizing nicotinic receptors located at the dopaminergic terminals in the VTA stimulates dopamine release which consequently results in reduction of drug intake. In addition, anabasine's more prominent effects at α7 nicotinic receptors may also differentiate it from nicotine."

How do you find your food brings you together with others? That's been an interesting thing I've kind of noted as diet shifts Because my food choices are quite non-Western at the moment (breakfast was seaweed salad, turmeric kimchi and saffron), I feel the pull away from much of our society. I feel food and social cohesion runs a very deep connective thread. How much social cohesion is promoted by food and drink? It seems to be beyond simple 'bringing people together via food'. While some of these foods I'm using may be healthier options, there's a social dimension that gets altered by using such. From restoring vitamin and mineral status, to wildly altering mood/emotional/cognitive parameters eg carotenoids and polyphenols, to their epigenetic consequences of different phytochemicals, to inflammatory changes which seem to tightly regulate social behaviours to the microbiome, so much seems to shift. Like I found as soon as I gave up alcohol, tolerating the inebriation and consciousness devolution that alcohol promotes to be undesirable, being around drinking culture was totally undesirable. As my food shifts, tolerating the insanity of the "world out there" shifts too. While I noted social mild shifts in things with plain planty diets, stronger with polyphenol enrichment which I attribute to some epigenetic activity, changes to inflammation, I feel like as soon as I started using more fermented food, there was a large shift. Higher dose carotenoids, too. Like a distaste for the insanity of the Western world started to wildly strengthen... does playing with the microbiome have the ability to shift group social dynamics that quickly?

Yesterday, Does higher dietary intake of different carotenoids, getting those serum levels up and getting them into my brain, have acute subjective beneficial CNS effects? With a little elevated polyphenols, playing with a diverse range of carotenoid sources in food. Lots of vibrant Tagetes flowers. A new food experience, too. Seaweed salad made with therapeutic doses of Alpinia galanga. Trying to make a stimulating CNS active, cognition enhancing salad beyond flower power kale salads. I bought a 50% fucoxanthin extract but wasn't impressed, so many extracts seem dodgy. See what I think of seaweed salads, try and have these more often, I like the taste. The most notable and predominant seaweed carotenoids, such as β-carotene, astaxanthin and fucoxanthin have remarkable biological functions and applications in human health, When I start having a drop in mood and health, my cognitive and emotional style changes. It becomes very 'locked in'/'preserved'. I stop approaching/seeking new experiences and get in pathological loops. Gradually today that rigid preserved pattern dissolved a bit, slowly, on the high intake of carotenoids (incl. a small bit of crocins, lycopene (few glasses of tomato juice), β-carotene, xanthophylls, fucoxanthin etc). Supplementation of carotenoids improves stress, serum cortisol, and general physical and emotional health but most studies are longer term. Research has found significant relationships between serum and brain concentrations of dietary carotenoids and various measures of cognitive function. Carotenoids significantly corresponded to global cognitive abilities including verbal learning, verbal fluency, memory recall, processing speed, and perceptual speed. In different populations, 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 Carotenoids have strong anti-oxidant and anti-inflammatory action in the brain, lowering inflammatory markers, and preventing cognitive decline. Mechanisms by which certain carotenoids may function include modulation of functional properties of synaptic membranes along with changes in their physicochemical and structural features and increasing perfusion. They have direct effects, some directly modulating NMDARs, others signal transduction molecules including in dopaminergic systems. Crocins have established monoaminergic effects, too. Carotenoids have also been shown to enhance gap junctional communication. Cortical carotenoids may be protective in nature and may also influence interneuronal communication and function via multiple mechanisms. Want to keep these in my diet longer term as cheaply and effectively as possible.