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Everything posted by Alchemica
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Please keep it to legal things to do with isopropyl
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Hi All. My community plant extracts died when people stopped that from eventuating but in that process, there was a rebirth. I went on a spirited journey to find my Heart and Soul. It's in helping people who are in the hells like I experienced for so long. Not packing small quantities of samples at cost for people. I've also started my own therapeutic community, Adelaide Therapy for Soul Community on facebook for all, including the disadvantaged to get together in the botanic gardens with soulful therapy in mind. Join in if you're in Adelaide. Lately I have developed a deep relationship with Cacao. I have been working on a therapy chocolate, rich in flavonols and alkaloids + minerals which is exceedingly hearty and therapeutic. It has helped me, now I want others to experience this medicine. I've been working on admixtures and noticed how Cacao when enriched with alkaloids is like a gatekeeper to a therapeutic heart-space for those feeling disconnected from themselves and community... the admixtures take it deeper... I think a Heart-strengthening legal therapy chocolate is highly viable. I see this as a potent catalytic therapy ally. In my goal to work with people in real rockbottom states who are totally disconnected from their selves, Hearts and those trying to help them, if we can catalyse a step towards connection, within oneself and mirrored by a supportive community, I see we can jump start new directions in life. These suffering souls, like I was, are severely hardened off, I aim to open them up to love. A mission to bring disadvantaged people to the Heart and into Community. I want to expand my heart space more to offer others the chance for Chocolate Therapy, I'll aim to run at a donation going towards costs. I'm going to invest a bit getting this happening and run at a loss. It sounds insane but after seeing how potently therapeutic a change I can make in my life through plant allies, I want to do the same for others and inspire a shift towards such healing, legally. Seeing I'm mainly wanting to cater to people where money is already an issue, I can't ask for money. I just ask that people use this medicine to inspire real life heart changes. That said, I will open myself to external donations from others if they want to support such a mission. I'm going to use a GoFundMe page to inspire grassroots cacao therapy for the disadvantaged. GoFundMe's fee is 5% from each donation you receive. The payment processor fee is 2.25% + $0.30 per donation. If you want to be more direct and know me, do it that way. PM me for paypal details! All donations are strictly for expanding my medicine circle. All funds will support local suppliers and ethical cacao products Not expecting I'll recover costs but this is a mission from the Heart, not the pocket so that's cool. Much love and gratitude for any support you can offer! ~~~ Cacao therapy is so synergistic as a whole medicine for the Soul. Extracting just the alkaloids takes part of the magic out but it looks like spicing up the magic of the raw cacao flavonols with solid levels of spirited methylxanthines is really therapeutic... A substantial interaction between cocoa flavanols and methylxanthines exists at the level of absorption, in which the methylxanthines mediate an increased plasma concentration of (-)-epicatechin metabolites that coincides with enhanced CNS/vascular effects commonly ascribed to cocoa flavanol intake. MTXs act through a variety of different molecular mechanisms: mobilization of intracellular calcium, inhibition of phosphodiesterases (PDEs), modulation of gamma-amino butyric acid (GABAA) receptors, inhibition of high affinity ATP-dependent cyclic nucleotide transporters and antagonism of adenosine receptors. The plasma levels that could be reached under dietary regimes and the fact that MTXs readily cross the blood-brain barrier indicate that these drugs inhibit adenosine receptors in the CNS; higher doses may be required to mobilize intracellular calcium, inhibit PDEs or modulate GABAA receptors, or to unselectively inhibit ABCC5 and ABCC4 transporters. Moreover, despite the physiological relevance, also under scrutiny is how caffeine, theobromine and theophylline are able to interact with native double helical DNA Cocoa and chocolate are not just treats -- they are good for your cognition: https://www.sciencedaily.com/releases/2017/06/170629101648.htm Health benefits of methylxanthines in neurodegenerative diseases: https://www.ncbi.nlm.nih.gov/pubmed/28074613 PM me if you can support this mission. Love and best wishes! https://www.gofundme.com/cacao-therapy-for-the-ill
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The Journey of an Upside Down Heart to Love and Spirit
Alchemica posted a topic in Creativity, Spirituality & Philosophy
I call this one "The Journey of an Upside Down Heart to Love and Spirit" It's been through the plants, Milly, family and support of my friends, I've gone from abysmal darkness to find a place of growth and upward evolution. I really struggled from an early age. It's been slow, bit of up and down but as you grow and regain conscious choice from long-term illness, you find a good place. I'm really new to any sort of creativity, I'm not an artist but this is like the way it feels to, through nature and lovely souls, grow into healthier place. This not a tea, just a mindful moment of reflection on Life. I've found deep healing in a mild plant spirit medicine approach. I've modified this from here: How to Connect with Plant Allies Our Plant Allies captivate us through our senses first, and then when we slow down enough to look deeper, we become engaged on a soul level. This is the heart of plant spirit medicine. Immersed in the energy of a Plant ally, we begin to get a glimpse of the world through it's eyes. We begin to understand an aspect of being-ness in a new way that we hadn’t seen before. We can apply this to our lives, the cycles we go through, our relationship patterns and habits of thought. When we are in creative mode, we are able to simultaneously give and receive. We give the Plant our awareness and attention, and we receive its healing vibrations and messages. As we create, we clear space within ourselves to listen. Find a way to work with you plant allies as to engage creatively. You are observing the plant in fine detail, etching it into your memory, and creating pathways between its image, your heart, and hands. You will be connected again to your experience with the plant, remember, and practice bringing it's vibration into your everyday thoughts, perceptions, and decisions. Trust your intuition and your unique creative process, as we interact more and more with our plant friends, we receive more and more ideas of how to interact creatively. As your energy and your plant friends energy merges, you begin to co create and manifest your most exquisite visions of harmony. It is helpful at this time to observe the thoughts, feelings, perceptions and sensations that arise in the body in response to the Plant. This information holds seeds of consciousness about how we can grow spiritually/emotionally in the area that comes to mind. The intuitive connection that is made between observation of the Plant and observation of oneself is a catalyst for a new cycle of awareness and understanding. Study a plant in its natural environment. Plants give us clues to help us identify how they might help us. By observing a Plants colour, shape, growth pattern and environment, we gather information and begin to make a connection with something we already know. ~~~ Today a mindful tea before I ventured into the World, fresh from the garden, for finding my Wings, a spiritual soul ascension tea. It's not just a procognitive nootropic tea, it's a spiritual tea. I really enjoy getting creative in the garden and making just simple sustainable medicinally healing teas. This one establishes connection between Earth, Self and the Heavens. Morning glory represents love, affection and longing but in a spiritual way, this represents my spiritual connection to Milly. Ginkgo also associated with duality, a concept that recognises the female and male aspects of all living entities and that is often expressed as yin and yang. Ginkgo celebrates duality that could be reunited in a single entity. For centuries, the ginkgo tree has been considered a symbol of hope and peace Brahmi is a Sanskrit word derived from “Lord Brahma” or “Brahman”. Lord Brahma is the divinity responsible for all of the creative forces in the world Basil Is a symbol of love and good wishes· Symbolises Love and good wishes, herbs of kings - love, holiness, purity, and sanctity Sage has a protective effect, "to save" Gardenia is one of the most frequently used herbs in Chinese medicine. -
The Journey of an Upside Down Heart to Love and Spirit
Alchemica replied to Alchemica's topic in Creativity, Spirituality & Philosophy
I still have moments I tune into these things, lately endogenously I found myself spontaneously creating a chakra Full Moon Mandala Did some reading, surely I'm not the only one who does these things? "The season of Spring presents a time for us to align with our inner truth, the seeds inside of us waiting to blossom with the droplets of rain and sun. One of my most loved rituals is the practice of creating an Earth Mandala, a Healing Circle, a Flower of Life, a cosmic diagram connecting us to the Universal oneness. It is an offering of prayer and love to Mother Earth and the Spirit of the land where you live. This ritual was inspired by the sacred Andean Despacho ceremony of the Inka tradition. Since ancestral times, people of the Andes have used this ceremony to connect themselves with the harmony of nature and to live in Ayni, in reciprocity and right relationship. To practice Anyi is to acknowledge the interconnection between human beings and the natural world that sustains us. In Peru, a Despacho ceremony is performed by the Q’ero shaman to honor Pachamama, Mother Earth or the Apus, the Mountain Spirits. Using various natural elements as offerings to represent the stars, rivers, clouds… the shaman creates a three dimensional Mandala composition as a symbolic act of respect for all of life." https://puakaihealing.com/earth-mandala/ I've been experiencing a strong connection to the natural world lately, plants, birds etc. "When a feather arrives for you, Spirit is reminding you of your spiritual origins and deep connection to your home beyond earthly realms." "Feathers come to us as gifts. They come from the sky, from the sea, from trees and deep grasses, even appearing within enclosed spaces never inhabited by winged creatures. They come to us unexpectedly, but not without purpose. Their messages may be startling, soothing or sudden, but they are always an opportunity for seeing – for finding answers to questions we may not even have known we were asking. What, then, is a feather? It is a part of a bird’s body, and it is a part of us. It exists for itself, to serve its primary purpose in the cosmos, and it exists in alliance with every other aspect of the cosmos. Just as we bring life-inspiring messages for others while simply fulfilling our own lives, so do feathers bring their messages to us. They remind us that we walk in a world overflowing with meaning." https://www.shamanicquest.co.uk/blog/2017/05/15/Shamanic-Practice-And-Feathers.aspx -
Visitation by birds
Alchemica replied to Strontium Dawg's topic in Creativity, Spirituality & Philosophy
I too like to see birds symbolically and as spiritual messengers. I've also been feeling attunement to all animals/insects on a deeper level. I feel it's more a personal relationship that you find in their presence than any general one but just observing the bird can form some relevant "lesson" or insight. For example, some have taught me that I need to be more friendly with their general friendly nature. Others reaching for higher transcendence of self through their flight A more detatched view on the earthly pleasures and greater spirit etc There's plenty on spiritual views on the net but see what inner work it brings to your awareness? -
Metaphors in nature - Please share your own
Alchemica replied to TheMooseZeus's topic in Creativity, Spirituality & Philosophy
This one - the dragonfly - came to me in a time where I was embracing change - new place, new attitudes, new behaviour, new light "...change what needs to be changed, survive, become better, and flourish!" -
You can eat the kale, do the meditations, sip on the plant medicine but how healing is that really? I got disenchanted with 'plant medicine' as it was often turning into a bunch of band-aid experiences and pits of continuous self-medication. I saw lots of people embarking on the same loop, it seemed to be a pathway of less healing than expected. Anyone else found that? I think we've often lost some aspect of simply nurturing something that doesn't give back to us with food or medicine etc. A deeper connection to the Web of Life. I started growing some non-medicinals, things that weren't providing me with anything, and noticed something... From the butterfly attracting Milkweed to Milly's forget-me-nots to Acacias I'd never had any interest in... In the past, a plant's worth was dictated to me by what it could do for food or medicine, a very ego-centric view on the plant. There was nothing spiritual or worthwhile about a plant being simply a living entity, the essence of respect was often not there/not as deep - what did it do for us other than provide a bit of oxygen?!? It's "just a plant"... I was centred around always taking something from a plant, be it food, medicine, boosts in self etc. If we treat humans in such a way, constantly dictating their worth by what they can do "for me/us" and with limited respect for their unique worthwhile existence, that's a very unhealthy view that's all too prevalent in society - I believe our human relationships are often mirrored in the way we treat the Earth. If we flip that "for me/us" around into what we can do "for them" without expectation of something in return, that's the start of some healing. In that flip, you also seemingly make room for healthy natural reciprocity Today I see the worth of a plant beyond that narrow view. I'm starting to nurture something that I don't expect anything in return from. The essence of each plant has it's own gift, beyond a phytopharmacological or nutritional cocktail, and deserves respect - a more eco-centric and spirited view Looking forward to Trees for Life
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The strong medicine of growing and nurturing 'non medicinal' plants - when "plant medicine" becomes disenchanting
Alchemica replied to Alchemica's topic in Creativity, Spirituality & Philosophy
Well said @Inyan Coming from only ever being interested in plants for medicinal aspects, to then finding the enjoyment of creating that nourishing connection to food, I always dismissed anything else as aesthetic gardening and pointless. Not saying food/medicine isn't important, I'm just surprised to find how the act of relationship with something that won't deliver a therapeutic brew or even food really breaks the addictive consumption mindset - something I was always struggling with -
Thiamine - how much do you really need for recovery?
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
Keep us in the loop on any improvements or anything you note @Xperiment. I doubt you got up to as much thiamine depleting shenanigans as I did but if you did, be liberal with doses... Longer term, I've noted it's not the panacea for me - don't expect it to be - if I get stressed I get symptom flares but they actually resolve over a bit of time whereas before nothing would shift a continuous spiral down. -
Thiamine - how much do you really need for recovery?
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
This continues to deliver day by day. So much so I think the quest for some stability might be over I find the effects are very dose dependent in line with the dose-response noted above - using 500mg+ (I haven't noted side effects up to 1.5g) and keeping those levels elevated throughout the day has given me some good stability, I might be able to reduce doses soon. Why did my brain feel daily like it was being eaten alive, was pure negative affect constantly over-riding my emotional world, was I in pure dysphoria with constant fluctuations in mental state and deteriorating cognition? This seems to be the closest I've found to a solution and an affordable one at that The encouraging thing is that on returning to what was my first point of call but really upping the thiamine dose with just healthy dietary diversity and maintenance, it feels like there's nothing too much needing continuous time investment in attempting 'fixing' which has been a super challenging loop for me to break free from when minute to minute your mental state, memory and cognition is doing weird things. Hopeful I can maintain that. I'm currently having manageable stable-ish days without extreme and constant mood, emotional and other weird neuropsychiatric stuff happening. That said, it's been a long time of symptoms so there's likely been damaging effects from that. I'm not saying it's at all perfect but it's workable and stable 'good enough'. I can actually do some things I want to do for a few hours, particularly manage some family time, without it being absolute torture for my fluctuating brain state. Get on with living life. -
Modulating 5-HT - dietary augmentation interventions
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
Switching this around, how do we use the social to modulate monoamines? Is 5-HT something that is successfully modulated by the social? That's the other thing that causes a drastic reduction in symptoms for me - nourishing social interaction. The serotonergic system itself is highly responsive to social influences and social isolation has been shown to affect endogenous 5-HT release and 5-HT turnover and leads to a reduction in the excitability of DRN 5-HT neurons. Sure, initially the elevated serotonergic states where nice but eventually things seem to return to a homeostasis, likely as seen in clinical studies with Trp augmentation "During the first week of treatment, there was a significantly greater decrease in depression scores. No significant differences were noted at later time points." and if you're adding additional Trp, are you potentially providing extra fuel for an activated kynurenine pathway? Upping the monoamines helped but... I mean really, is fancy supplementation really alleviating issues at the source and improving life, or just a band-aid for real problems, like persistent social isolation? Part of me says, fix the aberrant underlying deficits and you'll start having better social approach and try more socialising whereas in reality, each "band-aid" is directing life force away from actively tackling the root causes. The bidirectional effects of the social on the biological could be more effective and stable than trying to up monoamines with anything. I've tried that approach before, a few times, but it's worth a retry. Riding through the nastiness of 'augmentation cost cutting', feeling quite extra crap, and more attempted action even though I feel crap. Often the only way that works... I'm at the point Trp isn't doing much more, other than inducing side-effects and becoming very blunting. More so than just switching favour between hedonic short-term rewards in favour of longer-term ones, actually feeling extremely anhedonic. It switched the impulsivity down, tackled negative emotional dysregulation well, for a bit. PRN stuff it feels. Do social factors induce cascading serotonergic abnormalities? It seems very difficult to climb back to any level of health if you condition social defeat and isolation. We too easily isolate and subordinate people with lower mental health, as they do to themselves, how much does that cascade into crippling mental illness? How much of a role does the serotonergic system play in that? Serotonin is probably most central in its relation to social status functioning [1] Changes in serotonergic function seems to directly affect perceived social status. "Social subordination leaves one fidgety, easily perturbed, and their behaviour seems to be largely controlled by external stimuli rather than being self-directed. [they are] prone to impulsive behavior including impulsive aggression." 5-HT appears - important in developing nourishing social contacts - contributes to the appraisal of the social emotional cues - increases the perception/interpretation of social stimuli - It stimulates pro-social behaviour, which leads to high levels of cooperation and improved perception of social cues In a simplistic framework: "Serotonin levels are not innate and inflexible. They are themselves the product of social status. The higher your self-esteem and social rank relative to those around you, the higher your serotonin level is. Experiments with monkeys reveals that it is the social behavior that comes first. Serotonin is richly present in dominant monkeys and much more dilute in the brains of subordinates. Cause or effect? Almost everybody assumed that the chemical was at least partly the cause: it just stands to reason that the dominant behavior results from the chemical, not vice versa. It turns out to be the reverse: serotonin levels respond to the monkey’s perception of its own position in the hierarchy, not vice versa." “Contrary to what most people think, high rank means lower aggressiveness, even in vervet monkeys. The high-ranking individuals are not especially large, fierce or violent. They are good at things like reconciliation and recruiting allies. They are notable for their calm demeanor. There is little doubt that the monkeys mood is set by its high serotonin levels. If you artificially reverse the pecking order so the monkey is now a subordinate, not only does its serotonin drop, but its behavior changes, too. Moreover, much the same seems to happen in human beings." - Genome The activity of 5-HT neurons is highly vulnerable to stress. Stress → social withdrawal/low mood → social isolation and continuous social subordination. Each of those declines is another hit to the functionality of the serotonergic system. It forms a negatively re-enforcing cascade. [1] https://www.ulm.edu/~palmer/TheBiochemistryofStatusandtheFunctionofMoodStates.htm "Serotonin dysregulation found in depression and other psychiatric disorders may go hand-in-hand with deficits in initiating social interaction, impaired learning from social interaction experience and making adverse decisions in social situations." -
Modulating 5-HT - dietary augmentation interventions
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
Thanks @tarenna and @LikeAshesWeFade for the kind words Still going with the Trp. Finding it really quite useful. It's not so much a mood boost as what I need Modulating 5-HT more given me a view on 5-HT beyond it being a way of increasing personal "happiness". I'm not more "happy" - it's deeper than that. It's also deeper than 5-HT making octopi cuddly with empathogens, too. I like the model where "Serotonin influences social behaviour by shifting social preferences in the positive direction, enhancing the value people place on others’ outcomes." Trp augmentation may "influence the way they feel and think about themselves in a social context" and "serotonin function is related to positive social preferences, that is, the positive valuation of others’ outcomes" Serotonin's effects appear to depend on the social context: "serotonin amplifies neural representations of positive social preferences, whereas serotonin depletion shifts neural value computations toward selfish or even negative social preferences" "Serotonin is concentrated in discrete brain regions known to regulate social cognition and decision-making that have been collectively called “the social brain”. Depleting serotonin in normal individuals shifts their behaviour toward lack of impulse control and short-term gratification at the expense of long-term benefits. Enhancing brain levels of serotonin causes people to become more averse to harming others" Depleting brain serotonin levels in normal individuals results in a shift away from cooperative behavior in favor of short-term gain and results in antisocial behaviour, increased uncontrolled aggressive behavior, feelings of anger, quarrelsome behavior, and self-injury Low functioning "compromises the decision-making process by altering the ability to distinguish the magnitude of differences between immediate versus long-term rewards" and increases the tendency to choose the less probable outcome Low Trp manipulations result in the use of more self-references, more negative words, and fewer positive words Reduced serotonin function indeed impairs ones empathic abilities. Serotonin is important for promoting behavioural suppression or withdrawal in the face of aversive predictions Serotonin modulates human concerns for harm and fairness Serotonergic activities might strongly influence the sharing effect of emotions. It plays important roles in the regulation of individual behaviours that organize social group dynamics. Read How serotonin shapes moral judgment and behavior Vitamin D and 5-HT I'm a month into the L-methylfolate with the later added amino acids. It's reduced some symptoms quite nicely but it's pricey when I have house expenses. Trp will definitely remain as a useful amino acid for me but I'm keen for more affordable monoamine modulating vitamin options - maybe massive doses of L-methylfolate aren't needed and I can just use a mg/day or something. I also note how much the sun does for me... when I get out there properly "Vitamin D acts not only to induce serotonin synthesis, but also functions at an indirect, molecular-genomic stage to mimic SSRIs and MAO inhibitors" [1] "Fine-tuning serotonin concentrations in the synaptic cleft, vitamin D may be able to steer neurological control of such processes as social behaviour and depression." It is "hypothesized that an association between vitamin D insufficiency and low central serotonin concentrations represents a common denominator in a myriad of neuropsychiatric disorders." How does this apply to health? The core symptoms of ASD fluctuated in severity with changes in serum vitamin D levels in children: high-dose vitamin D3 regimens may ameliorate the core symptoms [2, 3] "...core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL." Vitamin D supplementation is associated with lower depressive and anxiety symptoms in psychotic illness [4] and addition of vitamin D to conventional antidepressive agents can improve antidepressive effect [5] I was always on the lower end dose when supplementing. A daily vitamin D intake of 1000–4000 IU (25–100 micrograms) should be enough to ensure optimal blood levels for most people [6] Anyone attest to benefits dosing higher? [1] https://www.ncbi.nlm.nih.gov/pubmed/30008960 [2] https://www.ncbi.nlm.nih.gov/pubmed/29629638 [3] https://www.ncbi.nlm.nih.gov/pubmed/27868194 [4] https://www.ncbi.nlm.nih.gov/pubmed/30245372 [5] https://www.ncbi.nlm.nih.gov/pubmed/29460820 [6] https://www.healthline.com/nutrition/how-much-vitamin-d-is-too-much -
Modulating 5-HT - dietary augmentation interventions
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
The recent dietary modification has given me baseline stable state where it feels feasible to attempt simple meditations, started that and try and incorporate that each morning, whereas before the dysregulation was something I couldn't at all over-ride. In SUDs, there is a brain-state shift from a hippocampal and PFC- mediated regulatory state to a more primitive and dysregulated amygdala and insula-mediated state underlying emotion dysregulation Few things I've noticed: Trp influences behaviour along the agonistic–affiliative axis, it regulates the tone of interactions along the axis that runs from agreeable to quarrelsome to overt aggression. Tryptophan - promotes prosocial behaviour. - promotes interpersonal trust. - causes greater sharing and helpfulness, greater perspective taking and emotion recognition. - improves control over antisocial behaviour - It allows regulation of aggression and positive social interactions, as well as emotional processing Serotonergic signalling impacts the two-way interaction between each of the following pairs: mood and social behaviour, mood and cognition, social behaviour and cognition and increases prosocial behaviours - Enhanced serotonergic function might promote effortful control over underlying action tendencies - Enhancing serotonergic function should decrease reliance on habitual, reflexive forms of self-regulation and increase the use of effortful, reflective forms of behaviour regulation - Enhanced 5-HT leads to blunted evaluative responses to both positive and negative stimuli Manipulations of serotonergic tone affect reward [1] and decision making [2]. Depleted states cause one to be significantly more perseverative over choices and (acutely) significantly less sensitive to reward (lower reward magnitude) For me, the impulsive reward chasing loops start to seemingly undergo some changes (serotonin has been proposed as a possible encoder of reward and facilitator of reward extinction): you go from impulsive action to greater conscious choice but it doesn't feel as impulsively rewarding to do things. It feels a little blunting. So those healthy addictions, for me gardening and daily walking, start to feel more effort-driven than impulse driven and require more effort in. If you're not careful, you can become content with inaction. Depletion of 5-HT enhances behavioural and brain responsiveness to aversive signals, while disinhibiting previously rewarded but now aversive behaviours [3]. Dysfunction by the serotonergic system in impulse control disorders reflect inhibitory impairment of the prefrontal cortex [4]. You want 'better'. It has been proposed "5-HT encodes beneficialness, and may signal motivation to either maintain or switch current behaviour, for example displayed by 5-HT’s role in facilitating patience for future rewards" [1] https://www.frontiersin.org/articles/…/fnhum.2017.00484/full [2] http://www.jneurosci.org/content/32/17/5833 [3] https://www.ncbi.nlm.nih.gov/pubmed/18069045 [4] http://europepmc.org/articles/PMC4117279 Imagine, after a long time of not knowing/feeling emotions or self-regulating them, you are now unable to avoid the blunt edges of tough emotions which are, after so long, alien influences. Sadness, anger, disappointment, frustration, boredom, annoyance, confusion, disgust, surprise, anxiety, guilt, shame, embarrassment. There is no more avoidance. Your escape route has gone. ‘Feeling all the feels’ is like being on a furious roller coaster, particularly when your emotional regulation route has always been psychopharmacological. There's not just the array of problems induced by self-medication but also over a decade of often supratherapeutic doses of potent psychotropics/ECT, including over neurodevelopmentally-sensitive timeframes when the prefrontal networks and skills in emotional regulation should have been developing. I'll attest that attempting meditation when all emotional regulation is in tatters and you have pure negative affect is plain frustrating, studies show that greater intact emotional regulation when meditating produces more benefits in affect regulation You can use attentional bias modification: mindfully focus on their breath, or on emotions. Breathing meditation and emotion-focused meditation may constitute effective emotion regulation strategies to deal with negatively valenced emotional states [1] Short meditation [2] enhanced mood (i.e., total mood disturbance, anxiety, and fatigue), cognition (i.e., attention, working memory, and recognition memory), and improved the response to acute stress Simple 13 min meditation [they used Journey Meditation (http://www.journeymeditation.com/) for 8 weeks has been studied. 8 weeks of brief daily meditation relieves feelings of negativity by decreasing levels of mood disturbance. It exhibited a similar range of cognitive benefits as the effects previously reported following longer duration, more intense meditation training If you get through regulating and managing persistent negative emotion, you start to feel the good ones in all their glory too. All of the lovely positive emotions such as; satisfaction, joy, elation, excitement, love, contentment, gratitude, hope, amusement, inspiration, awe, interest. [1] https://www.ncbi.nlm.nih.gov/pubmed/30146138 [2] https://www.ncbi.nlm.nih.gov/pubmed/30153464 The world of emotions Key to this employment of equanimity to reduce emotional reactivity is the intentional cultivation of awareness towards emotional information. I was shutting down that world. "Limiting cognitive elaboration in favor of momentary awareness appears to reduce automatic negative self-evaluation, increase tolerance for negative affect and pain, and help to engender self-compassion and empathy in chronically dysphoric individuals" [1] - cognitive elaboration often automatically triggers negative self-judgments that cannot be voluntarily overridden "Dysregulation of fronto-limbic control regions may lead to maladaptive, ruminative, and egocentric attention contributing to depressive affect. In mood disorders, cognitive control appears to be impaired, there is compromised connectivity between the PFC and limbic regions such as the amygdala. Thus, activating PFC regions in efforts to reappraise negative feelings may backfire, bringing attention to focus on dysphoric mood without a commensurate reduction in the intensity of negative feelings." Instead, you begin observing, describing, acting with awareness, being nonreactive, and being nonjudging. When emotional information is consciously attended, you evoke less of an amygdala response and engaged greater prefrontal cortical resources. By deploying attentional resources to recruit a network that limits habitual elaboration and self-referential narrative "automatic recruitment of temporally-extended, self-referential narrative generation may undergo a form of neural extinction, restoring autonomy to the central executive system and freeing it from its habitual applications For me, some of the skills I'm trying to bolster are: 1. Acceptance of emotional responses (ACCEPTANCE) 2. Engaging in goal directed behavior (GOALS) 3. Impulse control (IMPULSE) 4. Emotional awareness (AWARENESS) 5. Emotion regulation strategies (STRATEGIES) Mindful emotion regulation can be construed as a process of ‘turning toward’ momentary experience - attention is positively directed towards present moment sensation, providing a non-conceptual and non-threatening focus for attention 6. Emotional clarity (CLARITY) Improving the self-regulation of attention might reduce the negative emotionality associated with ruminative thought patterns and the tendency to suppress thoughts, both of which have been associated with craving and relapse in addictive behaviours [2] The development of an attitude of acceptance (i.e. a nonjudging/nonattached view of experiences) could reduce negativity affectivity by reinforcing distress tolerance abilities in relation to several experiences (e.g. craving, stress, anxiety) [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303604/ [2] https://www.ncbi.nlm.nih.gov/pubmed/30216741 Tryptophan and ASD I always had strong affinity for serotonergics but addressing it at the dietary level is so much more sustainably promising for me than other approaches. Trp, B-vitamins and magnesium have been used. While radically boosting prosociality through empathogens is being researched for autism, I feel it often needs to be addressed at a more fundamental and sustainable level. A slow and steady, easily integratable and sustainable induction of mood, emotion and greater prosociality can seemingly be had through safer dietary serotonergic interventions. "Low brain tryptophan availability… could be one of the possible mechanisms involved in the alteration of serotonergic function in autism.” "Serotonergic abnormalities were reported in ASD. Research indicates that the reduced levels of serotonin are correlated with the occurrence of impulsive and aggressive behavior, fatigue, depression episodes, insomnia and increased sensitivity to pain. There is evidence that pharmacological treatment is aiming the reduction of the serotonergic neurotransmission results in worsening of autistic symptoms" [1] "Often, families observe that anxiety and subsequent frustration leading to aggression can be better controlled by administering this supplement on a daily basis. Likewise, more focus and attention may accompany administration of tryptophan" [2] It seems to have quite prominent socio-emotional qualities in the way I'm using it that have not really been researched in ASD "BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes." [3] Lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder. Lower 5-HT synthesis were hallmarks of AS [1] https://link.springer.com/article/10.1007/s11011-017-0045-x [2] http://www.theautismdoctor.com/tryptophan-to-treat-autism/ [3] https://www.ncbi.nlm.nih.gov/pubmed/30033880 It also targets another issue for me: Recent findings suggested the serotonin system may be an effective target for prevention and treatment of mild cognitive impairment “Now that we have more evidence that serotonin is a chemical that appears affected early in cognitive decline, we suspect that increasing serotonin function in the brain could prevent memory loss from getting worse and slow disease progression.” Researchers have tried with limited success to treat Alzheimer’s disease and cognitive impairment with antidepressants such as SSRIs What if it's as simple as tryptophan as a starter? I was skeptical about simple tryptophan, assuming it could worsen pathology through often noted disturbed tryptophan metabolism. L-Tryptophan (TrP) enriched diet protect against memory deficits during physiological aging 5-HT modulates BDNF mRNA levels. TrP significantly elevates the number of 5-HT immunoreactive fibers and this correlated with BDNF increase in the FC and hippocampal region "...enhanced TrP intake and the consequent increase in 5-HT neurotransmission may act as a modulator of BDNF system suggesting a possible mechanism for the protective role of serotonergic system on memory impairment occurring along normal aging process." [1] "data suggest that enhanced TrP intake, and in consequence a potential increase in 5-HT neurotransmission, might be beneficial in preventing age-related detrimental features by inhibition of hippocampal apoptosis." [2] https://www.healio.com/.../serotonin-may-play-important... [1] https://www.ncbi.nlm.nih.gov/pubmed/26444078 [2] https://www.ncbi.nlm.nih.gov/pubmed/27889579 Targeting alexithymia Working through spectrums of emotions and getting some quite pleasant positive ones for once. My emotional world has consistently much improved, as has the range of accessible emotions, I have to learn to put words to them more. Finally looking forward to the new place now that I'm not stuck with such negative unprocessed emotions over-riding me. I like this take. "Alexithymia, a personality trait involving difficulties in identifying and describing one’s own emotional feelings and an externally oriented or concrete thinking style, has been reported to be strongly associated with alcohol misuse" [1] "We argue that emotion processing deficits result in a diminished ability to put words to emotions, or articulate feelings, with the consequence that feelings cannot be acted on with goal directed behaviour, but are instead treated as undifferentiated emotion distress, prompting repetitive compulsive behaviours." In alexithymia, "Instead of dampening amgydaloid activity (and subsequent neuro-endocrine release) in order to identify and label emotion in order to cognitively process, alexythmics may do the opposite. They appear to increase amgydaloid and neuro-endocrine activity, which recruits more automatic, implicit and motoric regions in responding to affective stimuli. Emotion is thus not labelled as a resource to be cognitive processed but almost treated in a compulsive threat or “fight or flight” stimulus; an undifferentiated emotion distress" [2] [1] https://www.jstor.org/stable/10.5406/amerjpsyc.131.1.0041 [2] https://insidethealcoholicbrain.com/2018/07/06/addiction-as-a-brain-disorder-of-emotion-regulation-part-4/ -
Anyone use CBD in the context of relapse prevention? Keen to hear any experiences with such. I've had good break aways from things like alcohol but relapse prevention is an under-addressed area in medicine. CBD is often good but limited by cost-prohibitiveness at the doses required for some. Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle Full text: http://sci-hub.tw/https://www.nature.com/articles/s41386-018-0050-8 The use of serotonergics in mood disorders is well established and their use in SUDs is gaining traction. Things like psilocybin can facilitate abstinence and behavioural change, what is there for relapse prevention? As an example for motivating substance abuse cessation: "A recent pilot study in alcohol-dependent patients on the efficacy of psilocybin in alcohol dependence showed a significant reduction in both percentage of drinking days and heavy drinking days, with large effect sizes. Furthermore, a recent study investigating psilocybin in tobacco dependence demonstrated that 80% of the participants had quit smoking after a 6-month follow-up, thereby substantially exceeding success rates for other behavioral and/or pharmacological therapies. In the latter study, participants were also asked why they thought psilocybin helped in quitting smoking. The most common reasons were ‘changing orientation toward the future, so that long-term benefits outweighed immediate desires (73%); strengthening participants’ beliefs in their ability to quit (73%); and changing life priorities/values, such that smoking was no longer more important than quitting (68%)’" [1] Successful serotonergic interventions activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. CBD has potential rapid acting antidepressant activity potentially mediated by 5-HT1ARS. CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia. Things like CBD are finding potential use as "relapse prevention aids": CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. This may be mediated by 5-HT1ARs. 5-HT1A receptors as a target through which CBD produced its proneurogenic/mood, anti-anxiety actions and amelioration of stress-induced reinstatement. While I believe the acute mood improvements and behavioural change often comes via 5-HT2ARs inducing 'new ways of thinking, motivating behavioural shifts and providing spiritual insight', maintaining efficacy is another intriguing question. New treatments for both treatment resistant depression and SUDs are urgently needed. 5-HT-mediated changes in emotion and stress regulation (HPA axis etc) can strongly affect both mood and addiction-related disturbances which often feed each other Problem is, while they're often effective, it's often not a great idea to keep throwing more 5-HT2A selective substances at your brain to ease pathology. Can you get at issues and restore emotional balance through 5-HT1ARs? DRN 5-HT1A receptor availability is linked specifically to the processing of aversive emotions in the amygdala and the modulation of amygdala-cortical connectivity. How much therapeutic potential comes from 5-HT2A vs 5-HT1A? 5-HT1A receptor agonists are effective against emotional changes produced by stressful stimuli - activation of the adrenocortical system via 5-HT1A receptors may facilitate some adaptive mechanism(s) involved in the recognition of and/or ability to cope with stressful situations While 5-HT2A receptor-mediated signaling is implicated in emotional processes, the neuroendocrine system, and behavioural flexibility what happens due to other serotonergic receptor actions? 5-HT1A receptors are believed to be crucial in physiological processes linked to emotional balance Altered 5-HT1AR expression is observed in emotional and behavioural disorders. Studies in Schizophrenia reported increases in 5-HT1AR density in the prefrontal cortex in the approximate range of 15–80% Recent studies in Alzheimer’s disease have shown that reduced 5-HT1AR binding in the temporal cortex correlates with aggressive behavior in Alzheimer’s disease It is proposed that the nonselective interaction of psychedelics with other 5-HT receptors contributes to behavioural effects, over being solely mediated by 5-HT2A Some investigators propose that postsynaptic 5-HT1A and 5-HT2A receptors have functionally opposing effects, that a disturbed balance of these receptors may be contributing to the pathophysiology of depression, anxiety, and impulsivity, and that restoring this balance is necessary for therapeutic action. 5-HT1A receptor agonism may act to buffer 5-HT2A-mediated psychedelic effects. While 5-HT2A receptors may strongly influence the emotional state of an individual, several researchers to propose that postsynaptic 5-HT1A and 5-HT2A receptors exert opposing effects in the regulation of mood. A disturbed balance between these receptors has been thought to contribute to depression but may also be relevant for SUD. Since restoring this balance is thought to be necessary for antidepressant action this may also be true for the treatment of SUD. It has been demonstrated that 5-HT2A receptor antagonism impairs behavioral flexibility by increasing perseveration, 5-HT2A agonism has a beneficial effect on behavioral flexibility while 5-HT1A receptors are involved in mediating the emotional state of individuals and patients with SUD. As for other 5-HT1A mediated plants as being potentially cheaper options, I found the Lotus embryo at high dose was so emotionally balancing, stress buffering and took the edge of the negative and gave some bias towards more positive thinking. I'm going to have more of that as a tea fairly regularly I think. [1]: https://www.tandfonline.com/…/full/10…/14737175.2016.1220834 Enhancing Meaning and Purpose Contrary to most mental health approaches which use agents that diminish the intensity of experience, thereby allowing individuals who are otherwise overwhelmed by feelings to adequately cope and function leading to a more flattened experience of the world, can we fight rising rates of psychopathologies by bolstering individual and social sense of meaning and purpose? [1] Here's a bit of the latest research working with stronger plant medicines I think the making of meaning and embodying purpose is so important. What meaning do you ascribe to your life? What are you doing today that gives you meaning and purpose? Simple things like that. Today my meaning making and purpose is getting some plants to people. "It makes me feel connected again. And not, flailing out there somewhere. Yeah. It's a purpose, you know? It's a purpose. And that's the whole thing is, I've been living life really without my own personal purpose ... I've– it's just been an unpurposeful life." - a study participant. Several studies have demonstrated correlations between feelings of meaning in life and increased psychological well-being, increased longevity, as well as reduced risk of suicidality and depression "Enhancers of meaning can be seen in the broader cultural context of late modernity's struggle to make sense and meaning of life in increasingly atomized, individualised, and stress-ridden societies." In AUDs, the content of psilocybin-induced experiences has been recently studied. Experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased "spaciousness" or mindfulness, and increased control over choices and behaviour were reported [2]. Much work is focusing on Motivational Enhancement Therapy (MET) therapy, a psychosocial treatment based on motivational interviewing, designed to build motivation through evoking the patient's reasons for change and strengthening skills to support the patient's goals around changes [3] More recently, meaning-making therapy have been used as the psychotherapeutic models. The amplification of meaning automatically entails amplification of placebo. A treatment of depression currently under development will use Acceptance and Commitment Therapy. Initial and still unpublished results have found significant increase in meaning in life following administration of psilocybin, as measured by the Meaning in Life Questionnaire. The experience of confronting an overwhelming, ineffable, and even unfathomable quality of the world is arguably facilitated to imbue the mind and the external world with vibrant significance. By causing mental and external phenomena to appear immensely more significant, we can facilitate a reenchanted experience of the world Recent studies have noted dramatic and variegated effects which include, among other phenomena, psychotherapeutic insights, creative breakthroughs, and mystical-type experiences, amplification of emotional volume and demanding that patients “face the demon.” Induction of spiritually meaningful experiences and experiences of ego dissolution, whose occurrence is often correlated with the success of therapy, but researchers have also suggested a numbers of other mediators including relational embeddness, embodiment, “the difficult struggle,” affect and catharsis, visions, and recovered sense of appropriate priorities [1] https://www.ncbi.nlm.nih.gov/pubmed/29559884 [2] https://www.ncbi.nlm.nih.gov/pubmed/29515439 [3] https://www.ncbi.nlm.nih.gov/pubmed/29515449
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Nicotiana alata - bringing the "rest of Tobacco's Medicine" to the picture
Alchemica posted a topic in Pharmacology, Chemistry & Medicine
If you want a nicotine buzz, seek elsewhere. If you want a healing tobacco, this may be of interest to you. My review on Nicotiana alata, which is grown mainly as an ornamental plant, although some authors classify it as traditionally used as smoking tobacco, mainly for religious purposes. It is often referred to as “jasmine tobacco” or “flowering tobacco” due to its abundant, beautiful flowers and mild sweet nocturnal fragrance. It's a different spirit to interact with than the majority of Nicotiana's, it seems useful for tapering off high nicotine content plants. We are used to interacting with the nicotine in tobacco, we often don't get the full spectrum of interacting with the Tobacco Spirit. Nicotiana alata is a nice ally to connect with for doing that. Phytoconstituents include alkaloids, tannins, phenolic compounds, proteins, terpenoids and saponins. I find it brings "the rest of Tobacco's Medicine" to the picture. For growth, it's super easy to maintain as a beautiful compact aesthetic plant. I didn't find it set seed prolifically, it was a struggle to get some seed. In my opinion, it could potentially be a better healing Tobacco for some situations, particularly Tobacco dieta - I included some of this plant orally and it seems friendly. That said, it's not suggested or recommended. While generally considered alkaloid-poor - one analysis puts nicotine concentration as low as 0.06%, it's often higher (it's possible it is actually more a nornicotine/anabasine/anatabine ally) - Nicotiana alata is a nice plant to grow and seems to have a subtlety of interacting with that is nice. Interacting with it attunes you to the subtlety of the tobacco's other healing constituents while putting aside the fiendish nature of nicotine. Alkaloid content seems to depend strongly on growing conditions. The total-alkaloid content in leaves from greenhouse-grown plants of N. alata was 0.2 μg.g-1 (of which – 68.8 % nicotine, 9.5 % nornicotine, 21.3 % anabasine, 0.4 % myosmine), while that in leaves from field-grown plants was only 0.04 μg.g-1 (100 % nicotine). Many of it's constituents are very healing, from the phenolic/flavonoids to the triterpenes which may be anxiolytics "HPLC analysis of triterpenes identified only betulin (251.12 μg/g) in the leaves of white flowers genotype, and betulin (284.30 μg/g) and betulinic acid (393.75 μg/g) – in that with pink flowers. Totally, 12 phenolic acids and 7 flavonoids were determined in the leaves. The most abundant free phenolic acid were chlorogenic (3796.21 and 2523.37 μg/g, respectively in white and pink forms) and other hydroxycinnamic acids (rosmarinic, sinapic, caffeic), and conjugated - vanillic acid (3077.34 and 4926.68 μg/g, respectively). The major flavonoids of both genotypes were: free - hyperosid (35.85 and 107.30 μg/g), and conjugated – apigenin (249.55 and 211.74 μg/g), luteolin, hesperetin and kaempferol. 19 components were determined (by GC/GC-MS) in the essential oils (representing 83.86 % and 67.09 % of oil content), among which the major were: phytol, solanone, cis-5-butyl-4-methyldihydrofuran-2(3h)-one, dihydro-β-ionone, α-ionene, β-damascenone, 1-methylnaphthalene. In the concretes were identified 19 components (82.03 % and 65.63 %, respectively), of which over 3 % were: isoamyl alcohol, oxynicotine, phytol, 4-mеthyl-1-penthanol, cotinine, 3-metyl-3-penthanol, 3-penthanone. The number of identified volatiles in the resinoids was 16 (94.93 % and 75.94 %), with major components: nicotine, phytol, eicosane, diethyl phthalate, dibutyl phthalate, solanone, furfuryl alcohol." Root cultures of Nicotiana alata Link and Otto, growing in a Murashige and Skoog medium, contained the following alkaloid composition: nicotine (5 %), nornicotine (58%), anabasine (10%), and anatabine (27%), all with the (S)-configuration with high enantiomeric excess. It intrinsically seems to have a better burn rate without complicated curing, that said I don't think it's a good smoking tobacco as the healing constituents probably don't smoke well. It's pleasant as a low nicotine snuff. -
Nicotiana alata - bringing the "rest of Tobacco's Medicine" to the picture
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
Do any of the nornicotine dominant Nicotiana have a history of traditional interesting use? I'm trying to suss out the novel tobacco's. I'm sick of relapsing on boring NRT nicotine only. From what I can find, N. tabacum, N, rustica, N. alata, N. langsdorffii all contain nicotine; N. sylvestris and N. rusbyi [N. tomentosiformis] contain nornicotine, while N. glauca contains anabasine. I've used N. glauca cautiously but didn't get heavily into it [covered the potential anti-addictive nature of anabasine in [1]] and the major nicotine containing Nicotianas. I want something different. I want to know what nornicotine is like as a dominant alkaloid? Exploring some cotinine would be neat, the predominate metabolite of nicotine, which has been "shown to reduce depression, anxiety, and fear-related behaviour as well as memory impairment in animal models of depression, PTSD, and Alzheimer's disease." [2]. "Nornicotine (N-desmethyl-nicotine) appears to activate different nAChR subtypes, has a better pharmacokinetic profile, and produces less toxicity than nicotine." [3] Note: the nornicotine in Duboisia hopwoodii has been stated in one (albeit old) paper to be d-nornicotine contrary to what is found in Nicotiana, which may be more toxic, potentially giving rise to the statement "Twentieth century chemical analysis found that both nicotine and nornicotine, a drug four times as toxic as nicotine, are usually present in Duboisia" [4]. Nornicotine occurs in several species, such as Nicotiana sylvestris and some Australian species [5]. N. sylvestris contained 0.44% alkaloids in one study but in another, had a total alkaloid concentration of 1%, nornicotine comprising 95% of the alkaloids [6]. Another reference [8] gives 4.8mg/g alkaloids, 82.2 % of that being nicotine. Nicotiana langsdorffii contained 0.22% alkaloids, 73% being nicotine, the rest nornicotine [7]. It is the dominant alkaloid in N. thyrsiflora (94.3% of the 5.1mg/g total alkaloids). It is said "The heated leaves of Nicotiana thrysiflora are used for rheumatism." In Nicotiana tomentosiformis, nornicotine makes up 79% of the 1.1mg/g total alkaloids. N. glutinosa contains 7.4mg/g with 77.4% of that being nornicotine [8]. "About 0.8% of nicotine is metabolized to nornicotine in the periphery. However, the biotransformation of nicotine to nornicotine also appears to occur locally in the brain, and brain concentrations of nornicotine have been shown to exceed those in the periphery" [9]. Nornicotine is proposed to result in additional activation of a7-type receptors, which may be important for effects on cognition and attention. Nornicotine inhibits striatal DAT function via a nAChR-mediated mechanism [10]. "The nAChRs mediating the nornicotine-induced inhibition of DAT function appear to be different from those activated by nicotine which increases DA clearance" Both nicotine and nornicotine were relatively potent partial agonists of rat α7 receptors with efficacies of approximately 60% and 50%, respectively, compared with ACh The efficacies of nicotine and nornicotine for α4β2 receptors were relatively low, compared with ACh, although nicotine was rather more potent than nornicotine and ACh. Nicotine was relatively efficacious for α3β4 receptors, although less potent at α4β2 receptors. Nornicotine was a relatively poor agonist for α4β2 and α3β4 receptors. The half-life of nornicotine in brain is 166 min, which is three times longer than that of nicotine (52 min) [1] http://www.shaman-australis.com/forum/index.php?/topic/45354-n-glauca-and-anabasine-as-anti-addictive-agents-some-theory/ [2] https://en.wikipedia.org/wiki/Cotinine [3] https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@[email protected]+8034 [4] https://en.wikipedia.org/wiki/Pituri [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727613/ [6] https://academic.oup.com/jee/article-abstract/30/5/724/2201756?redirectedFrom=fulltext [7] https://naldc.nal.usda.gov/download/IND43969765/PDF [8] https://www.degruyter.com/downloadpdf/j/cttr.1990.14.issue-6/cttr-2013-0610/cttr-2013-0610.xml [9] https://pdfs.semanticscholar.org/6a2f/0b3328d07bab7dc4bd6164172bcecb9e25b5.pdf [10] https://www.ncbi.nlm.nih.gov/pubmed/17146768 For more nicotine containing plants: For a breakdown of normal tobacco: Nicotiana tabacum Alkaloids 11.462 mg/g Nicotine 94.8% Nornicotine 3.0% Anabasine 0.3% Anatabine 1.9% N. alata is generally very low on nicotine but allows the other non-alkaloid constituents of tobacco's medicine to be explored. N. megalosiphon contained 0.22% alkaloids, 100% being nicotine N. quadrivalvis had in one study a nicotine content of approximately 0.16% in one study. It was the main native tobacco that was once widely cultivated by numerous tribes for medicinal and religious purposes Another reference gives Alkaloids 7.76 mg/g Nicotine 94% One early trier found the such tobacco "very pleasant," adding, "it does not affect the nerves in the same manner..." Nicotiana clevelandii Alkaloids 8.945 mg/g Nicotine 98.5% Nornicotine 0.3% Anatabine 1.2% Thanks @Micromegas -
Ethnopharmacology of Love - β-caryophyllene for the lovesick?
Alchemica posted a topic in Pharmacology, Chemistry & Medicine
Ethnopharmacology of Love Background: Elixirs conferring eternal youth or inducing amatory and erotic attraction have been searched for without success. Lovesickness is a widespread affliction resulting from unrequited love and/or the impossibility for physical and emotional union. The symptoms are reflections of altered dopamine, serotonin, noradrenaline, testosterone and cortisol levels and range from frenzy and intrusive thinking to despair and depression, sharing traits with the neurochemistry of addiction and compulsive behavior disorder. Although it can seriously impact the quality of life, lovesickness is currently not considered in official disease classification systems. Consequently, no official therapeutic guidelines exist, leaving subjects to seek the cure on their own. Methods: We review literature of the past 2000 years dealing with the concept, diagnosis and the healing of lovesickness and contextualize it with neurochemical, ethnomedical, and ethnographic data. Since neurobiological and pharmacological connections between the love drive and the sex drive exist, we review also the literature about herbal an- and aphrodisiacs, focusing on their excitatory or calmative potential. Results: An overall consensus regarding socio-behavioral regimes exists for dealing with lovesickness from historical through contemporary literature. The herbal drugs used for treating lovesickness or inducing love passion do not possess the alleged properties. The pharmacological effects of aphrodisiacs are heterogeneous, including dopaminergic and adrenergic activities, but there is no evidence for any serotonergic effects. The libido-regulating properties of anaphrodisiacs seem to be associated with sedative and toxic effects or decreasing testosterone levels. CB2 receptors expressed on dopaminergic neurons of the ventral tegmental area, part of the brain’s reward circuit, implicated with addiction, orgasm and strong emotions such as love, might constitute a new therapeutic target. Conclusion: The common food additive and CB2 agonist β-caryophyllene might have the potential to attenuate dopaminergic firing, quenching the reward and thus motivation associated with romantic love. From Greek mythology to modern history, cultural expressions and implications of love, sex and procreation is and was organized along hierarchical lines that put men on top. The neuronal predispositions and activities associated with falling in love will probably forever remain nature’s and Eros’ secret. Copaiba oil, ~50% β-caryophyllene, appears safe orally at low doses An update on the pharmacology of BCP - orally active potent CB2 full agonist and PPARα/γ agonist. - Analgesic, anti-inflammatory, anti-amyloidogenic, insulin-sensitising, anti-alcoholism, anti-cancer, cardioprotective, hepatoprotective, gastroprotective, neuroprotective, nephroprotective, antioxidant, antimicrobial and immune-modulator effects - Exerts anxiolytic and the anti-depressant effects via CB2 agonism - Activates TrkA receptors and induces neuritogenesis by a mechanism independent of NGF or cannabinoid receptors - potent antagonist of α7-nAChRs - exhibits synergy with µ-opioid receptor dependent pathways - Neuroprotection via prevention of microglial activation and inflammatory cytokine and chemokine expression: β-caryophyllene reduced astrogliosis and microglial activation as well as the levels of COX-2 protein and the mRNA levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the cerebral cortex, inhibits pathways triggered by the activation of toll like receptor complex - CB2Rs modulate striatal dopamine release - PPARγ activation prevents the negative emotional effects of stress and exerts anxiolytic actions - CB2 agonists may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation. β-caryophyllene is an attractive molecule with therapeutic potential for the treatment of pain, Alzheimer's disease, anxiety, depression, Parkinson's, schizophrenia, various neurodegenerative conditions, brain injury, diabetes and metabolic disorders -
Probiotic turmerics for mental health and pro-inflammatory CNS conditions
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
Yeah, feel you on that, sorry to hear things are a struggle for you. I got disconnected again and the only way I've recently been able to reconnect is through plants. It takes my head off the social situation which is hard to manage with anxiety, social anhedonia and not finding common ground etc. Churned out a bunch of Ashwagandha tubestocks through winter that did well in the greenhouse, ready for spring. Joined the local grow free group. I've been forcing myself to connect with new people, even strangers, by giving the plants away. It just makes an awkward social encounter more positive. A reason to try. Just breaking that pattern of isolation through a plant can be potent. You can rebuild some social skills etc. Transfer interests from one domain to another etc -
Probiotic turmerics for mental health and pro-inflammatory CNS conditions
Alchemica posted a topic in Pharmacology, Chemistry & Medicine
I put myself on daily probiotic turmeric. Been doing that for a while now. Anyone use it as a brain tonic? I whip up a couple of strong (20g) turmeric, ginger, black pepper and occasionally saffron probiotic sludges a day The more probiotic turmeric combos I get into me, the more I see how much I was probably running on likely extreme neuroinflammation. It's a robust shift, some really positive glimpses at something when I mega dose, some days not always feeling wonderful but on the whole small steps that are generally positive, using pretty much all the polyphenol classes and including the turmeric concoctions at a high dose in a good diet. I'm sticking with this, hoping an antidepressant effect becomes apparent.. So far, the most robust improvement I've had is in self-regulation (which was in tatters) buffering to better levels, along with getting sleep (quite a bit of sleep debt built up), more so than mood. Quite profound is the way these probiotic turmeric combos seem to be modulating aberrant reward related stuff. It's very anti-addictive but at the same time I'm stopping so many locked in behavioural loops that nothing at all left seems rewarding anymore. Push through it, hope I can write some new eudaimonic pathways Inflammation and mental health: Research indicates that mood disturbances and psychiatric disorders are closely related to CNS or whole body inflammation [1]. The prevalence of inflammation, measured by one marker only, in the diagnostic groups of psychotic disorders, mood disorders, neurotic disorders and personality disorders was 32%, 21%, 22% and 42%, respectively [2]. ' Inflammation was consistently found to affect basal ganglia and cortical reward and motor circuits to drive reduced motivation and motor activity, as well as anxiety-related brain regions including amygdala, insula and anterior cingulate cortex, which may result from cytokine effects on monoamines and glutamate [3]. Higher levels of inflammation are associated with longitudinal changes in brain function in regions important for cognition [4]. Increasing evidence points toward an involvement of the immune system in MDD pathogenesis. Inflammation can affect monoaminergic and glutamatergic neurotransmission [5]. Negative symptoms of schizophrenia are associated with increased inflammation [6]. Inflammation may at least partly mediate resting state functional connectivity via effects on mesolimbic and mesocortical dopaminergic systems [7]. Inflammatory measures were positively related to striatolimbic resting-state functional connectivity but negatively related to corticostriatal resting-state functional connectivity Chronically elevated levels of inflammatory markers, for example, are associated with clinical depression, post-traumatic stress disorder (PTSD) and many other psychological and behavioral issues and likewise these conditions often have elevated impulsivity. Inflammatory mediators promote a general trade-off towards focusing on immediate versus delayed outcomes. Inflammation is particularly influential on impulsivity - higher active inflammation – as quantified by plasma levels of IL-6, TNF-α, and white blood cell count – predicted more impulsivity. The relationship remained significant when controlling for factors known to covary with both inflammation and impulsivity [8] "Better understanding of the outcomes associated with impulsivity of inflammatory origins may yield low-cost interventions that can ameliorate behavioral problems notoriously resistant to current treatment strategies. For example, anti-inflammatory medications may be helpful as adjunct treatments for behavioral disorders related to impulsivity, such as substance abuse or certain mental illnesses." [1] http://www.dailymail.co.uk/…/Cambridge-psychiatrist-claims-… [2] https://www.ncbi.nlm.nih.gov/pubmed/29544672 [3] https://www.ncbi.nlm.nih.gov/pubmed/29173175 [4] https://www.ncbi.nlm.nih.gov/pubmed/29304217 [5] https://www.ncbi.nlm.nih.gov/pubmed/29604382 [6] https://www.ncbi.nlm.nih.gov/pubmed/29499967 [7] https://www.ncbi.nlm.nih.gov/pubmed/29689344 [8] https://repository.tcu.edu/handle/116099117/20630 More on neuroinflammation Mental illnesses and ASD seem to be strongly related to neuroinflammation, activation of inflammation in animal models leads to behavioural abnormalities. That said, it is suggested to be at best one cause of depression [1]. Schizophrenia and autism spectrum disorders share core symptoms and overlap in many ways pathologically, mainly by extensive microglial activation and similar behavioural attributes, this microglial activation also extends to brain injuries. The neuroprotective effect of curcumin is mainly mediated by blockade of microglial cell activation [2]. Psychological stress activates inflammation and that this activation would be found to predict the later development of pathology. Social isolation/feeling lonely is associated with systemic inflammation. There is evidence that a range of psychosocial stressors lead to elevated microglial activity [3]. Neuroticism has also been associated with higher levels of inflammatory markers while conscientiousness has been associated with lower inflammatory markers [4]. Chronic neuroinflammation and the loss of neurotrophic factors promotes 'locked in' behavioural inflexibility and promotes the pathogenesis of disorders such as addictions and feeds antisocial personality traits [5]. A multitude of studies support the notion that inflammatory processes form an integral part of the mechanisms precipitating addictions [6]. It appears elevated neuroinflammation is important throughout the cortico-striato-thalamo-cortical circuit of obsessive compulsive disorder, too [7] See Resident evil: Inflammation and depression [1] http://www.psychiatrictimes.com/special-reports/introduction-inflammation-connection [2] https://www.ncbi.nlm.nih.gov/pubmed/18214347 [3] https://www.ncbi.nlm.nih.gov/pubmed/26847047 [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544833/ [5] https://www.ncbi.nlm.nih.gov/pubmed/28810156 [6] https://www.ncbi.nlm.nih.gov/pubmed/29054292 [7] https://www.ncbi.nlm.nih.gov/pubmed/28636705 Microglial activation - a pathological player? Activated pro-inflammatory microglia trigger anxiety- and depressive-like behaviours, mainly by increasing the expression of pro-inflammatory mediators and neurotoxins in stress-sensitive brain regions. Injury, stress, toxic exposures and social stress can induce microglial over-activation [1] It is proposed M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases [2]. While activated M1 microglia may exacerbate injury by producing neurotoxic substances when overactivated for prolonged times, activated M2 microglia (the anti-inflammatory and tissue-reparative phenotype) protect neighboring cells by removing cell debris and releasing trophic factors for brain repair. Curcumin promoted microglial M2 polarisation and inhibited M1 polarisation. Long-term depression is a progressive disease and elevated microglial activation and inflammation play a role, it is suggested targeting the inflammatory process is needed to prevent neuroprogression [3]. Our gut microbiota is critical for modulation of the HPA axis and thus the stress response and brain processes such as myelination, neurogenesis and microglial activation and can effectively modulate behaviour and influence psychological processes such as mood and cognition. The gut microbiota is essential for the maintenance of microglia in a healthy functional state, which is necessary for the prevention of neurodevelopmental and neurodegenerative disorders [4]. Microglia have more recently emerged as key players in regulating neuronal network excitability [5] and reward. Activated microglia within reward circuitry result in disruption of dopaminergic signaling and reward behaviour. Activation of microglia by addictive drugs or other causes results in a proinflammatory dominance of the innate immune system, which is then critically synergise on the neurocircuit of reward and dependence [6]. Repeated drug-induced microglial activation produces progressive increases in microglial reactivity, further potentiating the neurobiological consequences of chronic drug use [7] Even acute inflammation impairs 'theory of mind' (ToM) explaining social-cognitive deficits in people that exhibit low-grade inflammation [8]. Inflammation, Self-Regulation, and Health: An Immunologic Model of Self-Regulatory Failure Exposure to stress, infection, and disease in early life increases proinflammatory cytokine activity, which decreases an individual’s self-regulatory ability. Poor self-regulation and poor health behaviours, which lead to greater exposure to stress and disease. As these dynamics continue over childhood and adolescence, compounded by social stressors, more stable differences in brain structure and function can develop that ultimately produce persistent impairments in self-regulation in adulthood. Dysregulated or enhanced neuroinflammation is argued to facilitate the etiology of mental disorders. Immune system activity — especially components of the immune system involved in inflammation — appear to impair numerous facets of self-regulation: inflammatory activity can impair both cognitive and emotional self-regulation. Markers of systemic inflammation have been associated with brain alterations that negatively impact executive function in humans: higher levels of proinflammatory cytokines at baseline predict lower executive function. Acute inflammatory challenges alter DLPFC response when individuals engage in tasks that require self-control, reduces resting glucose metabolism in the ACC in humans, which is a brain region critically important in self-regulation and reduces functional connectivity between the medial PFC (mPFC) and brain regions involved in mood and emotion. Inflammatory activity impairs sensitivity to reward. Inflammatory activity may impair self-regulation by reducing motivation and may either help or hinder self-regulation by decreasing sensitivity to reward. Inflammation may modulate mesolimbic and mesocortical dopaminergic systems. "Prolonged or severe stress exposure disrupts homeostatic or ‘healthy’ communication between the CNS and peripheral immune system, shifting immune signaling toward a proinflammatory state. Part of this response includes elevated and prolonged proinflammatory signaling in the CNS that is argued to be linked with stress-related psychiatric disorders." There is mounting evidence that social stress activates microglial cells in the central nervous system. Microglial activation is positively correlated with psychiatric disorders. Pro-inflammatory cytokines including IL-1β and TNF-α, can reduce the availability of serotonin, dopamine and noradrenaline by increasing the expression and function of reuptake transporters, reducing synthesis or decreasing monoamine precursors and also act on the glutamate pathway and together with astrocytes stimulate the increased release of this neurotransmitter and decreased brain-derived neurotrophic factor, which ultimately leads to excitotoxicity [9] Elevated pro-inflammatory cytokine levels caused by microglia activation, often induced by social stress, contributes to the development and persistent anxiety-like behaviour [10] [1] https://www.frontiersin.org/articles/10.3389/fnbeh.2017.00207/full [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276905/ [3] https://www.karger.com/Article/Abstract/470805. [4] https://www.wjgnet.com/1007-9327/full/v23/i30/5486.htm [5] https://www.hindawi.com/journals/np/2013/429815/ [6] https://www.ncbi.nlm.nih.gov/pubmed/22707932 [7] https://www.colorado.edu/lab/bachtell/research/neuroinflammation-and-addiction [8] https://www.ncbi.nlm.nih.gov/pubmed/29742460 [9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660717/ [10] https://www.nature.com/articles/npp2016102 Why turmeric? Turmeric, a source of curcuminoids, including the essential oil containing ar-turmerone [1] is a neuroprotective and neuropharmacological drug. It may be used in neurodegenerative disorders [2] including MS [3], depression etc. Curcumin may be used as an effective and safe modality for treatment in patients with depression, with a better tolerability profile and safety than SSRIs [4]. Patients receiving curcumin showed increased levels of BDNF relative to baseline, whereas patients receiving placebo showed declines relative to baseline but results did not show more distal effects on cognition or clinical symptoms for patients with schizophrenia [5] Curcumin may increase the concentration of monoamines available to interact with receptors, alleviating depression Curcumin strongly inhibits inflammatory cytokines like nuclear factor-kappa B, NLRP3 inflammasome, and interleukin-1B. this may help explain its antidepressant activity. There's suggestion that curcumin may be useful for treating human motivational symptoms The study findings that epigenetically, cooking with/using whole turmeric is superior to using turmeric extract preparations seem to match my experiences - those 'bioavailability enhanced commercial products' or curcumin extracts (even with piperine) just don't personally compare to solid dose of whole turmeric etc IMO. Something about it fermenting in the gut, activity of the volatiles, or high volume of dispersion/absorption of the curcuminoids through using the actual powder, I'm not sure? Particularly fermented with quality probiotics. Even a curcumin free water turmeric extract has effects on mood . At least 235 compounds, primarily phenolic compounds and terpenoids, have been identified from C. longa. What's interesting about using whole turmeric is curcumin-free turmeric components such as those in a possess numerous biological activities, including neuroprotective, anti-inflammatory, anticancer, and antidiabetic activities. Volatiles like aromatic-turmerone exerts beneficial effects on the brain - inhibiting microglial activation, preventing brain damage caused by neuroinflammation and increasing neural stem cell proliferation . Bisacurone has been identified as another of these components, also with anti-inflammatory effects. [1] a) https://www.ncbi.nlm.nih.gov/pubmed/28849618 b ) https://www.ncbi.nlm.nih.gov/pubmed/25928248 [2] https://www.ncbi.nlm.nih.gov/pubmed/22742420 [3] https://www.ncbi.nlm.nih.gov/pubmed/29079885 [4] https://www.ncbi.nlm.nih.gov/pubmed/23832433 [5] https://doi.org/10.1016/j.schres.2017.09.046 The effect of curcumin on serotonin appeared to be dose-dependent, at high doses curcumin also increased dopamine and to a lesser extent noradrenaline. Additionally, the effect of curcumin on the serotonergic system was possibly related to its interaction with 5-HT1A/1B and 5-HT2C receptors. In studies, regarding behavioural changes; the effect of curcumin was more pronounced than fluoxetine. Curcumin raised brain GSH and reduced brain MDA, TNF-α and IL-6 contents Importantly, curcumin normalises the levels of dopamine in the frontal cortex of rats and exerts biochemical and morphological effects of the on the PFC and hippocampus. Curcumin enhances the level of neurotrophic factors such as brain derived neurotrophic factor (BDNF) There have been signs of antidepressant properties through an interaction of curcumin with dopamine receptors and an increase in brain dopamine levels. Supplementation of curcuminoids to standard antidepressants showed a significant reduction of anxiety and depression in patients with major depressive disorder Moreover, curcumin extracts significantly improved depressive symptoms and demonstrated anxiolytic effects in patients with atypical depression. There was a significant improvement of sustained attention, working memory tasks, and mood after curcumin treatment. Curcumin showed a significant reduction in SGA‑induced body weight gain on the rats. It exerts hypoglycemic, antioxidant, antitumor, and anticarcinogenic activities. It also prevents tardive dyskinesia Why probiotic? Influence of gut microbiota on neuropsychiatric disorders Got a broad spectrum of probiotics gong on. Along with things like L. plantarum which significantly reduced anxiety-related behaviour and altered GABAergic and serotonergic signaling in the brain, it also ameliorated cognition deficits but also restored ACh and the histopathological features to control group in an AD model, I'm using a lot of L. rhamnosus rich food which has anxiolytic and mood effects: Lactobacillus rhamnosus, can dramatically alter GABA activity in the brains of mice. It reduces stress-induced elevation in stress hormones. Enriching food with Bifidobacterium longum which decreases anxiety and may improve mood among anxious animal models. Lactobacillus casei which cultures appeared to improve mood among those only with a low/depressive mood at baseline. Bifidobacterium animalis which scavenged free radicals and decreased MAO activity. "The development of the forebrain, esp. the neocortex, in social mammals and ultimately primates and humans depends on correct and timely signals from microbial symbionts—which is disturbed, when the microbiota is absent or disturbed. Likewise when the microbiome is disturbed, there is evidence of increased hypothalamic–pituitary–adrenal (HPA) axis activity in response to acute stress. The immune pathway within the brain–gut–microbiome axis may be a plausible mediator of the effects of this axis on social behaviour" Recent data provide evidence that related bacterial species can interact specifically with a variety of different neuronal populations. For example some bacteria affects the functioning of CNS neurons in the hippocampus and amygdala, and alter PFC funtioning. They can alter vagal tone, HPA axis activity, neuroinflammation/microglial activation, alter serotonergic transmission, levels of brain-derived neurotrophic factor, NMDA receptor subunit expression, GABAergic signalling and receptor expression etc [ref] There are also links to a role for oxytocin. Altering the microbiome has been shown to do things like: -improve mood, but only in those who have poorer mood at baseline and alter anxiety related measures -reduce cortisol output in response to an acute stressor -alter brain activity when processing information related to emotional facial expressions -improvement in sustained attention in healthy older adults The first clinical trial of probiotics in bipolar disorder found probiotics lowered the rate of rehospitalisation, building on previous research that has found promise for these in depression, anxiety, cognition, and autism Supplemental probiotics to combat brain-related dysfunction offers a promising approach [1]. Evidence suggests [2] that chronic administration of Lactobacilli and Bifidobacteria strains can have effects on areas of the brain related to emotion, mood, memory, and somatosensory processing - probiotic ingestion attenuates emotional reactions and decreases activity of certain brain regions when measuring brain responses to emotional stimuli Along with improved depression, anxiety, anger, and anxiety in adults [3], probiotic intake for 4-6 weeks altered neural activity in brain regions that control central processing of emotion and sensation in healthy women but no change in gut microbial composition was detected [4]. In a more recent study, a slight change was detected in the microbiome and [5]: Probiotics improved self-reported behavioural measures of positive affect and cognitive reactivity Probiotic administration influenced the behavioral scores for depression and anxiety questionnaires, significantly increasing positive affect and blunting vulnerability to depression in terms of hopelessness and risk aversion Probiotics improved memory performance and altered brain activation patterns Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks In major depression, probiotic (Lactobacillus helveticus and Bifidobacterium longum) resulted in an improvement in BDI score compared with placebo whereas no significant effect of prebiotic supplementation (galactooligosaccharide) was seen [6] “The Social Network” – How the Gut Microbiome Governs Our Social Behaviour [1] https://www.ncbi.nlm.nih.gov/pubmed/29701810 [2] https://www.ncbi.nlm.nih.gov/pubmed/29698377 [3] https://www.ncbi.nlm.nih.gov/pubmed/20974015 [4] https://www.ncbi.nlm.nih.gov/pubmed/23474283 [5] https://www.tandfonline.com/doi/abs/10.1080/19490976.2018.1460015 [6] https://doi.org/10.1016/j.clnu.2018.04.010 There seem to be changes in the microbiota that are associated with substance use [1] across an array of SUDs and eating disorders [2] Ethanol drastically changes the microbiome and increase in gut permeability and induces a pro-inflammatory responses. Microbiome alterations were shown to be correlated with alcohol use disorder-related symptoms, i.e. craving, depression and anxiety and manipulations in the gut microbiota may affect cocaine-related behaviors (Animals with reduced gut bacteria showed an enhanced sensitivity to cocaine reward and enhanced sensitivity to the locomotor-sensitising effects of repeated cocaine administration [3]) and methamphetamine [4]. There is a strong negative influence of alcohol dependence on gut microbiota [5] and "Intestinal flora between cocaine users and non-cocaine users and have found that cocaine users have a higher mean relative abundance of Bacteroidetes and a lower abundance of Firmicutes than non-users; are more likely to smoke; have a lower mean percentage of body fat; and consume more alcohol than non-users." Phytonutrients impact the microbiome “eat the rainbow” AND eat prebiotic and probiotic foods" so to do omega-3's: Some of the health-related benefits of omega-3 may be due, in part, to increases in butyrate-producing bacteria. You can shift the microbiome with probiotics. Some of the other non-LAB are also now available as supplements. Probiotic intake induced an increase in Proteobacteria and in the Clostridiales spp. Patients taking probiotics had an increased numbers of butyrate-producing bacteria, especially Faecalibacterium and Clostridiales spp. Probiotic intervention modulated the fecal concentrations of butyrate in a manner dependent on the initial levels of short-chain fatty acids (SCFAs) [things like live B. bifidum cells affected the relative abundance of dominant taxa in the fecal microbiota and modulated fecal butyrate levels] [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472629/ [2] https://www.ncbi.nlm.nih.gov/pubmed/28482009 [3] https://www.ncbi.nlm.nih.gov/pubmed/27752130 [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575146/ [5] https://microbiomejournal.biomedcentral.com/.../s40168... Black pepper - more than a spice and bioavailability enhancer... "During the time of Hippocrates the pepper was used as both a spice for food and as a medicine. The Asian world has long considered black pepper to be an important spice for detoxifying and as an anti-aging compound. It is widely used in different traditional systems of medicine like Ayurvedic and Unani System of medicines" Black pepper is itself used as an analgesic, antiinflammatory, anticonvulsant, antioxidant, antidepressant and cognitive-enhancing agent. It contains 5-10% pungent acid-amides, with piperine as its main compound and several others, such as the N-isobutylamide guineensine which is a nanomolar inhibitor of cellular uptake of the endocannabinoid anandamide. Recent studies on the pharmacological actions of piperine have demonstrated its antioxidant activity, antiinflammatory [1] and cognitive-enhancing effect following long-term oral administration. It performed as well as memantine in an Alzheimer's model [2]. It reduces cholinesterase levels and amyloidal plaque formation [3]. It is a potent anti-inflammatory [4]. The antidepressant-like effects might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake, along with inducing BDNF promoter, increasing brain-derived neurotrophic factor expression in the hippocampus and promoting neurite outgrowth [5,6]. It predominately seems to be mediated via the serotonergic system by enhancing 5-HT content [7] It exerts anxiolytic effects by GABAergic and nitrergic systems [8] It exerts anticonvulsant effects [9] due to antioxidant actions, as well as TNF-α reduction, along with effects on inhibitory amino acids and on the GABAergic system [10] and analgesic properties dependent on the opioid system [11] Piperine pre-treatment time-dependently improves the bioavailability of poylphenols, including flavonoids/green tea catechins and curcumin, through the reversible and selective inhibition of UGTs and SULTs. It also increases the bioavailability of things like ashwagandha, rosmarinic acid and a variety of drugs [12]. Enzymatic inhibition by piperine resulted in increased bioavailability of many drugs and nutrients e.g. amoxicillin, ampicillin, acefotaxime, carbamazepine, ciprofloxacin, norfloxacin, metronidazole, oxytetracyclin, nimesulide, pentobarbitone, phenytoin, resveratrol, beta-carotene, curcumin, gallic acid, tiferron, nevirapine, and sparteine by different types of mechanisms. Curcuminoids and piperine could inhibit drug metabolism but is "unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes." [1] https://www.ncbi.nlm.nih.gov/pubmed/28185326 [2] https://www.ncbi.nlm.nih.gov/pubmed/28939403 [3] https://www.ncbi.nlm.nih.gov/pubmed/26023568 [4] https://www.ncbi.nlm.nih.gov/pubmed/28185326 [5] https://www.ncbi.nlm.nih.gov/pubmed/29063362 [6] https://www.ncbi.nlm.nih.gov/pubmed/17701559 [7] https://www.ncbi.nlm.nih.gov/pubmed/21477634 [8] https://www.ncbi.nlm.nih.gov/pubmed/25149996 [9] https://www.ncbi.nlm.nih.gov/pubmed/28352353 [10] https://www.ncbi.nlm.nih.gov/pubmed/23313550 [11] https://www.ncbi.nlm.nih.gov/pubmed/24388894 [12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458266/ Ginger: This itself functions as a bioavailability enhancer. Ginger has also a broad anti-inflammatory properties and may be useful in auto-immune conditions including MS. Ginger and its constituents, such as 6-gingerol, 6-shogaol, 6-paradol, zingerone, and dehydrozingerone, are effective for ameliorating the neurological symptoms of neurodegenerative conditions. Ginger and neurodegenerative disorders: -
Optimising the Music Therapist for Spiritual Emergence or Psychedelic Therapy
Alchemica posted a topic in Creativity, Spirituality & Philosophy
While I'm not playing with psychedelics, spiritual experiences through 'milder' plant medicines, or endogenous, can be of similar intensity. Lately I've been having a pleasant, peaceful spiritual emergence. "...the next dimension of our BEing is ushered in from the wings and we feel the call to move into another phase, leaving what was ‘less’ behind and embracing the new ‘more’. Our messes bring us order through feeling our inner chaos. The clouds part, the seas calm, the wind ebbs, and we are shifted lovingly into our reborn state, to continue finding our courage and love, our sacred aspects that bring us into wholeness and Oneness again and again, more and more, one step, one trip at a time." How a Spiritual Awakening Lifted My Depression and Anxiety "Until I let myself experience emotions in their entirety, I believe I never fully understood what they were and how exactly they ruled my life. For me, experiencing anxiety entirely-through opened the door to seeing all emotions in their complete definition. The separation between my compassionate, loving self and what was once perceived as a different outside world, ceased to exist anymore. I now saw the oneness in everything. As a human, I see two paths to dealing with emotion. I keep myself from experiencing it fully and thus get the illusion of separation or an illusion of an Other. The second and only other path to handling emotion is to allow myself to experience it entirely to create the space for love, compassion and non-judgment to understand the oneness. I now understand happiness and sadness, calm and chaos, as I perceive light or sound, and it has lifted me from my struggle. The experience of depression is quite paradoxical. It’s a solitary experience that only allowed me to gain the awareness which reconnected me with people and the surrounding world. So… what in the world do I do with this now? I’ve learned that we cannot make each other see no matter how much we try. We must spread love to give each other the space to feel comfortable enough to take the painful dive inward. For it is dealing with inner turmoil that I now believe can lift us to a place of pure equality, full of love and compassion we all seek. It is a love and compassion that I rediscovered in myself and I believe we are all gifted with from the beginning." The quality of the altered state predicts treatment outcomes in treatment resistant depression ( the quality of the experience—in particular, mystical traits such as “oceanic boundlessness”—correlates strongly with a decline in depression). I've been requiring a good music therapist. I'm having some experiences of unity, spiritual experience, bliss, insightfulness, meaning etc. Music is helping me. What music are you therapeutically journeying to in life these days? Without things to to facilitate personally meaningful experiences that can lead to sustained changes in behaviour and outlook, particularly for isolated people who might be journeying more solo, you get really stuck. We need to learn good structure of music therapy - first establishing calm and safety, heading towards onset and building towards peak experiences - grouped together as ascent, and re-entry was named descent. Music with strong evocative emotional sentiments was only played during peak, on the assumption that an important pre-requisite is for the individual to first feel calm and safe and that more evocative music would enable an activation of autobiographical and therapeutically significant when played at peak We need some good spirited playlists that are humanly emotionally evocative, open you to new worlds, supportive and guiding (maybe some thought provoking stuff in it), and promote empathetic mental imagery. Your 'psytrance' isn't therapeutically good IMO, neither are any of the classical music playlists tailored to psychedelic therapy I've heard. While several of the musical works originally included in playlists for therapy are very familiar today. Examples include Samuel Barber—Adagio for strings and Beethoven—Piano Concerto 5. These personally aren't desirable. Thankfully they're shifting more to predominantly contemporary music such as the ambient, neoclassical, contemporary classical, as well as traditional/ethnic music styles which I think is more suitable. Psychedelics and spiritual experiences significantly modulate music-evoked emotion, music-evoked mental imagery, and perceived personal meaningfulness of music "...music had both "welcome" and "unwelcome" influences on patients' subjective experiences. Welcome influences included the evocation of personally meaningful and therapeutically useful emotion and mental imagery, a sense of guidance, openness, and the promotion of calm and a sense of safety. Conversely, unwelcome influences included the evocation of unpleasant emotion and imagery, a sense of being misguided and resistance. Correlation analyses showed that patients' experience of the music was associated with the occurrence of "mystical experiences" and "insightfulness." Crucially, the nature of the music experience was significantly predictive of reductions in depression 1 week after psilocybin, whereas general drug intensity was not." The hidden therapist: evidence for a central role of music in psychedelic therapy. http://sci-hub.tw/10.1007/s00213-017-4820-5 -
Ketone body esters as acute 'mood lifters'?
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
Tomorrow, spike those ketones in the name of a healthy brain experiment and see what I think of it as a "neurotherapeutic" and "promising anxiolytic strategy" [1], see if there are hints of enjoyable prosociality which would be nice. "Use of βHB as an efficient neurotherapeutic relies on increasing blood βHB levels so as to encourage entry of βHB to the brain." [2] The main problem with using βHB as a therapeutic lies in being able to deliver sufficient βHB to the brain, due to the limited uptake of βHB across the blood brain barrier and the difficulty in sustaining high enough levels of βHB in the blood - uptake can be increased by instigation of dietary changes, such as a high fat diet or regular ingestion of medium chain fatty acids. Any keto nuts suggest better (other than ketone esters) than BHB+MCTs? I want to feel it as acutely as possible... Thinking to go from intermittent fasting/low carb to using short term BHB + MCTs as my diet for a bit. Ketone bodies upregulate neurotrophins, reduce neuroinflammation and hyperexcitability, causing potent neuroprotection. They also drive growth and myelination, enhance synaptic plasticity, cognition and neuronal stress resistance, improving learning and memory. Exogenous ketones also improve oxygen utilisation, especially in the central nervous system There are concerns regarding the level of Ca and K provided by supplementing BHB salts, which can rise to toxic levels if excessive doses are administered, so adherence to dose recommendations is required [3] In the body, "Exogenous ketone supplementation causes blood glucose to decrease significantly, likely due to the acute increase in insulin sensitivity. Therefore, exogenous ketones may present a potential therapy for type-2 diabetics via regulation of blood glucose.". "BHB + MCT raises blood BHB levels much higher than BHB or MCT in isolation, with a peak just over 1.30mmol/L. Even more important is that blood BHB levels do not seem to readily fall back to the normal levels of 0.2mmol/L. Even after 8 hours blood BHB levels are 0.5mmol/L, which is over double the normal level, and they look to be only very gradually falling. Blood BHB levels look like they will be elevated for the best part of a day, but the most significant rise being between 1 and 4 hours after ingestion." [4] Consumption of MCTs produces a mild ketosis which has been estimated to contribute up to 8–9% to brain energy metabolism and it is well tolerated. In comparison, "In human tests, 30ml of MCT oil was able to raise blood BHB levels to about 0.55 mmol/L. This is just over half the effect that BHB salt supplementation had. MCT oil supplementation spiked blood BHB levels at just under an hour, and drops to normal levels after 3 hours. Interestingly, BHB levels continue to fall below normal levels of 0.20mmol/L to 0.12mmol/L. The low blood BHB levels show no real indication of normalising after 8 hours." While the low ketone levels generated by MCT supplementation have been demonstrated to partially reverse the memory deficits of Alzheimer’s dementia, exogenous ketones have the potential for greater memory-improving effects, with maximum effect likely occurring at a beta-hydroxybutyrate blood level of 4 mmol/L or higher, the level at which ketone transport into the brain is maximised. Human pilot studies and case studies suggest that ketogenic diet and ketogenic supplement-induced ketosis is a potential therapeutic approach in the treatment of epilepsy, Alzheimer's disease, autism spectrum disorder, and schizophrenia Ketone bodies may exert their effects through modulation of GABAergic, glutamatergic, and adenosinergic system. Administration with no need for energy restriction might also be a promising intervention to improve the neuronal activity and ameliorate the degeneration of CNS. Noted antidepressive and anxiolytic effects It an efficient mitochondrial fuel, improving energy metabolism Enhances GABAA receptor function, upregulates GABAergic activity [may increase GABA concentration], enhances inhibitory glycine receptors Decreases brain glutamate, alters the response of NMDA receptors, L-type Ca2+ channels, reduces neuronal firing rates, mediated in part by Katp channel activity and GABAB signaling It interacts with an inflammasome in immune cells to reduce production of inflammatory cytokines and reduce inflammation. inhibitor of histone deacetylases resulting in upregulation of genes involved in protection against oxidative stress and regulation of metabolism Supplementation with βHB has been shown to extend the lifespan of C. elegans by 20% [1] https://www.frontiersin.org/articles/…/fnmol.2016.00137/full [2] https://www.ncbi.nlm.nih.gov/pubmed/27826689 [3] https://blog.undoctored.com/beware-exogenous-ketones/ [4] https://ketosource.co.uk/exogenous-ketones-how-they-work/ By afternoon, I'm normally crashing in mood, grumpy and tired, not that the morning is much better. I got a paradoxical lift changing my diet for once, but then the typical diet shift anergia kicked in. From a couple of days of IF, gave the BHB salts a whirl. Solid dose, 12g BHB and some MCTs. Really, the ketone elevations offered by even large doses of the salts aren't that huge but "can help your body transition into ketosis with less misery and hunger pangs." potentially. The combo of MCTs and BHB is said to be better for BHB elevations. Beta hydroxybutyric acid is antidepressive and anxiolytic. It enhances inhibitory glycine receptors at concentrations observed in humans clinically. In addition, beta-hydroxybutyric acid enhances GABAA receptor function at these concentrations. Subanesthetic concentrations may contribute to lethargy and impairment of consciousness [1] and has abilities to alter physical properties of cell membranes [2] [1] https://www.ncbi.nlm.nih.gov/pubmed/17717222 [2] https://www.ncbi.nlm.nih.gov/pubmed/23339286 By 45min, there's a very mild energetic lift, wouldn't say much more than MCTs alone. Some restoring energy, stability of mood again and a little potential anxiolysis. Functionally nice as a mild meal tonic. Enough to get another bout of exercise in, which seemed to attune me to it more. It was pleasant exercise. Just a calm, centred functional bit of exercise. Didn't feel so neurotic. Got for another bit of exercise - just level headed. All in all, maybe the BHB salts are useful but not likely to be problematic. It may be therapeutically useful to for the times I crave alcohol (I've now been abstinent quite awhile), "In ethanol dependence, it is suggested the following occurs "energy deficiency (“starvation”) of the brain → stimulation of production of ketone bodies → partial transition of the brain from exclusive using of glucose as the energy substrate to partial use of ketone bodies as such substrate. Under such conditions, the brain begins to be dependent, to a significant extent, on the level of these bodies in the blood, i.e., on the degree of ketonemia. With any decrease in this index, the biological requirement to replenish the amount of these compounds develops. Since rapid synthesis of ketone bodies can be readily initiated by introduction of ethanol into the organism, this organism tries to realize the corresponding behavioral reaction, i.e., to consume alcohol." [1] MCTs themselves compensate for the brain energy deficits in direct proportion to the level of plasma ketones achieved. MCT-fed rats exhibited reduced anxiety-like behaviors and enhanced social behaviour [2] Data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production [3] [1] https://link.springer.com/article/10.1007/s11062-016-9596-4 [2] https://www.ncbi.nlm.nih.gov/pubmed/29908242 [3] https://www.ncbi.nlm.nih.gov/pubmed/27517611- 1 reply
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Ketone body esters as acute 'mood lifters'?
Alchemica posted a topic in Pharmacology, Chemistry & Medicine
Recently got into the fasting. I like the mood stability and uplift. Firstly has anyone used the commercial 'BHB exogenous ketone' salts and got an acute nice noteworthy mood reaction? There are commercial βHB salt products - quite pricey - but I want to know if anyone has heard of the cheap ketone esters, particularly super cheap (and fragrant!) ethyl acetoacetate, being used safely orally? I'm not going to slack off using will power to fast for my added uplift but I'm curious... it could be quite nice as an acute quite enjoyable mood lifter. Is it the βHB, or is acetoacetate a nice mood lifter? Ketones, particularly BHB, upregulate GABAergic tone but are they 'enjoyable' acutely orally administered? "...researchers don’t know the exact cause of these [euphoric] feelings. Acetoacetate, acetone and BHB, or any of their metabolites, may all be involved, as well as the effects of low blood sugar, which can cause euphoria and giddiness." People felt remarkably well, and experienced a mild intoxication: not dissimilar to the effects of ethanol. Bloom speculated that acetoacetate had caused the inexplicable jubilation. [1] Aside from acute prosocial anxiolytic effects which I deem as an important therapeutic area to address in many conditions, I'm also primarily looking for sustainable better health in my life, as are many people with epilepsy, Alzheimer's disease, autism spectrum disorder, and schizophrenia etc. My intermittent fasting is proving interesting, mood stabilising and uplifting in conjunction with other measures, pushed that quite a bit but it's personally not sustainable to run an extreme 'deprivation diet'. Just skipping breakfast and healthy meals at the other times with my exercise is probably my best bet. There are a few suggestions on ways to stay in a fasting state during IF [1]. Caved in and thought I had to try the most economical βHB salts, to get a gauge on it's effects. Probably get around to doing some trials with that this week. It is suggested elevations of β-hydroxybutyrate may partly mediate the beneficial effect of IF in CNS conditions. "Brain BHB concentration increased from a nonfasted level of 0.05 +/- 0.05 to 0.60 +/- 0.26 mM (after second day of fasting), increasing further to 0.98 +/- 0.16 mM (after the third day of fasting)" [2] While βHB salts or other supplements "aren’t a great fat loss tool – they’re simply ways of increasing your blood ketones" and increase energy in, I'm more generally looking for the therapeutic benefits of ketones on the brain for the moment. Both would be nice - I'm getting really good kJ intake reductions and maintaining my exercise so hoping. Unfortunately, with exogenous ketone administration, blood βHB reached low levels (<1 mM) and a high amount of salts, consumed βHB, was required to achieve ketosis. That said, this is still roughly equivalent to three days of fasting. That said, gastrointestinal symptoms were reported in a large number of participants. βHB has antidepressant and antianxiety-like effects and results in modulation of multiple systems, including GABA, Glu, adenosine, neurotrophic etc and even in the presence of glucose exerts beneficial CNS effects, also exerting epigenetic effects (β-hydroxybutyrate is a HDAC inhibitor). Dietary ketone salts are often racemic mixtures of the two optical isoforms of βHB, despite the metabolism and actions of L-βHB being poorly understood ~12 or ~24 g orally administered ketone salts elevated D-βHB concentrations (D-βHB Cmax 1.0 mM) which returned to baseline within 3–4 h. [3] [Another study found 0.5 g/kg bw at 2 h elevated D-βHB, with a mean value of 0.598 ± 0.300 mM [4], 0.38 g/kg bw caused only a rise to 0.3-0.4 mM βHB in trained athletes [5]. The ketone salts contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h. L-βHB is still neuroprotective but not much is known about it's CNS effects More cheaply, one can increase βHB in the brain 90 minutes after ingesting coconut/MCT oil, which improved paragraph recall in adults with impaired memory. Preliminary studies also show ketones can improve working memory in both young and old subjects [1] http://siimland.com/what-breaks-a-fast-while-intermittent-fasting/ [2] https://www.ncbi.nlm.nih.gov/pubmed/11043913 [3] https://dx.doi.org/10.3389%2Ffphys.2017.00848 [4] https://www.ncbi.nlm.nih.gov/pubmed/29850235 [5] https://www.ncbi.nlm.nih.gov/pubmed/29966721 "Conversion of ketone bodies (KBs) to ketone esters (KEs) eliminates KB acidity, making the KEs suitable vehicles for the delivery of KBs to the blood circulation via the gastrointestinal route. Ingestion of KE can directly increase plasma KBs to levels within the range achieved during fasting. The degree of KB elevation attained is readily controlled by the dose size Studies have demonstrated that orally or intravenously administered 1,3-butanediol or glycerol esters of βHB are safe and well tolerated in animals and that the orally administered 1,3-butanediol monoester is also safe and well tolerated in humans" [2] While 1,3-butanediol esters are ideal as they are readily metabolised in a manner similar to ethanol without the deleterious effect of ethanol metabolism, with subsequent conversion to βHB and, eventually (at the peripheral tissue level), to AcAc, I'm curious if ethyl acetoacetate might be healingly enjoyable orally administered? While using diet is superior for weight loss than supplementation, there are a few people talking of acute βHB effects @12g of the salts: "...there was an unmistakable uplift in mental clarity, mood and energy. This continued for a number of hours. The energy & focus was clean" It seems βHB is nicely anxiolytic in studies but maybe not intoxicating, the anxiolysis correlated with increased level of βHB . Human pilot studies and case studies suggest that ketogenic diet and ketogenic supplement-induced ketosis is a potential therapeutic approach in the treatment of epilepsy, Alzheimer's disease, autism spectrum disorder, and schizophrenia. Ketone bodies may exert their effects through modulation of GABAergic, glutamatergic, and adenosinergic system It has also been demonstrated that administration of exogenous ketone supplements (normal food + ketone supplements and/or medium chain triglyceride/MCT), such as ketone ester (KE), ketone salt (KS) or their combination with MCT oil (e.g., KSMCT) induce rapid and sustained nutritional ketosis https://www.frontiersin.org/.../10.../fnbeh.2018.00029/full "Administration with no need for energy restriction might also be a promising intervention to improve the neuronal activity and ameliorate the degeneration of CNS" [6] Just curious, couldn't spot it done anywhere... From risk assessment of Ethyl Acetoacetate Acetoacetate is an endogenous product of accelerated fat metabolism. Absorption of ethyl acetoacetate via the oral route is demonstrated in animals It may be anticipated that ethyl acetoacetate is partially cleaved already in the gastrointestinal tract due to acidic pH values or by bacterial activity. In a first metabolic step the absorbed portion of ethyl acetoacetate will be hydrolysed into 3-oxobutanoic acid and ethanol by the unspecific esterases of the blood. The acid moiety is an endogenous product within the lipid metabolism and is further metabolized predominantly to carbon dioxide and water; ethanol will be metabolized on known pathways. In animals, acute toxicity by the oral, dermal, and inhalative routes is low as judged by tests with rats. The substance demonstrated no or only mild skin irritation and mild eye irritation in tests with rabbits. Valid human or animal data on sensitization are not available. Following repeated oral exposure of ethyl acetoacetate in rats, no treatment-related adverse effects (including haematology, clinical chemistry, gross necropsy and histopathology) were reported up to 1,000 mg/kg bw/d. Note: Levels above 10 mmol/L of ketone bodies are associated with ketoacidosis. -
Probiotic turmerics for mental health and pro-inflammatory CNS conditions
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
Thanks for the kind words @Xperiment Likewise, had been wondering how you were traveling. Hope things are OK, feel free to chat with a message if ever needed. It's nice to not be in the continued pep of mixed weird moods, which turned into a bit of a nose dive, driven by grief and anger and other emotions I was struggling with in part but it's nice to get a day like today where I had the balance of positive mood, social contact, meaningful activity all working etc. -
Probiotic turmerics for mental health and pro-inflammatory CNS conditions
Alchemica replied to Alchemica's topic in Pharmacology, Chemistry & Medicine
I needed a bit of extra help with my mood over winter so went back on a minimal SSRI dose. Recently, I've been cautiously exploring how things like turmeric and saffron to go with that SSRI, which I don't find alone effective. The spices etc seem quite tailorable to be used to 'level up' when mood needs a more acute lift. . I've explored conventional pharmacotherapy extensively, shifting thinking/psychological stuff and other strategies, with little sustained benefits, at many times the side-effects of conventional pharmacotherapy caused more problems than solutions and sent me off dangerously self-medicating. Also I've explored herbal options too, finding some that some helped somewhat with excellent side-effect profiles. I'm currently giving the synergy of healthy dietary phytochemicals and minimal Western medicine a go. Does it hold promise, the best of both worlds for treatment resistant conditions? I still side with improvements being bio-psychosocial-spiritual but if you're biologically bed-ridden/housebound with debilitating symptoms, you can't tackle the other dimensions properly. One thing I'll say, is conventional pharmacotherapy as a standalone for mental illness is poorly effective for MANY people. Even coupled with psychological stuff. That said, our plant medicines aren't panaceas. Diet doesn't cure everything. The medicinal spices had enough potential merit, tolerability, evidence-base and safety to make it something worth considering as continued tools, especially useful for milder symptoms but efficacy waned relying on it as standalone for myself, as things like my fermented turmeric concoctions. While curcumin alone shows antidepressant efficacy, supplementary administration of curcumin to antidepressant therapy may reverse the development of depression and enhance the outcome of antidepressant treatment, also offering more rapid relief of depressive symptoms [1]. Same with saffron, it's got me through some really dark times off antidepressants but once again, efficacy waned for mood. Saffron did seem unique for psychotic spectrum stuff, crocins not only modulate the HPA axis and NMDARs but the DAergic system in a way that may be of relevance for schizophrenia-like behavioural deficits. These spices are useful tools and seem to have limited potential for interactions with SSRIs. While saffron is useful alone, showing efficacy equal to SSRIs [2], saffron could effectively prevent reaching the criteria of metabolic syndrome [3] and it significantly augmented SSRIs, both reducing side effects [4,5] and augmenting efficacy [6] I normally use bulk Iranian saffron but spotted a cheap Saffron + Curcumin (BCM-95, which is turmeric volatiles enhancing the bioavailability of curcumin, so piperine interactions with pharmaceuticals aren't problematic). I found I could kind of chase a saffron buzz a bit, as this product, I might be more sparing. [1] https://www.ncbi.nlm.nih.gov/pubmed/26066335 [2] https://www.ncbi.nlm.nih.gov/pubmed/27701683 [3] https://www.ncbi.nlm.nih.gov/pubmed/24955550 [4,5] https://www.ncbi.nlm.nih.gov/pubmed/23280545 https://www.ncbi.nlm.nih.gov/pubmed/22552758 [6] https://www.ncbi.nlm.nih.gov/pubmed/25484177 My mood has been so pathological, absolutely crap, so I'm trying a few things at once. Got into waking early (partial sleep deprivation as needed), keeping up exercise and skipping breakfast and having ALCAR as a meal replacement. have to tackle my body and brain at the same time particularly before they get even more out of whack, the two are linked. Things like saffron are established as being useful preventing metabolic abnormalities but ALCAR is cheap. "Scientists have noted a connection between depressive disorders, primarily seen as brain-based, and, insulin resistance (IR), a modifiable metabolic pro-inflammatory state that is typically seen as peripheral. Treating IR can with drugs or behavioural interventions can ameliorate, or possibly prevent, depressive disorder and its long-term consequences including dementia at various stages of the life course. Acetyl-L-Carnitine (LAC) is an endogenous molecule that regulates glutamate homeostasis and promotes healthy mitochondrial function, among other actions. Acetyl-L-carnitine presents a significant link between altered peripheral and neural function in the context of stress and depression. It has epigenetic action in reactivating neuroplasticity by restoring an inhibitory tone upon the release of glutamate driven by elevation of a stress-induced decrease in histone acetylation. Administration is also known to ameliorate insulin sensitivity in patients with type 2 diabetes Disruption of LAC function is an example of a molecular mediator that indicates a lack of resilience leading to negative outcomes. Indeed, epigenetic alteration of LAC is a marker of IR. Importantly, modulation of LAC levels is an example of capacity for flexible adaptation—thus LAC function can be reinstated and result in amelioration of changes associated with glutamatergic damage. LAC supplementation while targeting IR (i.e., reducing peripheral hyperglycemia, hyperinsulinemia, and hypertriglyceridemia) leads to antidepressant-like responses seen after few days of administration, while responses to standard antidepressant medications require repeated weeks of administration in the same animal models" https://www.ncbi.nlm.nih.gov/pubmed/29180223 Full text: http://sci-hub.tw/10.1016/j.neuropharm.2017.11.038 Quickly, that combination resulted in a good mood improvement and symptom reduction. -
Have you had those moments, after a loss or something where life shifts quite dramatically that you want to share? Lately, I've even had to set up my own 'Life Output Plant Box'. Slowly flowing things through it. Some of my Brahmi plants going to a 'Grow Free' box. Acacia's. When I'm struggling for sleep, I've been turning to midnight propagation of Delosperma's, Lobelia's. Salvia elegans etc - Plant's I've known and Loved going to new homes. Milly seed going out. Compiling up my experiences when life was a science experiment in life to try and help others. Through Death, I've had these transcendent, hearty, connecting wholesome pretty 'endogenous' spiritual experiences that have sanctified life for me and given me some momentum and faith and passion and most import, love and empathy, caring more about what's important. It's slow to undo rigidity but it's a positive step. New lenses for how to live my life through expanding Heart. Love. Gratitude. Compassion. Passion, Contribution. Non-judgemental connection. In a step by step way. Love was previously a shallow biological/psychological construct. Now it's the Divine Spiritual essence organising the Universe. I have respect for life that is quite profound. I want to do something with mine, at least keep growing positively. Not waste away without making more beneficial differences. I accept journeys of transformation etc, not so resonant with pathology constructs anymore. I see life as a journey of hard times, good times, growth through positive experiences, profound ones as well as pain, so much of life is about transformation, life is about alchemising the darkness that holds you back so you can be the best you, and learning. I see a natural healing 'emergence' that often unfolds, if we get out of the way. I feel inspired to not be so half-hearted in my efforts, to put aside negativity, to push myself forward into hearty-expansive connecting community growth, take some healthy steps to explore new life experiences, treat myself gently with love and compassion, do the same to others, be gentle and loving and uplifting with words, even considering one day it would be nice to get some more education in mental health etc or something small so that I can guide people through these experiences compassionately. It's compelled me to not isolate myself as ill and unworthy of friends etc, unworthy of people's time etc, I've seen a silver lining to feeling like life was always downward spirals, it's put me back into self-empowerment to make loving choices, stopped me thinking my voice is not worthy of talking to people etc, that I have nothing worth contributing to people's lives, to the community, to put loving presence and attention more into people, amplifying listening to people, connecting with people, finding out more about people, supporting their journey, learning - Life and Nature has taken on this Sacredness to me etc. Playing small in the world... not living a life that bringing any meaning, purpose or satisfaction. I've found passion, adopted more open-hearted receptivity to people whereas before I had walls that blocked me in the flow of ever opening to someone. I was full forward, analysing, rigid etc Yang into life without receiving other's worlds, with ego-concepts of love, little deep gratitude, little humility etc - illness can leave you really fragmented and energetically offline. I've made space to care about a You, as you are. Not to fix people, just compassionately love and encourage and support. Found holiness, divinity in the simplest of things
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