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Alchemica

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  1. Alchemica

    psychotropic water kefir

    There's been a bit of research into fermentation of different plants with either lactic acid bacteria or yeasts. I've tried to summarise a bit of it here The Science of Fermented Fruits, Veggies and Plant Medicines - Pharmacology, Chemistry & Medicine - The Corroboree (shaman-australis.com) The bacteria and yeasts are in a way potentially mildly psychoactive, hence their often-termed action as "psychobiotics". I've only tried milk kefir, which is interesting in it's own way, as the kefir peptides are too mildly psychoactive but you're right, fermenting a plant into the mix is an interesting concept and worth exploring more. There's the classic example of Sceletium which I've tried to explore here with yeasts yeasts to encourage bioconversion.pdf Let us know if you do any experimenting
  2. Stuck with this for awhile and there's been the slow but gradual return of some seemingly simple cognitive functions when used catalytically with effort and attempting to retrain my mind. For example, I was unable to sit and watch something as simple as a short youtube clip and follow the video. I've lately got back into watching inspirational short videos that I'm enjoying and can now watch something like a 30min clip which was previously totally unfeasible. I've started to embrace the need to do a lot more simple cognitive remediation in my day, for example getting back into colouring in an adult colouring books etc as an activity It hasn't all been linear for recovering some levels of very basic functionality, the cognitive fatigue associated with essentially retraining and forging some new connections of some basic cognitive functions has been extreme and literally left me floored and sometimes come at the expense of maintaining functionality in other domains.
  3. Alchemica

    Coscinium fenestratum & Berberine

    There seems to be several factors that limit berberine's bioavailability to the <1% mark: poor absorption extensive metabolism efflux back to the intestinal lumen by the action of permeability glycoprotein (P-glycoprotein, P-gp) As piperine from black pepper works on the cytochrome metabolism and P-gp level, it may very well be worth considering but haven't seen it done Things that have been studied are detailed here The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches the phospholipid-berberine complexes including things like encapsulating it in lecithin seem to have some significant effects on bioavailability in studies but wasn't able to personally tell how effective it was, lets just say I had lots of experiments happening.
  4. Alchemica

    Coscinium fenestratum & Berberine

    Thanks for the writeup. I explored a long time ago, also made up a mix of berberine hydrochloride with lecithin trying to improve it's bioavailability and was interested in it's CNS effects and beneficial metabolic effects, the CNS effects particularly related to it's sigma-1 agonism, prolyl oligopeptidase activity and monoaminergic effects Berberine may offer benefit in the control of psychotic and depressive symptoms, along with metabolic side effects. It has a broad range of CNS relevant pharmacological actions, including sigma-1 agonism, acetylcholinesterase inhibition and a range of neuroprotective effects including neurotrophin-mediated neuroprotection (NGF). There are some limitations to its use, including bioavailability and difficulties in reaching active levels in the CNS. “The potential use in schizophrenia was suggested when berberine was found to act as a D2-receptor antagonist, although it was also noted that dopamine level was increased in the brain as partly responsible for its antidepressant mechanism. It is unclear if these influences on dopamine level and action may counter each other, diminishing the proposed antipsychotic effect. Future studies may also elucidate whether berberine will exacerbate extrapyramidal motor symptoms due to the blockade of D2 receptors. On the other hand, it was proposed that the anxiolytic effect of berberine resulted from its antagonism at 5-HT2 receptor. This finding may indicate less severe motor side effects, if there are any, when berberine is used as an antipsychotic since atypical antipsychotics also act via 5-HT2 receptor blockade. A possible advantage of berberine over other antipsychotics is its ability to inhibit prolyl oligopeptidases, the activity of which is elevated in psychosis and not targeted by antipsychotics at present.”
  5. I'm just using a likely high asarone Acorus calamus essential oil. I don't want to make it a long-term addition but something to get out of a rut. Early days but small subjectively useful shifts, combined with little lifestyle shifts when I can seem to help slightly. I get very rigid in my routines and behaviours, so if this is a way to potentially plasticise my mind and behavioural repertoire a bit that could be good That could be useful and possibly minimise toxicity? I know some people simply chew the calamus rhizome, that seems to be the suggested way to use the Japanese Sweet Flag SAB sells for stimulant effects. This intranasal spray is a bit more full on with quite significant levels of asarone which I think would be hard to reach via plain herb Yeah that one's Acorus gramineus, it's got a diverse range of constituents that have interesting pharmacology aside from asarones. Still, whilst it seems to have quite prominent TCM use etc, I'd probably stick with chewing it etc as you mention My notes on A. gramineus
  6. A few days in and perhaps the most robust change has been with potential anti-addictive activity, for me being able to say no to smoking which resurged recently and I wasn't able to get on top of (EDIT less sustained anti-addictive potential than I'd hoped). The regulation of neurotrophins, particularly GDNF [1], seems to have quite profound effects on addictive processes, the GDNF pathway implicated in the anti-addictive action of things like ibogaine. Some stability in mood developed over the extreme negative mood states and even some uplift, whilst still having profound motivational deficits and ability to initiate and maintain goal-directed activity. Been trying to have glimmers of sustained attention to focus on tasks like watching short bursts of movies or TV shows which is still incredibly challenging As the administration via intranasal pathways directly into the olfactory bulb is likely to target the neurotrophic activity directly into the OFC and frontal lobes, it interests me how it could impact severe hypofrontality [2] particularly with regard to OFC functioning where damage can cause neurobehavioural issues For a long time I've been walking around like a headless chook with aberrant motor functions, this seems to reduce the 'headless chook' wandering a bit
  7. Thanks for your input and kind words DL. Hope you get some improvement of your residual symptoms. Initially there's not much robust acute improvement but symptoms were severe at baseline so not expecting quick results. If anything perhaps some destabilisation of mood etc but I sometimes feel that can be a part of the 'solve et coagula' of life. I particularly wonder if, as a significant portion of my symptoms was through an inhalation suicide attempt, this might be a very direct way to target the damaged pathways, particularly into the OFC, quite directly. They did some research using aromatherapy for inhalant abuse, this is like the next level up, intranasal aromatherapy. A novel approach of substitution therapy with inhalation of essential oil for the reduction of inhalant craving: A double-blinded randomized controlled trial
  8. Very limited availability of these two Mind Mend Cognitive Blend https://pdfhost.io/v/wIuDteWuV_mind_mend Polyphenol blend https://pdfhost.io/v/2XXhGA8me_polyphenol_blend
  9. I have a small quantity of research material left over from my brief TLC study on it, if anyone is curious to do any complimentary research on it let me know. There are no studies I can find on possible alkaloid constituents yet. Heteropterys angustifolia - A preliminary TLC study het ang.pdf
  10. Nose-to-brain delivery of asarones for CNS conditions? Ayurvedic medicine and traditional Chinese medicine (TCM) use Acorus preferably to treat central nervous system (CNS) related diseases such as epilepsy, insanity, mental weakness, or insomnia, Calamus has been widely used internally in both Chinese and Ayurvedic medicine for degenerative central nervous system disorders associated with communication, focus, memory and learning but there are concerns regarding the safety of such orally. The ability of asarones to induce such a broad range of neurotrophic factors (NGF, BDNF, GDNF, CNTF in a dose-dependent manner), alongside other neuroprotective and neurorestorative pharmacological actions, intrigues me. Pharmacologically, α- and β-asarone at lower doses (<50 mg/kg) exhibits a wide range of therapeutic activities such as antidepressant, antianxiety, anti-Alzheimer, and anti-Parkinson effects [1]. Asarones as a therapeutic are limited by poor absolute bioavailability when administered orally, less than 10%, because it is highly lipophilic and has poor solubility in water, coupled with extensive gastrointestinal and/or hepatic first-pass metabolism. There are concerns potentially harmful effects, such as genotoxicity particularly through accumulation in the liver where "both α- and β-asarone can cause hepatomas and might possess mutagenic, genotoxic, carcinogenic, and teratogenic effects". Because the amounts of asarone accumulated in liver may reflect its hepatotoxicity, there is special significance to reducing the amount of asarone in liver. Efforts have been centred on exploring nose-to-brain delivery of asarones, particularly as nanoemulsions [1,2] In humans, 20mg asarone has been added to memantine for AD [3] "...intranasal administration of asarone showed significant nose-to-brain transport, especially in the olfactory bulb, and such treatment yields equivalent or higher concentrations in other brain tissues compared to intravenous or oral administration" I'm personally curious as to whether a simple spray of asarones emulsified in water with a polysorbate emulsifier, delivered via a nasal spray bottle may be simple enough to make a readily available nose-to-brain delivery system "polysorbates [are] a promising excipient to increase drug concentration in both plasma and brain via intranasal route". The main beneficial actions of asarones, as described by [1], are summarised as: " (1) antioxidant properties; (2) the regulation of various neuroprotective signaling pathways; (3) the reduction of aggregate formation and promotion of the clearance of pathogenic protein aggregates; (4) anti-inflammatory properties; (5) the inhibition of microglial activation; (6) the activation of NTFs-mediated neuroprotection; and (7) the modulation of neurotransmitter levels associated with behavioural functions and neuronal cell survival." Actions of asarones on the CNS, taken from [1] Normal vs diseased brain aspects Asarone functions as a neuroprotective effect in both in vivo and in vitro models of neurodegeneration - Enhance BDNF via TrkB and activate the ERK pathway, triggering antidepressant-like effects - Significantly promoted the expression and secretion of neurotrophins, such as nerve growth factor (NGF), BDNF, and GDNF, in a dose-dependent manner. Also effects on CNTF - Maintain equilibrium between glutamate and GABA in the hippocampus, enhancing learning and memory abilities. β-asarone induced the high potentiation of GABAARs -Anxiolytic effects of asarone were partially due to maintaining the balance between excitatory/inhibitory transmissions and attenuating neuronal hyper-excitability of excitatory neurons in the basolateral amygdala. - modulates microglial morphological dynamics, may functionally relate to its influence on neurogenesis - Other monoaminergic effects, particularly antidepressant effects mediated by noradrenergic (α1 and α2 adrenoceptors) and serotonergic (particularly, 5-HT1A receptors) systems. - Enhances tyrosine hydroxylase activity with relevance to Parkinson's My current line of thinking is to make an emulsion of a polysorbate emulsifier with calamus oil 1:1 in water and explore that. Any input appreciated. 1:1:2 Calamus EO:polysorbate solubiliser:saline administered by nasal spray has got quite a strong bit of burn to it but not totally intolerable. Nasal sprays are normally less than 140uL/spray meaing at 25% EO concentration {assume 80% asarones), about 28mg asarone per spray may be possible. Even at that dose, each spray is quite painful but it may be feasible to - via multiple doses scattered through the day - reach a therapeutic dose of asarones intranasally with such. References: Balakrishnan, R.; Cho, D.-Y.; Kim, I.-S.; Seol, S.-H.; Choi, D.-K. Molecular Mechanisms and Therapeutic Potential of α- and β-Asarone in the Treatment of Neurological Disorders. Antioxidants 2022, 11, 281. https://doi.org/10.3390/antiox11020281 Lu, J., Fu, T., Qian, Y., Zhang, Q., Zhu, H., Pan, L., Zhang, M. (2014). Distribution of α-asarone in brain following three different routes of administration in rats. European Journal of Pharmaceutical Sciences, 63, 63–70. . https://doi.org/10.3390/10.1016/j.ejps.2014.06.006 Pan L, Zhou J, Ju F, Zhu H. Intranasal delivery of α-asarone to the brain with lactoferrin-modified mPEG-PLA nanoparticles prepared by premix membrane emulsification. Drug Deliv Transl Res. 2018 Feb;8(1):83-96. doi: https://doi.org/10.1007/s13346-017-0438-8. Dong, Haiying; Wu, Shuqin; Hu, Nan; Xing, Guihua (2018) Efficacy of tenuigenin and β-asarone as augmentations for memantine in the treatment of Alzheimer’s disease https://doi.org/10.1097/WNR.0000000000000952
  11. Following up with a TLC comparison to Tabernaemontana pandacaqui (Banana Bush) seeds T. pandacaqui | PDF Host
  12. I'll start to add some items slowly here that are available. PM me if interested. First up, plain 50g ceremonial cacao hearts (single strong serves) as single or double packs {Edit: only one single heart available]] Possible small donation to a charity of your choice. Single or double packs Heart-centred Cacao with Rose, Saffron and Kanna (low dose) ~50g. Please do not combine with pharmaceuticals or MAOI plants etc [Limited quantity available, EDIT: only 2 single hearts available] Possible small donation to a charity of your choice. Single packs. Tulsi and Rose tea [EDIT: out of stock] Possible small donation to a charity of your choice Functional foods [cognitive and polyphenol blends] still on the way.
  13. Alchemica

    Fermenting San Pedro Cactus

    You'd want the products that are intermediates to ethanol formation (pyruvate/acetaldehyde) to condense with the phenethylamine and under acidic conditions, undergo a Pictet-Spengler reaction to form THIQs (below). It wouldn't be a high conversion rate as conditions wouldn't be optimal but you'd likely get some conversion, which given the potency of the compounds, may be enough 1-Me-THIQ has actually found some putative therapeutic actions, "1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous antidepressant and parkinsonism-preventing substance that demonstrates neuroprotective activity." I've tried to cover some fermentations of plants here The Science of Fermented Fruits, Veggies and Plant Medicines - Pharmacology, Chemistry & Medicine - The Corroboree (shaman-australis.com) Yeasts are known for reducing some alkene (C=C) and carbonyl (C=O) compounds, which is more applicable to things like mesembrine-type alkaloids in Sceletium
  14. Alchemica

    Fermenting San Pedro Cactus

    This is an interesting concept. In theory, you could get a tetrahydroisoquinoline form from pyruvate/followed by decarboxylation = equiv. acetaldehyde and mescaline like such. This would bring it's pharmacology potentially more in line with the Lophs. The pharmacology of these THIQ's isn't well studied but they seem to be relatively potent serotonin agonists (nM) for a diverse range of serotonin receptors aside from more classical 5-HT2ARs eg pellotine In Vitro and In Vivo Evaluation of Pellotine: A Hypnotic Lophophora Alkaloid | ACS Pharmacology & Translational Science https://pubchem.ncbi.nlm.nih.gov/compound/613648
  15. Thanks for the wise input @Ishmael Fleishman. I tend to think people seeking ceremonial cacao are of a different mindset than tastes alone so may tolerate some differences but have to see I want to keep it away from business models and involving payment for goods for several reasons, being more a project I self-fund but agree, making it sustainable is essentially an impossible challenge if one does that but we'll see. A project to do, that I value, more than a sustainable business venture, is the aim Thanks again for the other points
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